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And so far, all the gear I’ve seen has been rather well-balanced in terms of advantages and drawbacks, meaning that overpowered god-builds feel unlikely, and creative stat-juggling should be quite the fun challenge. However, for those who’ve been waiting five years for another hunter x hunter web game adventure, I don’t think x hunter online will be good enough. An ancient robot who devoted his life to give birth to his children?
If you’re in the mood for a more competitive battle, x hunter game’s “hunter x game” player-versus-player (PvP) mode, much like the battlegrounds in hunter x hunter game online, pits two teams against one another in a battle to the death. But hunter x hunter games has a loot system. hxh game involves gathering piles of loot, something which is addictive for veteran RPG gamers.The portable screen magnifies small details that are lost when the console is docked.
 Be prepared to play the hunter x game beyond the first main ending; that’s simply the end of the first part, and the full Hunter X Online plays out over five different endings. Canonically strong team combinations.Though Nintendo’s limits on full Excel-spreadsheet nerdery may be a shortcoming in the eyes of those who revel in such systems, if the idea of an RPG is to role-play then shouldn’t I be able to slay the final boss if I, the player, role-playing as the hero, am skilled enough? It’s odd that hunter x hunter browser game and now Zelda champion such outside-the-box thinking when it ought to be role-playing hunter x hunter mmorpg games that consider such matters the most heavily. Because while the traditional – and less obvious – fighting hunter x hunter online game archetypes are present and correct, from all-rounder hunter x online game, to nimble, acrobatic hunter x hunter mmorpg online, to tricksy, technical, trap-setting Dr.
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As the most extensive renewable energy (23,000 TW/year) in nature, how to realize its efficient and reasonable development and utilization has always been a research hotspot for scientific researchers. From the current development stage, the utilization of solar energy mainly focuses on three aspects: solar power system, solar thermal system and solar fuel system. However, the intermittent problem of regional light source caused by Earth rotation greatly limits the continuous conversion of solar energy to other energy sources, so that it cannot meet the continuous energy demand in daily production and life. In response to the problem, scientists put forward the corresponding energy reserve strategy. By combining the photoelectrochemical system with the secondary cell or liquid flow cell system, the conversion and storage of solar energy are realized, and the energy supply and demand caused by the intermittent light source are effectively solved. However, the multi-system connection has the disadvantages of complex system, high cost and serious energy transmission loss. Therefore, how to design the integrated solar energy storage system rationally has become the next research problem that researchers need to solve.

 

Recently, Shaojun Dongs team at Changchun Institute of Applied Chemistry, Chinese Academy of Sciences realized the continuous transformation and storage of solar energy under an integrated system by constructing a bio-photoelectrochemical model based on water/oxygen circulation, providing a new research idea for the efficient use of renewable energy.

 

The team designed the bio-photochemical system to use polypyrrole solid-state capacitive electrodes as energy storage modules to make the energy storage process safer and easier. In the process of solar energy storage, the water/oxygen molecules in the system can spontaneously form a cycle without the participation of additional sacrifice reagents and other redox pairs, which greatly improves the safety of the equipment and reduces the cost.

 

In addition, the modular and integrated structural design of this system enables it to be adjusted and optimized according to different circumstances and better meet the practical application needs of many aspects. Experimental data analysis showed that the conceptual model obtained maximum power density outputs of 0.34 ± 0.01 and 0.19 ± 0.02 mWcm-2 under light and dark field conditions, respectively, and showed stable solar accumulator cycle performance. By changing the capacitance of the energy storage module (polypyrrole capacitive electrode), the charge/discharge time can be effectively regulated. In this research work, the construction of bio-photoelectrochemical model of water/oxygen cycle promotes the development of cross-integration among photoelectrochemical system, bioelectrochemical system and capacitor system on the one hand, and also provides certain guiding significance for the future research and development of green rechargeable devices on the other hand. The results were recently published in the Journal of the American Chemical Society, (2019, 141, 16416-16421), and were supported by the National Natural Science Foundation of China and the Ministry of Science and Technology of China.

 

About Author

As a biotechnology company, Lifeasible is specialized in agricultural science, offering a wide variety of agro-related services and products for environmental and energy solutions.

 

Our plant breeding and culture services support increasingly stringent safety and quality standards in the agricultural industry. Relying on our revolutionary techniques, various molecular breeding services and molecular diagnostic methods are offered for a wider range of agriculture-related sectors.

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According to reports, the rapid spread of COVID-19 has led to a surge in the number of suspected infections and close contacts. The early detection of the virus can not only enable the infected person to be treated in time and reduce the risk of death, but also can effectively control the source of the infection and cut off the transmission route through isolation.

 

Generally, there are two detection strategies for infectious diseases: nucleic acid detection and immunological detection. Nucleic acid detection is the detection of viral RNA genome, including gene sequencing, quantitative real-time PCR, digital droplet PCR, gene chip and Loop-Mediated isothermal amplification. Immunological detection is the detection of specific antibodies produced by viral antigens or by human immune responses, including immunochromatographic strips, enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA). 

 

The following compounds provieded by BOC Sciences can be used in the production of COVID-19 test kits:

 

Guanidine thiocyanate

Guanidine thiocyanate is a colorless crystal or white powder, soluble in water. It is an anticoupling agent and a strong protein denaturation agent, which can dissolve proteins, and quickly separate the nucleic acid from nuclear proteins. The combination of guanidine thiocyanate and mercaptoethanol is able to inhibit the activity of RNase. The combined action of guanidine thiocyanate and sodium dodecyl sarcosine can denature proteins and release RNA.

 

Guanidine hydrochloride

Guanidine hydrochloride, white or yellowish in color, is used as a protein denaturator. As a strong denaturation agent for extracting total RNA from cells, guanidine hydrochloride solution can dissolve proteins, destroy the secondary structure of nucleoproteins dissociated from nucleic acids. In addition, guanidine hydrochloride and other reducing agents can inactivate RNA enzymes. Using dicyandiamide and ammonium salt (ammonium chloride) as raw materials, crude guanidine hydrochloride products can be obtained at 170-230.

 

Tris(hydroxymethyl)aminomethane

Tris(hydroxymethyl)aminomethane is a common buffer in molecular biology and cell culture. Tris buffer has a high buffering capacity, high solubility in water, and is inert to many enzyme reactions, which makes Tris a very satisfying buffer for many biochemical purposes. It is generally used to stabilize the pH of reaction system and has a strong buffering capacity between pH 7.5 and pH 9.0. Tris-HCl buffer system can also be used to stabilize the pH value in the gel. Tris buffer is widely used as a solvent for nucleic acids and proteins. Due to the low ionic strength, Tris buffer can also be used for the formation of intermediate fibers in nematodes. "TE buffer" prepared by adding EDTA into Tris hydrochloric acid buffer can be used for DNA stabilization and storage.

 

HEPES

HEPES buffer, mainly composed of 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, is a non-ionic amphoteric buffer with good buffering capacity in the pH range of 7.2-7.4. Its greatest advantage is that it can maintain a relatively constant pH value in open culture or cell observation. Under these conditions, the cap of the cell culture bottle should be tightened to prevent the small amount of carbonate needed in the culture solution from being dispersed into the air. HEPES is difficult to dissolve in any other solvents, but it is readily dissolves in water, and does not precipitate with polyvalent metal ions. In addition, most natural factors such as temperature, concentration, medium salinity, and ion composition do not affect the dissociation of HEPES, so the stability of HEPES is excellent.

 

DTT

DTT, short for DL-dithiothreitol, is used to block the formation of intramolecular or intermolecular disulfide bonds between cysteines in proteins. The effect of DTT on proteins is that it can reduce disulfide bonds in proteins. One of the uses of DTT is as a reductant for sulfhydrylated DNA. Sulfur atoms at the ends of sulfhydrylation DNA tend to form dimers in solution, especially in the presence of oxygen. This dimerization greatly reduces the efficiency of some coupling experiments, such as DNA fixation in biosensors.

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3.2 The immunoregulatory effect of mesenchymal stem cells on B cells

B cells are pluripotent stem cells derived from bone marrow. With the stimulation of antigens and T cells, they proliferate in large quantities and further differentiate and develop into plasma cells capable of secreting antibodies. Mesenchymal stem cells have a certain inhibitory effect on the proliferation and differentiation of B cells. Mesenchymal stem cells can induce B cell proliferation and differentiation through cell contact. These conclusions may be related to the cell purification method, culture environment and detection time point, etc., and further research is needed. In addition, the functions of B cells secreting antibodies and expressing chemokine receptors CXCR4, CXCR5, and CCR7 are inhibited by mesenchymal stem cells, while the secretion of B cell costimulatory molecules and cytokines is not affected by mesenchymal stem cells.

The effect of mesenchymal stem cells on B cells is achieved through cell contact, and PD-1 / PDL-1 pathway is an important way for mesenchymal stem cells to inhibit B cells. Studies have shown that PD-1 can dephosphorylate some key signal transducers of BCR signaling by accumulating phosphatase, thereby hindering BCR signaling and inhibiting B cell activation. In addition, there are studies suggesting that T cells play an important role in the immune regulation of mesenchymal stem cells to B cells. Mesenchymal stem cells inhibit the proliferation and differentiation of B cells, but require the interaction between T cells and mesenchymal stem cells.

In addition to the key role of cell contact, mesenchymal stem cells regulate B cell function. Soluble cytokines also play a role that cannot be ignored. The study found that mesenchymal stem cells secrete CCL2, and achieve immune regulation of B cells by suppressing transcriptional activator protein 3 and inducing the production of paired box protein 5 (PAX5). In the mesenchymal stem cell co-culture system, the m RNA expression of Blimp-1 is significantly reduced, and the m RNA expression of PAX-5 is increased. Inhibiting the expression of Blimp-1 and promoting the expression of PAX-5 can inhibit the proliferation and differentiation of B cells.

3.3 The immunomodulatory effect of mesenchymal stem cells on NK cells

NK cells are short for natural killer cells. It is different from T cells and B cells; it does not require specific antibodies to participate in the killing of target cells or antigen-specific sensitization. The main role of NK cells in the innate immunity of the human body is to distinguish normal and abnormal cells by recognizing the ligands of corresponding activated receptors and inhibitory receptors on target cells. They also play a role in immune surveillance.

Mesenchymal stem cells can inhibit the proliferation and function of NK cells. NK cells are stimulated by activated cytokines, resulting in high expression of NK cell surface activated receptors NKp30, NKG2D, NKp44, CD69. The activated receptors on the surface of these cells are closely related to the function of NK cells. When NK cells and mesenchymal stem cells are co-cultured, the expressions of NK cell activation receptors NKp30 and NKG2D will be reduced, and NKp44 will not be expressed. Therefore, mesenchymal stem cells inhibit the cytotoxicity of NK cells by inhibiting the expression of NK cell activation receptors.

FN-γ plays a key role in the inhibition of mesenchymal stem cells on NK cells. The sensitivity of mesenchymal stem cells to NK cytotoxicity can be reduced by the presence of IFN-γ. The role of IFN-γ may be to induce mesenchymal stem cells to overexpress HLA molecules and interact with the inhibitory receptors of NK cells, thereby inhibiting the cytotoxicity of NK cells. Indoleamine 2,3-dioxygenase, prostaglandin E2, HLA-G play a major role in the inhibition of mesenchymal stem cells on NK cells. The HLA-G receptor is expressed on the surface of a leukocyte called LILRB, and can be expressed on the surface of T, B, and NK cells. The interaction of HLA-G / LILRB2 blocks the MEK / ERK signaling pathway and inhibits the cytotoxicity of NK cells. Adding indoleamine 2,3-dioxygenase or prostaglandin E2 to the mixed culture of mesenchymal stem cells and NK cells can restore the proliferation of NK cells to a certain extent. In the presence of IFN-γ and tumor necrosis factor alpha, mesenchymal stem cells interact with NK cells, mesenchymal stem cells secrete prostaglandin E2, and subsequently prostaglandin E2 can promote indoleamine 2,3-dioxygenase synthesis. In addition, the inhibitory effect of mesenchymal stem cells on NK cells is concentration-dependent. As the ratio of NK / mesenchymal stem cells increases, the inhibitory effect of mesenchymal stem cells on NK cells weakens.

3.4 The immunomodulatory effect of mesenchymal stem cells on dendritic cells

Dendritic cells are important antigen-presenting cells, derived from pluripotent hematopoietic stem cells. Immature dendritic cells have extremely strong antigen uptake, processing and processing capabilities. After ingesting the antigen or being stimulated, immature dendritic cells (CD14-, CD1a +) can differentiate into mature dendritic cells (CD80 +, CD83 +, CD86 +), and during this process, their antigen uptake and processing capacity will be significantly reduced, and their ability to present antigens and stimulate immune responses will be enhanced. Dendritic cells are presented to the corresponding CD8 + T cells and CD4 + T cells through the abundant antigen peptide-MHC class Ⅰ molecular complex and antigen peptide-MHC class Ⅱ molecular complex on their membrane surface, thereby activating T cell response and allowing T cells provide costimulatory molecules to fully activate T cells.

Mesenchymal stem cells can inhibit the differentiation of pluripotent hematopoietic stem cells into dendritic cells and the maturation of dendritic cells. Under the stimulation of granulocyte-macrophage stimulating factor / interleukin 4, the co-culture of mesenchymal stem cells and monocytes reduced the expression of CD1a and the high expression of CD14, indicating that the differentiation of dendritic cells was inhibited. In addition, under the stimulation of lipopolysaccharide, mesenchymal stem cells were co-cultured with dendritic cells, the expression of maturation marker CD83 of dendritic cells was decreased, the expression of costimulatory molecules CD80 and CD86 on the surface of dendritic cells was decreased, and the expression of costimulatory molecules CD80 and CD86 on the surface of DR was decreased, the expression of antigen presentation molecule HLA-DR was decreased, and the secretion of interleukin 2 was decreased, indicating that mesenchymal stem cells inhibited the maturation of dendritic cell. When the ratio of mesenchymal stem cells / monocytes is high (1:10), the inhibitory effect of mesenchymal stem cells on the differentiation of monocytes into dendritic cells can be completely achieved by soluble factors. When the ratio of mesenchymal stem cells / monocytes is low (1:20 or 1:40), mesenchymal stem cells exert their inhibitory effect mainly through cell contact. Mesenchymal stem cells can inhibit the differentiation of CD34 + -derived CD14 + precursor cells and monocytes into CD1a + dendritic cells, and inhibit the maturation and function of dendritic cells. The addition of macrophage colony stimulating factor and interleukin 6 antibody can reduce the expression of CD14, but cannot restore the expression of CD1a, suggesting that macrophage colony stimulating factor and interleukin 6 are involved in the suppression of mesenchymal stem cells.

The inhibitory effect of mesenchymal stem cells on the differentiation and maturation of dendritic cells indirectly leads to the inhibition of T cell activation, thereby suppressing the adaptive immune response. Mesenchymal stem cells have an inhibitory effect on dendritic cells through cell contact and soluble factors. This inhibitory effect may also involve macrophage colony stimulating factor, interleukin 6 and prostaglandin E2, and its specific mechanism needs further study.

At present, there are many clinical trials on the immune regulation of mesenchymal stem cells, and different mesenchymal stem cell isolation methods and different mesenchymal stem cell sources have different effects on the immune regulation of mesenchymal stem cells. Mesenchymal stem cells play an immunoregulatory role in the microenvironment, and different microenvironments also have different effects on their immune regulation.

References

[1] Che N, Li X, Zhang L, et al. Impaired B cell inhibition by lupus bone marrow mesenchymal stem cells is caused by reduced CCL2 expression. J Immunol.2014;193(10):5306-5314.

[2] Ribeiro A, Laranjeira P, Mendes S, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther.2013;4(5):125.

[3] Nekanti U, Dastidar S, Venugopal P, et al. Increased proliferation and analysis of differential gene expression in human Wharton's jelly-derived mesenchymal stromal cells under hypoxia[J]. International Journal of Biological Sciences, 2010, 6 (5) :499-512.

[4] Boxall SA, Jones E. Markers for characterization of bone marrow multipotential stromal cells[J]. Stem Cells International, 2012, 2012, 975871.

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Potential therapies for SARS-CoV-2 can be divided into two categories: one directly targets the novel coronavirus, and the other is human-oriented. Viruses must enter the host cell to replicate in order to function. Therefore, antiviral drugs can be designed for a series of targets in the process of virus interaction with cell receptors, gene replication, transcription and translation when the virus invades host cells and completes its life cycle. In addition to the above drug research and development against the virus, we can also take the human body as a guide to find therapeutic drugs for the immune response caused by the virus. In the early stage of viral infection, the human body's own immunity can be appropriately improved/activated by the activation of interferon or innate immune receptors to fight the virus. For severely advanced/immune hyperactive patients, since patients are attacked by their own immune system, they can consider using immunosuppressive drugs or mechanisms to adjust. In addition, it can also be treated against the mechanism/target where the host and the pathogen interact with each other. Currently, the main treatment methods for the disease include small molecule drugs, biomacromolecule drugs, gene therapy, cell therapy, traditional Chinese medicine therapy, and medical devices. The potential applications of them in the treatment of SARS-CoV-2 are as follows.

 

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Chemical small-molecule drugs: Small-molecule drugs are currently one of the types of drugs that are expected to be used for the treatment of SARS-CoV-2. There are now multiple small-molecule drugs in clinical trials, and their effectiveness and safety against the coronavirus needs to be further verified.

 

Biomacromolecule drugs: These drugs have high specificity and strong continuity and compliance in the body, but their production cost is high, and because they only act on the cell membrane and outside the membrane and cannot enter the cell, so the target is limited. At present, no specific antibodies have been found to conduct clinical trials in the research of the coronavirus. At the same time, by extracting neutralizing antibodies from the plasma of some recovered covid-19 patients with sufficient concentration of effective antibodies, the potentially harmful components can be removed to treat critically ill patients, but it is unlikely to be promoted on a large scale.

 

Gene therapy: A disease treatment method developed in recent years. It usually uses transgenic methods to make up for missing functional genes or strengthen gene functions. A variety of methods have been developed, such as precise gene editing. However, there is no gene therapy for the coronavirus. This method is generally for chronic, long-term viral infections, such as gene editing of human cells, so that the pathogens lose the ability to infect the cells, or suppress the virus gene expression through RNA interference.

 

Cell therapy: Also a disease treatment method developed in recent years. One of the cell treatment methods is to supplement and replace the missing cells, such as the use of stem cells; one is to regulate the body's immunity by cytokines secreted by the transplanted cells, and this way is not to supplement or replace the cells, and then the transplanted cells will disappear; the other is that the transplanted cells can target and attack specific harmful cells, such as the specific recognition and removal of cancer cells by CAR-T cells. Cell therapy has been studied in the treatment of the SARS-CoV-2, such as the use of mesenchymal stem cells for immune regulation. In the future, we can also consider using specific stem cells for tissue repair and regeneration; organoids derived from stem cells can be used for disease modeling and drug screening.

 

Medical device treatment: In addition to drug treatment, respiratory support treatments that rely on medical devices, such as oxygen therapy, invasive mechanical  ventilation, extracorporeal membrane oxygenation (ECMO), and circulation support, also played an important role in the treatment of severe and critically ill patients with COVID-19.

 

Traditional Chinese medicine treatment: SARS-CoV-2 belongs to the category of "epidemic" diseases of traditional Chinese medicine. Its research idea is different from Western medicine. It does not aim at a specific target but cures the disease in a systematic way. Through in-depth observation and treatment of patients, on the basis of summarizing and analyzing the diagnosis and treatment schemes of traditional Chinese medicine across the country, combing and screening the treatment experience and effective prescriptions in various regions, it is necessary to judge its effectiveness and safety through rigorous clinical trials.

 

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RNA interference (RNAi) is a revolutionary discovery in genetic research. RNAi can specifically silence endogenous or exogenous target genes, which is a rapidly developing gene control technology with broad application prospects. Since Tuchl et al. found in 2001 that artificially synthesized double-stranded small interfering RNA (siRNA) can efficiently silence the expression of target genes in mammalian cells, the life science field has set off a wave of basic and applied research on siRNA. With the gene silencing mechanism, significant progress has been made in the development of siRNA drugs to treat diseases.

In August 2018, the world’s first siRNA drug, Onpattro (Patisiran) was approved by the FDA for the treatment of patients with polyneuropathy caused by hATTR.

Onpattro is the world's first drug developed based on the Nobel Prize achievement RNA interference technology. In 1998, Andrew Fire and Craig Mello revealed the RNAi phenomenon for the first time in C. elegans, and won the Nobel Prize in Physiology in 2006 for this discovery. The approval of the first siRNA drug in 2018 takes 20 years. Onpattro's approval marks a major breakthrough in the field of RNAi medicines, and small nucleic acid medicines are finally dawning.

According to statistics, among disease-related proteins in the human body, more than 80% of the proteins cannot be targeted by current conventional small molecule drugs and biological macromolecular preparations, and are non-drugable proteins. Gene therapy aimed at treating diseases through gene expression, silencing and other functions is considered by the industry as the third generation of therapeutic drugs after chemical small molecule drugs and biological macromolecular drugs. This kind of therapy achieves the treatment of diseases at the genetic level, not restricted by non-drugable protein. As the most mainstream type of RNA drugs in gene therapy, siRNA drugs are used to treat diseases from the level of mRNA. Compared with chemical small molecular drugs and biological macromolecular drugs, they have a higher efficiency at the protein level.

In 2004, Bevasiranib, an siRNA drug developed by Opko in the United States, launched a clinical trial for the treatment of wet age-related macular degeneration. This is the first clinical trial related to siRNA in the world. Subsequently, many global pharmaceutical giants, including Pfizer, Sanofi, Roche, and Merck, joined the development queue of siRNA drugs.

Unfortunately, the development of the Bevasiranib project has failed in phase III due to poor clinical results, and other latecomers have not been spared. The reason is that the poor targeting, off-target effects and stability of RNAi drugs are the most important constraints that affect their efficacy. Many factors have led to the efficacy of these drugs being far less than expected, but also accompanied by serious insurmountable medication side effect.

From the perspective of technical requirements, siRNA after intravenous injection is easily degraded by nucleases, has high renal clearance, poor cell uptake efficiency, and clinical application is limited. The success of siRNA drugs depends on the development of drug delivery system technology, especially the ability to delivery carrier technology that transports RNAi safely and efficiently to specific therapeutic targets in the body.

As the world's first approved siRNA drug, Patisiran adopts the LNP drug delivery system to encapsulate RNAi drugs in liposomes, which can be administered by intravenous injection. The liposome coating greatly improves the stability of the drug and the targeting of liver tissue can ensure that the siRNA will not be filtered by the kidney and will be gradually taken up by the target cells of the liver tissue during the blood circulation. This is the key to Patissiran to overcome the above major constraints and get approved for marketing.

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Proteolysis targeting chimeras (PROTAC)

Proteolysis targeting chimeras (PROTAC) is currently a very hot drug development technology and is considered by the industry as a star of small molecule drug development. One end of this type of bifunctional small molecule is a ligand that targets the target protein, and the other end is a ligand that binds to E3 ubiquitin ligase, which is then connected by a linker of a certain length. In this way, the target protein and E3 ubiquitin ligase can be brought closer together, so that the target protein is labeled with ubiquitin, and then degraded by the ubiquitin-proteasome pathway.

The main advantages are as follows:

  1. Targeted degradation "non-drugable targets", such as KRAS, STAT3, etc.;
  2. Overcome tumor drug resistance;
  3. Extend the action time;
  4. PROTACcan affect protein enzyme function and regulation Non-enzymatic function.

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The development history of PROTAC

The technology has been developing for 20 years. Proteinix researchers submitted a patent application for the degradation of specific proteins using small molecule compounds based on the ubiquitin mechanism in 1999. Two years later, Dr. CraigCrews and Dr. Raymond Deshaies designed a series of bifunctional small molecules based on peptide compounds to induce the degradation of methionine peptidase 2 (MetAP-2), and formally proposed the concept of PROTAC. However, because these compounds, which are based on large and bulky peptides, are difficult to connect to cells, the first generation of PROTACs failed. Until 2008, the Crews team designed the second-generation PROTACs that can be used to degrade the androgen receptor (AR) based on E3's ubiquitin protein ligase MDM2. In 2015, the Crews team designed a new generation of PROTACs based on the new E3 ubiquitin ligase VHL and CRBN ligands to reduce the level of multiple proteins by more than 90%. It was also this year that James Bradner, head of research and development at Novartis, published a new generation of PROTAC molecules based on thalidomide analogues in Science, thus detonating the entire field. In 2013, Crews established Arvinas, the world's first company to develop drugs using PROTAC technology.

What is optimistic about this technology is that the world's first PROTAC drug ARV-110 developed by the company is intended to be used for the treatment of castration-resistant prostate cancer. It has entered the stage of clinical phase I research. The initial data of clinical phase I indicate that ARV -110 has good oral availability and good safety and tolerability.

About ARV-110

ARV-110 is the world's first oral bioavailable PRAOTC small molecule drug, which selectively targets the degradation of androgen receptor (AR). In May 2019, ARV-110 received FDA fast-track approval, mainly for the treatment of metastatic trend-resistant prostate cancer (mCRPC).

In developed Europe and the United States, mCRPC is the second most frequent malignant tumor among men, and it has also been a difficult treatment and a hot spot in clinical research in the field of prostate cancer. At present, the first-line treatment drugs mainly targeting the androgen receptor target (AR) include abiraterone and enzalutamide. In addition, in March 2020, the American Society of Clinical Oncology Genitourinary System Cancer Symposium (ASCO-GU2020) discussed that for patients with mCRPC carrying DNA damage repair mutations (DDM), Abiraterone is more effective than Zalu for first-line treatment. Amine has a tendency to have better therapeutic effects. The use of androgen receptor targeting (ARAT) drugs (Abiraterone or Enzalutamide) for first-line treatment of mCRPC patients will result in more survival benefits for patients, especially for intraductal carcinoma of the prostate (IDC-P). However, for patients with AR gene or gene enhancer amplification or AR point mutations, the current first-line treatment drugs are less effective, and 15-25% of patients do not respond to second-generation hormone therapy such as abiraterone and enzalutamide. Most patients with responsiveness will eventually develop severe drug resistance, leading to a poor prognosis. The PRAOTC molecule ARV-110 targeting androgen receptor degradation currently shows excellent activity in clinical models of AR mutation and overexpression.

The mechanism of ARV-110

To overcome these challenges and improve current treatment options, ARV-110 uses the ubiquitin-protease system to degrade the AR protein that plays a key role in the development of prostate cancer. It is different from traditional inhibitors and does not need to be inhibited by "occupying" receptors. In addition, the PROTAC drug can also work repeatedly to degrade the newly transcribed target protein, so it can overcome the increase in target protein expression and mutations in the target protein. The specific molecular structure has not yet been announced.

Related preclinical studies

In preclinical studies, ARV-110 has shown promising activity as a targeted degradation agent for AR. In a model sensitive to enzalutamide, ARV-110 showed a reduction in prostate-specific antigen (PSA) similar to enzalutamide, and the dose was lower. In the model of enzalutamide resistance, ARV-110 can significantly inhibit tumor growth.

Clinical trials

On May 29, 2019, the FDA approved a phase I, open-label, dose-escalation clinical phase I trial to evaluate ARV in patients with metastatic castration-resistant prostate cancer who had previously received at least two systemic therapies -110 safety, tolerability, pharmacokinetics and pharmacodynamics. The trial is expected to enroll 36 patients, 18 years of age or older and have received at least two approved CRPC systemic therapies (at least one must be abiraterone or enzalutamide). Patients with progressive mCRPC must undergo ADT (prostate cancer androgen deprivation therapy) or orchiectomy.

The latest clinical data

On May 13, 2020, the latest safety-related data and early efficacy data of the Phase I clinical trial (NCT03888612) were published in the abstract of the American Society of Clinical Oncology (ASCO). To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARV-110, mCRPC patients who have previously received at least 2 treatment regimens (including enzalutamide and/or abiraterone) are taken orally once daily ARV-110. Endpoints include dose-limiting toxicity (DLT), adverse events (AEs), pharmacokinetics (PK), biomarkers (eg AR mutation analysis), RECIST (evaluation criteria for the efficacy of solid tumors) and PSA (prostate specific antigen) responses. As of January 2020, there were 18 patients participating in the trial. The doses were divided into 4 groups, namely 35 mg (3 cases), 70 mg (4 cases), 140 mg (8 cases), and 280 mg (3 cases). Among them, 12 patients were previously treated with enzalutamide and abiraterone; 14 patients had received chemotherapy. One of the 18 patients had grade 4 (Gr) dose-limiting toxicity (DLT, 280 mg) while taking the cholesterol drug Rosuvastatin (DLT, 280 mg) and hepatic transaminase AST/ALT increased, followed by acute renal failure. The second patient had grade 3 (Gr) dose-limiting toxicity when taking the cholesterol drug rosuvastatin and hepatic transaminase AST/ALT also increased. After stopping rosuvastatin, ARV-110 treatment can be continued. In these two patients, in view of the significant increase in rosuvastatin plasma concentration at the same time as AST/ALT, the use of rosuvastatin and ARV-110 should be banned at the same time. In addition, there are no other relevant grade 3/4 adverse events (AE) reported. 15 patients underwent PSA response assessment (not including 1 patient who stopped treatment due to disease progression and 2 patients who had just started treatment). Eight of these patients had an initial dose of 140 mg. Two patients in the 140 mg dose group had a PSA reduction of greater than 50%. The two groups had previously received enzalutamide and abiraterone, chemotherapy, bicalutamide and radium 223, and other treatment options. One patient had 2 AR mutations known to cause enzalutamide resistance. Another patient also received an unconfirmed partial RECIST response (confirmation test to be determined). At the time of data cut-off, patients undergoing longer cycles (8 weeks and more than 21 weeks) of treatment trials are still ongoing.

The latest clinical trial data shows that ARV-110 has acceptable safety. The maximum tolerated dose (MTD) has not been established and the phase 2 recommended dose (RP2D) is still being tested. In addition, for patients receiving enzalutamide/abiraterone treatment, ARV-110 has shown anti-tumor activity, of which 2 patients have been confirmed by PSA response, and 1 of them is related to tumor reduction.

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C5 is the first complement molecule that forms the membrane attack complex (MAC). C5 is composed of ax and β chains connected by disulfide bonds. alpha chain is 115 KDa and the β chain is 75 KDa. There is no intra-chain thioester bond molecular weight of 190 KDa. The 74-75 arginine-leucine bond near the N-terminus is where C5 convertase acts. Under the action of C5 convertase, a small fragment C5a with a molecular weight of 11 KDa was cleaved into the liquid phase. C5a is the most potent mediator of complement lysis fragments with allergic toxins." Current studies indicate that high concentrations of C5a may reduce tumors by increasing Gr4 CD11b bone marrow cells in peripheral blood. Surface CD4, CD8T cells promote the formation of tumor blood vessels and inhibit apoptosis to promote tumor growth. Low concentrations of C5a can inhibit tumor growth by stimulating immune cells and blocking the cell cycle, or low concentrations of C5a can stimulate M1 phagocytes and NK cells to tumor. On the surface, both M1 phagocytes and NK cells have a certain anti-tumor effect and thus exhibit an indirect anti-tumor effect. Therefore, the tumor-related value of C5a has a certain concentration dependence. The concentration of C5a on the tumor surface may be the key to inhibition or promotion its performance. In addition, it has also been reported that the C5a receptor expressed on the surface of the tumor can significantly enhance the tumor's invasiveness, and the cytokines stimulated by C5a such as hepatocyte growth factor can also enhance the tumor's invasiveness.

At present, the research on the relationship between C5 and parenchymal organ fibrosis has been widely carried out. Boor et al.6 found that the mechanism of C5 involvement in parenchymal organ fibrosis may be related to the C5a receptor expressed on the cell surface, C5a stimulation-related cytokines and changes in parenchyma. Organ hemodynamics is related, on the other hand, there are studies that C5a has a biological relationship with liver regeneration. The three sites included in this study are all SNPs that are currently confirmed to be functional in the C5 gene. The rs17611 allele A was mostly severe cirrhosis patients and the rs2300929 allele C was mild cirrhosis patients. The C5 gene polymorphism has a clear relationship with the cirrhosis process. In another aspect, studies have indicated that the C5 serum concentration of carriers of rs17611 allele A and rs2300929 allele T is significantly higher than that of non-carriers. There is no relationship between C5 activity and C5 gene polymorphism, which suggests that there may be other factors affecting C5 activity. The gene polymorphism at rs25681 has also been shown to be associated with susceptibility to periodontitis. As in previous studies, this study also verified that there was a linkage disequilibrium among the three sites included, so that haplotype analysis was performed to obtain more genetic specificity than unit site analysis.

The results of this study show that the risk of HCC is significantly increased in those who carry the rs17611 allele G, rs25681 allele C and rs2300929 allele C, and the haplotype rs17611G-rs25681C-s2300929C can increase the risk of HCC. However, study showed that the C5 serum concentrations of carriers of rs17611 allele G and rs2300929 allele C were significantly lower than those of non-carriers, and low concentrations of C5a showed a certain anti-tumor growth effect, which is obvious different from this study. Different clinical phenotypes due to different diseases in different populations have been confirmed in a number of clinical genetic studies. In addition, Halangk et al. did not find C5 gene polymorphism and the degree of cirrhosis is related. This also shows that genetic polymorphism and clinical phenotype are not the same-there are many influencing factors in the corresponding relationship. How the C5 gene polymorphism affects its serum concentration is still unclear, and the tumor-related role of C5a is still unknown.

Since the liver is the main place for complement synthesis (80% to 90% of the complement components in plasma are synthesized in hepatocytes), hepatic stellate cells, Kupffer cells, and hepatic sinusoidal epithelial cells all express C5a receptors. These objective conditions clarify the role of the complement system in liver diseases, this study is the first to propose a correlation between C5 gene polymorphism and HCC susceptibility. In the future, screening and follow-up can be carried out in high-risk populations under the premise of improving the correlation between C5 gene polymorphism and C5 serum concentration and the pathogenesis of C5a serum concentration and HCC, to accurately assess the risk of HCC in individuals, so as to reach the early stage of preventing HCC.

Early detection and early treatment in the prevention and treatment of malignant tumors can significantly improve the patient's prognosis and quality of life. With the extensive use of genome-wide scanning technology, linkage analysis, family analysis and SNP as the third-generation genetic markers, we can gradually achieve early screening of malignant tumors or other diseases to obtain better clinical results. At present, C5a receptor blockers have been confirmed in experiments that can significantly slow down the progress of liver cirrhosis and reduce the content of collagen in liver cells. In addition, C5a-containing tumor vaccines can be used to inhibit tumor growth. Therefore, based on individualized early treatment considerations, if the C5 gene polymorphisms shown in the results of this study can be used as one of the basis, it may be more helpful for the development of related biological agents. The development of interrupted HCC helps to strengthen the prevention and treatment of HCC, further reduce the incidence of high-risk patients, reduce the mortality of HCC patients, and improve the prognosis of patients.

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A group of proteins that make up connective tissues and interstitial cells of animals are mainly collagen, elastin, and proteoglycans. Tissues and organs are formed by cell adhesion and connection of these three components. They not only have the functions of maintaining cell morphology, mechanical support and weight bearing, but also play a role in defense, protection, nutrition and repair.

 

The initial process is to synthesize on the cytoplasmic ribosomes, and then enter the endoplasmic reticulum through the signal peptide sorting pathway to continue to synthesize, and some continue to synthesize in the cytoplasm. Generally, secreted proteins must go through the ER pathway through the Golgi It is secreted by the body, and the structural protein itself has a retention signal that will not be secreted and reaches the point of action through the intracellular transport pathway.

 

British scientists wrote in the latest issue of the Proceedings of the National Academy of Sciences that they have discovered the origin of the protein structure responsible for the metabolism of Earth's life. These simple molecules provide power for the early life of the Earth and can serve as chemical signals for Teams such as NASA use it to find life on other planets.

 

According to a report from the Physicists' Organization Network on the 16th, in the latest research, scientists at Rutgers University's "Evolution of Nanomachines in Geosphere and Microbial Ancestors" (ENIGMA) team traced the enzyme (protein) The evolutionary process found 3.5 to 2.5 billion years ago, the earliest two metabolic proteins in the evolution of life. The ENIGMA project aims to reveal the role of the simplest proteins that catalyze the earliest stages of life.

 

In the latest study, the ENIGMA team studied two protein "folds": a ferredoxin fold that binds to iron-sulfur compounds, and a "Rossman" fold that binds to nucleotides (a component of DNA and RNA). They believe that these two folds are likely to be the earliest structures of early metabolism. Moreover, there is evidence that the two folds may have a common ancestor. If true, this ancestor may be the first metabolic enzyme in life on Earth.

 

Researchers explain that proteins are amino acid chains, and the 3D path of amino acid chains in space is called folding. Ferredoxins are metals found in modern proteins that allow electrons to shuttle around cells to promote metabolism. Electrons flow through solids, liquids, and gases and power living systems. Other planetary systems must also have the same electricity in order for life to thrive.

 

ENIGMA principal researcher Paul G. Folkovsky said: "We believe that life is made up of very small parts, which then make cells and eventually produce complex organisms like humans. Now we have found It is these building blocks that ultimately lead to the evolution of cells, animals and plants. "

 

Research collaborator Vicas Nanda, a professor of biochemistry and molecular biology, said: "We know very little about how life originated on Earth, and the latest research allows us to understand and discover the earliest metabolic proteins. "

 

It is reported that researchers will conduct tests in the laboratory to better understand the origin of life on Earth, and hope to observe how the life of other planets originated accordingly.

 

Many proteins are important substances that make up the structure of cells and organisms, and are called structural proteins. For example, the components of feathers, muscles, hair, spider silk, etc. are mainly structural proteins.

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A 300 Watt LED grow light is a popular choice among many indoor gardeners for a number of reasons. These lights are available in sizes, styles, and shapes to fit just about any indoor garden. A LED panel is also a great choice for anyone interested in growing plants in large numbers. One of the benefits to choosing a 300 Watt LED light instead of a more conventional incandescent bulb is the fact that they produce very little heat and use only a fraction of the electricity of more traditional grow light choices.

Heat is an important thing to keep in mind when purchasing a grow light. Because a 300 Watt LED grow light is very cool to the touch, there is no need for a gardener to worry about drying out the plants or causing drought like conditions. Incandescent bulbs actually produce more heat than light. When a light bulb creates heat, it is a sign of wasted energy. The truth is that incandescent light bulbs are the most inefficient lighting choice available on the market today. Even a fluorescent bulb is a better choice for energy conscious gardeners, although they are not as efficient as a LED panels.

Another benefit to using a 300 Watt LED grow light is that, because of their low heat, they can actually be placed much closer to the plants. This is especially beneficial for plants that require intense light for long periods of time. A LED panel will also outlast just about any other type of light available on the market. In fact, LEDs have been shown to last five, 10, and even 15 years in certain applications. This means that a gardener does not have to be concerned about constantly replacing burned-out grow lights.

A person should keep in mind, however, that a 300 Watt LED grow light is going to be considerably more expensive than some of the cheaper alternatives on the market. Their higher initial investment has put some budget conscious gardeners off of the idea of purchasing LED grow panels. While it is true that a person will have to pay more at first, they will more than make the money back in lower energy costs, fewer replacement purchases, and healthier plants overall. When an individual really thinks about it, a 300 Watt light really is a smart choice. Please keep this in mind when purchasing your lighting supplies.

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1800W LED Grow Light

WHY HYDROPONICS?

Hydroponics enable us to grow plants indoors with great results. A lot of plants will grow indoors with ease with just water as the feed however these will not produce large flowers or thickened foliage, simply adding a quality feeding schedule will spurn the plant on no end with just daylight from outdoors as the light signal. You can not regulate these plants cycles though because you can not change our weather and lighting times, this is where artificial light came into hydroponics in the first instance, to supply a constant light signal at timed intervals, regardless of the time of year. It was soon noted that these plants beneath 'hydroponics lighting' reacted to there natural growth pattern by the lights being on for 16 to 18 hours a day and if switched to 10-12 hours a day there flowering cycle was ignited. By pure accident fighting with the elements from the cold outside was it discovered that the stronger this light source the greater these plants growth rate was spoke volumes when it came to flowering. Of course light alone will not produce growth or flowering at high rates unless the air is full of Co2 and the feeding is of quality minerals and nutrients.

GROWING PLANTS INDOORS

And so 'Growing Plants Indoors' began. Followed by the odd Hydroponics retailer, to serve the community of course, however these retailers never wanted to share the science behind hydroponics as the harder it is for you to achieve what your mate can, (or the retailer), the more money you will spend trying. Then The World Wide Web ( www.) was discovered and hydroponics retailers fell out of the sky and growing plants indoors became common place. However the more 'spicy' variety of plant being the choice for many a youth bringing hydroponics into disrepute but what was discovered was that one of the fastest growing plants in the World could be grown indoors with ease resulting in unheard of yields along with the shear fact that these plants contain certain properties that help the medically sick. Further more as the years passed Supermarkets began to grow their own fruit, vegetables, flowers and herbs in great quantities due to the British weather being so uncertain, leaving our farmers hanging by threads. Today it is estimated that there are over 40,000 Hydroponics Farms, growing plants indoors to supply the Supermarket demands. Around 2.5 million Brits grow their own fruit and veg, some in gardens and allotments but the majority are growing indoors with better yields than those ever recorded growing outdoors. Tomatoes are by far the leader in the novice gardeners choice 'first grow', followed closely by Chillies. Both thrive growing indoors, infact in 26 years I have not found a plant that can not be grown in Hydroponics indoors.

SO HOW DO WE DECIDE WHAT HYDROPONICS TO USE INDOORS?

There are many methods firstly to ponder over, all done correctly will result the same but different methods can speed up the growth or vise versa the flowering, mastering which one works best for yourself is the answer but firstly understanding the methods science will make a better grower out of you resulting in untold yields. Once your method is chosen to suit yourself and your growing environment (grow room / grow tent / grow cabinet) the choice of system or Pot if using pot culture.

To decide how many plants your going to grow you must first decide what strength of light you are going to use. One too strong for the grow room will resulting in too much heat and again vise versa too small may be too cold, one thing for sure is your room will change the amount of heat it uses and produces if it is hot or cold out side. This is where fan speed controllers, fans and carbon filters are required to maintain fresh Co2 is sourced and the old removed along with heat and some moisture. Before choosing your light ensure you are purchasing one to meet the targeted yield. It is a known fact that Fruit can only be flowered to match the light, gram per watt. i.e. 600 watt lamp produces 600 grams of dry, cured fruit or herbs. A choice of timed feeding is now simplified with the ever increasing range of cycle timers appearing on the market. With a good model bearing variations of timings from 15 seconds to 6 hours of feeding at intervals from 6 hourly to every 15 minutes the correct feeding schedule cam be maintained with great ease and satisfaction you know the plants are getting the feed without having to manually feed each plant, which could take you a long time if you had a large crop or two.

The main factors left and the most important is the choice of fertiliser, minerals and nutrients you are to use. Of course not only do they have to be suited for the chosen method you are incorporating they have to suit the plant you are growing and the cycle the plant is in.

(a) Grow feed is known as Vega or vegetation feed, (b) Flower feed is known as Flores or floral feed. Next you have to take into account each main stage of the plants life from start to finish with additives.

This is not to be confused with the plants cycle.

  1. Root protection, your plants will require root protection in their early days to encourage roots to grow then secondly to keep these new roots healthy. Root nutrients and additives should be given until flowering. Many root additives can be added to the foliar feeding and used until flowering or fruiting starts.
  2. Vegetation Foliage, this is to be encouraged to flourish as the foliage is the plants main air intake routes. For this Nitrozymes are pre-added to the Vega feeds but also adding a separate additive of pure Nitrozymes will boost the foliage and growth rates immensely. For those using soils, Coco and such like substrates will benefit from also adding products such as Cannazyme which contain enzymes and minerals to repair the deadening roots and turn them into feed for the soils and plants.When the flowering cycle begins all feeds used in Vegetation is not used with exception to Cannazyme for those using soils, with hydro the roots are fed oxygen via an air pump pushing air into the nutrient reservior through air diffusers, this ensures the root zone is fed with oxygen and will keep the roots from dying and rotting. Continued use of root additives is highly beneficial.
  3. Flowering feeds are more complex in that each one has to be at critical timings to enable full yielding. Firstly Floral feed is required which will tell the plants recepticles to switch into flowering mode along with the change in lighting timings. All floral feeds contain the basics required to feed your plants the necessary minerals to flower successfully however plants really do need that extra push to reach high yields.Flower boosters are recommended and can be used from day one of flowering along with your floral feed to flourish growing plants indoors. Around weeks 4-6 your plants will now also require added Phosphurs and Pottasium (PK) on top of the booster and floral feed. Cannazymes are then required to repair the root zone from the harsh chemicals found in the Phosphurs and pottasium feeds (PK). This you add into the flower booster and floral feeding schedule thus ensuring the roots can uptake the water required to clean the plants substrates cleaning the minerals and nutrients telling the plant to finish its cycle. A supplement known as Flush is widely available and helps to (a), tell the plant to finish its flowering cycle (b), cleans the substrate, roots and stalks of existing feeds, and (c), Flush cleans out the plants of unwanted salts. Foliar feeding of flower boosters is highly recommended from day one of flowering until Flush has been applied. Not all flower boosters can be added to the plants using foliar feeding.

WHERE TO SOURCE YOUR HYDROPONICS?

Hydroponics and growing plants indoors is simple which is why so many people across the World are now taking part in growing their own produce, whatever that may be with the vast amount of options of variety of plants available to grow in either seed form or clones. We at Down The Road! Supplies Ltd take pride in offering hydroponics products, equipment and services. We are alone in the services we offer such as zero percent finance to help break the initial costs. Along with this, any persons wishing for their own grow room designed, built, hydroponics products supplied and installed, along with full feeding schedule then please contact us to arrange an appointment through our online store or phone 01926 632999.

Hydroponics is a science that whilst simple to learn, will enthral you for years to come. The possibilities are endless using hydroponics equipment, anything that grow's in the wild can be grown using hydroponics cultivation methods, benefiting from speeding up the growth cycle of any plant species, offering the grower complete control over feeds, cycles, lighting and climate.

Caring for those indoor plants has always been a challenge: even in well-lit rooms, many plants are not able to receive sufficient light to grow as fully as they would otherwise. LED Grow Lights with full spectrum are ideal for all kinds of Indoor Growing Plants veg and bloom at all growth stages. LED Grow Lights can also be used for large-scale cultivation of plants, crops, flowers, cannabis/marijuana and fruits.

Home Grow Pro Shop specializes in LED Grow Lights for home-growers. We provide a memorable shopping experience by offering quality full spectrum LED Grow Lights with top-notch, prompt customer service.

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  1. Types of antibiotics in milk
  2. a. β-lactams

β-lactams include penicillins and cephalosporins, which are often used in the clinical treatment of dairy cattle and other livestock individuals and are left in the milk.

  1. Tetracyclines

Common types of Tetracyclines have tetracycline, chlortetracycline, oxytetracycline, doxycycline, etc., which is a class of broad-spectrum antibiotics.

  1. Aminoglycosides

Common types of Aminoglycosides include gentamicin, streptomycin, dihydrostreptomycin, neomycin, spectinomycin, etc., which are aminoglycoside antibiotics commonly used in livestock.

  1. Chloramphenicol

Chloramphenicol includes the following three compounds: chloramphenicol, thiamphenicol, and florfenicol. These drugs are strictly restricted veterinary drugs, and some countries prohibit their use.

  1. Macrolides

Common types of Macrolides are erythromycin, gentamicin, lincomycin, spiramycin and salinomycin.

  1. Sulfa

Common types of Sulfa are sulfadiazine, sulfadimethoxine, sulfadiazine, sulfadiazine, etc. Trimethoprim is a sulfamethoxin synergist and is not used alone.

  1. The hazards of antibiotic residues

Antibiotic residues have different degrees of harm to human health, ecological balance, dairy product prices and international trade in dairy products.

  1. The detection method of antibiotics in milk

1). Traditional microbiological testing method

The microbiological detection method appeared earlier. Since its appearance, it has greatly improved the development of antibiotic detection methods. Its measurement principle is based on the antibiotics have a certain inhibitory effect on the physiological function and metabolism of microorganisms, which is consistent with clinical applications. It takes a long time and has a large rate of error. At present, the most commonly used methods are TTC method, Delvotest SP method, BY method, etc.

2). Internationally accepted testing methods

Relatively speaking, it is an earlier universal measurement method applied in the world. Its principle is: if the milk contains antibiotics, add bacteria (Streptococcus thermophilus) and cultivate for 2.5-3h, adding the TTC indicator (triphenyltetrazolium) does not cause a reduction reaction, so the sample is colorless. If the milk contains no antibiotics, the sample is red. Relatively speaking, this method is relatively low-cost, but time-consuming, so its application is not too wide, and its development is subject to certain restrictions.

3). Blue and yellow detection method

This method is a broad-spectrum microbial inhibition method, relatively speaking, it takes a short time, you can check the residue of antibiotics in a short time, as long as you can draw a conclusion by color comparison. As a result, there is a certain error rate for the detection obtained by this detection method, which is easy to cause false detection, but it is short in time and low in cost.

4). Modern instrumental analysis

This method mainly uses modern instruments to detect and determine the type of antibiotics remaining. The most commonly used methods are chromatography, fluorescence, capillary electrophoresis, and chromatography-mass spectrometry. Use different theories and adopt different methods for testing, improve the standard of testing, and strengthen the quality of testing. Relatively speaking, this method has a fast separation speed, high efficiency, and automatic control. It can detect the specific content of antibiotics, and the results are more accurate. However, the sample to be tested needs a series of pretreatments, which is tedious and time-consuming, and must have the corresponding price. It is generally used in large laboratories, suitable for accurate determination.

5). Biochemical Immunity

This has been gradually developed in recent years with the development of new technologies. It combines the specificity and reversibility of antigens and antibodies, and is an analytical technique. The basic principle is the competitive combination of antigens, which can be divided into enzyme-linked immunoassay (ELISA), fluorescent immunoassay (FIA), immunoassay technology and conventional physical and chemical analysis technology combined methods. Several methods have their own advantages and disadvantages, and we must pay attention to their comprehensive use to improve the quality and accuracy of detection. Judging from the results of its practice, it has a good detection effect on the current status of antibiotic residues, and its sensitivity is extremely high, reaching the level of ng; the detection is fast and specific. Relatively speaking, this method has a high degree of specificity, and each time an antibiotic is tested, a corresponding antigen or antibody must be prepared or purchased, resulting in a higher test cost. Therefore, the biochemical immunoassay cannot replace conventional analytical methods such as chromatography or spectroscopy, and can only serve as an important supplement.

6). Specific kits

The so-called special kit method is based on the culture of agar medium containing Bacillus and PH indicator at a certain temperature, generally maintained at about 65 celsius, spore development and growth, reduce the pH value of the medium; under the action, the blue (purple) color becomes green-yellow. Antibiotic residues in raw milk inhibit the growth of microorganisms and the production of acids. Since no acid is produced, the color will not change.

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Somatic pluripotency reprogramming technology can transform differentiated somatic cells into induced pluripotent stem cells (iPSC) by using reprogramming transcription factors (mainly Oct4, Sox2 and Klf4). This technology was first published in 2006 by Professor Yamanaka and because of that, he won the Nobel Prize in Physiology or Medicine in 2012. However, the exact molecular mechanism involved in this technology is still to be studied.

A recent research team led by Ralf Jauch, Vikas Malik and others has revealed the initial molecular mechanism of transcription factor-induced somatic pluripotency reprogramming and clarified the temporal dependence of pluripotency reprogramming on Oct4 and Sox2 for regeneration Medicine and research on induced pluripotent stem cells provide new theoretical models.

The research results were published in the August 2 issue of Nature Communications.

The Jauch team is focused on studying Oct4 and Sox2 transcription factors and how they play a leading role in the reprogramming process. After comparing the combination of wild-type and mutant Oct4 with Sox2 by using genomics technology, they were surprised to find that Sox2 instead of Oct4 is the key factor to turn on somatic cell reprogramming.

In the initial stage of reprogramming, Sox2 “attacks” and “awakens” the so-called pluripotent genes in somatic cells, which is the primary condition for activating them. At this stage, Oct4 is not important for the inhibition of somatic characteristics, and plays an optional role. However, in order to finally open the relevant gene network to establish pluripotency, Sox2 and Oct4 work closely together to complete this work. In the later period of reprogramming, Oct4 gradually played a leading role. Once the cells become pluripotent stem cells, the dependence of the maintenance of pluripotency on the binding of Oct4 and Sox2 is greatly reduced. Since Oct6 binds to different genomic loci and lacks the bias of binding to Sox2, it cannot replace Oct4 for pluripotency reprogramming.

These findings have answered some controversial issues in the field of pluripotency reprogramming research, and will provide directions for transforming Sox2, Oct4 and related factors to more quickly, efficiently and reliably perform cell reprogramming, and ultimately achieve clinical applications of stem cells and regenerative medicine.

Original title: Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2

Original source: https://www.nature.com/articles/s41467-019-11054-7

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There are three main methods for protein structure prediction: homology modeling, folding recognition and de novo calculation. All those methods are used to predict unknown protein structures. Since the amino acid changes generally occur in the inflection region on the surface of the protein, the main chain structure of the protein, especially the hydrophobic core, is not susceptible to sequence changes. Therefore, the homology modeling method is the most widely used. Homology modeling uses the protein crystal structure homologous to the target sequence as a template to predict the three-dimensional structure of the target sequence. The conservation of the tertiary structure of a protein is far greater than that of its primary structure. Theoretically, secondary or tertiary structure can be obtained from the primary structure, that is, the amino acid sequence can determine the structure of a protein. Therefore, homology modeling is a practical method for predicting structure from sequences. This method has two prerequisites: First, there are one or several resolved structures in the homologous protein of the target sequence. Second, the homology between the target sequence and the protein is high.

The definition of homology modeling

Homology modeling is also called comparative modeling. Its principle is that similar sequences have similar structures, that is, two sequences with homologous relationships have similar structures. When the homology of the two sequences is greater than 30%, the homology of the sequences can imply that the two are structurally similar. The higher the homology of the sequences, the higher the accuracy of the structural model.

The basic principles of homology modeling

1. The structure of a protein is uniquely determined by its amino acid sequence, by the primary structure. In theory, it is enough to obtain its secondary and tertiary structure.

2. The conservative type of tertiary structure is much larger than that of primary structure. And the sequence identity of template protein and target protein needs to be greater than 30%

The main steps of homology modeling

It generally includes the following seven steps:

1. Select template and alignment sequence: search for template protein with known crystal structure from protein database and use BLAST and other tools to align the sequence;

2. Determine whether there is a template available: template sequence and target sequence similarity "30%;

3. Construct the main chain structure: apply the atomic coordinates of the template structure to the target to generate a basic main chain skeleton and then adjust the main chain atom position to make the bone structure conform to the stereo-chemical principles;

4. Construction of ring chain: One method is to model based on the known ring zone structure. Another method is to predict from scratch based on the principles of quantum chemistry;

5. Modeling and optimization of the side chain: use the target sequence fragments to search the rotamer database to obtain similar fragments, and then construct the side chain structure of this fragment according to its spatial orientation. Finally, the energy is minimized to find the lowest energy point, that is, the stable conformation;

6. The overall structure is optimized: there is usually unreasonable contact between atoms in the three-dimensional model obtained through the above process, which needs to be eliminated by methods such as simulated annealing and molecular dynamics.

7. Structural evaluation: The most common evaluation criterion is RMSD, which represents the root mean square deviation of the corresponding atoms between the target protein and the template protein. It can also be submitted to the SAVES server for verification.

With the improvement of prediction methods, homology modeling has been widely used in drug design and protein design. It can interpret the relationship between protein structure, function and sequence. In the post-genomic era, homology modeling will surely become a bridge between genetic engineering and protein engineering.

With comprehensive modeling services, designing and engineering novel antibodies with desired therapeutic properties, Creative Biolabs offers a variety of antibody structure modeling services for researchers:

l Homology antibody modeling

l Loop structure refinement

l Modeling of the framework regions

l Side chain modeling

l Antibody modeling assessment

 

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What is a phosphorylated antibody?

Antibodies produced against a phosphorylation site in the state of phosphorylation and dephosphorylation of a substrate, so that the phosphorylation and dephosphorylation of the substrate and the change in antibody binding type are used to investigate whether the substrate is phosphorylated, thereby studying changes in protein activity. After the immunogen is phosphorylated, the antibody prepared with it is called phosphorylated antibody.

The significance of phosphorylated antibody

Post-translational modifications are essential for protein biological functions and play an important role in many key regulatory mechanisms of life phenomena. Among them, protein phosphorylation is one of the most common important post-translational modifications. It participates in almost all cellular activities in the body, it is closely related to many biological problems such as signal transduction, cell cycle, proliferation and metabolism, growth and development, and cancer mechanisms. Phosphorylation is usually the addition of phosphate (PO4) groups to proteins under the action of kinases, most commonly on serine (S), threonine (T) or tyrosine (Y) residues. Since phosphorylated proteins can play a complex role, accurate and precise quantification of phosphorylated proteins at the cellular level is essential for deciphering and understanding cellular functions.

The difference between phosphor specific antibodies and ordinary antibodies

  1. The detection of phosphorylated antibody is based on the protein in an active state (phosphorylation).
  2. Phospho-antibodies are only designed for phosphorylation sites. It is a site-specific polyclonal antibody, which has some characteristics of monoclonal antibodies.
  3. Synthesis of common antibody (polyclonal antibody): prokaryotic expression protein-> purification-> immunize animal-> harvest antibody.
  4. Synthesis of Phosphorylated antibody (phosphor specific antibodies): artificial synthesis of peptides containing phosphorylation sites-> artificial phosphorylation in vitro -> link haptens-> immunize animals-> harvest antibodies.
  5. A large part of phosphorylated proteins are transcription-related factors. Therefore, phosphorylated antibodies and common antibodies are used to detect the same protein, in situ detection may have different cell localizations. Phosphorylated transcription factor moves from the cytoplasm into the nucleus.
  6. In general, the experimental results of phosphorylated proteins are more directly related to molecular functions. Ordinary antibodies measure the content of the protein and cannot know its active state. Phosphorylated antibodies measure the level of phosphorylation of the protein, focusing on understanding an active state of the protein.
  7. Phosphorylated antibodies are mainly prepared for phosphorylation sites, and detect the protein's changes when the cells are stimulated (whether the phosphorylation level is increased or decreased). Ordinary antibodies (mainly prepared for peptides at non-phosphorylated sites) mainly detect the expression of the protein in tissues, cells, tissue distribution, or localization in cells, and can be used as an internal reference for changes in phosphorylation levels.

The application of phosphorylated antibodies

  1. The level of protein phosphorylation is often related to protein activity: many signaling pathway proteins are caused by a series of cellular responses by changing their phosphorylation level after certain stimulation, but their protein content may not change much.
  2. Phosphorylated antibody: Prepared for specific phosphorylation sites, and detect changes in the protein's functional state (enhanced or weakened) when the cell is stimulated.
  3. Non-phosphorylated antibody: It mainly detects the expression of the protein, tissue distribution or cell localization in tissues or cells, and can be used as an internal reference for changes in phosphorylation level.
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Laminated products are composed of two or more layers of resin-impregnated fibers or fabrics that are laminated and combined with heat and pressure.

 

Introduction

Laminated products are composed of two or more layers of resin-impregnated fibers or fabrics that are laminated and combined with heat and pressure. It can be a plate, tube, rod or other shapes. Laminated products can be processed into various insulation and structural parts, which are widely used in motors, transformers, high and low voltage electrical appliances, electrical instruments and electronic equipment.

Laminated products are made of fiber paper and cloth as substrates, impregnated or coated with different adhesives, and are hot-pressed and rolled into a layered electrical insulation material. Organic fiber-based substrates include wood fiber paper, cotton fiber paper, cotton cloth, and polyester and aromatic polyamide synthetic fibers. Inorganic fiber substrates include non-alkali glass cloth and asbestos. Commonly used adhesives are phenolic resin, epoxy resin, melamine resin, silicone resin, diphenyl ether and polyimide.

 

classification

The performance of the laminate depends on the substrate and adhesive and the molding process.

According to its composition, characteristics and heat resistance, laminated products can be divided into the following two.

(1) Organic substrate laminates-with wood pulp insulation paper, cotton fiber paper, cotton cloth, etc. as reinforcement materials. Long-term use temperature can reach 120 ℃, and synthetic fiber products have also been developed as reinforcement materials.

(2) Inorganic substrate laminates-with inorganic glass fiber cloth, alkali-free glass fiber felt, etc. as reinforcement materials. The long-term use temperature is 130 ~ 180 ℃, even higher temperature, which varies with the adhesive resin.

Laminated plastic products are divided into laminates, laminated tubes, laminated rods and molded laminates according to shape and use. Copper-clad laminates for printed circuits and adhesive paper capacitor sleeve cores used as capacitor sleeves for high-voltage electrical appliances are two special types of laminated plastic products.

Laminate: including laminated paperboard, cloth board, glass cloth board and copper-clad laminate. ①Laminated paperboard: It is made of insulating paper impregnated with synthetic resin glue and hot pressed. It has good dielectric properties, mechanical properties and mechanical processing properties, and is suitable for various insulating structural parts in electrical equipment. ②Laminated cloth: It is made of cotton cloth impregnated with synthetic resin glue and hot pressed. It has good mechanical processing performance, its hardness, cleavage resistance and impact strength are better than cardboard, but its electrical performance is not as good as laminated cardboard, and its use is the same as laminated cardboard.

 

③Laminated glass cloth: It is made of alkali-free glass cloth impregnated with different synthetic resins and then hot pressed. Its mechanical properties, heat resistance, and water resistance are higher than laminated paperboards and cloth boards, but the bonding strength is slightly worse. Uses are the same as laminated cardboard. ④Copper-clad laminate: made of alkali-free glass cloth or cotton fiber paper impregnated with phenolic resin or epoxy phenolic resin as the substrate, and coated with electrolytic copper foil on one or both sides of the substrate, and then hot pressed. It has good mechanical properties and dielectric properties and high peel strength. Mainly used as a printed circuit board for electronic equipment.

Rolled laminated products: including paper, cloth roll products and capacitive tape cores. ① Paper and cloth roll products: It is made of insulated winding paper, cotton cloth, glass cloth impregnated or coated with synthetic resin, and then rolled, impregnated and dried. Commonly used resins are phenolic resin, epoxy phenolic resin, modified silicone resin, etc. Paper and cloth roll products can be made into rod, tube or tube. Its dielectric properties and mechanical strength are higher than those of general plastic-pressed products, but lower than those of laminates and cloth sheets. Mainly used as insulating structural parts. ②Capacitive tape core: It is made of winding paper coated with synthetic resin, then dried, hot rolled and heat treated. During rolling, every certain thickness, a layer of aluminum foil is inserted as an electrode. It is a series capacitor with adhesive tape as the medium. It can be used as an insulating core at the leading end of high-voltage transformers and switches. ③Molded laminated products: It is made of insulating paper, cotton cloth, glass cloth, etc. impregnated with synthetic resin, and hot-pressed by forming mold. It has rod-shaped molded products, V-rings and other special shaped molded products. Has high mechanical properties, dielectric properties and moisture resistance. Mainly used as insulating structural parts of motors, electrical appliances and other equipment.

 

 

About us

Matexcel is a leading service provider in materials science, with years of commitment to supply better polymers, nanoparticles and other materials for worldwide customers from both academia and industry. We offer a full range of materials covering polymers, metals, ceramics and natural materials, in addition to professional consultation service in manufacturing and characterization. Here are some our products: si3n4 name,recombinant human collagen, kda manufacturing, lom 3d printing, etc.

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In a new study, researchers from the National Institute of Diabetes and Digestive Diseases, the National Cancer Institute, the Shake Institute for Biology, and the Scripps Research Institute have discovered a key part of how a powerful class of HIV drugs bind the HIV intasome. By solving for the first time the three-dimensional structure of this intasome when combined with different drugs, they discovered what makes this class of drugs so effective. This study provides important insights that may help to design or improve new therapies for HIV. The relevant findings were recently published in the journal Science, and the paper was entitled “Structural basis for strand transfer inhibitor binding to HIV intasomes”.

 

Dmitry Lyumkis, corresponding author of the paper and assistant professor of genetics laboratory at the Shake Institute for Biological Research, said, "The drugs we studied are the latest compounds available in clinical practice today, with several important preclinical molecules. Until then, no one knows exactly how they bind to this HIV intasome. A better understanding of the effects of these drugs will help us to improve them and design new therapeutic compounds."

 

HIV intasome are a key structure of this viral infection, which consists of HIV protein integrase and viral DNA strands, and are formed when this virus invades human cells. This intasome enters human cells and subsequently undergoes the necessary chemical reaction, thereby integrating the genetic material of this virus into human DNA.

 

Some drugs called integrase strand transfer inhibitor (INSTI) successfully block this intasome; when it cannot integrate viral DNA into the human genome, HIV is not able to infect human cells. Currently, four INSTI drugs are approved by the US Food and Drug Administration (FDA), and some are under development.

 

Despite the success of these molecules, efforts are still being made to investigate how to inhibit HIV intasome, mainly due to the difficulty in isolating such intasome for structural studies. In the past, most studies on HIV intasome and INSTIs were performed on another retrovirus called prototype foamy virus (PFV). In 2017, Lyumkis and colleagues first solved the structure of purified HIV intasome (Science, 2017, doi: 10.1126/science. Aah5163).

 

In this new study, Lyumkis's team went further: they obtained the structure of the HIV intasome when blocked by one of four INSTIs—the commercially available drug bictegravir; and three experimental compounds called 4f, 4d, and 4c. They used single-particle cryo-electron microscopy (an imaging technique they helped optimize) to reveal the structure of each HIV intasome-drug complex.

 

The first observation of Lyumkis is that these drugs are different when combined with HIV intasome than when they are combined with PFV intasome. For example, compound 4f loops back to itself when bound to PFV intasome, but remains relatively flat when bound to HIV intasome, and these details can help improve the binding properties of potential future molecules.

 

Dario Oliveira Passos, co-first author of the paper and a researcher in the Lyumkis laboratory, said, “So far, everyone is still using PFV intasome structures to rationally think and understand the mechanism of action of these drugs. But we found that if we want to make further progress, this field does need to move forward and study HIV intasome structure.

 

Min Li, co-first author of the paper and a researcher at the National Institute of Diabetes and Digestive Diseases, said, “We and many others have worked for decades to achieve the goal. Excitingly, we can finally understand the detailed working principles of such HIV inhibitors and help develop new drugs.”

 

These structures also reveal why these drugs are so effective and what makes them so outstanding in avoiding drug resistance. Lyumkis and colleagues found that these INSTIs fill the entire space usually occupied by DNA. This means that if HIV intasome undergo mutations that prevent INSTI drug binding, it will also make this intasome unable to invade human cells.

 

Finally, these very high-resolution structures obtained by these researchers allowed them to observe detailed information about how these drugs interact chemically with this binding pocket and how these INSTIs displace water molecules to do this, which provided them with more information to let them know what makes INSTIs clinically successful.

 

Lyumkis says, “In previous structures, we understood the biological properties of HIV intasome. But in this paper, we really begin to gain insight into how INSTI drugs target these important viral intasome from a therapeutic perspective.

 

These researchers are planning to carry out more studies on these experimental drugs, especially compound 4d. Based on preclinical testing and new structural insights, this compound is more expected to be resistant to HIV than other compounds. They also want to better understand what changes occur in the structure of HIV intasome in the event of resistance to INSTI drugs. Lyumkis says this may help them design more effective drugs in the future.

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Since the discovery of carbon nanotubes by Japanese physicist Sumio Iijima in 1991, the atomic structure and properties of carbon nanotubes have attracted great interest from scientists. Carbon nanotubes have extremely high specific surface area, excellent mechanical properties (the theoretical axial elastic modulus and tensile strength of carbon nanotubes are 1~2TPa and 200Gpa, respectively), and thermal properties (heat-resistance temperature of carbon nanotubes under vacuum is up to 2800 °C) and the electrical properties (the electron carrying capacity of carbon nanotubes is 1000 times that of copper wires). These properties of carbon nanotubes make them an ideal filler in the field of composites. The carbon nanotube composite material can be easily processed and fabricated into a structurally complicated member, and does not damage the structure of the carbon nanotube during processing, thereby reducing production costs. Therefore, carbon nanotube composite materials have been extensively studied.

 

There are three main preparation methods for carbon nanotube composite materials: liquid phase blending, melt blending and in-situ polymerization. Among them, the liquid phase blending method is the most commonly used preparation method.

 

Liquid phase blending

The solution method refers to the use of mechanical or magnetic stirring, or high-energy ultrasonic to separate the agglomerated carbon nanotubes and uniformly disperse in the polymer solution, and remove the excess solvent to obtain the carbon nanotube composite material. The advantage of this method is that it is simple to operate, and it is mainly used to prepare membrane materials. Xu et al and Lau et al. used this method to prepare CNT/epoxy composites and reported the properties of the composites. In addition to epoxy resins, other polymers such as polystyrene, polyvinyl alcohol, polyvinyl chloride, etc. can also be used to prepare composite materials by this method.

 

Melt blending

The melt blending method is to disperse carbon nanotubes in a polymer melt by shear force applied by a rotor. This method is especially useful for preparing thermoplastic polymer/carbon nanotube composites. The advantage of this method is mainly to avoid contamination of the composite by solvent or surfactant, but this method is only suitable for polymers that are resistant to high temperatures and are not easily decomposed. Jin et al. used this method to prepare PMMA/MWNT composites and studied their properties. The results have shown that the carbon nanotubes are uniformly dispersed in the polymer matrix without significant damage and the storage modulus of the composite material is improved.

 

In-situ polymerization

The in-situ composite method refers to dispersing carbon nanotubes in a polymer monomer, adding an initiator, and initiating in-situ polymerization of the monomers to form polymer/carbon nanotube composites. This method is considered to be an effective method for increasing the dispersion of carbon nanotubes and enhancing their interaction with the polymer matrix. Jia et al. prepared PMMA/SWNT composites by in-situ polymerization. The results have shown that the main reason for the strong bonding between the carbon nanotubes and the polymer matrix is that AIBN opens the π bond of the carbon nanotubes during the initiation process, thereby allowing the carbon nanotubes to participate in the polymerization of PMMA. The use of surface-modified carbon nanotubes to prepare PMMA/carbon nanotube composites not only increases the dispersion ratio of carbon nanotubes in the polymer matrix, but also greatly enhances the mechanical properties of the composite.

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Selecting an indoor LED Grow Light set up is not as straightforward as you might imagine. To begin with, you might think that you would simply invest in a light, dangle it up above the plant, plug it in and watch the magic happen. This could not be farther from the truth, which can be both a good and a bad thing. This is a positive thing because being forced to spend some time and understand how to do something new is rewarding. There's unquestionably a learning curve when attempting to understand the best way to grow plants indoor with LED Lights; but it can definitely be rewarding and fun to understand. The bad thing about all of this learning is that it might be slightly overwhelming when your first getting started. Here are a few of the things you'll need to be familiar with when getting started as a hydroponic gardener.

First of all, why don't we just ask the question on everyone's mind, "Do Led Grow Lights actually work?" There are more an more testimonials and independent studies sprouting up all over the Internet that demonstrate "YES" LED Grow Lights really do work, and they work pretty good. While many studies will show, at current technology levels, HID Lights may generate slightly better yields when compared with LED's. The advantage of LED's is that they will last as much as 8 times longer, run cooler and function more efficiently which will end up helping you save a ton of money over the long haul. These new kind of Indoor LED's operate at a very low voltage which means that they consume up to 90% less power than other kinds of common grow lights such as Metal Halide or High Pressure Sodium lights.

Even though utilization of these new grow lights has only recently been useful for growing plants, it is quickly gaining traction as a result of many benefits provided by this kind of indoor gardening. Several people stated that LED's are excellent for vegetative growth but they were missing the power to actually fruit a plant. This is because most other grow lights use 120 degree lenses. This is considered a wide-angle lens, as it disperses the light over a broad area (even to the walls!). Penetration is the key to good results with any LED, as it directly influences the rate of light absorption. For any plant to absorb light effectively, light must pass through or "penetrate" the leaf. With inadequate light intensity, a plant will use just a small percentage of the light they're given, as that is not being "delivered" to them.

The best thing about using LED's is that they make it possible for people to grow plants or pretty much any kind of plant species for that matter, almost anyplace they desire. As long as you have soil, water and something to hold everything together, then you can have your own private piece of jungle in your home. These new LED style lights can even make it easier to grow the plants in your home without having to expose them to direct sunlight. These new LED's have been adjusted to reproduce the specific spectrum's of the suns light that plants need to start photosynthesis. Using this type of focused light, there is far less wasted light and energy. These lights may not be the most popular choice being used by hydroponic plant growers today, but starting off small with one of these Energy Efficient Grow Lights will certainly be a great help to the environment as well as your pocketbook. Everybody has to start somewhere in regards to saving the environment, and full spectrum LED Grow Lights are a good place to begin.

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The 5.11 tactical store is the one roof where all tactical gear needed by the law enforcement officers can be located. The store sees to the clothing needs of both law enforcement and firefighting units.

Tactical Shirts

Tactical shirts are best suited for off-duty as well as on-duty wear. With these shirts, you don't need to go through the hassle of changing clothes frequently since you can also use the shirts at home attending to other home matters. These shirts are ultra lightweight and are designed of cotton and polyester, making them comfortable for use and also durable. You may choose 5.11 tactical shirts that are ideal for everyday tasks as well as climatic conditions. The pouches or pockets featured in the shirts are capable of holding maps, tickets, phones and other petite objects.

Tactical Pants

For better match, you can choose the 5.11 tactical pants for the 5.11 tactical shirts; this provides both professional and casual look. The pockets featured in the pants can take in flashlights, utility knife or baton. If you need the best suited clothing for adventures such as hiking and hunting, the 5.11 tactical pants will meet this need. You can find these pants in wide range of colors such as gray, black, sage, khaki etc. Recently; these special pants have become very popular among the military, law enforcement and fire fighting experts. You can also find these pants for women, featuring self-adjusting tunnel waistband. The tactical clothing provides professional and neat appearance.

Tactical Boots

You also need a pair of tactical boots to complete your tactical clothing outfit; these boots feature excellent comfort and superb elements. For instance, they have moisture wick lining that keeps the wearer's feet dry and convenient. This implies no itchy or sticky feeling on your feet. Indeed, these boots feature cutting edge elements that offer nothing but excellence all the way. The boots have been designed to be light weight so that you can maintain good speed while on motion. The tactical boots also feature insole foam which provides cushioning and ultimate comfort to the user. A number of these boots also feature side zipper to facilitate swift removal when necessary. You will also find oil and slip resistant technology in these shoes, making protection of the feet from slippery and oily surfaces possible.

Tactical bags

Another essential accessory to fit the 5.11 tactical items is the tactical backpack and bags; they are used to keep the accessories, as well as other emergency weapons needful in the course of special operations. These bags provide sufficient room as they have compartments. You can find them in wide range of sizes based on the kind of accessories you desire to store. The thrilling thing is that the bags have dividers that will help the user achieve easy identification of accessories and to help keep the items in place. You will not suffer from broken handles or straps since the carrying handles as well as the shoulder straps are made of heavy-duty nylon, so that the bag can carry heavy items without the straps and handles weighed down.

These and more are the 5.11 tactical clothing items and accessories that are available.

 

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6-2020xmensxoutdoorxwidextoesxwaterxshoe

This article tries to narrow the definition, but not to exclude shoes, but to purify the discussion and how I think they should be described.

I believe minimalist shoes can be described in three words; closest to barefoot. So I would describe true minimalist shoes with a different term; "barefoot-style shoes." If you listen to some manufacturers their definition is much broader. I don't believe that the manufactures can define this category in this case. I think it needs to be defined by healthcare professionals. Interestingly they probably wouldn't define it as a category at all. They would say that whatever shoes you buy should be comfortable, non-restrictive, as close to bare feet as possible while still maintaining some level of protection. If it were possible, they would probably recommend going barefoot as much as possible, particularly for your kids.

It's all about maintaining the health of your feet as you age. In our younger years our feet are growing and need to be free and unrestricted so that they can grow properly. In those years we probably go barefoot much more than we do as we get older. Once you're grown it's just as important to go barefoot as much as possible, but life interferes and it isn't always convenient or desirable.

What is the theory behind barefoot-style shoes? It is that our body provides all the cushioning and stability we need for walking and running barefoot without the added weight of shoes. So, barefoot-style shoes try to approximate that condition by being very flexible and basically flat with zero incline from front to back. They also allow your toes to spread out like they do when you're walking or running barefoot, while providing some protection from life's intrusions like stones and sticks. Even though they do provide a layer of protection, they also give you a feel for the ground that you cannot get with other shoes and are typically very lightweight. If you are not already, you should be aware that there is a whole movement around running in bare feet that is also very popular though adding a little extra "skin" for the rest of us is probably reasonable.

That's not to say that immediately switching to barefoot-style shoes is the best approach, particularly for runners. If you're not used to going barefoot, then barefoot-style shoes will take a cautious and pragmatic approach to adapt your walking or running style. Barefoot-style shoes force walkers and runners to go back to basics and adapt to allow their feet and legs to provide primary cushioning and stability. Many say though that once they've gone barefoot-style it's hard to go back!

This article is not designed to advocate barefoot-style shoes, but just to put it forward a brief opinion about how to describe them as part of minimalist shoes. I do suggest going barefoot as much as possible and to keep your feet unrestricted and healthy. You should also consider trying, with your healthcare professional's advice, a brand of barefoot-style shoes.

Five Finger shoes are one of the best Barefoot Minimalist Shoes that can effectively exercise the muscles of the feet and calves, thereby improving running posture and better preventing injuries.

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History of organic photovoltaic cells

Photovoltaic effect refers to the phenomenon in which a potential difference is generated between different regions of a semiconductor or a combination of semiconductors and metals that are illuminated by light. The term "photo-voltaic" appeared in English in 1849, which means that electromotive force is generated by light, that is, light generates volts. With the gradual understanding of the physical properties of semiconductors and the advancement of processing technology, in 1954, researchers from Bell Laboratories in the United States discovered that when silicon was doped with a certain amount of impurities, it became more sensitive to light. The first solar cell with practical application value was born in Bell Laboratories in 1954, marking the arrival of the era of solar cells.

 

Basic principles of organic photovoltaic cells

The basic principle of organic photovoltaic cells is similar to inorganic solar cells:

(1) After a certain amount of light is irradiated to an organic photovoltaic device, a photon having energy is absorbed by the organic semiconductor layer, and an electron is excited to transition from the valence band to the conduction band, leaving a vacancy at the valence band. This vacancy called holes and the holes have a positive charge.

(2) In conventional semiconductors, the excited electrons and formed holes move freely toward the opposite electrode. In conductive polymers, the electrons and holes formed by the excitation of incident photons will exist in a bound form, that is, they become excitons.

(3) Usually these electron holes are formed when excited by photons. If they are in the electric field or at the interface, these electron hole pairs will be separated into electrons and holes, which are called charged carriers. Photocurrents are formed during the migration of charged carriers.

 

Classification of organic photovoltaic cell materials

According to mechanical properties and processability, organic photovoltaic cell materials can be divided into insoluble materials, soluble materials, and liquid crystal materials. These materials usually include small molecules or oligomers, polymers, and liquid crystal molecules. Among them, oligomers or monomers capable of absorbing visible light are called chromophores, those with solubility are called dyes, and those without solubility are called pigments. At present, the polymer materials used in photovoltaic device research mainly include polythiophene (PTH) derivatives, polyphenylacetylene (PPV) derivatives, polyparaphenylene (PPP) fluorene derivatives, polyaniline (PANI) and other polymer materials.

 

Advantages of organic photovoltaic cells

Compared with inorganic solar cells, organic solar cells have the following advantages:

(1) Compared with the materials used for inorganic solar cells, the raw materials of organic semiconductor materials are widely available, cheap, light weight, high environmental stability, and have a high absorption coefficient (usually> 105cm-1) and good photovoltaic effect.

(2) The preparation process of organic solar cells is more flexible and simple. It can be prepared by vacuum evaporation, coating, printing or spraying. The energy consumption of organic solar cells in production is lower than that of inorganic materials, and the production process has no environmental pollution. Organic solar cells can be processed on flexible or non-flexible substrates, and have the characteristics of large manufacturing area, ultra-thin, cheap, good flexibility and so on.

(3) Organic solar cell products are translucent, easy to decorate and use.

 

Application prospects of organic photovoltaic cells

As fossil energy is limited and non-renewable, finding an alternative energy source has become an important task to maintain the sustainable development of the global economy. Photovoltaic power generation directly converts solar energy into electricity, which is a green renewable energy source with high commercial development value. And it is expected to become one of the main energy sources at the end of this century. With the continuous improvement of photovoltaic cell manufacturing technology and the continuous rise in the price of fossil energy, the photovoltaic power generation industry has entered a stage of rapid development. The international community is also increasingly optimistic about the development prospects of the photovoltaic power generation industry. The International Energy Agency (IEA) predicted in the solar photovoltaic roadmap published in May 2010 that the proportion of photovoltaic power generation in total global electricity will reach 1.3% in 2020 and rise to 4.6% in 2030.

 

Conclusion

The current research direction of photovoltaic cells is to develop efficient and low-cost battery materials and manufacturing technologies. Organic polymer photovoltaic cells use conjugated polymer as the photovoltaic material, and the manufacturing process is simple, the cost is low, and they can be manufactured on a large area, which makes the research of organic polymer photovoltaic cells more and more important. Although the research of polymer photovoltaic cells has made remarkable progress in recent years, its photoelectric conversion efficiency is still very low. Only by obtaining highly efficient and stable photovoltaic cells can the commercialization of polymer photovoltaic cells be achieved. The improvement of the efficiency of organic polymer photovoltaic cells can be achieved through the selection of materials and optimization of the structure of photonic and optical devices.

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Background

As one of the most common and important protein modification methods, protein glycosylation has always been the focus. In the past years, the commonly used method of N-linked glycoproteomics research is to analyze released glycans or de-glycosylated peptides separately. This strategy reduces the difficulty of analysis, while it also lost glycosite-specific glycosylation information. In recent years, mass spectrometry strategies and methods for intact glycopeptides have been gradually established. Generally, to achieve the identification and quantification of intact glycopeptides, the first step is to enrich glycopeptides from complex samples to reduce the affects from non-glycosylated peptides, then the mass spectrometry parameter settings need to be adjusted to satisfy the fragment features of glycopeptides, importantly the related software also need to be developed for the precise identification of the peptide sequence and glycan structures or compositions of the intact glycopeptides. These three main aspects of the strategies for mass spectrometry-based intact glycopeptide analysis are discussed in this article.

1. Enrichment strategy for intact glycopeptides

In glycoproteomics research, the research object is usually complex biological sample. The dynamic range of protein abundance in the sample varies greatly. At the same time, many glycoproteins have low abundance. All or specific glycoprotein groups are studied. Enrichment will help to identify more glycoproteins. In addition, because glycosylated peptides often only account for 2% to 5% of protein digested peptides, the signal during mass spectrometry analysis is easy to be inhibited by non-glycopeptides, so the primary problem faced by glycoproteomics research is the effective separation and enrichment of glycoproteins / glycopeptides, that is, the removal of non-glycoproteins / non-glycopeptides.

The methods currently available for the enrichment of intact glycopeptides include hydrophilic interaction liquid chromatography (HILIC), lectin affinity and boric acid affinity, etc. HILIC is based on the strong hydrophilic property of the polyhydroxy-rich sugar chain structure, which enables the separation of glycopeptides and non-glycosylated peptides, and can maintain the integrity of the sugar chain structure, both for N-glycopeptides and for O-glycopeptide. However, due to the weak interaction between the sugar chain and the stationary phase, glycopeptides that only link monosaccharides or oligosaccharides (such as O-glycopeptides) are often not well enriched by HILIC. Lectins are a class of sugar-binding proteins that can specifically recognize and bind to specific glycosyl sequences in structure-specific monosaccharides or glycans. Their binding to sugar chains is non-covalent and reversible. After the glycoprotein or glycopeptide is captured by the lectin, the glycoprotein or glycopeptide is usually eluted with a specific monosaccharide by competitively binding the lectin, thereby achieving enrichment of the glycoprotein.

2. Intact glycopeptides analysis by mass spectrometry

2.1. Intact glycopeptide in MS1

During the mass spectrometry analysis, due to the high complexity of biological protein samples, the samples enriched with glycopeptides are usually still doped with many non-glycosylated peptides, which often interfere with the mass spectrometry of intact glycopeptides. At present, there are some simple and effective methods to screen the mass spectrum peaks of intact glycopeptides from the spectrum of first stage of mass spectrometry (MS1). These primary screening can effectively reduce the mass spectrum of non-glycosylated peptides. Analyze time to increase the opportunity for the identification of intact glycopeptides. The methods reported include:

2.1.1. Direct identification of molecular mass

The fundamental basis is that the concept of molecular mass is determined by defining the molecular mass of 12C as 12, and the molecular mass of other elements is determined by comparing with the molecular mass of 12C. Elements can be divided into exactly positive integers according to mass (Such as 12C, 12.00000), or greater than a positive integer (such as 1H, 1.00783; 14N, 14.00307) or less than a positive integer (such as 16O, 15.99491; 32S, 31.97207). Usually in peptides, N and H content is the highest, their actual mass is slightly larger than the molecular weight after rounding, and in glycopeptides, O and S content is relatively high, their actual mass is slightly smaller than the molecular weight after rounding. So for the molecule Glycopeptides of equal mass and ordinary polypeptides without glycosylation, the molecular mass of glycopeptides is usually smaller than polypeptides. This feature can be used to distinguish glycopeptides from ordinary polypeptides. Froehlich et al. used this method to simulate experiments, and got a simple classifier that can distinguish the glycopeptide precursor ion from the peptide precursor ion, and divide the integer part and fraction part of the mass of the glycopeptide / peptide into equations to classify the glycopeptide. In the mass spectrometry mass accuracy is 10ppm, the method can identify intact glycopeptides with a sensitivity of more than 89% and a specificity of more than 93%. With the emergence and popularity of higher resolution and mass accuracy mass spectrometry, it can identify intact glycopeptide. The specificity of the peptide will be further enhanced. However, this method requires that the sugar chain portion of the glycopeptide occupies a large molecular mass ratio, that is, the content of oxygen atoms (O) in the glycopeptide is high, which is more distinguishable from ordinary peptides.

2.1.2. Isotope distribution identification

Because most intact glycopeptides (especially N-glycopeptides) contain more oxygen (O) than non-glycosylated polypeptides, and the isotope of the O element in nature contains 2u difference between 16O and 18O, which is different from the peptide Other major elements C, H, N, etc. (there is only 1u difference between isotopes). Therefore, intact glycopeptides and ordinary peptides usually have different isotope abundance distributions, and their characteristic isotope peak patterns can theoretically be used to identify MS1 Whether the detected molecule is a glycopeptide precursor ion peak. However, the premise of the application of this method is to detect accurate isotope abundance, which is rarely used alone in actual applications. However, the direct identification of molecular mass is used in conjunction with the isotope abundance. Combined with high-resolution and high-precision mass spectrometry, it is theoretically feasible to identify intact glycopeptides at the level of the MS1 precursor ion. Direct identification of the intact glycopeptide at the MS1 level, and then selective MS2 analysis can increase the glycopeptide precursor ion to achieve the purpose of maximum analysis and identification of intact glycopeptides.

To be continued in Part II…

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  1. JAMA: Wuhan public health intervention significantly controls the large-scale outbreak of new coronary pneumonia

On April 10, 2020, Wu Tangchun, Hua Sheng University of Science and Technology, Wei Sheng, and Lin Xihong of Harvard University published a newsletter entitled "Association of Public Health Interventions with the Epidemiology of the COVID-19 Outbreak in Wuhan, China" online in the top medical journal JAMA. The research paper found that among the 32,583 laboratory-confirmed COVID-19 cases, the median age of female patients was 56.7 years and that of females was 16,817 (51.6%). The daily confirmed case rate peaks in the third stage (traffic restrictions and family segregation stage), and then decreases in geographic areas, gender and age groups, except for children and adolescents, whose confirmed case rate continues to rise.

Throughout the period, the daily confirmed case rate of local health care workers (130.5 per million people) was higher than that of the general population (41.5 per million people). During these five periods, the proportion of severe and critical cases fell from 53.1% to 10.3%. The risk of severity increases with age: the risk of serious or critical illness in the elderly (≥80 years old) is higher (proportion is 41.3%) compared with the population in the 20-39 age group (the proportion of severe and critical cases is 12.1%).

In summary, a series of multifaceted public health interventions are related in time to improved control of the COVID-19 outbreak in Wuhan, China. These findings may contribute to public health policies in other countries and regions.

  1. NEJM: Large-scale clinical trial is released, Radecivir can treat severe patients: 68% of patients have observed improvement in clinical symptoms

On April 10, 2020, Jonathan Grein and others published a research paper titled "Compassionate Use of Remdesivir for Patients with Severe Covid-19" online in the top international medical journal NEJM. The study analyzed data from 53 critically ill patients. 22 in the US, 22 in Europe, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation, and 4 (8%) were undergoing extracorporeal membrane oxygenation. During the 18-day median follow-up period, 36 patients (68%) had improved oxygen support levels, and 17 of 30 (57%) patients who received mechanical ventilation had extubated the tube. A total of 25 patients (47%) were discharged and 7 patients (13%) died; among patients receiving invasive ventilation, the mortality rate was 18% (6 out of 34), while patients not receiving invasive ventilation 5% (1 out of 19).

In general, among patients receiving sympathetic use of remdesivirr (reduxivir), clinical improvement was observed in 36 of 53 patients (68%). The measurement of efficacy will require randomized, placebo-controlled trials of remdesivir treatment.

  1. Significant progress made by in the field of epidemiology and propagation dynamics of coronavirus disease (COVID-19).

"The Lancet Infectious Diseases" recently published the important progress made by Yu Hongjie's group at the School of Public Health of Fudan University in the field of epidemiology and transmission dynamics of coronavirus disease (COVID-19) in 2019. The study aims to explain the epidemiological characteristics and dynamic changes of transmission dynamics parameters of COVID-19 in areas outside Hubei Province, mainland China. The article emphasizes that the effectiveness of prevention and control measures is only applicable when the measures are in place. If the existing public health interventions are relaxed or major changes in crowd behavior occur, it may lead to increased follow-up transmission. Given that COVID-19 is spreading globally, the results of this study not only provide important scientific evidence for China to formulate prevention and control strategies, but also provide important references for other countries in the progress of the epidemic.

The results of the study show that the median age of the cases is 44 years old. As the epidemic progresses, the proportion of minors and elderly people aged 65 and above has increased. Although about 20% of China's total population is minors, the proportion of minors in confirmed cases is only 5%. The above results do not yet indicate that minors have a lower susceptibility risk or have a lighter clinical manifestation after infection. Because the epidemic is due to the 2020 winter vacation and the Chinese New Year, schools in China are closed. The reduction in the number of school-age children may be related to a lower risk of infection, but further research is still needed.

The average time between case onset and admission was shortened from 4.4 days before January 27 (95% CI: 0.0-14.0) to 2.6 days from January 28 to February 17 (95% CI: 0.0-9.0). The time from onset to admission and isolation has gradually shortened, reflecting the faster action of governments at all levels to control the epidemic. The average incubation period is 5.2 days (95% CI: 1.8-12.4), and the 95% quantile (10.5 days) indicates that tracking and medical observation of close contacts is very important for the detection of cases with a longer incubation period. The average intergenerational interval is 5.1 days (95% CI: 1.3-11.6), which is shorter than the estimated intergenerational interval of early cases in Wuhan in the previous studies (7.5 days). The shorter intergenerational interval outside Hubei Province may be related to the shorter interval from onset to admission. The average intergenerational interval is shorter than the incubation period, indicating that the case may be infectious before symptoms appear.

Andrew S Azman of the Johns Hopkins University Bloomberg School of Public Health and Francisco J Luquero of Epicentre, France, under the title "From China: Hope and Experience in Controlling COVID-19", wrote an expert review for this study, stating: " Yu Hongjie's group used public data to answer the key epidemiological characteristics of COVID-19 in China, and found that the effective reproduction index of nine severely epidemic areas outside Hubei Province fell below the epidemic threshold by the end of January 2020, effectively slowing the epidemic of local transmission. The author also found that the incubation period and the intergenerational interval have a similar length of time, indicating that the case is contagious before or shortly after the onset of symptoms. " Transparency and timeliness have surpassed most countries, and rapid data analysis and model research have provided important decision-making basis for other countries in the progress of the epidemic. Based on limited historical information on newly emerging infectious diseases, the Chinese government weighed the economy, social and public health and other aspects, the most stringent prevention and control measures have been adopted the country ’s similar measures have provided important advance experience. The results of this study have increased confidence in the possibility of the epidemic being quickly controlled globally. "

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Definition of antibody affinity maturation

Antibody affinity maturation refers to a state of immune function that normally exists in the body. In humoral immunity, the average affinity of the antibody produced by the second response is higher than the initial immune response. This phenomenon is called antibody affinity maturation. It is due to the genetic mutation of the antibody forming cell itself and the selective activation of the B cell clone by the antigen. This functional state of the body is the result of long-term evolution and continuous adaptation to the external environment, and is of great significance for the body's defense and maintenance of its own immune monitoring.

Significance of antibody affinity maturation

Currently, the development of pharmaceutical antibodies is mainly based on hybridoma cells or in vitro antibody libraries. Through antigen design and antibody screening, people initially obtain positive hits, and then further pass a series of biological property detection and functional verification, and finally obtain antibodies with medicinal potential. In the actual research and development process, the antibodies obtained after routine screening have many aspects that need more detailed improvement, including affinity, immunogenicity, half-life, etc. In the field of antibodies, many related researches and practices have been done over the years. Among them, antibody affinity maturation is one of the important research directions.

Theoretically, the increased affinity of antibodies will help to improve the specificity and efficacy of antibodies, help to reduce the dosage of drugs, and reduce toxic and side effects. Although the actual research work proves that the increase in affinity and the increase in antibody titer are not always linear, especially in the treatment of solid tumors (refer to Weinstein's "binding site barrier" hypothesis), in many cases, this linear relationship is obvious. In addition, the development of mature technology of antibody affinity not only helps the development and quality improvement of antibody drugs, but also helps people better understand the mechanism of antibody interaction with the target and better understand the function of the target.

Commonly strategies used for in vitro antibody affinity maturation

According to the principle of in vivo antibody affinity maturation, in the process of in vitro antibody affinity maturation, the selection of mutation regions and how to introduce mutations are a key issue. The current mutation strategies are mainly divided into three categories, random mutation, substitution and directed mutation. One of the strategies for antibody affinity maturation is to simulate high-frequency mutations in somatic cells, and screen for antibodies with high affinity for antigens through cell mutation and display of antibody proteins.

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  • Chain replacement

Chain replacement is to retain the heavy chain or light chain of a specific antibody, and the other chain is combined with a randomized complementary chain to select higher activity mutant strains. By fixing one of the two chains of the antibody and constructing a replacement library with sufficient diversity for the other chain, random combinations are likely to produce the best chain combination, and new antibodies with high affinity can be obtained through phage display antibody screening. Light chain replacement is often used in chain replacement.

  • Site-directed mutation

Due to the affinity maturation of natural antibodies, the regions where high-frequency mutations of somatic cells occur are not evenly distributed, but are mainly concentrated in the CDR regions that directly contact the antigen. During the in vitro maturation of the antibody's affinity, the CDR region is the most commonly selected site-directed mutation region, so that it can obtain sufficient sequence diversity without destroying the protein structure. When performing site-directed mutation on CDRs, multiple CDRs can be changed in parallel or optimized step by step.

  • DNA shuffling

DNA shuffling is a technology that uses homologous antibody genes to cut them into fragments of no more than 50 bp using deoxyribonuclease I, and then randomly combines them to perform PCR amplification to complete anti-rest genes. It contains the process of randomized cutting, recombination and screening of antibody fragments, which mimics the natural process of affinity maturation of antibodies and accelerates the speed of directed evolution in vitro.

Antibody affinity maturation based on antibody libraries is not essentially different from antibody library-based antibody screening. Both are in vitro high-affinity antibody screening. The focus is still on two aspects, namely, library construction and selection of screening systems. The difference is that the library used in the latter is not biased in construction or synthesis or only has a limited bias against an antigen; while the library used in the former is constructed based on the determined antibody sequence template. The strategy of building a library can be divided into two large categories: one is to build a larger library, random mutation of antibody CDR regions or even the entire V region; the other is to build a smaller library, focusing mutations on antibody sequences on a specific area. As for the method of introducing mutations, the simpler is error-prone PCR, but it is difficult to achieve good mutation effects. Another popular method is to design mutations on primers, that is, artificially synthesize primer libraries with mutation regions. There are many specific design methods, including controlling the number of mutated bases, controlling the probability of occurrence of various bases at each site, etc., in order to meet the needs of library capacity and bias.

  • Error-prone PCR

Error-prone PCR is currently the most commonly used antibody mutation technique, which can randomly introduce mutations in the entire length or part of the region of the antibody gene. When the polymerase amplifies the target sub-cause, by applying a polymerase with a high mismatch rate or adjusting the reaction conditions, a mutation is randomly introduced into the target gene at a certain frequency, and random mutagenesis is repeated through multiple rounds of PCR, Cumulative mutation effect, and finally obtain a random mutant of the target protein.

 

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DNA sequencing technology, that is, technology to determine the DNA sequence. In molecular biology research, DNA sequence analysis is the basis for further research and transformation of target genes. The current technologies used for sequencing are the dideoxy chain end termination method invented by Sanger et al. (1977) and the chemical degradation method invented by Maxam and Gilbert (1977). These two methods are very different in principle, but they are based on nucleotides starting at a fixed point and randomly ending at a specific base, resulting in four groups of A, T, C, G with different length A series of nucleotides are then detected by electrophoresis on urea-denatured PAGE gel to obtain the DNA sequence. At present, Sanger sequencing method has been widely used.

 

Introduction

DNA sequencing technology is also called gene sequencing technology.

The human genome is composed of four letters A, T, G, and C. The vast and intricate divine book of life is like a treasure trove, holding secrets that people have been eager to know for thousands of years. DNA sequencing technology is like "opening the door of sesame seeds". The mantra is our golden key to open the treasure trove. The first method in the world to determine the DNA sequence was invented by the British biochemist Frederick Sanger. Since then, the speed of DNA sequencing has been accelerating. The 2001 human genome sketch cost 437 million US dollars and took 13 years. By 2007, the birth of the first complete human genome sequence map cost only $ 1.5 million, and it took only three months to complete. On January 2, 2009, scientists from California Pacific Biosciences, Jonas Kaurrach, Stephen Turner and their research team published a paper in the journal Science, saying that they compared nanotechnology with chip technology in combination, a new sequencing method was invented, which is 30,000 times faster than the existing technology.

 

DNA sequencing technology

The principle of Sanger sequencing is to use a DNA polymerase to extend the primers bound to the template of the sequence to be determined. Until one chain termination nucleotide is incorporated. Each sequence determination consists of a set of four separate reactions, each of which contains all four deoxynucleotide triphosphates (dNTP), mixed with a limited amount of a different dideoxynucleoside triphosphate (ddNTP). Because ddNTP lacks the 3-OH group required for extension, the extended oligonucleotide is selectively terminated at G, A, T, or C. The termination point is determined by the corresponding dideoxygenation in the reaction. The relative concentration of each kind of dNTPs and ddNTPs can be adjusted, so that the reaction can get a group of chain termination products with hundreds to thousands of bases. They have a common starting point, but terminate at different nucleotides, and can be separated by high-resolution denaturing gel electrophoresis. After gel treatment, X-ray film autoradiography or non-isotopic labeling can be used for detection.

 

DNA sequencing strategy

Taq DNA polymerase is extremely thermally stable at 95 ° C. The sequencing-level Taq DNA polymerase used in this system is a modified product of Taq DNA polymerase. It has a very good effect on double-stranded DNA templates, has a high degree of accuracy, can produce uniform bands, and has a low background.

 

Material

The purified DNA to be tested can be single-stranded or double-stranded.

Scientists placed thousands of waveguides on a microarray chip etched with nanostructures. This is a miniature, hollow metal tube with a diameter of about 20 nanometers and a volume of about 1 femtoliter. A DNA molecule plus a DNA polymerase molecule can fill up the space in the tube. In this way, thousands of sequencing reactions can be performed simultaneously on a small chip. Especially valuable is that when performing sequencing reactions in such miniature waveguides, the interference will be significantly reduced, which means that the accuracy can be greatly improved.

 

In the current product, there are about 3,000 waveguides on each chip. Pacific Biosciences intends to launch this level of product in 2010. According to the company’s founder Turner, by 2013, one million waveguides will be placed on each chip, and the complete sequence of the human genome will be measured within half an hour, with an accuracy of 99.999% and a cost of less than $ 1,000.

Although Dr. Michael Metzke of Baylor College of Medicine in Texas said that Turner ’s outlook is too optimistic, such an amazing speed makes us seem to see the previous progress of computer CPUs-the number of transistors on integrated circuits, every 18 Months will double, and performance will double. Someone commented that DNA sequencing technology will follow computer technology and communication technology to become the third "Moore's Law" subject industry.

 

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