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  2. Plots of land where nothing has previously been developed on are quite rare these days, especially in urban areas. No matter if the land is purchased for farming or house building, checking the soil for contamination is extremely important, in order to avoid hazardous chemicals from coming in contact with anything that’s being developed on in or in the nearby sites. Up until recent years, environmental laws were more relaxed and it was not uncommon for waste was dumped close to where the products were used. Chemicals can persist in the soil for decades and can be really dangerous, especially if it comes in contact with crops or animals. Fortunately, there are multiple solutions that have been developed to treat the soil and restore its fertility. The Dangers of Soil Contamination To put it simply, soil contamination occurs when the soil comes in contact with pollutants, mostly due to hazardous past activities that were conducted on the site. The concentration of pollutants becomes higher than normal, often spreading to the nearby areas and polluting the neighbour lands as well. People have often reported dealing with contaminated soil, due to recent demolition or construction work developed close to their homes or farms. Living or working in close contact with contaminated soil increases the risk of chemical exposure through skin absorption or inhalation of chemicals. If corps are being planted on such lands, they can quickly absorb chemicals from the soils that travel from their roots to their leaves, fruits and seeds and eventually reach the people who consume the produce. Before coming in contact with the human body, soil contamination can also affect crop quality, by decreasing the fertility of the soil and alter its structure. The crops will develop poorly and, over time, the soil will become less productive and even completely infertile due to large quantities of toxic chemicals. Soil contamination can also lead to water pollution. After rain, the surface runoff can carry the polluted soil and mix it into different water sources. This way, the water fills with toxic chemicals, which make is unfit for humans, plants or animals. Low levels of contamination can produce reactions such as nausea, fatigue, rashes or headaches, while exposure to high levels of contamination can even result in neurological or reproductive disorders. Studies have reported that prolonged high chemical exposure can also increase the risk of cancer. The most vulnerable are usually elders, pregnant women and especially children, who often play in gardens and ingest soil particles from touching their mouth with dirty fingers. In such situations, the health risks are much higher. Common Soil Contamination Reasons In urban areas, lead is the most common soil contaminant, mostly because it used to be found in the compounds of exterior paint. It is very easy for old paint to disintegrate and fill the soil around the house with flakes that can contaminate it. Avoiding to grow crops or do digging near buildings that could have been painted with such old paint is one simple way to avoid contamination. Heavy metals and industrial chemicals are also present in urban areas, though they are more likely to be found in industrial areas, rather than residential. There is a wide range of activities that can lead to soil pollution, such as mining, that can release sulfuric acid, mercury and acid into the soil. Fuel storage can release hydrocarbons, while agricultural and industrial waste can pollute the soil due to leaks, spills or pipeline ruptures. Even light industrial or agricultural activities conducted on the site can result in some sort of contamination. Some of the most common reasons are: · Pesticides: after World War II, people started using DDT, an insecticide that turned out to be extremely dangerous for the environment, to deal with rodents, weeds and insects that threatened their crops. In 2011, traces of DDT were still found in human bodies, despite being banned almost 30 years ago. · Industrial pollution: improper disposal of chemical waste from various types of industries has led to soil acidification and contamination with heavy metals, oils and toxic chemicals. · Poor irrigation: bad irrigation practices have led to increased soil salinity, while improper maintenance of irrigation canals and intensive farming slowly degraded the soil over time. · Urban activities: disposal of solid waste is another form of soil pollution, most common from plastic or batteries, which contain lithium that causes soil leaching. Sewerage leaking can also damage soil quality or change its chemical composition. Dealing with Contaminated Soil Testing soil for contamination is quite easy and many laboratories offer such services. Private companies and public universities also offer soil testing services, which can reveal all the information needed. Some of these services are mail-in and the labs will provide instructions on how to properly collect soil samples and send them through. After the test reveals the level of pollution, there are a few procedures that can help deal with contaminated land. · Soil Washing: this is often considered to be the best technique to treat heavy metal and hydrocarbon contamination. Soil washing is a process that involves physically separating the contaminated particles from the soil by using heat or water to remove them. · Bio-piles: this process involves excavating the soil, forming it into piles and mixing it with soil amendments. The piles are enclosed and an irrigation system pumps air and nutrients through the soil. The treatment time varies between 3 and 6 months, after which the excavated soil is returned to its original location. · Soil Stabilization: typically used to treat sub-grade materials, such as clays or granular materials, the process is used to enhance the physical properties of the soil. It uses reduction and oxidation to incorporate additives into the soil, until it achieves the desired properties and the contaminated soil become non-hazardous. The decontamination process can vary, depending on the type of pollutants that are found in the soil and the contamination period. After decontamination, the disposal of the contaminated remains must be carried out according to local regulations, to avoid polluting other areas.
  3. Protein is mainly composed of chemical elements such as carbon, hydrogen, oxygen and nitrogen. It is an important biological macromolecule. All proteins are multimers formed by the connection of 20 different amino acids. After Forming proteins, these amino acids are also called as a residue. The boundaries between proteins and peptides are not very clear. Some people believe that the number of residues required for a functionally acting domain is called a polypeptide or peptide if the number of residues is less than 40. To function biologically, proteins need to be properly folded into a specific configuration, mainly through a large number of non-covalent interactions (such as hydrogen bonds, ionic bonds, van der Waals forces and hydrophobic interactions); in addition, in some proteins (especially in the case of secreted proteins), disulfide bonds also play a key role. In order to understand the mechanism of action of proteins at the molecular level, it is often necessary to determine the three-dimensional structure of a protein. Structural biology has been developed by studying protein structure, using techniques including X-ray crystallography, nuclear magnetic resonance, etc. to resolve protein structures. A certain number of residues are necessary to exert a certain biochemical function; 40-50 residues are usually the lower limit of the size of a functional domain. Protein size can range from such a lower limit up to thousands of residues. The current estimated average length of proteins differs between different species, typically about 200-380 residues, while eukaryotes have an average protein length of about 55% longer than prokaryotes. Larger protein aggregates can be formed by many protein subunits; for example, by the polymerization of thousands of actin molecules to form protein fibers. Discovery history In 1959, Perutz and Kendrew analyzed the structure of hemoglobin and myoglobin, solved the three-dimensional structure, and won the 1962 Nobel Prize in Chemistry. Pauling discovered the basic structure of the protein. Based on the X-ray diffraction data, Crick and Watson proposed a model of the three-dimensional structure of DNA. Received the 1962 Nobel Prize in Physiology or Medicine. After the 1950s, Hauptmann and Karle established a purely mathematical theory for the direct determination of crystal structures using X-ray analysis, which has epoch-making significance in crystal research, especially in the study of macromolecular biological substances such as hormones, antibiotics, and proteins. And the molecular structure of new drugs played an important role. They were awarded the 1985 Nobel Prize in Chemistry. Structure type Protein molecules are covalent polypeptide chains formed by the condensation of amino acids end-to-end, but natural protein molecules are not loose random polypeptide chains. Each natural protein has its own unique spatial structure or three-dimensional structure, which is often referred to as the conformation of the protein, ie the structure of the protein. The molecular structure of a protein can be divided into four levels to describe its different aspects: Primary structure: A linear amino acid sequence that makes up a protein polypeptide chain. Secondary structure: a stable structure formed by hydrogen bonds between C=O and N-H groups between different amino acids, mainly α-helix and β-sheet. Tertiary structure: The three-dimensional structure of a protein molecule formed by the arrangement of multiple secondary structural elements in three dimensions. Quaternary structure: used to describe a protein complex molecule that is functionally formed by interactions between different polypeptide chains (subunits). In addition to these structural levels, proteins can be transformed in multiple similar structures to perform their biological functions. For functional structural changes, these tertiary or quaternary structures are usually described in a chemical conformation, and the corresponding structural transformation is referred to as a conformational change. About us Our products and services are used worldwide in research fields for diverse applications, including basic research, drug discovery, and diagnostic study. Here are some our products like: Cryo-EM,membrane proteins,virus-like particle service,VLP construction,etc.
  4. Adjuvant Selection is the main method for finding molecular genetic markers, vaccines like bacterial vaccines, cancer vaccines, RNA vaccines, MAS breeding and so on. Major methods for finding molecular genetic markers DNA markers are divided into two types: type Ⅰ markers, mainly are some single genes, and used to compare the homologous loci varieties of relative distance and chain and linear correlation; Ⅱ type markers, mainly high polymorphism, information content rich DNA fragments, is one of the most commonly used microsatellite marker. Through Adjuvant Optimization, more and more kinds of molecular markers were introduced, including restricted fragment length polymorphism (RFLP), random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), and Microsatellites. At present, there are 2,505 markers in the world's pig research, including 1,391 microsatellite markers. Ⅰ type 873, type Ⅱ mark 1632. The main methods to search for molecular genetic markers are candidate gene method and genome scanning method. 1. Candidate gene method as a candidate gene for a trait, it is usually some genes whose biological functions and nucleic acid sequences are known, and they are involved in the growth and development process of the trait. These genes may be structural genes, regulatory genes or genes that affect the expression of traits in biochemical metabolic pathways. Candidate gene method research should follow certain steps, such as candidate gene selection primer design, gene specific fragment amplification, polymorphic locus search and so on. Candidate gene search USES genes that are thought to have a direct physiological function for a trait to find QTLS. In addition, genes found in other species that control some traits can be studied as candidate genes for pigs. For example, the h-fabp gene affects the backfat thickness and intramuscular fat content of pigs (Gerbens et al., 1999). 2000; 2001); The melanocorticoid receptor 4 (MC4R) gene was significantly correlated with the intake, backfat thickness and growth rate of pigs (Kim et al., 1999; 2000). 2. Genome scanning: all genetic information is stored on the 19 pairs of chromosomes of the pig. Reference families were established, such as meishan European and American pig species, wild boar big white pig, and their hybrid offspring were used to find QTL through genetic markers. The most effective design is the genotype analysis of F2 generation isolation population. Figure 4-2 is a simple schematic diagram of single genetic marker and linkage QTL analysis. Alleles of genetic markers and their linkage QTL in F1 generation were heterozygous. In the F2 generation isolation population, the ratio of the three possible genotypes per seat should be 1:2:1, when the average performance of marker genotypes is compared, the existence of linkage QTL can be analyzed. Anderson (1994), such as reported with a wild boar by the results of the large white building reference group, using the 105 DNA markers in the genetic map, the separation of F2 generation 200 pigs linkage analysis research found that on chromosome 4 seat back fat and control the growth rate, the average genetic effect 24 g/d and 5 mm, respectively, the equivalent of F2 DaiQun total phenotypic variation of 12% and 18%. Daily weight gain can differ by more than 50g between two extreme homozygous genotypes, resulting in a 10kg weight difference at market time in pigs. (iii) MAS breeding In pig breeding selection, it is difficult to determine the sex efficiency of low heritability (e.g., reproductive traits), high cost of measurement (e.g., disease resistance), phenotypic values (e.g., lean meat rate) or limited sexual performance (e.g., milk production) early in development. It is estimated that the selection of the marker before the determination of the offspring can increase the selectivity response by 10%~15%. The MAS of compatriots who choose to combine can be increased by about 40%. Combining multiple genetic markers and trait information, the selectivity response can be increased by 50%~200%. Using marker selection in cross breeding can predict and make full use of heterosis. Molecular genetic markers can also be applied to early selection and screening and detection of large populations to select populations with desired genotypes. For example, there is little progress in the improvement of pig litter, a low genetic trait, by traditional methods. Rothschild et al. found in 1994 that the estrogen receptor (ESR) gene was one of the main genes responsible for the litter size of pigs, which could control the total litter size of 1.5 pigs and the live litter size of 1 pig in the meishan synthetic line of China. In the Chinese two-flower face hybrid population, the agricultural university of China not only confirmed the results of Rothschild et al., but also found another main gene locus controlling the number of piglets - FSH, which can control the total number of piglets and the number of live piglets by 2.0. Although MAS can improve the effectiveness of selection and the annual amount of genetic improvement, its effectiveness is also affected by many factors. In addition to the heritability of traits, the intensity of selection, and the size of the selected population, the determinants are the linkage between genetic markers and QTLS. Zhang (1992) pointed out that each QTL could be specifically detected by using genetic markers closely linked to QTL, and the final selection of genetic markers would be equivalent to the selection of QTL itself. Therefore, genetic markers closely related to QTL must be obtained in order to improve MAS efficiency. Resources at present, through the establishment of the pig family, has some related to the growth, reproduction and carcass, meat quality of QTL mapping in some microsatellite nearby, such as on chromosome 3 microsatellite Sw2427 - Sw251 area and daily gain of pigs, on chromosome 4 S0101 - S0107 area and back fat belly fat, 7 chromosome S0064 S0066 regional composition and has a strong correlation between birth weight and body. It can be predicted that with the discovery of more genetic markers closely linked to QTL, MAS will be applied more effectively in practical breeding.
  5. 3 Cancer vaccine adjuvant selection The initial aim of formulating vaccines in adjuvants was to deliver the antigen in a poorly metabolizing and slowly degrading substance. The intention was to favor the slow and sustained release of the antigen to be captured by antigen-presenting cells (APCs) and be subsequently presented to T cells. Aluminum salts are widely used to favor T helper cell 2 (Th2)-mediated humoral immunity, but they are less efficient for promoting Th1-dependent immunity. To this aim, water-in-oil adjuvants have been developed to create a depot of the antigen at the site of the injection. The next generation of vaccine delivery agents includes nanoparticles such as silica or liposomes or synthetic polymers, which are ideal vehicles to be taken up by dendritic cells (DCs) patrolling within the subcutaneous tissues. However, the challenge with such supports is to selectively promote DC uptake while eluding the systemic reticuloendothelial network of macrophages, which routinely clear circulating particles. In addition to these substances designed to favor delivery of the antigen to APCs, today’s therapeutic vaccines also contain another class of adjuvants aimed to deliver danger signals to activate the immune system, as antigen alone may fail to prime effective T cell responses or even induce tolerance. 4 The choice of cancer vaccine delivery system The choice of delivery systems and route of immunization depends on the end use of the vaccine. For practical reasons and minimal side effects, most prophylactic vaccines are administered via the skin, usually by subcutaneous injections in the epidermis or the dermis. These two locations are ideal, as they are enriched respectively in Langerhans DCs and dermal DCs, both cell populations being very efficient in capturing and processing antigens. The oral route is also very convenient and is used by vaccines against polio, typhoid fever, cholera, and rotavirus. The oral route is, however, more challenging in view of the extreme conditions in the gastrointestinal tract, including the low pH in the stomach and the presence of microbiota, which may degrade the antigen before it reaches the lymphoid organs. Moreover, the usually tolerogenic gut environment may not be ideal to generate a strong systemic immune response. With regard to therapeutic vaccines used to treat chronic noncontagious diseases such as cancer, atopy, or diabetes, both immediate cellular effector responses and long-term immunity are desired to guarantee the continuous immune-surveillance of the disease. Although prophylactic vaccines for global immunization programs must be simple, inexpensive, and given via a noninvasive route, therapeutic cancer vaccines can benefit from more complicated technologies and use more invasive routes of delivery if beneficial for the patient. There is a very large array of cancer vaccines under development which use various delivery systems, and which are being tested in clinical trials. Other delivery routes tested in therapeutic cancer vaccines range from subcutaneous and intradermal to more invasive intraperitoneal and intranodal injections, to optimize antigen uptake by APCs and favor a local potent immune response. For instance, particulate therapeutic vaccines such as virosomes or nanoparticles can be injected in LNs using an ultrasound-guided imaging procedure. Although most of these strategies are still in the development stage, the potential to achieve strong and long-lasting antitumor responses is high, owing to new delivery systems and better understanding of T cell memory development. Reference [1] FUTURE II Study Group. Quadrivalent vaccine against HumanPapillomavirns to prevent high-grade cervical lessions. N Engl J Med, 2007, 356(19): 1915 [2] Olsson SE, Villa LL, Costa RLR, et a1. Induction of inmmne memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/1 1/16/18 LI virus-like particle (VLP) vaccine. Vaccine, 2007 (25): 4931 [3] Harris JE, Ryan L, Hoover Jr HC, et a1. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Orwol, 2000, 18(1): 148 [4] Berd D, Maguire Jr HC, Mastrangelo MJ, et a1. Treatment of human melanoma with a hapten — modified antologous vaccine. Ann NY Acad Sci, 1993, 690(8): 7 [5] Remann R, Goldschmidt AJ, Richter A. Adjuvant therapy of renal cell carcinoma patients with an autologous tumor cell lysate vaccine: a-year—follow—up analysis AnticancerRes, 2003, 23(2A): 969 [6] Mitchell MS, Kan — Mitchell J, Kempf RA, et a1. Active specific im-munotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res, 1988, 48(20): 5883
  6. 3 Benign Mucous Membrane Pemphigoid 3.1 Clinical manifestations Conjunctival and oral mucosal damage accounted for 60% to 90%, patients with nasal, pharyngeal, genital and anal mucosa accounted for about 25%, skin involvement is rare, skin damage is very similar to the lesions of bullous pemphigoid, but the time is short, and the stenosis or adhesion caused by scar healing and scar formation is characteristic. 3.1.1 Eye damage The eye is the only affected part, and the damage usually occurs asymmetrically. After 1 to 2 years, the contralateral eye mucosa is involved. There are symptoms of catarrhal conjunctivitis. Transparent blisters can be found and quickly ruptured. Subsequently, scar atrophy, conjunctival and bulbar conjunctiva adhesions, eye movement involvement, tendon varus leading to secondary corneal changes, corneal opacity, scar formation of the tarsal plate with mucosa, atrophy of the gland and blockage of the lacrimal duct, thus corneal dryness, discoloration and blinding ulcers are formed. 3.1.2 Mucosal damage Multiple blisters quickly form painful erosions and the scars heal. If the damage occurs in the tongue ligament, the contracted scar can limit the movement of the tongue. Damage that occurs in soft palate, tonsil, and buccal mucosa may limit food intake. The genital area of the vulva can form a head adhesion, a vaginal stenosis, and the like. 3.1.3 Skin damage The incidence of skin damage is only about 25%, the damage is a tension blisters, the blister wall is not easy to rupture, occurs on erythematous skin, one or more parts. Healed with atrophic scars. If bullae occur in the head, scarring hair loss may occur. Generalized lesions are extremely rare, and even if there are secondary scar formation. Benign mucosal pemphigoid can occur repeatedly for several years without significant effect on general health. The faster the disease progresses, the worse the prognosis. Due to eating difficulties, malnutrition and cachexia may occur, and the incidence of blindness is approximately 20% to 60%. Although extremely rare, there have been reports of cancerous changes in the scars of the oral mucosa. 3.2 Laboratory examination 3.2.1Histopathology: typical epidermis blister, no spine release. Infiltration of inflammatory cells composed of lymphocytes, plasma cells, and eosinophils can be seen in the upper dermis. Subsequently, there were a large number of fibroblasts with superficial dermal fibrosis and vascular hyperplasia and scar contracture. 3.2.2 Immunofluorescence: direct immunofluorescence of skin mucosa to detect IgG and C3 deposition in the basement membrane zone, and IgA and C3 deposition were also observed. The homogenous linear deposition was almost the same as that in bullous pemphigoid. The positive rate of indirect immunofluorescence detection of anti-basal membrane circulating antibodies was <10%, and the titer was low. If the DIF is negative, the fresh tissue should be removed from the erythema around the lesion for repeated testing. 4 Pathogenesis of Pemphigus In the plasma of patients with pemphigus, there is anti-Dsg3 and/or anti-Dsg1 IgG, and no anti-Dsg2 antibody exists. This autoreactive antibody binds to its corresponding antigen, leading to a series of clinical pemphigus. The emergence of performance. In the active phase of pemphigus vulgaris, the serum is mainly pathogenic IgG4 subclass and IgG1, while in the serum of patients with long-term remission, there are low-valency IgG1 subclasses, IgG4 and Dsg1 and Dsg13 on keratinocytes. The combination causes the loss of adhesion between cells, leading to the release of intercellular cells and the formation of blisters in the epidermis. The antigen Dsg produced in the MMP autoimmune disease belongs to the transmembrane component of desmos, belonging to the cadherin superfamily in the adhesion molecule, whose gene is located at 18q12.1. Dsg is divided into three categories: Dsg1, Dsg2, and Dsg3. Among them, Dsg2 is expressed in all tissues with desmosome, including monolayer epithelial cells and myocardial tissue. Dsg1 and Dsg3 are mainly restricted to stratified squamous cells. Current studies have shown that Dsg1 and Dsg3 are target antigens of pemphigus foliaceus (PF) and pemphigus vulgaris (PV), respectively. The relative molecular mass of Dsg3 is about 130 kD. which is mainly distributed on the surface of keratinocytes in the basal layer of the epidermis and the upper layer of the basal layer. The relative molecular mass of Dsg1 is about 160 kD, which is mainly distributed on the keratinocyte membrane in the upper layer of the epidermis, with the advantage of granular layer and subgranular layer expression. The Dsg3 and Dsg1 molecules, like other cadherin molecules, have five tandem repeats of approximately equal size extracellular domain (EC), each of which is approximately 100 amino acid residues in length, of which EC1 the region corresponds to the extracellular amino terminal residue and EC5 is at the carboxy terminus. The difference between Dsg1 and Dsg3 is mainly due to the homology of the 1 to 4 extracellular domains of Dsg1 and the homology of the 5 extracellular domains of Dsg3. Unlike classical cadherins, Dsg1 has a longer intracellular fragment, and the extracellular fragment of Dsg3 is slightly longer than Dsg1, but its intracellular domain is slightly shorter and has no glycine/serine-rich region. In the five extracellular domains of the pemphigus antigen, EC1, EC2, and EC4 have relatively large homology and can be specifically recognized by the plasma of pemphigus patients. Therefore, these epitopes are called "an immune-dominant epitope, or a "pathogenic epitope," an antibody that specifically recognizes an epitope is called a "pathogenic antibody." The pemphigus antigen contains at least one "pathogenic epitope" in the EC1 -2 region, and antibodies against EC1 -2 are closely related to the pathogenesis of pemphigus. The recombinant protein expressed by the EC1 -2 and EC3 -4 gene sequences of Dsg3 only reacted with the plasma of pemphigus patients, and the response rates of the two were 57.9 % and 52.6%, respectively, and the bullous pemphigoid, system Lupus erythematosus and normal people do not respond. This indicates that EC1 -2 and EC3 -4 are antigen-specific and have a high affinity with pemphigus antibodies, thus providing a new approach for serological diagnosis and identification of pemphigus. In Dsg1 and Dsg3, when either function is lost, the other can partially compensate for its function. This theory explains the tissue specificity of the loss of intercellular adhesion caused by autoantibodies in pemphigus patients. Because Dsg1 and Dsg3 have a certain distribution pattern, the difference in anti-Dsg antibodies also leads to differences in the clinical manifestations of pemphigus. By inserting the Dsg1 gene into Dsg3 knockout mice to form a transgenic mouse capable of expressing Dsg1, it was found that Dsg1 can compensate for partial Dsg3-mediated loss of intercellular adhesion function, which is confirmed genetically. 5 Treatment Glucocorticoid is preferred for the treatment of pemphigus. Most scholars at home and abroad are empirical drugs. There are ethnic and regional differences in the choice of hormone dose. At present, the severity of the disease is not unified by using the scoring system. If the two are linked to the hormone dose and applied to the clinic, the treatment plan will be more reasonable. Determine the initial dose of hormone according to the ABSIS system: ABSIS skin severity score ≤10, give 30 ~ 40 mg / d, skin score of 10 ~ 50, 60 mg / d is appropriate, skin score > 50 points, give 80 mg /d. If the skin lesions are not controlled for 5 to 7 days, increase the dose by 50%. Reduced indications: Daily new blistering number <5, no new erythema; no obvious exudation of erosion surface; pemphigus antibody titer decreased earlier; ABSIS skin score decreased by more than 35%. The long-term use of large doses of hormones can easily lead to many drug reactions. Therefore, the combination of immunosuppressive agents, including azathioprine, cyclophosphamide, mycophenolate mofetil, etc., is generally used to reduce the number of hormones and shorten the treatment time. At the same time, it can be combined with an immune-modulator (Amlalazine, etc.), plasma exchange method and in vitro. Photochemotherapy, etc. Randomized controlled observation of prednisone combined with mycophenolate mofetil, azathioprine and prednisone alone in the treatment of 42 cases of pemphigus, combined with the ABSIS system to assess the severity of the disease before and after treatment, the results show that the three treatment days The short-term efficacy and safety of acne are similar, but prednisone combined with mycophenolate mofetil reduces the dose of hormones most significantly. In recent years, some biological agents and treatments have become new choices for the treatment of pemphigus, such as rituximab, high-dose intravenous immunoglobulin (IVIG), immunosorbent assay, TNF-α antagonist and hematopoietic stem cell transplantation therapy. For the severe bullous disease such as pemphigus, detecting the Dsg ELISA index has certain guiding significance for judging its severity. However, if medical workers are to accurately grasp the changes in their condition, they also rely on an effective and widely recognized scoring system to provide a reliable clinical basis for the treatment and adjustment of pemphigus. At present, there are few clinical applications of ABSIS and PDAI. Both have their own advantages and disadvantages. If they can be combined, it is expected to improve the evaluation method. The correlation between the disease scoring system and antibody levels, and the number of hormones controlled by scoring will be important research topics. Many new drugs and treatments have emerged in recent years, and multi-center large-scale clinical trials are still needed to explore the best treatment options. Reference [1] Barnadas MA, Rubiales MV, Gich I, et al. Usefulness of specific anti-desmoglein 1 and 3 enzyme-linked immunoassay and indirect immunofluorescence in the evaluation of pemphigus activity [J]. Int J Dermatol, 2015, 54(11): 1261-1268. [2] Daneshpazhooh M, Kamyab K, Kalantari MS, et al. Comparison of desmoglein 1 and 3 enzyme - linked immunosorbent assay and direct immunofluorescence for evaluation of immunological remission in pemphigus vulgaris [J]. Clinical & Experimental Dermatology, 2014, 39(1): 41-47. [3] Nakahara T, Takagi A, Yamagami J, et al. High anti-desmoglein 3 antibody ELISA index and negative indirect immunofluorescence result in a patient with pemphigus vulgaris in remission: evaluation of the antibody profile by newly developed methods [J]. Jama Dermatology, 2014, 150(12): 1327-1330. [4] Pfutze M, Niedermeier A, Eming R. Introducing a novel autoimmune bullous skin disorder intensity score ( ABSIS) in pemphigus [J]. Eur J Dermatol, 2007, 17(1): 4-11. [5] Murrell DF, Dick S, Amagai M, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus [J]. J Am Acad Dermatol, 2008, 58(6): 1043-1046. [7] Chams-Davatchi C, Rahbar Z, Daneshpazhooh M, et al. Pemphigus vulgaris activity score and assessment of convergent validity [J]. Acta Med Iran, 2013, 51(51): 224-230. [8] Sebaratnam DF, Frew JW, Davatchi F, et al. Quality -of-Life Measurement in Blistering Diseases [J]. Dermatol Clin, 2012, 30(2): 301-307. [9] Mahajan VK, Sharma NL, Sharma RC, et al. Twelve-year clinicotherapeutic experience in pemphigus: a retrospective study of 54 cases [J]. Int J Dermatol, 2005, 44(10): 821-827. [10] Agarwal M, Walia R, Kochhar AM, et al. Pemphigus Area and Activity Score (PAAS) --a novel clinical scoring method for monitoring of pemphigus vulgaris patients [J]. Int J Dermatol, 1998, 37(2): 158-160.
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  8. Life is hectic and people want their homes and gardens to be attractive and low maintenance. It is why composite deck boards are so suitable for outdoor living – they don’t need to be stained and they don’t splinter or rot. True, composites do fade just a little bit at first from sun exposure, but then they settle down and the fading stops. Trendy for Residential- or Commercial Properties Composite boards are sought after for the residential market as well as for business properties. Composite decking suppliers have hollow- or solid boards which can be used for garden decking – patios, swimming pool decks, sun decks, entertainment areas and more. Making use of a wood plastic composite material, the plastic decking makes sure you can enjoy the beauty of the outdoors without worrying about ongoing maintenance. You get lots of options too – decks in lots of colours and textures. Less Seams and Screws than Wood Also, wood planks are essentially sold as 2.9mboards, but composite deck boards are much longer. The advantage of this is that you have fewer seams on the deck. With composite decking, you can use stainless steel decking screws, while products also come with a clip or tongue-and-groove assembly. You don’t see unsightly rows of screw heads. Installing composite decks is quick too with joining systems. Coping with all kinds of Weather Whatever trendy aesthetic features you’re looking for with composite deck, there are different shades to choose from. With composite boards, you can get truly creative. These boards have also been designed to cope with different climates without you having to worry about staining too soon. Known also as Wood-Plastic Composite, this man-made material even has the natural look and feel of a hardwood floor. Many composites are made from recycled plastic and wood flour mixture, making them far friendlier on the environment than other deck types. Most boards are made from Polyethylene or Polyvinyl Chloride and you can buy them from a store or online. The Look of Real Wood A beautiful deck simply becomes an outdoor extension of a home, and it cleverly mimics the look of real wood. It will look amazing and the best part there’s no painting, oiling or staining needed. You simply wipe it down with warm water and a gentle cleaning product. r, so you can be sure your deck will look brand new year after year. The best part about these boards is that you can say good-bye to old greying, warped, splintered wood which clashes with your sparkling pool. Rather welcome a stylish composite deck that looks beautiful in all kinds of weather year in and year out.
  9. What is 3D cell culture? Three-dimensional cell culture is based on the common three-dimensional culture model of the scaffold, which can better simulate the natural environment in which the cells grow. Three-dimensional cell culture (TDCC) refers to the co-culture of vectors with different materials in three dimensions and various kinds of cells in vitro, so that cells can migrate and grow in the three-dimensional spatial structure of the carrier. Three-dimensional cell-carrier complex. Frontier knowledge about 3D cell culture research Three-dimensional cell tissue plus tensile culture model of the United States flexcell company Tissue Train tensile stress stimulation three-dimensional hydrogel stent cell tissue culture system. Functional highlights of the three-dimensional cell tissue augmentation culture model: after burning three-dimensional cell tissue culture and stretching three-dimensional cell tissue culture in the true sense of three-dimensional culture - the system with a variety of coated surfaces (Amino, Collagen (Type I Or IV), Elastin, ProNectin (RGD), Laminin (YIGSR) collagen hydrogels for extracellular matrix scaffolds in biomaterial scaffold studies, compared to traditional nanofiber scaffolds and porous scaffolds, hydrogel scaffolds The network contains a lot of water, which can supply cell nutrients well, and can also cross-link bioactive factors to regulate cell growth and differentiation. Therefore, hydrogel scaffolds can better simulate the tissue-like physics required for cell growth. The spatial structure has high plasticity, relatively simple manufacturing process and convenient clinical application. Three-dimensional cell tissue pressure-carrying culture system model of American three-dimensional cell tissue after-force culture model Three-dimensional cell culture in three-dimensional cell culture 1) The system provides periodic or static pressure loading of various tissue, three-dimensional cell cultures; 2) based on the deformation of the flexible film substrate, uniform force; 3) Real-time observation of the reaction of cells and tissues under pressure; 4) can selectively block stress loading on cells; 5) Simultaneously have multi-channel cell pull force loading function; 6) Up to 4 channels, 4 different programs can be run simultaneously, and multiple different pressure deformation rate comparison experiments are performed; 7) Multiple frequencies (0.01-5 Hz), multiple amplitudes and multiple waveforms can be operated in the same program; 8) Better control of waveforms under ultra-low or ultra-high stress; 9) A variety of waveform types: static waveform, positive rotation waveform, cardiac waveform, triangular waveform, rectangle and various special waveforms; 10) computer system for pressure loading cycle, size, frequency, duration precise intelligent control typical application range: detection Biochemical reactions of various tissues and cells under pressure. Three-dimensional cell tissue augmentation culture model. Three-dimensional cell tissue stretchestensile force loading culture system model of American flexcell company Three-dimensional cell culture three-dimensional cell tension loading culture 1) The system provides axial and circumferential stress loading on two-dimensional, three-dimensional cells and tissues; 2) based on the deformation of the flexible film substrate, uniform force; 3) The reaction of cells and tissues under stress can be observed in real time; 4) can selectively block stress loading on cells; 5) Simultaneous multi-channel cell pressure loading function; 6) In combination with the Flex Flow parallel slab flow chamber, fluid shear stress can be applied while pulling the cells; 7) Up to 4 channels, 4 different programs can be run simultaneously, and multiple different tensile deformation rate comparison experiments are performed; 8) Multiple frequencies, multiple amplitudes and multiple waveforms can be operated in the same program; 9) Better control of waveforms under ultra-low or ultra-high stress; 10) Multiple waveform types: static waveform, positive rotation waveform, cardiac waveform, triangular waveform, rectangle, and various special waveforms; 3 Three-dimensional cell cultures in life applications: Customized 3D cell culture services are common in our lives, and there are also 3D cell culture related products on the market. Creative Bioarrayoffers 35 human cell systems with over 160 different cell types. Moreover, we also provide our customers primary cells from over 13 types of other animals. These cells taken from living tissue are extremely accurate as they are literally coming from the source and are available from many sources on the human body. These living samples can give extremely accurate information about the cells in vivo and give relevant information regarding the living systems. Not only canCreative Bioarray offer such a wide range of primary cells of humans, but we also have a selection of primary cells of animals for comparative testing. Bone cells, which are found within the bone tissue, are responsible for bone production, maintenance and modeling. There are three different types of cells that found only in the bone. The osteoblasts are derived from mesenchymal stem cells and its function is bone matrix synthesis and its subsequent mineralization. The osteoclasts are large cells that dissolve the bone and osteocytes are cells inside the bone. At Creative Bioarray, we offer 6 types of human primary bone cells including: Human Bone marrow-derived endothelial Cells, Human Osteoblast Cells, Human Osteoblasts (HOB), Human Osteoblast Cells (Postnatal), Human Calvarial Osteoblasts (HCO) and Human Osteoblasts-femural (HO-f). The method we use to isolate endothelial cells was developed based on a combination of established and our proprietary methods. These cells are pre-coated with PECAM-1 antibody, following the application of magnetic beads pre-coated with secondary antibody. Human osteoblasts may be used for various types of in vitro, in vivo, or regenerative medicine studies in normal or diseased systems. In addition, they may be used in bone development studies.
  10. We all like to take pride in being environmentally-friendly. There’s just something that feels good about being kind to the environment around us. However, it’s nice when that kindness lines up with getting us some extra money as well. Here are some great ways to do your part for the environment while putting some much-needed green into your own wallet. Scrap Metal Recycling We’re sure you’ve all seen or heard those commercials about cash for junk cars. The truth is that you can make some good money with the help of scrap metal services. Whether you have an old car you’re looking to get rid of or other extra metal items that are just taking up space in your yard, calling a scrap metal service can help to clean up your space and score you some green as well. Government Solar Tax Incentives Solar panels are becoming a popular way to help save energy costs and reduce our carbon footprint. In fact, many towns are implementing solar panel incentives for those who install these systems. The federal government has been on a rally to offer tax incentives to those homeowners and business owners who upgrade their properties to run on solar power. This type of energy also supplies the power grid that you’re connected to with energy. The power company will also pay you for the units of energy that you feed into the power grid. This means a double payday for you, once from the electric company and twice for the tax break. Reduced Gas Expenditure When you think about air pollution, one of the first things you may think about is your car. When you drive to and from work every day, your car releases air pollution into the environment. It also costs you money in gas to do so. Instead, you can sign up with a carpool group from your work or local community. This way, you can share the cost of gas. This means that you’ll be paying out less money in your monthly gas expenditure than if you were to drive by yourself each day. Going green doesn’t have to be a difficult task. This holds especially true when you set yourself up to receive some monetary incentive from doing so. The above are a few great ways to consider going green that will be able to put some green in your pockets. We’re sure you’ll be able to keep coming up with more little ways to change your environmental impact while cashing in.
  11. When it comes to environmental responsibility, Australians are among the leading citizens who are striving to do their part. Many Australians understand the importance of global conservation and have made efforts to protect the planet’s vital ecosystems. This includes personal life choices as well as enacting eco-friendly governmental policies to protect their local environment. Here are some of the main ways that many Australians are protecting the planet. Implementing Strict Pet Travel Laws Australia has some of the strictest laws in the world that govern how pets are allowed to travel and which types of species are allowed to enter the country. Many of these laws are intended to prevent foreign species migration that has historically been known to wreak widespread havoc on the country’s crops and ecosystems. Australia even requires all cats and dogs that are brought into the country to have special microchips implanted to show that each pet meets strict health standards. This prevents the spread of parasites and diseases that could be transmitted to their own wild and domestic animals. Eliminating Plastic Bags Numerous Australian companies have worked to eliminate plastic bag usage to help the environment. Unlike other materials, plastic isn’t biodegradable and remains in existence indefinitely. Discarded plastic bags that end up on roadways, in oceans or in other areas where they don’t belong can be deadly for animals that unknowingly ingest them. To try to solve this problem, nationwide efforts in Australia have been made to encourage shoppers to use reusable bags made of cloth and other material so that plastic bags no longer need to be used. Shoppers who opt for single-use plastic bags are often charged an additional fee by stores. Switching to Septic Systems Instead of using standard sewer lines that contribute to water pollution from human waste, many Australians are having domestic septic tanks installed on their properties. These special tanks are able to clean and conserve water instead of sending it out to the ocean. Once these tanks are full, they can be emptied by professionals with little hassle. This prevents a lot of the problems that come from the traditional sewage systems that dump wastewater into local lakes, rivers, and oceans. This introduces contaminants to different ecosystems, whereas domestic septic tanks treat the water on site and allow for much of the wastewater to even be recycled back into the home for use in lawn sprinklers and toilets. Installing Solar Panels Solar panels offer a great way to get energy from the renewable sources, and large numbers of Australians have had these panels installed on their properties. Solar panels offer a better, greener alternative to getting power from more environmentally hazardous sources such as gas, coal or electricity. People living in the country have also come to love solar energy because of its cost-effectiveness and ability to lower utility bills. Entire communities in Australia have been constructed surrounding the ideals of renewable living, and solar panels play a significant role in powering these communities. Australians take pride in their efforts to protect the environment. While they, like the rest of the world, aren’t perfect yet, they strive to improve their policies and protect their local and global environment. Other countries can learn from Australia’s conservation efforts and follow suit to make the planet safer for all people, animals and ecosystems.
  12. Robotic Pallet Wrapping Machine Advantages

    Many businesses that manufacture and sell products pay little attention to the packaging methods and processes that they are using, until they realise how many options they have, and as a result end up wasting huge amounts of money year after year. Packaging however is one aspect that businesses of all types, within all niches, should take seriously – Often the first aspect of a product that consumers see, playing a huge part in buying decisions. Not only this but unless the correct packaging methods are chosen businesses can end up wasting money, time and more! With this in mind we are here today to put forward what we consider to be one of the greatest packaging options – The robotic pallet wrapper. Hiring or purchasing a robotic pallet wrapper, also known as an automatic pallet wrapper can make a business's daily operations much more manageable, with just some of the benefits of using robotic pallet wrapping machines including the following: • Pallet wrapping using robotic or automatic machinery provides goods with amazing protection against damage, dust and moisture, ensuring that all products are securely wrapped to reduce that chances of them becoming damaged, contaminated, or both! • Investing in a robotic pallet wrapping machine can drastically reduce the chances of accidents and injuries in the work place, with these machines taking care of the entire pallet wrapping process and requiring far less tedious labour from employees. In addition to this as these machines fully wrap pallets unaided, less labour cost or required, or staff members can spend the time on other, more important tasks. • Pallet wrapping using pallet wrapping machines frees up times for workers, but as well as this, allows for many more pallets to be wrapped per hour – increasing business efficiency amazingly. • Pallet wrapping using a pallet wrapping machine uses far less shrink film that when wrapping by hand, allowing for even more money to be saved, and less waste. • Pallet wrapping products allows for companies to have improved inventory control, this is because it is much easier to count and manage pallets than it is thousands of much smaller individual items. These are only some of the benefits that companies can take advantage of when investing in robotic pallet wrapping machines too. With many greater benefits to consider, if you are even considering investing in one of these machines, we highly recommend that you contact your shrink wrap provider today who will be able to help you further, providing you with all of the information that you need.
  13. Many people regard designer brand for their footwear as the only way to go and businesses that offer those brands tend to get patronized more often. Wholesale shoes and boots is the way for retail businesses to go to take advantage of the latest fashion trends on the market at discounted prices. Even for those who have a liberal spending budget for their business and gets the styles that they want when they first come out, let's face it, that getting a discount on the quality that shows off business sense, good taste, and stylish sensitivity leaves more money in your pocket for other needs such as more inventory or bonuses to employees for exceeding sales quotas. There are those who believe that what you put on your feet can make or break the entire look of a clothing choice and in part, there is some truth to this. Poorly fitting shoes or those that are worn with the heel lifts wearing out can make a brand new suit look dingy. With wholesale boots or wholesale shoes, especially designer names that people readily recognize, a retailer can give people the option to create a perfectly polished look that speaks volumes about taste, style, and fashion sense, and no one has to know that the designer boots or shoes did not cost the full price; including the customer making the purchase. A wide variety of wholesalers offer great choices in wholesale shoes and boots, and not just designer names, for those who do not have to have a brand name label on their feet to reflect their personal fashion sense. A properly fitted shoe or boot is essential to foot comfort, whether it is for a busy day at work or a dazzling night out on the town. Getting stylish and trendy bargain wholesale shoes in flats, platforms, stacked heels, clogs or whatever style is desired, is the ticket to avoiding paying a fortune to resell footwear to the public with a handsome profit for your business. Whether your business is attempting to appeal to those with a shoe fetish or just has a reputation for providing the public with a variety of shoes to choose from, wholesale shoes are fantastic choices. Many wholesalers provide instant access to the wholesale boots and shoes market and make it possible take advantage of great prices whether for low quantities or high volume stocking up. When it comes to designer quality, some big names have remained constant over the years, and at the same time the introduction of newcomers to the industry has broadened the selection and made it possible for retailers who swear by designer selections to help their customers stay outfitted from head to toe in their ideal choices. Getting wholesale boots and wholesale shoes, whether design or everyday style, can be the ticket to providing customers with the luxury and comfort their feet deserve in every season. Whether the quest is for women, men or children's selections, a little due diligence can put these discounted designer brands and others right at the ready for those who want to have a big name in their footwear selections on the premises, but don't want to have to spend a fortune to get them. Wholesale shoes and boots in designer varieties are the sensible way to stay trendy and maintain your establishment's spending budget at the same time. View More: Wholesale Shoes China
  14. Recycling is a key component of sustainability that allows you to do your part for the environment. It's also a great way to help green companies make more products or services that you like to use. However, not all recyclable materials should go in your standard recycling bins. You'll find a few examples of things that you can recycle in other ways below. Cords This category really applies to any durable material that you can tie into a knot. If it meets these basic criteria, don't recycle it. These types of things are what the industry calls "tanglers." There's a good chance cords will get caught in the recycling machinery and shut down operations while workers get them out. Power cords, in particular, are made entirely of recyclable material, but the outer coating and the metal wire inside cannot be recycled at the same time. The best option is to contact businesses that offer services that will take your complete cords and recycle them properly. Liquids It's a bad idea to recycle most liquids the traditional way. Even safe liquids such as juices and milk might contain a mixture of hazardous chemicals or things that might ignite under the right conditions during processing. If you’re looking to recycle a container such as milk jugs, juice cartons, bottles, and other common carriers, it’s important that you rinse out all of the previous liquid before recycling, otherwise, it has to be sorted out and thrown away as contaminated. For more hazardous liquids, such as gasoline or acids, search online to find local community and government programs that handle the safe disposal of these liquids. Wrappers Wrappers for chips, candy, and other food items that are sealed usually aren't recyclable. The reason for this is that the bags use several layers of different materials, and we don't yet have the technology to separate and recycle all of them. For now, these should go in the trash along with the other non-recyclables. Even if something is labeled as being made of recycled materials, that doesn’t necessarily mean that it can be recycled again due to this method of layering materials. When in doubt, call the manufacturer or speak to your recycling service for more information. Food Large chunks of food make recycling bins and equipment prone to contamination by bacteria and dirty in general. These issues can compound further and make it harder for equipment to recycle everything else. Most recycling services such as Green Bins list explicitly in their accepted materials that they do not accept food waste. You shouldn't recycle large bits of household food. However, this doesn't mean you can't recycle packaging that has some minor food residue still on it. No one expects food packaging to be completely free of leftover residue. We recommend that you compost any larger quantities of food waste. The act of recycling can be a multi-part process depending on the materials in question. People working in this industry work hard to process large amounts of recyclable material every day. We can make things easier for them by being aware of what they can and cannot use so that they aren’t forced to halt operations repeatedly for otherwise avoidable sorting of unusable materials. Make sure to do your research and be aware of what your recycling service does and doesn’t take so that you aren’t forcing them to take something that will end up in the landfill anyway.
  15. When we are speaking about the cities of the future, we are speaking of green cities, cities that have directed their efforts to transform into sustainable spaces. When referring to these cities we often call them smart cities, and Stockholm can be described as a smart city because it became a green city with the help of the funds it received from the EU. Stockholm is considered a lighthouse city in Europe, together with Cologne and Barcelona meaning that other cities and countries should follow its example and inspire from its projects to improve the living conditions and to enhance their sustainability. Stockholm is a smart city because it understood that at the present times it is vital to becoming greener if we want to preserve the planet we are living on. The city hopes that by 2020 to remove all the fuel use, a policy that places it among the smartest cities worldwide. And if it were to compare it with other cities not only from Europe but from other continents, we can easily say that it is one of the greenest destinations. Most of the cars and taxis that run the streets of Stockholm are powered by bio-fuel, generated from sewage. Bio-fuel is available at multiple petrol stations around the town, and the administration wants to expand its use to lorries and larger vans because at the present moment they are the most pollutant sources when it comes to vehicles. They base their assumption on the idea that if 100 persons are going to the toilet, they power one car, and if we put together the organic household waste people are creating then the amount of bio-fuel can easily grow, and so does the number of cars powered by organic fuel. What innovative projects does Stockholm support? Alongside the numerous projects, the city has started with the purpose to enhance the sustainability levels, they are also collaborating with Fortum, an energy business that can transform the heating system of the city. They plan to use the heat produced by stadiums, supermarkets and data centres to provide heat to the residents of Stockholm. The city has more than 2.800 km of pipes underground designed to heat the over 10,000 building where residents are living, therefore they would reduce the waste they experience nowadays when they are using hot water to create them comfortable living conditions. Another project has in plan to use the wasted heat of a stadium that can host around 30,000 persons to heat the restaurants, houses and shops located close by. This is one of the trends that has gained popularity in Sweden during the last years, because we can encounter numerous projects that have similar purposes. Sweden has started numerous campaigns to convince companies to adopt eco-friendly strategies. For example, they want to convince companies to locate their data centres close to Stockholm where the heat they generate can easily be re-used. They also recommend businesses to adopt all the possible measures to transform their activities into sustainable ones. For example, the simple installation of a can press called a 'burkpress' in Sweden can help them reduce the amount of waste they are generating. Companies are encouraged to collect different types of rubbish accordingly. Sweden does its best to recycle the waste produced by its residents. They are asked to place different types of waste into different coloured bags. All the bags are taken to a central system where it is sorted with the help of an optical sorting machine. The sensors installed in the system can easily identify the different colours of the bags and they can measure the quantity and type of waste people throw away to understand what areas require extra attention and education. In Stockholm tourists can stay in eco-friendly hotels The eco-friendly action has taken over all the sectors of life in Stockholm, and the hospitality industry does no exception. When choosing a hotel in Stockholm tourists know that it is quite difficult to make a wrong decision. They can choose from 90 hotels that are bearing the Nordic Swan Label that shows their compliance with strict health and environmental regulations. Stockholm has the highest number of eco-friendly hospitality facilities in the world. For example, HOBO one of their green hotels is decorated to meet the preferences of millennials. It offers the vibe of a hostel because the rooms are big enough to include a bathroom and a bed, but the experience is the only one that counts. You will not find a phone in the room, the guests have to use their cell phone if they want to contact the reception. In the lobby of the hotel, the guests can find edible plants, a feature not many hotels have. The cafes and restaurants are also eco-friendly in Sweden And if someone has the misconception that the hospitality industry is the only one that promotes sustainability, they are wrong because they are also known for the great number of eco-friendly cafes and restaurants they have. The locals and tourists can eat in vegetarian restaurants at affordable prices, something not many vegetarian restaurants in the world offer. The vegetarian restaurants do not serve only main dishes, but also raw desserts, cider and beer. For the ones who want to eat a complete dinner there are numerous restaurants that serve dishes made from organic and locally sourced meats and vegetables. All the restaurants and cafes have an outdoor patio where people can spend the time to enjoy the fresh air and to boost their immunity. They can warm themselves with the blankets they find on the seats if they consider that the temperatures are too chilly. The restaurants from Stockholm are famous worldwide for the farm-fresh ingredients they use to prepare their tasty dishes. The eco-friendly restaurants from Stockholm serve house-made ice-cream, bee pollen, hazelnuts and baked apples, all came from organic sources. Stockholm is on the road of only becoming greener, no one can say that the journey has always been smooth and without bumps, but their efforts are totally worth.
  16. Commuting is a tradition that probably dates back practically to the invention of the automobile. Over the decades, though, increased population density, urban sprawl and ever-increasing vehicle ownership have increased commute times substantially. Even worse, they’ve turned commuting into a miserable, environmentally damaging slog for many people. While we all know finding alternative ways of getting to work helps the environment, there are some other benefits. Improved Health A daily drive to work doesn’t just seem to damage your health, it actually does damage your health in demonstrable ways. For example, it drives up your blood sugar levels, which increases your chances of developing diabetes. It also drives up your blood pressure. Higher blood pressure puts you at risk for heart disease and stroke. Commuting can cause chronic backaches, damage sleep quality and reduce cardiovascular health. Simply put, commuting is bad for you. Finding alternatives, such as public transit or riding a bicycle to work, helps offset these negative effects. Reduced Risk of Accident There are millions of automobile accidents in the US every year. While many of these accidents are comparatively minor fender-benders, some of them cause serious injuries or death. There is a direct relationship between how much time you spend driving and your chances of getting into an accident. The less time you spend driving, the fewer chances you have of getting into an accident. As an added bonus, if you don’t get into an accident, you also don’t need to enlist the services of an automobile accident attorney. Better Sense of Well-Being In addition to the physical costs associated with commuting, you also face costs to your overall well-being from a daily commute. A commute can create feelings of isolation and increase your stress levels. Both of these factors can cripple your sense of well-being. Switching from a daily drive to another mode of commuting, such as public transit, walking or biking can actually lead to an overall increase in your sense of well-being. This holds true even when other stressful events happen in your life. While car ownership and a daily commute might well be part of American culture, it doesn’t follow that commuting is a good thing. In fact, the evidence suggests it’s terrible for your health, mental well-being and overall risk. Giving up the daily drive for public transit, walking or biking is actually good for your health, well-being, and decreases your risks.
  17. The Ayana Resort and Spa is a leading five star hotel resort in Bali. It is built and set in a unique landscape that excites and rejuvenates its guests by just being there. Perched high on the side of a cliff, it overlooks the vast ocean waters and is a paradise for travelers and honeymooning couples from all over the world. Renowned for its uniqueness in design and service, it is best if you visit the hotel in person for a firsthand experience of world class hotel service. What to expect at the hotel 1. Unique architecture, setting and beauty As part of a well-known Bali Indonesia 5 star hotels group, the Ayana Resort and Spa is uniquely built offering a unique architectural structure and is set on a beautiful piece of land that overlooks the ocean. As a result, it offers stunning views of the ocean, sunsets and sunrises and also provides a relaxing ambience that makes you relax and take in the views without a worry in the world. As part of its unique architecture, is a rooftop bar that is set on a rock that naturally rises from the ocean, and is fittingly named the Rock Bar. 2. Private villas For honeymooners, the hotel offers exclusive and private vials. These villas are elegantly decorated and furnished ensuring that their guests are comfortable and relaxed in their rooms. Additionally, the villas offer a beautiful view of the ocean and each villa has a private infinity swimming pool that seems to pour into the ocean. Built for privacy and intimacy, you will enjoy your blissful honeymoon stay in the villas in the hotel. Service is quick and efficient and can be easily accessed by the guests in the private villas. 3. Award winning spa service The Ayana Resort and Spa is also specially built and designed to offer spa services. The numerous spas located in this hotel have won worldwide awards for their unique setting and world-class service that they provide. The spas in this hotel have a unique relaxation therapy known as Aquatonic Seawater Therapy. Being located right next to the sea, you will enjoy the sounds of the waves hitting against the rocks that the spa is set on as you get your relaxing massage. 4. Bars and restaurants The Ayana Resort and Spa is also suitable for regular visits, meals, family outings and networking and socialization sessions. This is evidenced by the close to twenty bars and restaurants within the premises. The most popular and prominent is the Rock Bar. Set on a rock within the ocean, it offers a unique panoramic aerial view of the vast ocean below and around the hotel. The numerous bars and restaurants offer a variety of world class cuisine prepared by highly trained chefs conversant with different cuisines to cater for all the guests in the hotel. 5. Swimming pools A swimming pool is an integral part of a hotel. It raises the stature of a hotel and provides a unique spot by the swimming pool where guests can mingle relax. The Ayana Resort and Spa shows its pedigree as a leader in Bali Indonesia 5 star hotels by offering their guests twelve swimming pools. With twelve swimming pools, guests can enjoy a splash in the cool waters of the swimming pools at any time the sun is out in this beautiful tropical island. The swimming pool beds also offer opportunities to relax, tan and bask in the sun for the hotel’s guests. 6. Private beach As a result of its location right next to the ocean, the hotel provides its guests with access to a private beach. Here, guests are able to enjoy the sandy beaches without having to jostle with crowds of people often found at public beaches. They are also able to enjoy a swim in the ocean for a well spent and relaxing afternoon at the hotel.
  18. Recycling is one of the best ways to reduce your carbon footprint, but figuring out which materials are recyclable can be confusing. Luckily, this process is going to be incredibly easy once you get the hang of it. Here is a closer look at a few tips that will help you determine which items and materials are recyclable. Organic Waste Many people are surprised to hear that most organic waste can be recycled. If you run a business that produces organic waste, then you should contact your local waste management company to see if they have a food waste recycling program. For homeowners, composting is a great way to get rid of food scraps and other organic materials. Setting up a compost bin only takes a few minutes, and you will have a constant supply of nutrient-rich compost. Metals Metals can be broken down and reused hundreds of times without changing their properties, and that is one of the reasons why many recycling companies pay for used metal products. A piece of metal that has been recycled multiple times is going to be just as strong and durable as new metal that was just pulled out of the earth. Most of the metals that you are going to come into contact with can be recycled, and that includes steel, aluminum, gold, copper, silver, and brass. Computers and Electronics While the vast majority of electronic devices can be recycled, you can’t just throw them in the recycling bin. Tossing your electronics in the trash is very bad for the environment, and you might be fined if you are caught. The best way to get rid of laptops, phones, televisions, and other electronic devices is to contact an e-waste company that does laptop recycling and other types of electronics recycling. Those organizations carefully break down electronic devices and separate all of the key components before recycling the materials. Paper Products As a general rule, paper products can be thrown into a recycling bin, but you need to make sure that there aren’t any other materials attached to those products. An example of that would be a pizza box that still has food debris on the inside. That food debris could damage the machines that break down and recycle corrugated cardboard. Some experts also suggest that you avoid shredding any paper that you plan on recycling. When paper is shredded, the fiber strands are shortened, and that makes it much more difficult to recycle the material. Recycling is great for the planet, but you need to keep an eye on what you are putting in your recycling bin. Throwing certain materials in those bins could contaminate huge piles of debris that would have been recyclable.
  19. Neutron scattering research at the Department of Energy's Oak Ridge National Laboratory has revealed clear structural differences in the normal and pathological forms of a protein involved in Huntington's disease. Huntington's disease, an incurable neurodegenerative disorder, starts as a genetic mutation that leads to an overabundance of "huntingtin" protein fragments, which form clumps in the brain. Valerie Berthelier of the University of Tennessee Graduate School of Medicine, who co-led the study published in Biophysical Journalwith ORNL's Chris Stanley, said the goal was to establish a baseline understanding of huntingtin's structure in order to eventually determine the true structural basis of Huntington's disease. "This is a very first step -- the hope is that we do this basic research to shed light on the structures of the protein," Berthelier said. "If we can start identifying any of these structures as toxic or potentially toxic, and then think about how drugs could interact with them, then we might be getting to the point of rationally designing therapeutics that would target those specific structures." The researchers conducted a side-by-side study of model protein systems in solution using a time-resolved small-angle neutron scattering technique at ORNL's High Flux Isotope Reactor. The use of neutrons, a non-damaging but highly penetrating particle, allowed the team to study the biological materials over time without degrading the samples' structural integrity. "We compared the normal and disease versions of the protein to see how they change over time," Stanley said. "You can see there's a discrepancy all the way from the early stages to the end-state fibrils." The study's results showed key differences in the ways mutant and normal huntingtin proteins take shape. The disease protein, for instance, initially forms aggregates of one to two peptides, whereas the normal version makes bigger aggregates, gathering seven or eight peptides together. These data on the very early stages of protein aggregate formation support a growing focus of the research in the amyloid field. Amyloid disorders, such as Parkinson's, Alzheimer's and Huntington's, all involve protein aggregation phenomena leading to a disease. "There is no strong correlation between neuronal cell loss and the amount of protein aggregates found in the brain," Stanley said. "You could have a case with a lot of aggregates but minimal symptoms -- and you can find the converse. Researchers think there must be something happening at the earliest stage that's giving rise to toxicity." Stanley says the team hopes to continue its research to obtain higher-resolution structural data and refine their understanding of the huntingtin protein. "We'd like to use this small-angle neutron scattering technique in combination with others to get a better idea for how these early structures are forming and also ask the question -- are they toxic or not?" Stanley said. The research is published as "Investigating the Structural Impact of the Glutamine Repeat in Huntingtin Assembly." Coauthors are Helen McWilliams-Koeppen, Erica Rowe and Tatiana Perevozchikova. Related Tags:Protein Structure, Electron Microscope, VLP Construction
  20. Overworked and stressed out? Look on the bright side. Some stress is good for you. "You always think about stress as a really bad thing, but it's not," said Daniela Kaufer, associate professor of integrative biology at the University of California, Berkeley. "Some amounts of stress are good to push you just to the level of optimal alertness, behavioral and cognitive performance." New research by Kaufer and UC Berkeley post-doctoral fellow Elizabeth Kirby has uncovered exactly how acute stress -- short-lived, not chronic -- primes the brain for improved performance. In studies on rats, they found that significant, but brief stressful events caused stem cells in their brains to proliferate into new nerve cells that, when mature two weeks later, improved the rats' mental performance. "I think intermittent stressful events are probably what keeps the brain more alert, and you perform better when you are alert," she said. Kaufer, Kirby and their colleagues in UC Berkeley's Helen Wills Neuroscience Institute describe their results in a paper published April 16 in the new open access online journal eLife. The UC Berkeley researchers' findings, "in general, reinforce the notion that stress hormones help an animal adapt -- after all, remembering the place where something stressful happened is beneficial to deal with future situations in the same place," said Bruce McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University, who was not involved in the study. Kaufer is especially interested in how both acute and chronic stress affect memory, and since the brain's hippocampus is critical to memory, she and her colleagues focused on the effects of stress on neural stem cells in the hippocampus of the adult rat brain. Neural stem cells are a sort of generic or progenitor brain cell that, depending on chemical triggers, can mature into neurons, astrocytes or other cells in the brain. The dentate gyrus of the hippocampus is one of only two areas in the brain that generate new brain cells in adults, and is highly sensitive to glucocorticoid stress hormones, Kaufer said. Much research has demonstrated that chronic stress elevates levels of glucocorticoid stress hormones, which suppresses the production of new neurons in the hippocampus, impairing memory. This is in addition to the effect that chronically elevated levels of stress hormones have on the entire body, such as increasing the risk of chronic obesity, heart disease and depression. Less is known about the effects of acute stress, Kaufer said, and studies have been conflicting. To clear up the confusion, Kirby subjected rats to what, to them, is acute but short-lived stress -- immobilization in their cages for a few hours. This led to stress hormone (corticosterone) levels as high as those from chronic stress, though for only a few hours. The stress doubled the proliferation of new brain cells in the hippocampus, specifically in the dorsal dentate gyrus. Kirby discovered that the stressed rats performed better on a memory test two weeks after the stressful event, but not two days after the event. Using special cell labeling techniques, the researchers established that the new nerve cells triggered by the acute stress were the same ones involved in learning new tasks two weeks later. "In terms of survival, the nerve cell proliferation doesn't help you immediately after the stress, because it takes time for the cells to become mature, functioning neurons," Kaufer said. "But in the natural environment, where acute stress happens on a regular basis, it will keep the animal more alert, more attuned to the environment and to what actually is a threat or not a threat." They also found that nerve cell proliferation after acute stress was triggered by the release of a protein, fibroblast growth factor 2 (FGF2), by astrocytes -- brain cells formerly thought of as support cells, but that now appear to play a more critical role in regulating neurons. "The FGF2 involvement is interesting, because FGF2 deficiency is associated with depressive-like behaviors in animals and is linked to depression in humans," McEwen said. Kaufer noted that exposure to acute, intense stress can sometimes be harmful, leading, for example, to post-traumatic stress disorder. Further research could help to identify the factors that determine whether a response to stress is good or bad. "I think the ultimate message is an optimistic one," she concluded. "Stress can be something that makes you better, but it is a question of how much, how long and how you interpret or perceive it." The eLife paper was coauthored by UC Berkeley colleagues Sandra E Muroy, Wayne G. Sun and David Covarrubias of the Department of Molecular and Cell Biology; Megan J. Leong of the Helen Wills Neuroscience Institute; and Laurel A. Barchas of the Department of Integrative Biology. Kirby is now a post-doctoral fellow at Stanford University. Kaufer's research was funded by a BRAINS (Biobehavioral Research Awards for Innovative New Scientists) award from the National Institute of Mental Health of the National Institutes of Health (R01 MH087495) and the National Alliance for Research on Schizophrenia and Depression. Kirby was supported by fellowships from the California Institute for Regenerative Medicine and the U.S. Department of Defense. Related Tags:FGFR4, FGF23, FGF2
  21. Often times in the summer you might lose your appetite or feel too full because of the heat. Or maybe you're running late in the morning and still need to eat breakfast. A quick and easy protein shake is a great way to get all the nutrients your body needs without feeling like you're stuffing yourself. MYTH: Protein shakes are for bodybuilders and will make me bulky. REALITY: If you read my last article about Toning Your Muscles, you now know that nobody becomes a bodybuilder by accident. Everybody's body needs protein and adding a supplement to ensure you get enough is only going to help in the effort to reshape your body. MYTH: Protein shakes will make me fat. REALITY: If you are eating too much and then you add in a protein shake on a regular basis, you may see some weight gain. In that case, use the shake to replace a meal or snack. If you're one of my clients, however, that is used to hearing from me "you're not eating enough!" this may be a good way to get some extra calories in. MYTH: It's not healthy to eat too much protein. REALITY: It's actually very difficult to eat so much protein that it has an adverse effect on your system if you're a healthy individual. The American College of Sports Medicine recommends every person eat 0.8x their body weight in kilograms of protein every day. For a 150lb person, this is about 68g protein every day. If you're concerned about your protein intake, consult your physician. If your physician expresses no concern then you're likely in the clear. Making sure you get enough protein in your diet is essential if you want to change the shape of your body. One of my favorite analogies is protein as the bricks to build the house that is your body. This analogy is detailed in my article Dieting Fads and Why They Don't Work. There are different kinds of whey protein powder that you can buy but be aware: a lot of them taste nasty! I've tried a lot of them and my some of favorites are Designer Whey, Pure Protein and Syntrax Nectar. Pure Protein you can actually find at Stop & Shop for $21 for a 2lb container. This should last you at least a month. You can click STORE on my website and then click Protein Powders to see what they look like or to order from Amazon. Whatever you decide to buy, make sure there is less than 5g of fat, carbs, and sugar, and more than 15g of protein per 1 scoop. And finally, adding a protein shake is merely an idea if you're looking for something quick and easy to get your protein in. By no means do you HAVE to include it. You can get all the nutrients your body needs from "real" food. Related Tags:Protein Expression, Bacillus Expression, Yeast Expression Systems
  22. As temperatures warm up in the spring, you can typically expect to see your water bill creep higher. One of the most significant reasons for this is because of extra water usage for lawn care and other exterior purposes. However, there are other reasons why your water bill may be higher during these seasons. Water waste is significant and problematic in many homes in the spring and summer. A closer look reveals how you may be able to rein in your water bills and save a substantial amount of money in the months ahead. Identify and Repair Leaky Pipes Once freezing temperatures have abated, any pipes that have ruptured over the winter may begin leaking water. Some of these issues are immediately apparent in the home. However, if the leaks are in your sprinkler system or other exterior pipes, they can be difficult to identify. Schedule plumbing maintenance in early spring to identify and repair these issues. Plumbing maintenance is also a smart way to address toilets that run frequently, slow drips in the bathroom faucet and other issues that can contribute to water waste in the home. Upgrade Your Sprinkler System If your sprinkler system is older or basic, it may not be equipped with weather sensors. Advanced systems can detect rain, humidity, temperature and other factors to determine how frequently your lawn requires hydration. This prevents you from wasting water by running a sprinkler when hydration is not yet needed. Harvest and Use Rainwater Another effective way to reduce water waste at home and to save money in the process is to invest in a rainwater collection system. By attaching a collection feature, such as a rain barrel, to the downspout on your gutter system, rain that falls onto your roof can be captured. When you need to wash your car, water your garden by hand or use water for other similar outdoor purposes, you can use this free water rather than paying money to tap into the public water supply When the concept of reducing your water bill originally came to mind, you may have thought about needing to make stressful and inconvenient changes in how you use water. While you could save money by cutting your time in the shower by half, you can see that there are easier ways to save water. Identify how each of these tips may apply to your home, and implement them today to enjoy immediate results.
  23. This article is intended to provide several analysis methods of a few important substances that they are well known. The first is bile acids analysis. Bile acid is an important component of bile and plays an important role in fat metabolism. Bile acid mainly exists in the intestinal and liver circulation system and acts as a protective role during recycling. Only a small amount of the bile acid enters the peripheral circulation. Bile acid analysis is of great importance to the research and development of clinical chemistry and bile acid drugs. As early as the ancient Chinese " Shennong's Herbal Classic " recorded the efficacy of carp gall. In addition, many important prescriptions, such as Bezoar powder and liushen pill, contain animal bile acids. Studies on bile acids in western countries began in the early 19th century, and quantitative studies began in the 1970s. The second is Catecholamines acids also known as pyrocatechol. Catecholamine is a neurotransmitter including catechins and amines. Catechins and amines are bound by an enzymatic process of l-tyrosine with sympathetic nerve, adrenal medulla and chromaffin cells. In general, catecholamine refers to norepinephrine (NA), adrenaline (Adr) and dopamine (DA). All three catecholamines are converted from tyrosine as precursors. As a neurotransmitter and hormone, catecholamine is closely related to people's health and disease. It is not only directly involved in behavioral activities or the regulation of neural functions such as blood pressure, heart rate, breathing and sleep, but also associated with some functional diseases such as schizophrenia and depression. Catecholamines Analysis began in the 1940s.With the deepening of the research on catecholamine, the analytical methods have been developing and improving all the time. At present, the research methods of molecular electrochemistry have become the leading one The third one is eicosanoids. Eicosanoids is a kind of bioactive unsaturated fatty acids, it is an important inflammatory factor, widely exists in body fluids and tissues, regulating many physiological and pathological processes. There are many kinds of eicosanoids in vivo, the content is low, and there are a lot of isomers. Therefore, the separation and analysis of eicosanoids in vivo are facing great challenges. As for eicosanoids analysis, Although there have been a lot of research on analytical methods, but still many problems waiting to solve. Neither extraction method has formed a standard extraction scheme for different biological samples. Therefore, the establishment of standardized extraction methods for different biological samples will greatly facilitate the eicosanoids analysis. The most powerful tool for analysis is the combination of chromatography-mass spectrometry. The characteristics of high sensitivity, high selectivity, high flux and high speed provide a good technical platform for the establishment of fast analytical methods. With the continuous development of various technologies, analytical methods will be continuously optimized and play a greater role in the research of biomarkers discovery, pathological mechanism and drug action mechanism. The last one is vitamins. There are two parts of vitamins analysis: water soluble vitamins analysis and fat soluble vitamins analysis. Vitamin is one of the important elements of human growth and development. At present, many foods are added with water-soluble vitamins, but there is a serious question whether they meet the requirements. Therefore, the development of research on it has certainly guiding significance for people's scientific intake and scientific control of the additive amount in food. Fat soluble vitamins are insoluble in water but soluble in fats and some organic solvents, including vitamin A, vitamin D, vitamin E and vitamin K. Fat soluble vitamins can be stored in large amounts in the body, mainly in the liver, so excessive intake will cause poisoning. Fat-soluble vitamins are becoming increasingly popular in clinical field. Thus, it is necessary to give reasonable attention to the analysis of the content and function of fat-soluble vitamins so that ensure the safety of use, maintain physical health.
  24. Fibroblast growth factor (FGFs) is a polypeptide composed of about 150-200 amino acids and exists in two closely related forms, namely, basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF). Its receptor (FGFR) belongs to the receptor protein tyrosine kinase, currently known FGFR mainly includes four types, FGFR1, FGFR2, FGFR3 and FGFR4. Clinically, FGFR overexpression and activation in tumor tissues are found to be associated with the occurrence of a variety of cancers, which can promote tumor angiogenesis and tumor cell proliferation. Therefore, FGFR is widely considered as an important drug target for anti-tumor, which has attracted extensive attention from pharmaceutical scientists in various countries. In vitro experiments, both types of FGF stimulated the DNA synthesis of osteoblast-like cells isolated from rat cranial cap. Meanwhile, bFGF stimulated the colony formation of differentiated chondrocytes in AGAR, playing a role in mitogen and morphology. AFGF can be formed by macrophages, cartilage and chondrocytes, which can stimulate the proliferation of immature chondrocytes and their progenitors. In vivo studies, FGF has been observed to promote the repair of articular cartilage. The expression of FGF was also found in the mouse fracture model by immunohistochemistry. In addition, fibroblast growth factor has the following main effects on the human body: 1. Effects on the skeletal system: It promotes the generation of a large number of osteoblasts and inhibits osteoclasts. To treat osteoporosis, femoral head necrosis, arthritis, rheumatism and diseases caused by calcium deficiency. 2. Effects on the digestive system: It can strengthen gastrointestinal function, promote the digestion of enzymes, increase appetite, treatment of chronic gastritis. 3. Effects on the blood system: It can strengthen the hematopoietic function of bone marrow, promote the generation of stem cells, and then generate a large number of red blood cells and white blood cells. Strengthening left ventricular thickness, enhancing myocardial elasticity, effectively treating heart disease. Effectively removing low density protein in the blood, preventing deposition in the blood vessel wall, and treating thrombosis. Here are some important FGFs members and their main functions below: 1. FGF2 Fibroblast growth factor 2(FGF2), also called the basic fibroblast growth factor(bFGF), is widely involved in cell growth, differentiation, migration, angiogenesis and tumorigenesis. The FGF2 gene is located at 4q26 of human chromosome, the length of which is 38kb, contains 3 exons and 2 introns. The active FGF2 can be combined with the fibroblast growth factor receptor (FGFR) which has the nature of tyrosine kinase receptor (FGFR) through heparin sulfate proteoglycans (HSPG), activate PKC, Ras /Raf /MEK/ERK, P13K, JAK/STAT and other signaling pathways, and participate in the regulation of cell proliferation, differentiation and malignant transformation. In the cardiovascular system, studies have shown that FGF2 is involved in cardiac hypertrophy caused by stress load and angiotensin. However, some studies also have shown that FGF2 can cause cell chromatin concentration, inhibit proliferation and cause cell apoptosis. Clearly, the cardiovascular role of FGF2 is not fully understood. 2. FGF18 FGF18 is a highly conserved protein composed of 207 amino acids, with 30% to 70% homology with other members of FGFs found. FGF18 exists in a variety of cell types, and its function is not limited to skeletal development, but can stimulate the proliferation of numerous mesenchymal cells, epithelial cells and tissues, including lung, kidney, heart, testis, spleen, skeletal muscle and brain. As a member of the growth factor family, FGF18 plays an important role in morphogenesis, tumor growth and other cellular and tissue development. Compared with other growth factors except wound surface repair, FGF18 has potential clinical value in the treatment of skeletal diseases such as chondrodysplasia, chondroplasia and bone repair, with a wider range of effects. The decreased expression of FGFR3 was also observed by studying the FGFR3 and STAT1 signaling pathways, suggesting that FGF18 may play a role independent of FGFR3. 3. FGF23 FGF23 is an endocrine protein synthesized by osteoblasts and osteoblasts. It has been confirmed that the main role of FGF23 is to regulate the level of blood phosphorus as a hormone, which plays an important role in the metabolism of calcium and phosphorus, parathyroid gland, as well as participates in the regulation of bone mineral metabolism. FGF23 is a protective factor for kidney, promoting urinary phosphorus excretion and maintaining stable blood phosphorus metabolism. In addition, FGF also has powerful functions and deep repair effect. The study of FGFs plays an immeasurable role in modern clinical medicine, surgery and cosmetic surgery.
  25. 1.Definition of vaccine adjuvant? What is a vaccine adjuvant? Before answering the question, let’s see what is an adjuvant. Adjuvant, also known as immunomodulator or immunepotentiator, originated from the Latin word "Adjuvare" and is meant to aid or enhance. An adjuvant is an additive of a vaccine. When it is mixed with an antigen and injected into the body, it can enhance the body's immune response to the antigen or change the type of immune response. It is a non-specific immunopotentiator and itself has no antigenicity. The ideal adjuvant not only enhances the immune response, but also provides the body with optimal protective immunity. 2.Application of vaccine adjuvant (1) Enhancing the immunogenicity, immune response rate and tolerance of purified or recombinant antigens; (2) Reducing the amount of antigen or the amount of inoculation required to achieve immunoprotection; (3) Improve the immune efficacy of vaccines in infants, the elderly or people with impaired immune systems; (4) As an antigen delivery system that takes up antigen through the mucosa, it can promote the absorption of the vaccine by the gastrointestinal mucosa. The concept of adjuvants is derived from ulcers formed at the site of inoculation and promotes the production of high levels of specific antibodies, even those produced by inoculation of unrelated substances can induce the production of highly specific antibodies; (5) Adjuvants can increase the infiltration of cells, prevent antigen degradation, transport antigens to specific antigen-presenting cells, enhance antigen presentation or induce cytokine release. 3.Classification of adjuvants At present, there is no uniform standard for the classification of adjuvants in the world. According to the chemical composition, it can be divided into aluminum salt adjuvant, protein adjuvant, nucleic acid adjuvant, lipid-containing adjuvant and mixed adjuvant. (1) Aluminum salt adjuvant Aluminum salt has been used clinically for more than 80 years and is the first classic adjuvant approved by the US FDA for human use. Many vaccine ingredients contain aluminum salts such as DTP vaccine and Haemophilus influenzae vaccine. Depending on the preparation process, vaccines with aluminum salts as adjuvants can be divided into two types: aluminum adsorption vaccines and aluminum precipitation vaccines. The aluminum adsorption vaccine is to add an antigen to an aluminum hydroxide or aluminum phosphate solution; and the aluminum precipitation vaccine is to add an aluminum suspension to the antigen solution. Aluminum hydroxide or aluminum phosphate is an aluminum adjuvant that is often used. The study found that aluminum adjuvant vaccine can reduce the amount of antigen used and enhance the strength and durability of the body's immune response. The mechanism of action of aluminum salts is still not clear. It is generally believed that the antigen-adsorbed aluminum salt particles form a gel state and are injected into animals to form an antigen reservoir. These insoluble particles can adsorb antigenic substances and increase the surface area of the antigen. In addition, the adjuvant can form a macrophage-rich granuloma at the injection site, delaying the absorption of the antigen, thereby prolonging the stimulation time of the antigen, and retaining the antigen for several days under normal conditions for a few weeks, and the antigen is taken at the injection site. Ability is enhanced. Studies have shown that aluminum hydroxide as an adjuvant can also activate Th2 cells to secrete IL-4, induce the expression of CD83, CD86 and MHC-II molecules, and then produce a Th2 type humoral immune response. Aluminum salts have many advantages as vaccine adjuvants, but there are also deficiencies. Although it can effectively induce a humoral immune response, it does not act on cellular immunity and cannot induce a cellular immune response. (2) Protein adjuvant Most of protein adjuvants belong to small molecule polypeptides or glycoproteins. A class of biologically active substances synthesized and secreted by immune cells and certain non-immune cells, generally cytokines, play an important role in the differentiation of Th cells. It can also enhance the function of NK cells and T lymphocytes, and has a wide-ranging effect on the immune response of the body. The use of a protein adjuvant in combination with an antigen enhances the immunogenic efficacy of the vaccine, and it can also be assembled into a plasmid and mixed with the antigen for injection. IL-12 is produced by monocytes and B cells and has a variety of biological activities. It can significantly reduce the number of bacterial invasions and increase the expression levels of IgG2a and IgA in the mucosa and immune system. It is a cytokine with broad application prospects. Adjuvant. It induces a Th1-type immune response, and the treatment of tumors and AIDS is in clinical trials. (3) Nucleic acid adjuvant In the process of researching vaccines, some nucleic acid substances are also found to have the characteristics of adjuvants. The most representative one is CPG DNA, in which the unmethylated cytosine deoxynucleotides and guanine deoxynucleotides are Unit oligomers, agonists of TLR9, are currently a hot spot in adjuvant research. It plays an important role in enhancing specific immune responses, inducing non-specific immune responses in the body, and regulating the type of immune response. The characteristic sequence of CPG-ODN can activate a variety of immune effector cells, such as T cells, B cells and NK and other immunocompetent cells, so CPG-ODN is used in more experimental studies. Bacterial DNA is a source of CPG-ODN, and its role includes enhancing both humoral and cellular immunity. It is more likely to be used in tumors and infectious diseases. It has not been reported that CPG-ODN has serious side effects on humans, but it has been found in animal models that CPG-ODN can induce autoimmune diseases. (4) Lipid-containing adjuvant Lipid-containing adjuvants include lipopolysaccharide (LPS) and liposomes. LPS is a Gram-negative bacterial outer membrane lipopolysaccharide, and lipid A is the main component of adjuvant action in LPS. The researchers co-immunized mice with LPS as an adjuvant to pertussis vaccine. The results showed that LPS not only improved the immune efficiency of the vaccine, but also reduced the occurrence of type I hypersensitivity. Liposomes are similar to biofilms. Ultrafine spherical preparations, usually formed by bilayers of phospholipids and cholesterol coated with antigens, are capable of transporting antigens and as adjuvants for vaccines. Liposomal adjuvants are not toxic and can reduce the toxicity of the antigen and can degrade in the host itself. Studies have shown that liposome vaccine delivery can enhance the body's humoral and cellular immune responses, and the structure of the liposome facilitates the presentation of antigens to antigen-treated cells. Studies have also shown that liposomes combined with Freund's reagent or aluminum hydroxide have a multiplier effect. However, it also has shortcomings, such as poor stability, easy oxidation, and high production costs. Therefore, current research on the application of liposomes has been suspended for medical research. (5) Mixed adjuvant MF59 is an oil-in-water emulsion which is a uniform droplet emulsion formed by mixing Tween 80, sorbitol trioleate and squalene under high pressure conditions. This mixed adjuvant can induce a local immune stimulating environment at the injection site, increase chemokines, cytokine levels, and accumulate MHC+ cells in the muscle. In addition, MF59 is also able to enhance the ability of dendritic cells to take up antigen. Because MF59 enhances the immunogenicity of influenza in people with low immunity, it was certified as an adjuvant to influenza vaccines in the 1990s. A large amount of data shows that MF59 is safer for influenza vaccines. (6) Aggregate structure adjuvant The researchers compared the immunopotentiating effects of three novel molecular aggregate formula adjuvants [RAM1, Glycolamide (RAM2) and 5th generation dendrimer (RAM3)] and evaluated these adjuvants ability of an adjuvant to enhance a Th1 or Th2 response when applied with a soluble protein antigen. In this study, ovalbumin (OVA) was used as an antigen, and the above three new aggregates were adjuvants, and tuberculin, Al (OH)3, and Freund's incomplete adjuvant were used as controls. Results RAM1 was superior to other adjuvants in the three adjuvants, and the induced cytokines were mainly Th1 type, and induced a Th2-type response in the late stage of inoculation. In this study, ovalbumin (OVA) was used as an antigen, and the above three new aggregates were adjuvants, and tuberculin, Al (OH)3, and Freund's incomplete adjuvant were used as controls. Results RAM1 was superior to other adjuvants in the three adjuvants, and the induced cytokines were mainly Th1 type, and induced a Th2-type response in the late stage of inoculation. To be continued in Part Two. Reference [1] Aguilar J C, Rodríguez E G. Vaccine adjuvants revisited[J]. Vaccine, 2007, 25(19):3752-3762. [2] Coffman R L, Sher A, Seder R A. Vaccine Adjuvants: Putting Innate Immunity to Work[J]. Immunity, 2010, 33(4):492-503. [3] Mata-Haro V, Cekic C, Martin M, et al. The Vaccine Adjuvant Monophosphoryl Lipid A as a TRIF-Biased Agonist of TLR4[J]. Science, 2007, 316(5831):1628-1632. [4] O'Hagan D T, Valiante N M. Recent advances in the discovery and delivery of vaccine adjuvants[J]. Nature Reviews Drug Discovery, 2003, 2(9):727-35.
  26. What is TCR? T cells are the main functional cells in the acquired immune system, which are responsible for identifying antigens and directing other immune cells to carry out immune responses. T cell antigen receptor on T cell surface plays a key role in antigen recognition. T cells play an important role in the immune system and can attack pathogens and cancer cells. T cell receptor (TCR) can recognize different ligands with wide affinity and participate in activating various physiological processes. TCR cell therapy customizes functional TCR, which has the best antigen recognition characteristics and uses the human immune system to fight cancer. The structure of TCR Figure 1. The structure of TCR T cells are the main components of adaptive immune response. The structure of their antigen recognition receptors has been confirmed. The cloned TCR consists of alpha and beta chains as heterodimers. TCR heterodimers mainly bind to several signal transduction subunits of CD3, CD3gamma, CD3delta and CD3E heterodimers and CD3delta homologous dimers. Different subunits of CD3 contain the activation sequence of tyrosine, the immune receptor, ITAM, but the number of each subunit is different. CD3gamma, CD3delta and CD3epsilon contain one, respectively, while CD3delta contains three tandem ITAMs, so that each T cell receptor can produce 10 ITAMs. Tyrosine phosphorylated ITAM can couple TCR with intracellular signal transduction pathways and recruit SH2 domain proteins, such as tyrosine kinase ZAP70, from TCR. However, there are still two hypotheses to explain why TCR complex contains so many signal transduction subunits and ITAM. One is that CD3 or ITAM alone may perform different signal transduction functions by recruiting unique effector molecules, and the other is that the main function of multiple TAMs is to amplify TCR signals. TCR signaling pathway TCR recognizes a peptide that binds to MHC molecules presented by antigen presenting cells (APCs). Single TCR can recognize different ligands (auto-peptide and foreign-peptide) with wide affinity. TCR is involved in triggering different functional outputs. In thymus, the binding intensity of pMHC and TCR signals determines the process of cell development and differentiation. When the binding force is between the minimum and the maximum, it promotes the survival of thymocytes and transforms into the mature stage of CD4*CD8 or CD4CD8*. If the TCR and pMHC are too low or too high, cell apoptosis will occur. Peripherally, the low affinity binding of autologous pMHC to TCR provides the strong survival signal necessary to maintain the initial T cells, and also promotes the full activation of autologous pMHC in high affinity encounters with foreign antigens. The intensity of TCR signal is crucial for the production of appropriate T cells. TCR signal transduction response guides the successful differentiation of CD4* T cells into different T helper cell subsets, and plays a key role in specific T helper cell subsets. The intensity and duration of TCR cells are related to the differentiation of memory T cells, and are also the basic determinants of T cell impotence or depletion. TCR signal is regulated by biochemical and molecular mechanisms, leading to signal amplification or attenuation. The mechanism of TCR regulation is complex and diverse, but it can be divided into three basic levels: early signal transduction effector molecule; signal molecule development stage; and dynamic regulation of TCR signal intensity. TCR binds to the MHC complex expressed on antigen presenting cells (APC) to activate TCR signaling pathway. SRC family protein tyrosine kinase LCK binds to the cytoplasmic domain of CD4 and CD8 common receptors, and is recruited to TCR through the co-binding of CD8 or CD4 with MHC or MHC class I complexes, respectively. LCK phosphorylation enables protein tyrosine kinase ZAP70 to bind to the CD3 chain. T cell activation cohesion factor LAT is phosphorylated, activated T cells, recruited multiple cohesion factors and effector molecules, forming LAT signal transducers. Activation of LAT-related effector molecules leads to signal transduction through three main signaling pathways: calmodulin, MAPK and NF-KB signaling pathways. Calmodulin signal transduction activates T cell nuclear factor (NFAT) for nuclear translocation; MAPK signal transduction leads to actin aggregation and activation of transcription factors FOS, JUN, AP-1; and NF-K B signal transduction causes nuclear translocation of REL and NF-K B transcription factors: These transcription factors synergize to cause T cell proliferation, migration, cytokine production and effect function. TCR is also usually associated with the activation of its common receptor CD28 or cytokine receptors (such as PI3K, AKT, PIP3, PTEN, JAK, STAT) and other signaling pathways. Application of TCR Tumor therapy T cells were modified by TCR gene to exert specific immune regulation or cytotoxic activity. It has great potential in the treatment of malignant tumors and other diseases. Tumor-associated antigen-specific TCR gene was transduced into T lymphocyte for the treatment of tumors, starting with melanoma. In addition to melanoma, some scholars have recently attempted to extend TCR gene therapy to the treatment of colorectal cancer, synovial cell carcinoma, neuroblastoma, lymphoma and other tumors. TCR DNA vaccine TCR gene can be used as a target gene for therapy besides being a guide gene for targeted therapy. In recent years, the use of TCR DNA vaccine to treat some diseases has been gradually carried out. TCR DNA vaccine is a kind of gene vaccine. Through the expression of antigen protein in the body, the body can induce specific immune response, selectively kill pathogenic T cells or inactivate them to play a therapeutic role. The future of TCR At present, two research hotspots in the field of TCR gene therapy are: (1) mutation of CDR region to improve the affinity of TCR transduction; (2) pairing of TCR A and beta chains. There are three main problems in TCR gene therapy in the future: (1) in vivo environment of T cells after transfusion; (2) quality problems of T cells after transfusion; (3) safety of transduction of TCR. In TCR gene therapy, antigen-specific TCR gene modified T cells in tumors and infectious diseases have achieved exciting results, which has proved to be a promising therapeutic strategy. Antigen-specific TCR gene-modified T cells have replaced the traditional effector cells and become the hotspot of this field. Although there is still some distance from large-scale clinical application and becoming a conventional treatment method, it is believed that TCR gene therapy will become more and more perfect and play a greater therapeutic role with the deepening of research.
  27. Abstract: As a key genetically engineered antibody, single-chain antibody consists of three parts, the antibody light chain variable region, the heavy chain variable region and a segment of the bridge polypeptide chain. The single-chain antibody not only has strong targeting, but also is not easy to dissociate, has a simple structure, is easy to operate and transform, and is advantageous for antibody library screening. At present, there are two main ways to construct single-chain antibodies: 1. Amplification of antibody light chain and heavy chain variable regions from hybridism cell lines, but the construction of single-chain antibodies has a rejection reaction. 2. RNA was extracted from canine spleen B lymphocytes, reverse transcribed into cDNA, and antibody variable region was obtained. The phage display antibody library technology is a new technology currently available for the preparation of human monoclonal antibodies. It uses the RT-PCR method to amplify the human immunoglobulin full set variable region gene and then recombine into the prokaryotic expression vector, and forms a fusion protein with the phage coat protein to express the antibody fragment on the surface of the phage, and screens by panning. The specific variable region gene can conveniently and efficiently perform high-throughput screening of antibodies, and opens up a simple and rapid production route for the preparation of human monoclonal antibodies. A key aspect of this technology is the construction of a library of human phage antibodies. Keywords: antibody library, single-chain antibody, construction Phage single-chain antibody library for pancreatic cancer Pancreatic cancer is one of the most malignant tumors known to date. Pancreatic cancer is the fourth leading cause of cancer death in Europe and America due to the insidious pancreatic cancer and lack of specific symptoms and signs. The phage antibody library technology has opened up new fields for the research of genetically engineered antibodies, and has been used in the diagnosis and prevention of infectious diseases, the identification of autoimmune diseases and viral diseases, imaging analysis of tumors and targeted therapy or gene therapy. The field shows great potential and broad application prospects. Compared with the traditional hybridism technology, the technology is simple, easy to produce, low in production cost, large in screening capacity, and can be prepared in large quantities by fermentation. The total RNA of peripheral lymphocytes of patients was extracted, and the H chain and L chain variable region genes were amplified by RT-PCR. The VL fragments were randomly spliced into ScFv fragments by SOE-PCR. The ScFv fragment was then cloned into a specific vector and electroporated into a competent strain, rescued by the helper phage M13K07, and a human phage single-chain antibody library of pancreatic cancer was obtained, which aims to lay a foundation for the biological treatment of pancreatic cancer. Pneumoconiosis phage single-chain antibody library At present, pneumoconiosis is still the most common type of occupational disease in China with the highest incidence rate, the risk of death, and the most serious harm to workers. So far, there is no cure for it, which can only be eliminated or reversed according to the condition. Delaying the progression of the disease, therefore, active prevention and early diagnosis are particularly important to improve the quality of life and prolong life. The construction method is similar to the above and will not be described again. Ribosomal display single-chain antibody library Ribosomal display is a new technology for the screening and identification of functional proteins completely isolated, avoiding the drawbacks of traditional in vivo screening techniques, resulting in increased library capacity and enhanced molecular diversity. It binds the correctly folded protein and its mRNA to the ribosome, forming an mRNA-ribosomal-protein trimer that links the genotype and phenotype of the protein of interest. In recent years, ribosome display technology is built on a single-chain antibody library and applications have made great progress. The main processes of ribosome display technology include: Construction of ScFv ribosome display template ScFv single-chain antibody in vitro transcription and translation Affinity screening and enrichment of ribosomal complexes Evaluation of screening efficiency In vitro evolution of ScFv molecules The ribosome display technology is completely in vitro, and has the advantages of simple database construction, large library capacity, and simple screening method, no need to select pressure, and the like, and the introduction of mutation and recombination technology to improve the affinity of the target protein, so it is a large-scale construction. Because it can screen high-affinity protein molecules in a short period of time, its emergence opens up a new way to prepare small molecule antibodies. It is believed that with the continuous solution of shortcomings such as system stability in ribosome display technology, it will have great application value for the construction of antibody libraries and the screening of small molecule antibodies. Anti-canine parvovirus single-chain antibody library According to the larger bacterial display technology of bacterial particles, antibodies can be displayed on the surface of bacteria and the binding of antigen and antibody can be monitored by flow cytometry (FCM) in real time by fluorescent labeling, and the antibody-expressing strain with high affinity can be sorted. Using bacterial endometrial display technology, the foreign gene is expressed together with the NlpA signal peptide, and the target protein is displayed in the bacterial inner membrane. The NlpA signal peptide can transport the fusion gene of interest to the bacterial periplasmic space, and utilizes 6 specific amino acids to form a serotonin bond with the outer membrane of the bacterial endometrium during the transmembrane process, anchoring to the outside of the bacterial inner membrane to form a bacterial display antibody library. The outer membrane of the bacteria is treated with lysozyme, and the antibody library is screened by fluorescent labeling specific antigen binding to FCM. The method utilizes a 6 amino acid short peptide to anchor the foreign protein, has no effect on the conformation of the expressed antibody protein, and maintains genotype and phenotypic association. The aim is to screen recombinant antibodies with affinity anti-CPV gene, and lay a foundation for neutralizing active antibodies in subsequent studies. The neutralizing antibodies can bind to neutralizing epitopes on the virus, prevent the virus from binding to the corresponding receptors on the cell surface, and prevent diseases. Evaluation The ultimate goal of building a library is to screen out various specific antibody molecules. Whether the antibody of interest can be screened, in addition to the affinity of the antibody of interest and the target antigen, the quality of the library is also a determining factor. A library of antibodies with greater capacity and diversity will ensure the success of the screening. In general, the storage capacity is positively correlated with the affinity of the antibodies screened. High-affinity antibodies can only be screened in a high-capacity antibody library. At the same time, it must have good diversity. For natural antibody libraries, a wider range of antibody gene sources can better ensure the diversity of antibody libraries. References [1] Baca M, Presta LG, O 'Connor SJ, et a1. Antibody humanization using monovalent phage display [J]. J Biol Chem, 1997, 272:10678-10682. [2] Lowenfels A B, Maisonneune P. Epidwminology and prevention of pancreatic cancer [J], Jpn J Clin Oncol, 2004, 349(5):238-242
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