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  1. Today
  2. Summary On January 31, 2020, a paper published by a virus expert at the Indian Institute of Technology and Biology caused a big controversy in the country. The paper points out that four fragments inserted in the new pneumovirus gene that are highly similar to HIV and are not very likely to com from natural evolution. This news has become the theoretical basis for conspirators. In fact, the conclusions in the papers was published informally by Indian scholars and the data provided by them cannot be obtained at all, and there are many “mistakes”. Several scientists have verified that the so-called "similar gene fragments with HIV" is a coincidence that these gene fragments are also widely present in other common viruses. Actually an officially published scientific paper pointed out that the new coronavirus is the result of coronavirus evolution, not artificial synthesis, according to the analysis of the characteristics of genome-wide evolution. The body Conspiracy theories are always something that people love to see, and whenever something new that cannot be explained with existing knowledge is revealed, corresponding conspiracy theories will soon appear. The novel coronavirus (hereinafter referred to as "SARS-CoV-2" according to WTO) is no exception. Since the novel coronavirus raged last December, multiple related conspiracy theories have emerged on social media. For example, the "novel coronavirus" is an American biochemical weapon specifically targeted at the Chinese. Such rumors are easy to refute, because the origin of the rumors is conspiracy theorists from non-scientific circles. There is no argument and it is pure speculation. But in the past few days, a message went viral on Chinese and English social media. The rumored news said that "Indian scientists have sequenced genes and found that "new coronavirus" has gene fragments not found in other coronaviruses, and these gene fragments are close to the human immunodeficiency virus HIV", and concluded that "these genes Fragments are likely to be artificially synthesized. " This statement spread immediately. If it was artificial, who made it? What is the purpose? Is the "novel coronavirus" really a biological weapon? This is certainly not the case! Papers by Indian scholars are not officially published, nor have they been peer-reviewed. The paper was put on the web page of bioRxiv by the author. This web is dedicated to publishing scientific papers that have not yet been formally published in academic papers, nor have they been peer reviewed. It is equivalent to a web database that allows everyone to take a quick look before the paper is officially published or for unpublished papers. The paper comes from the well-known Indian Institute of Technology in India, entitled “Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag”. This article is a professional thesis, which is difficult for ordinary people to read. Let me explain briefly. The author got the genetic map of the "novel coronavirus" virus (thanks to Chinese scientists, the virus was isolated for the first time and the complete sequencing was completed, and then made public and provided to scientists around the world for research). Compared with other coronaviruses, it was found that the gene maps of "new coronavirus" and other coronaviruses were 96% the same, and only 4% were different. These 4% have about 1,200 base pairs. Among the 1,200 base pairs of transcribed amino acids / polypeptides, four inserts were found to have gene sequences not found in other coronaviruses. After analyzing these four inserts, it was found that the three-dimensional structure formed by them is likely to exist on the tip of the spinous protein on the surface of the virus, which is the part that initially contacts the host cell. The author then compared the genetic sequences of these inserts with the HIV virus and found that they were very close to the genetic sequence of at least one HIV. The author then concluded that their discovery is unlikely to have been accidental. The author's words stop here. But this will undoubtedly make people start to associate. If this new virus has a structure that other family viruses do not have, these structures will still help the virus enter the host cell, and it is very close to the HIV virus, and it is unlikely to be a natural product. This is too suspicious. Is it really a synthetic virus? American scientists verified that the "novel coronavirus" and pointed out that there is indeed fragment close to HIV, but it is not unique. These gene fragments are also widely found in other common viruses. Dan Samorodnitsky, a popular science author on Massive Science, is a former biologist, current science writer, and an extremely serious person. He came to this article and used the so-called unique and only 4 inserted gene fragments similar to HIV to study it again with a gene sequencing tool. The results are as follows: The first inserted gene fragment is indeed very close to some of the HIV gene sequences. But the author did not know whether it was accidentally or intentionally ignored that this gene fragment also exists in many other viruses. For example, this gene sequence is also found in the most common streptococci, which lives in human bronchial viruses, and many types of viruses have this gene fragment. It lists the other microorganisms that match the first inserted gene fragment 100%. The second fragment test is the same. The second insert is indeed close to a certain section of HIV, but it is also found in the most common herpes virus, the cytomegalovirus (a virus that causes kissing disease) that is very easy for adolescents, and the virus that infects tomatoes. The other two clips are no exception. Not only exist in "novel coronavirus" and HIV, but also in many other common viruses, such as plant flavivirus, bovine papilloma virus and so on. Therefore, the fact that this article intentionally or unintentionally ignores is that although the "novel coronavirus" he pointed out does have genetic fragments close to HIV, it is by no means unique, and these gene fragments are also widely found in other common viruses. The role of these four so-called unique inserts in this epidemic is unknown. Based on this alone, it is speculated that this "novel coronavirus" virus was artificially manufactured, and even the conspiracy theory of biological weapons is not true. To be continued in Part Two…
  3. Yesterday
  4. During the last few years, remarkable progress has been made in stem cell therapy, which leads to the flourishing of stem cell clinics claiming they can heal a number of diseases with stem cell therapy. However, FDA says it's unproven and is working to regulate them. The past few years has seen so many for-profit stem cell clinics popping up around the United States, advertising that they can treat everything from arthritis to Alzheimer’s just by several injections with each one costing $5,000 to $20,000. However, cases have shown that patients of these clinics have developed tumors, suffered infections and even sight loss after unapproved procedures. So, is stem cell therapy an effective treatment or just false hope? Some information is necessary for those who are curious about stem cell therapy. l What is stem cell therapy? Just like the stem of a plant will produce branches, leaves, and flowers, stem cells are undifferentiated cells that can produce several different kinds of cells. They originate from two main sources: adult body tissues including bone marrow, blood and blood vessels, skeletal muscles, etc. and embryos in which stem cells can differentiate into more cell types than adult stem cells. Stem cell therapy, also known as regenerative medicine, is the use of stem cells to help patients’ bodies repair damaged tissue by intravenous or intramuscular injection. l What types of diseases does stem cell therapy work for? Theoretically, any condition in which there is tissue degeneration can be a potential candidate for stem cell therapies given that they can produce all kinds of cells. However, up to now, the use of stem cell therapy is quite limited. For the last 50 years or so, there have been patients successfully treated with hematopoietic stem cells, commonly known as bone marrow transplants. This remains the prototype for how stem cell therapy can work. New clinical applications for stem cells are currently being tested therapeutically for the treatment of musculoskeletal abnormalities, cardiac disease, liver disease, autoimmune and metabolic disorders and other advanced cancers. However, these new therapies have been offered only to a very limited number of patients and are experimental rather than in standard practice. l What are the advantages of stem cell therapy? A common problem of transplantation is the risk of transplant rejection. Using autologous stem cell therapy, this risk can be avoided. What’s more, there is also no risk of communicable disease transmission. Stem cell transplantation is usually by infusion or injection instead of complicated surgeries; thus, patients needn’t worry about scars, complications or the side effect of general anesthesia. “In 2012, professor Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine for the discovery of induced pluripotent stem cells, which shows greater potential of stem cells to help us understand and treat a wide range of diseases, injuries and other health-related conditions.” Said a senior scientist in Creative Biolabs, a leading company providing stem cell therapy development services. However, their current applications as treatments are sometimes exaggerated by “clinics” looking to capitalize on the hype by selling treatments to chronically ill or seriously injured patients, and there is still a lot to explore about how they work in the body and their capacity for healing. With the continuous development of technology, stem cells will trigger a medical revolution, becoming the third treatment method after drugs and surgery. A series of diseases and injuries that are difficult to treat now will eventually be gradually rescued.
  5. Last week
  6. Study details PROTAC design of degrading FKBP12 In this study, FKBP12 was selected as the target protein for the following reasons: First, FKBP12 protein is widely expressed in mammals. By binding to the Ca2 + -release channel (RyR receptor), FKBP12 regulates Ca2 + signaling to travel important functions, especially in the heart. Second, because FKBP12 is a highly conserved protein, this chemical knockdown strategy is expected to be used to generate large animal models with targeted protein knockdown (for example, pigs and non-human primates). Third, the global knockout of FKBP12 by common methods can cause embryonic death from severe developmental heart defects (eg, hypertension, tight ventricles, and ventricular septal defects). The role of FKBP12 in adult heart function and disease development remains elusive. Rapamycin has been shown to be a potent and specific ligand for FKBP12, which regulates mTOR signaling with high affinity (kd = 0.2nm). Therefore, researchers designed a PROTAC that degrades FKBP12 by linking rapamycin (a FKBP12-specific ligand) and pomalidamine (a specific ligand that binds to CRBN-containing E3 protein ligase) via polyethylene glycol. This heterobifunctional molecule ubiquitinates FKBP12 via CR3B-containing E3 ligase, and degrades FKBP12 via the proteasome pathway. Therefore, researchers synthesized a series of PROTACs and measured their potential to degrade FKBP12 in Jurkat cells. Researchers named the chimeric molecule with rapamycin and pomalidomide as RC32, which showed the most effective FKBP12 degradation ability. After treating the cells for 12 hours, it caused 50% protein degradation, DC50 = 0.3 nM . To determine whether RC32-induced ubiquitination degradation was caused by FKBP12 degradation via the ubiquitin-proteasome pathway. Researchers treated the cells with the proteasome inhibitor bortezomib or carfilzomib before adding RC32. In fact, inhibition of the proteasome completely blocked RC32-induced FKBP12 degradation, suggesting that this degradation is via the ubiquitin-proteasome pathway. The addition of the FKBP12 inhibitor rapamycin or the CRBN inhibitor pomalidomide effectively blocked the degradation of FKBP12 by RC32, further confirming that this degradation requires the combination of RC32 with FKBP12 and CRBN. It is worth noting that when degrading FKBP12.6, RC32 did not induce significant degradation of FKBP51 and FKBP11 in Jurkat cells. The use of a certain amount of RC32 can control the degradation of FKBP25. However, RC32 has no effect on the phosphorylation of S6K and S6, which may be beneficial for dividing the independent function of mTOR in FKBP12. When RC32 was washed away, FKBP12 protein levels completely recovered within 96 hours. To further evaluate the efficiency of RC32, tests were performed using different cell lines from different species and primary cells. FKBP12 is effectively degraded by RC32 in a highly consistent pattern in cells from humans, rats, mice and chickens. Importantly, RC32 showed high degradation efficiency in primary cardiomyocytes, which indicates its potential to degrade FKBP12 in vivo. Rapid and effective degradation of FKBP12 in mice and rats by RC32 After confirming the high degradation potency in cell lines and primary cells, researchers used RC32 to induce protein knockdown in mouse, rat, pig, and non-human primate models. These models are valuable tools for studying human diseases. Although mice and rats have been widely used in scientific research, it is much more difficult to construct protein knockdown models in pigs and non-human primates. Pig xenotransplantation is particularly attractive in biomedical research. Although non-human primates are more relevant to studying human diseases and developing treatment strategies, genetic modification of monkeys is very expensive, time-consuming, and technically challenging. These limitations in large animal models have severely hindered their application in biomedical research. Therefore, researchers tried to use PROTAC as a chemical method to construct a representative protein knockdown animal model and study the function of target proteins. Researchers first investigated the effects of RC32 on mice. Surprisingly, after only 1 day of treatment with RC32 (intraperitoneal injection, 30 mg / kg, twice daily), FKBP12 protein was not detected in most organs of the treated mice, and the brain was removed. Interestingly, significant degradation of FKBP12 also occurred in the eyes. In contrast, RC32 has no effect on the degradation of FKBP12 in brain tissue, which may be due to the inability of RC32 to cross the blood-brain barrier. Interestingly, after 1 day of treatment (30 mg / kg, twice daily), RC32 was able to degrade FKBP12 for about 1 week. In addition, FKBP12 was recovered in different organs / tissues after RC32 was discontinued. Interestingly, the recovery rate of FKBP12 in the heart was the slowest in 13 days after RC32 was discontinued. After discontinuing PROTAC, FKBP12 mRNA levels showed an acute and compensatory increase, then quickly recovered and remained at near-normal levels. To degrade the FKBP12 protein in the brain, researchers use intraventricular (i.c.v.) administration. As expected, FKBP12 in tissues from the i.c.v. treated brain was degraded, while levels in other organs / tissues were not affected. FKBP12 is widely expressed in the nervous system and is known to regulate the localization and processing of amyloid precursor proteins. The study results suggest that local protein knockdown in the brain may open up a new avenue for treating Alzheimer's disease. When RC32 was delivered orally, FKBP12 was significantly degraded in mice, which highlights the clinical potential of oral PROTAC, which is more convenient than previously reported dependent injections. In addition, only two intraperitoneal injections every 20 hours (20 mg / kg; Figure 3e, f), high degradation efficiency was found in Sprague-Dawley rats. To be continued in Part III…
  7. The future is upon us, and it seems bleak. The depleting resources and the changing temperatures have created a dreadful environment for the generations to come. Given the damaging effects of global warming and climate change, scientists and energy research consultants are looking to create green energy with the help of renewable sources. One source that is fast becoming the talk of the town is biomass. This energy source is derived from organic materials, including plants and animals, and is used as a fuel for various industries across the globe. Scientists rely on different methods to produce energy using biomass. One method that is extremely popular and convenient for the millions of users is burning the energy source to create heat. The heat energy produced powers steam turbines that generate electricity. Burning biomass produces heat in thermal systems with the help of Combined Heat and Power (CHP). Converting feedstocks into liquid bio-fuels is one application of using the product. This helps the users in harvesting gas from landfills with the help of anaerobic digesters. Although the energy source is classified as a green source of energy, there are still question marks regarding its use. Scientists and experts feel that burning trees during the harvesting season can contribute negatively to the environment. Before we give a final verdict regarding the use of the energy source, let’s take a look at some other benefits it offers and the reasons for its popularity. Benefits of Using Biomass The Paris Agreement in 2015 set clean air targets for countries. Since then, companies and governments are looking for suitable alternatives to the traditional sources of energy. The objective is to find greener alternatives to the energy source and contribute positively to the air around. Biomass seems like an excellent alternative for countries looking to change their energy consumption. According to a report by the World Bank, biomass contributes to 14% of world total energy use; this accounts for 50EJ of energy from biomass. This is expected to increase to the figure of 150EJ by the year 2035. The incredibly versatile source of energy allows you to produce power by burning it directly. You can convert the product to liquid biofuels and harvest it as gas from anaerobic digesters and landfills. The sun is the source of energy for biomass, which means that the plant matter can grow relatively quickly. Since it does not take much time and effort to re-grow and depends on a never-ending source of energy, it is classified as renewable. Materials such as sawdust obtained from lumber mills are used to produce the energy source. You can also use chicken litter and residue from crops for the production of biomass. There are a vast number of waste materials that can create biomass. However, you require wood to source energy. Advocates of biomass consider the sourcing of the organic matter a sustainable process, as it allows the user to clear sick or dead trees from an area. The US Forest Service also considers a sustainable resource that can help the country in meeting 30% of the US petroleum demands. The country considers it a valuable resource because it helps in meeting 30% of petroleum consumption. While countries like the US and India are depending on the energy source for fuelling their industries, some critics are vocal against the over-dependence of burning trees. Negatives of Using Biomass Professor John Beddington, a scientific advisor to the UK government during the period of 2008-13, warned about the use of biomass. According to the scientist, the excessive burning of trees means a significant increase in the levels of carbon emission globally. An increase in carbon emission will reduce air quality and lead to global health problems. Professor Beddington then goes on to advise world leaders to focus their attention on alternative sources of energy. Sources of energy that are less damaging to the environment include solar and wind energy. Additionally, he claims that burning biomass is not a clean process either. He blames the lower burning temperature of wood and the carbon intensity it has within for the excessive carbon emissions. Wood releases four times more carbon than fossil fuels. Similarly, another research found out that power plants responsible for burning biomass produce 65% more carbon dioxide per megawatt-hour than plants producing fossil fuels. The report also found out the process of burning biomass also leads to air pollution as it contains elements such as nitrogen oxides, lead, and carbon monoxide. Many of the elements are carcinogenic, signalling a great health hazard for the populations. Another risk of using the energy source is that it can lead to depletion of forests. Since farmers and stakeholders of the primary sector are looking to reduce the cost of operations, they prefer using wood rather than other methods to burn biomass. We all are aware of the adverse effects of depleting forest settlements. Climate change and the effect on ecology are some side effects of the depleting forest resources. The forests are also our one real weapon against climate change as they form carbon sinks to combat the rising levels of carbon emissions. Conclusion While the benefits of using biomass are an excellent incentive for countries and scientists to use the energy source, critics don’t welcome it as a natural alternative to coal. The use of biomass should be subject to more scrutiny and transparency, as governments should look to limit its use to affordable levels. To reach a conclusion regarding the use of biomass, producers, and governments alike need to ask themselves, “what are the advantages of renewable energy." The use of biomass should not contradict with the benefits of using renewable energy.
  8. Abstract: Exosomes have shown great potential in drug delivery, disease diagnosis, etc, and now are found to play a role in diabetes. Just like a stuffed suitcase unloaded from the belly of a cargo plane, molecular backpacks called exosomes are constantly produced from the cells of the body. Each backpack is filled with a variety of materials that might be opened by another cell. By sending these biological packages, cells communicate with each other through shared proteins and genetic materials. Due to the unique function of exosomes as intercellular messengers, the ability to change the biological activity of recipient cells, and their therapeutic potential in disease diagnosis and targeted drug delivery, the relationship between exosomes and different kinds of diseases has received widespread attention in recent years. One of them is diabetes, as exosomes are found to play an important role in insulin sensitivity, glucose homeostasis, and vascular endothelial function. Diabetes is a common metabolic disorder, which is characterized by dysfunction of insulin secretion by pancreatic β cells and varying degrees of insulin lack. Organs such as the pancreas, liver, muscle, or fat are all involved, and communication between these organs is a key to maintain glucose homeostasis. Type 1 diabetes mellitus (T1DM) and Type 1 diabetes mellitus (T2DM) have different pathogenesis. T1DM is due to the gradual loss of insulin-producing cells, resulting in low or none secretion of insulin. T2DM is due to the body's production of insulin resistance. Although the pathogenesis of T1DM and T2DM is different, their pathogenic factors, pathophysiology, disease progression and complications are related. Exosomes and T1DM Exosomes contain powerful immunostimulatory substances. Exosomes released by insulinomas can stimulate the autoimmune response of non-obese diabetic (NOD) mice. This research shows that exosomes are the autoantigen carriers of NOD mice and have strong immune activity, which may be the trigger of autoimmunity in NOD mice. Islet cell transplantation is an effective method for the treatment of autoimmune T1DM. Explants that are specifically released into the blood circulation by islet transplantation are of potential diagnostic value in distinguishing recurrent autoimmune and immune rejection from islet β-cell injury. Biological markers that can be used in the diagnosis of islet transplantation. Exosomes isolated from MSCs have immunomodulatory effects and can improve islet function by increasing the number of regulatory T cells and their anti-inflammatory products IL-4 and IL-10, so they can be used to treat T1DM. Exosomes and T2DM Exosomes carry important biological information about the pathogenesis of T2DM. The exosomes and the miRNAs they carry pass from the adipose tissue through the blood and penetrate into the skeletal muscle and liver. The reaction induced during this tissue migration may directly lead to the intercellular communication of T2DM and metabolism-related disorders. The miRNA contained in the exosomes secreted by islet cells regulates β-cell function in a paracrine manner, and this situation is significantly different between normal and T2DM patients. Due to the complexity of clinical manifestations of different types of diabetes, sometimes it cannot be identified by current laboratory methods. Therefore, it is urgent to find a marker that can reflect pathophysiological characteristics or disease progression in real time. At the same time, such markers should be cheap and easy to obtain. “Studies have shown that exosome marker can be used for early diagnosis and staging of diabetes, and exosome itself is also a target for the treatment of diabetes.” Said a scientist of Creative Biolabs, ‘more importantly, it can help to monitor the response of patients with diabetes to treatment and thus provide personalized treatment.” With years of exploration in exosome services, Creative Biolabs has been committed to bringing together highly skilled experts applicable to exosome services to support exosome applications in diagnostics and novel therapeutics development, including sampling, analysis, manufacturing and exosome-based application services.
  9. A house is not just a building - it's a system with inputs and outputs. Maintaining a home takes work, and can generate significant environmental pollution. Environmentally conscious homeowners also face a mismatch between the technology available at the time of their house's construction and what's available now. Fortunately there are many home upgrades that can reduce your house's environmental impact. Water Pollution Water is one of your home's most important inputs and outputs. Whether your water comes from a well or a municipal water supply, you may be concerned with biological hazards, toxins, and excessive hardness in your water. Plus, there's a risk of these pollutants flowing through and affecting not just you but also your downstream environment. In both cases, installing home water treatment systems is a home upgrade that can protect your health, extend the life of your water-using appliances, and reduce the burden on septic systems or municipal water treatment systems. Another benefit is improved taste - staying hydrated with your own tasty tap water is more environmentally friendly than drinking bottled water. If your toilet, washing machine, or dishwasher is nearing the end of its life, choose a more water-efficient replacement. Consider installing low-flow nozzles on sinks and showers. Air Pollution Home heating and indoor air quality are issues whose importance to homeowners has risen in tandem with fuel prices and worries about climate change. There are two major home upgrades that can reduce your home's contribution to air pollution: first, insulating the walls, attic, and foundation of your house, and second, upgrading your heating appliance. Replacing combustion appliances (furnaces, boilers, wood stoves, kerosene heaters, etc.) with electrical heating appliances is ideal; replacing them with more efficient combustion appliances is a close second. But if you pursue these upgrades without first ensuring that your house is properly insulated and air-sealed, you may be throwing your money away. Ground Pollution If you have a yard or a community garden plot, you can use that land as part of your home's waste disposal systems. Upgrade your home by starting a compost pile - diverting your food waste will reduce the strain on our landfills, and by keeping grass clippings and other yard waste out of storm drains, you will also help protect groundwater quality. There are many options for homeowners looking to reduce their environmental impact. To find more information, consult home improvement professionals, national standards organizations, and government resources.
  10. MSCs and inflammation Since the study found that bone marrow MSCs inhibit the proliferation of T cells, scientists have found that MSCs can widely inhibit the activation and function of a variety of immune cells, including macrophages, granulocytes, natural killer cells, and dendritic cells, T cells and B cells. MSCs not only inhibit T lymphocyte proliferation, but also inhibit the differentiation of initial T cells into Th1 and Th2 cell subsets, and promote the production of regulatory T cells (Treg). Moreover, MSCs can indirectly induce Treg by affecting dendritic cells. In addition, MSCs can promote the conversion of pro-inflammatory type I macrophages to anti-inflammatory type II macrophages, treat sepsis, and down-regulate natural killer cell activation induced by IL-2 or IL-15. This series of powerful immunoregulatory functions has given MSCs the possibility of treating a variety of inflammation-related diseases, and truly realized the efficient clinical application of MSCs. The immunoregulatory effects of MSCs are closely related to various secreted factors, including TGF-β, NO, IDO, TSG-6, PGE2, IL-1 receptor antagonists, IL-10 and chemokine CCL2 antagonist variants. The diversity of MSCs immune regulation mechanisms may be due to the differences in their species and tissue sources and their microenvironment. In fact, the immune suppressive function of MSCs depends on the stimulation of interferon-γ (IFN-γ) and TNF, IL-1α or IL-1β. Blocking IFN-γR or using IFN-γR61 / 61MSCs cannot effectively exert the immunosuppressive effect of MSC. Stimulated by the above-mentioned inflammatory factors, MSCs express high levels of IDO, iNOS, and ligands of CXCR3 and CCR5, among which chemokines recruit T cells to reach around MSCs, thereby expressing immunosuppressive factors that inhibit T cell function. At this point, there is a close interaction between MSCs and inflammation. A deep understanding of the interaction between MSCs and inflammation is of great significance in guiding the rational clinical application of MSCs and understanding the pathological mechanisms of inflammatory diseases. In addition to inflammatory factors, other factors are also involved in the "authorization" process of MSCs' immunosuppressive functions. For example, stimulation of Toll-like receptors (TLRs)-TLR3 and TLR4 can activate the immunosuppressive effects of MSCs. MSCs also respond to different inflammatory stimuli and activate different signaling pathways to regulate specific immune responses. These research findings not only help us better understand the mutual regulation of MSCs and the inflammatory microenvironment, but also have important guiding significance for discovering or improving the application potential of MSCs in different diseases, especially immune disorders. MSCs and immune regulation The ability of MSCs to regulate immunity depends on the type and concentration of various inflammatory mediators in their microenvironment. Different inflammatory states greatly affect the therapeutic effect of MSCs on diseases, suggesting the plasticity of MSCs immune regulation. Studies have found that MSCs can effectively treat graft-versus-hostdisease (GVHD) under strong inflammation, but if MSCs are infused on the same day as bone marrow transplantation, that is, when the inflammatory response has not yet begun, the treatment effect is not significant. In addition, MSCs have little effect on experimental autoimmune encephalomyelitis in remission. From this point of view, the immunoregulatory ability of MSCs does have a strong plasticity, which is closely related to the inflammatory state. In the pathological process of inflammatory diseases, high levels of inflammatory factors are often closely related to the acute phase of the disease, while in the chronic or remission phase, the inflammatory factors present relatively low concentrations, which may be the body's self-repair phase. "Checkerboard gradient" concentration was used to detect the immunoregulatory function of MSCs under different concentrations of inflammatory factors (IFN-γ and TNF-α). It was found that the dynamic changes of inflammatory factor levels can affect the immunoregulatory function of MSCs, making them exert immunosuppression or immunostimulatory effects and lay the foundation for the research of the plasticity of immune regulation. The main reason is that low levels of inflammatory factors are not enough to induce MSCs to express high levels of iNOS or IDO. Instead, they will recruit lymphocytes to the surrounding MSCs to secrete a large amount of chemokines and exacerbate the inflammation response. Therefore, NO and IDO are the “switches” that regulate the immune regulatory function of MSCs. MSCs also exhibited similar immune-enhancing functions in low-dose concanavalin A-activated T-cell co-culture systems. In addition, antigen-sensitized MSCs can be stimulated with low-dose IFN-γ to activate cytotoxic CD8 + T cells as antigen-presenting cells. The above studies suggest that high inflammatory levels stimulate MSCs to exert immunosuppressive functions, while low inflammatory environment levels stimulate MSCs to exert immune promoting effects. Although the mechanism network that regulates MSCs activity in different inflammatory environments has not been clarified, plasticity is the most reasonable explanation for the phenomenon that MSCs exert different immune regulatory functions in different environments. During the inflammatory process, the cytokines, chemokines and related immune cells of the immune system are dynamically changed, and different immune cells play different functions. Among them, effector T cells and regulatory T cells are important cells that promote inflammation and fight inflammation, respectively. Th1 and Th17 belong to effector T cells with pro-inflammatory effects, and IFN-γ, TNF-α, and IL-17 produced by them lead the pathological process in a variety of autoimmune diseases and infections. In the pathological process of these diseases, MSCs are also recruited to the site of inflammation to participate in regulating the inflammatory response and assist tissue repair or regeneration. Cytokines at the site of inflammation are essential in conferring immunosuppressive function to MSCs, and the synergy between IFN-γ and TNF-α is particularly important. In addition, the presence of IL-17 can enhance the stability of iNOS mRNA in MSCs by regulating the RNA-binding protein AUF1, and significantly promote the immunosuppressive function of MSCs. Therefore, the type and concentration of cytokines in the inflammatory microenvironment determine the immune regulatory capacity of MSCs. Immunosuppressive factors such as TGF-β, as important factors to maintain the body's immune balance, are also commonly found in the inflammatory microenvironment. TGF-β receptors I and II are expressed on MSCs and regulate their differentiation and regeneration. When TGF-β, IFN-γ, and TNF-α co-stimulate MSCs, the immunosuppressive function of MSCs is significantly reduced, which is related to the down-regulation of iNOS or IDO expression by TGF-β through signal transduction factor Smad3. It is worth mentioning that MSCs can produce a large amount of TGF-β. Therefore, the negative regulation of TGF-β on the immunosuppressive effect of MSCs can be used as a feedback regulation to maintain the inflammatory state of the injury site and regulate tissue regeneration. In addition to TGF-β produced by MSCs, IL-10, which often has similar immunosuppressive effects as TGF-β, can also block the immunosuppressive function of MSCs. From this point of view, cytokines known for their immunosuppressive effects can exert their immune-promoting functions by acting on MSCs. To be continued in Part Three…
  11. Earlier
  12. Electronics, although useful, don’t last forever. In fact, you’re more likely to replace your electronics than your car. As time goes on, it’s not uncommon for electronics start to lose efficiency until they become useless. Once your electronics start to go up, you may opt to recycle them. However, there are a few things you need to do before you recycle them. Here are three things to do with aging electronics before you recycle them. Wipe the Memory Before even thinking of electronics recycling, the first thing you need to do is erase the memory. Unfortunately, some people often get rid of their old electronics without formatting the system first. If you’re recycling something like an MP3 player, then there’s really no need to wipe the system. However, if the electronic you’re recycling is a phone or a computer, then it’s an absolute must. Phones and computers save every piece of personal and sensitive information through cookies. Recycling one of these devices without wiping the memory clean opens the door for many problems. If the wrong people get ahold of this information, they can steal your identity or hack into your personal accounts. In most cases, formatting the system should be located in the settings or control panel of the device. Take Out the Battery Once you’re done formatting the system’s memory, the next thing you need to do is take out the battery. You may be wondering why removing the battery is relevant. It’s important because old batteries can be hazardous. Old batteries are more prone to damage, which can cause the fluid to leak out. The battery fluid is highly flammable and can also cause explosions. Even if it doesn’t cause those sorts of problems, battery fluid is harmful for the environment, so ensure that they’re disposed of responsibly. Review Your State Laws Last, but not least, make sure to check out the laws of your state. Some areas, like New York City and California, have a rule where it’s illegal to throw away electronics. If you are caught breaking this law, you might have to pay a massive fine. Furthermore, it’s important to stay attentive when disposing of your electronics. You don’t want to accidentally put them in the trash. Look carefully for places that have electronics recycling and dispose of your old electronics there. You can never be too careful when recycling electronics. If you do need to dispose of your electronics, make sure you do it the right way.
  13. Background Prior to the first severe acute respiratory syndrome (SARS), a limited number of coronaviruses were known to spread in humans, since they causu only mild illnesses, such as the common cold. After the SARS pandemic in 2003, coronaviruses apparently cross species barriers and cause infections that threaten human life. The 21st century has experienced the spread of two previously unrecognized coronaviruses worldwide with high pathogenicity, namely severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome corona Virus (MERS-CoV), as well as the 2019-nCoV, which is still spreading in the world, especially in China. Since November 2002 in China, SARS coronavirus has experienced unprecedented transmission from person to person, accompanied by high mortality. Joint efforts worldwide have enabled rapid identification of SARS coronaviruses, and have made significant scientific advances in epidemic prevention in a short period of time. In addition, zoonotic transmission of SARS from December 2003 to January 2004 provided researchers with a line of insight into the origin of this new coronavirus. It is worth noting that the SARS pandemic was announced in 2004 when no more infections were detected. Subsequently, some suspected SARS-Cov viruses found in bats showed the ability to infect human cells without pre-adaptation, suggesting that SARS-Cov or similar SARS-Cov viruses may reappear. Ten years later, in June 2012, in Saudi Arabia, another highly pathogenic novel coronavirus, MERS-CoV, was isolated from the sputum of a male patient who died of acute pneumonia and renal failure. Nosocomial infections have been reported, and international travel has caused the MERS-CoV virus to spread to countries outside the Arabian Peninsula, making it a global pathogen. In May 2015, the Middle East respiratory syndrome broke out in South Korea due to a person returning from the Middle East. Based on lessons learned in the management of the SARS epidemic over the past decade, unprecedented advances have been made in revealing the biological properties of MERS. Scientific advances have enabled us to make rapid and systematic progress in understanding the epidemiology and pathogenesis of MERS-CoV disease. The common characteristics of SARS-CoV and MERS-CoV SARS-CoV and MERS-CoV share several important common characteristics— preferential viral replication of the lower respiratory tract and viral immunopathology, which contribute to hospital-wide transmission. This article mainly focuses on the epidemiology and pathogenesis of these viruses, including our current understanding of their biological characteristics, transmission, and replication in the host. Covs' S protein plays a key role in viral infection and pathogenicity. As the key surface trimeric glycoproteins of Covs, they are guided into host cells. This article reviews the structure and function of S protein and the therapeutic methods targeting S protein. In addition, we will explore how the interaction between coronavirus and host leads to pathogenic outcomes, discuss potential treatment options, and describe the development of prevention and treatment strategies that are closely related to the pathogenic process for SARS-CoV and MERS-CoV. Although several potential therapies for SARS and MERS have been identified in animal and in vitro models, the lack of human clinical trials has hindered the development of these potential countermeasures. An overview of 2019-nCoV In the context of the current transmission of new coronaviruses, in order to control the spread of the virus and improve the prognosis of patients, it is urgent to develop public health and medical control methods. Whole-genome sequencing revealed that the new coronavirus (2019-nCoV) has very strong sequence similarity with its close relative, SARS coronavirus (SARS-CoV). The spike protein of 2019-nCoV infected host target cells showed some key non-synonymous mutations relative to SARS-CoV, which may lead to the less effectiveness of existing treatment methods and drugs targeting SARS coronavirus spike protein for 2019-nCoV. In addition, key drug targets, including the RdRp protein and 3CLpro protein, share a very high sequence similarity of greater than 95% with SARS-CoV. Therefore, this article proposes four potential drugs (ACE2 polypeptide, Remdesivir, 3CLpro-1 and a new vinyl sulfone protease inhibitor) that may be used to treat 2019-nCoV infection. At the same time, this article also summarizes the previous work on the drug research of these targets, hoping to provide guidance for future research on broad-spectrum anti-new coronavirus drugs. To be continued in Part II…
  14. Not recycling will eventually cease to be an option. The environment can’t continue to support a society that focuses on single use items and disposing of them in the landfill. Here are some of the reasons that you should recycle as much as possible. Pollution Reduction Rubbish that’s sitting in a landfill emits greenhouse gases and other harmful chemicals that are impacting the rate of climate change. This means that the more rubbish there is, the more damage is being done to the Earth. You can help by focusing on recycling much of your household rubbish. For example, purchasing reusable packaging and reusable items eliminates the amount of rubbish that has the potential of finding its way into a landfill. Less rubbish equals less harmful chemicals entering the atmosphere. Land Preservation The amount of space that a landfill requires means that there’s less space for you and other wildlife. Living near a landfill is also an unpleasant experience because of the smells and noise pollution that inevitably go with them. More animal habitats can also be preserved when you decide to recycle your items instead of tossing them out. All of this additional land could be preserved and potentially have more trees on it that would contribute to helping to reverse climate change. Resource Conservation Resources are a very valuable commodity. Throwing these resources into a landfill isn’t a good use of them. Recycling items like scrap steel reduces the amount of damage that’s done to the planet. This is due to the fact that new metal sources don’t need to be mined and refined to make the products that you require. The mining and refinement process is also contributing to the increased rate of climate change and is impacting the world around you. Ocean Impact Plastics are a big problem in the oceans. Marine life is being harmed because of these floating plastic islands that may be intentionally discarded there. If this trend continues, you’ll see a major impact in the food chain. Other animals consume marine life and this will mean that your food could become tainted with these plastic particles. Scientists don’t know the extent of what this will mean for you, but increasing your recycling efforts can help to stop this destructive cycle. Recycling is imperative to the continued health of the planet. Consider the ways that you can help in the fight against climate change by investing in a recycling regiment.
  15. We’ve all heard that going solar can save you money by reducing, or eliminating your electric bill. Homeowners can sometimes get a rebate for installing a grid-tied solar system. However, how much do you know about the different types of home solar systems? Grid-tied Solar Systems A grid-tied solar system is tied to the electrical grid maintained by your local utility company. As your solar panels produce energy, it’s sent back to the grid. Your home may not necessarily use the electricity your solar panels produce. Instead, you would get credits for the amount of energy your home produces. A grid-tied solar system is what you’ll generally receive a rebate for installing. That’s because it directly benefits the utility company. It can reduce your electric bill to zero, as long as your panels keep putting out enough energy. The Shortcoming of Grid-tied Solar Systems You may have heard that during natural disasters, although people had solar panels, they still suffered from a power outage. Often, that’s because all of the electricity their solar panels produced was sent to the grid. When the grid went down, their power went out too, despite the panels on their roof. Solar-Plus-Storage System If you want your home to be energy-independent, you need a storage system. That means, you need solar batteries to store the energy your solar panels produce. You can still send power to the grid, and also, store electricity in your batteries in case of a grid-down disaster. A typical car battery won’t do, you’ll need what is called a deep-cycle battery. Deep cycle batteries are designed to be charged and recharged, over and over again. Deep cycle batteries can be lead-acid, like your car battery, or lithium-ion, like in your rechargeable electronics. Most home systems use lithium-ion batteries. They hold a charge longer than lead-acid, as well as a longer life span. However, they’re more expensive. Making Solar-Plus-Storage Work in Your Homeowner The first thing you’ll need to decide is how many solar batteries you will need. You’ll need to calculate the energy use of your home, and then purchase enough batteries to store that amount of energy. Next, you’ll need to decide where to put the batteries; solar batteries can take up quite a bit of room. The garage is a good place to place them. Please do your research, to calculate how much battery you will need, as well as the different types and brands available.
  16. When you are trying to embrace a waste-free lifestyle, you can get overwhelmed by all the information and choices. Luckily, there are some simple tools that can make the transition easier. Reusable Dishes If you are like most people, you probably go through quite a few disposable containers, utensils, and even straws. Avoid that by finding a functional set of reusable plates and utensils that you can carry with you. Look for dishes that are made from sustainably sourced materials like bamboo. Don't stop at your plates, either. Start packing glass containers to bring leftovers home when you eat out. A Composter A large part of what is thrown out can actually be composted safely at home if you know how to get started. Pick a composting system that fits your lifestyle, taking care to find out if there are any restrictions on outdoor compost bins or piles where you live. You can build a nice sized kitchen composter that can even accommodate bones and dairy from a simple plastic bucket and spigot. It will work to start decomposition while giving you copious amounts of free compost tea. Just find a plastic bucket supplier and you are in business. Dish Towels Start paying attention to how many paper towels you toss every day and you will quickly see why reusable dish towels can help decrease your household's trash. There are several ways to go, depending on your personal preferences. Crochet or knitted dishcloths are attractive and durable. They are great for scrubbing dishes, but, if you are going to be cleaning up wet spills or cleaning windows, you'll probably want terry or flannel dishcloths instead. Bulk Soaps This may seem like a silly thing, but just take a moment to think about how much waste is in every single bottle of body wash or cleanser that you use, and you'll see why it is actually important. You can find unwrapped bars of soap at many health and natural food stores and farmer's markets. If you are feeling crafty, try your hand at a DIY soap recipe. There are plenty of choices to meet the condition of your skin and hair, and most use commonly available ingredients you might already have on hand. Maximize Your Impact When shopping for any products, look for durable items that will last in minimal packaging to really cut back on what is tossed out. Also, look to repurpose older items before you throw them away.
  17. Experiencing plumbing issues like a clogged drain and blocked sewage pipes is quite common for homeowners. However, no one wants them to happen. But if it happens even, there’s nothing to be depressed!! If there’s a problem, there’s always a solution! Today’s post talks about two fantastic plumbing solutions that can help you in unclogging your drain or sewage pipes effortlessly. Plumbers call them hydro jetting and snaking. To know more about these extraordinary techniques related to drain cleaning Melbourne or that of any other region, keep reading this post! Let’s Start With Snaking… Snaking is a classic approach to unclog the drain. With this method, the plumber takes an auger. Auger is like steel cable that has a coil; similar to cork-screw in one end. It works as a piercer when a plumber inserts it in the sewage pipe. With the help of the auger, the plumbers remove obstructions, and your clogged drain becomes unclogged. What are the Benefits of Snaking? Snaking has proven effectiveness. There’s no better alternative than snaking if you want to clear basic drain clogs. Moreover, it doesn’t harm the sewage pipes. It’s a gentle process that can be used for old pipes as well. Besides, since snaking is efficient in removing obstacles from the drainpipe, it warns you about critical issues like the presence of a harmful object in the line. In a one-liner, if you want to clear basic clogs from your sewage pipes, snaking can do wonder! However, every good comes with some touch of evil. And snaking is of course, not an exception to the fact. It’s not a permanent solution, and there will always be the risk of clog accumulation in the future. Now it’s the Time to Focus on Hydro Jetting! Hydro jetting is the process, in which a plumber forces a stream of water in the sewage pipe. The pressure is set at 3000-8000 PSI (Pound per Square Inch). This is such a massive pressure that it can easily blow out any obstacles in the pipelines. The list includes hair, grease as well as tree roots. What are the Benefits of Hydro-Jetting? Hydro jetting is one of the most effective methods of cleaning ornery drain clogs. For this reason, it’s highly recommended for cleaning complicated drain clogs. Besides, it’s a versatile method that can be used for both residential and commercial purposes. The only downside of hydro jetting is none other than its forceful approach. For this reason, it’s not suitable for old or damaged pipelines. What’s the Best Method to Clean Drain Clogs, Snaking or Hydro-Jetting? Well, it entirely depends on the severity of the clog and the condition of the pipes. Hydro jetting works as a power-pack. On the other hand, snaking works as the primary method of clearing clogs. To know what the best fit solution is for you, consult with an experienced plumbing agency. They will help you in making the right decision. However, when you call a professional plumber, make sure you’ve requested them to conduct a holistic check. It will help you to detect several issues like the need for hot water system replacement Melbourne or in other areas, carbon monoxide test etc. So, what’s stopping you? Ring up the best plumbing agency near you today and get your job done at the earliest.
  18. In this era of environmental crisis, we all must do our part to reduce waste. Reducing food waste is something everyone can do to benefit the environment. The sad fact is, more than one third of all the food produced in the word goes to waste, and one billion people could be fed by the food wasted in Western Countries alone. Many people, especially those in heavily urbanized areas, are extremely ignorant when it comes to knowing where their food comes from. In one survey, the majority of urban dwellers did not know that their meat and dairy products came from living animals. Unfortunately, the survey did not query the respondents as to where they did think meat and dairy foods came from, which could give valuable insight on how to improve public perception about food production and consumption. Reducing Retail Food Waste One area of concern with vast room for improvement is retail food waste; the amount of food thrown out by grocery stores and restaurants is tremendous. If you work in a grocery store, you could convince the management to donate unused or out of date food to a food bank. Likewise, if you own, or work in a restaurant, consider purchasing equipment that conserves resources, such as hamburger moulder equipment that measures precise amounts of food so that you don't use more or less than you need. Also, at the end of the day, you could offer prepared, perishable, unsold food to those in need. Eliminating Food Waste at Home There are many ways to reduce or completely eliminate your home food waste. First, don’t buy food you’re not going to eat. Sometimes, for our health, we think we should eat something we really don’t like. Be honest, even if you buy it, you probably won’t eat it. Second, if you have children, be mindful of their portions. Children probably waste more food than adults, simply because they can’t eat a large portion. Many children are also picky eaters, and will refuse to eat food they don’t like. Another way to reduce food waste is to compost; composting involves turning vegetable food waste into healthy garden soil. If you have a yard, consider starting a compost pile. It will not only help to reduce food waste, but it can also be used to grow your own organic vegetables. Another healthy strategy for reducing food waste is to make your own bone broth; rather than throwing out your chicken or beef bones, you can boil them down into an incredibly nutritious broth. This broth can be used in many different healthy recipes. It’s up to us all to take action, and reduce food waste in any way we can. The environment depends on it.
  19. The new year is finally here, making it the perfect time for a new resolution. For small business owners, a great resolution is to reduce unnecessary waste. Not only is eliminating excess waste beneficial for cutting costs, it also minimizes the impact on the environment. Since the average person creates four pounds of trash daily, imagine the amount of trash that accumulates from an entire staff? Practicing sustainability helps the environment and saves businesses money. Double-Sided Printing Believe it or not, there are businesses that still use printed sheets. Between constantly paying for paper and replacing ink cartridges, making copies can become extremely expensive. By printing on both sides, there are fewer sheets and materials that need to be purchased and recycled. Donate Excess Goods After realizing there are excess items that can be considered waste, it’s better to donate them rather than throw them away. For instance, if new inventory comes in or a product is discontinued, finding someone who can use those materials is a better way to repurpose them and cut garbage costs. Frequently Train Employees Understanding sustainability is only half the battle. It is important to inform employees of any changes that can make eliminating waste easier. It is important to inform employees on both how and why these precautions are being taken. For instance, if there is a new recycling policy, inform them on why it is beneficial for the business. It is also necessary to have regular meetings to share the triumphs and failures so the team can exchange feedback on how to improve on setbacks. Everyone staying on the same page is a key component of success. Digital Tags For retail businesses, paper tags can become expensive. Instead, using a digital price tag can save money on both paper tags and employees having to tag the items. Research shows that the initial investment in these digital tag machines pay themselves off within two and a half years, which eventually allows for the profits to be spent elsewhere. Digital price tag machines also can be instantly updated with a click of a button, which can display the original and sale price simultaneously. The new year creates new opportunities for small businesses to make a profit. The best way to do so is recycling old products, communicating sustainability tips to employees, and cutting labor costs by using digital tags.
  20. It is an unfortunate fact that many homeowners are damaging the environment without even realizing it. In addition to efficiency issues that could potentially be wasting quite a bit of energy, your home might also be filled with a variety of harmful toxins. You may be surprised to realize that your house is killing the environment, but do not fear! There are some simple steps you can take to have a more eco-friendly home. Here is a quick look at some of the most common ways that many homes hurt the environment and a few steps that can be taken to address those issues. Inefficient or Damaged HVAC System In the average home, the heating and cooling system is responsible for most of the energy consumption. That is just one of the reasons why you must make sure that your HVAC system remains well-maintained and is working at maximum efficiency at all times. In addition to having the entire system serviced at least twice a year, you must also immediately contact an air conditioning repair specialist if you ever notice any unusual problems. Some of the most common signs of a damaged HVAC system include skyrocketing energy bills, unusual noises, different temperatures in every room, and unpleasant smells coming from the vents. Toxic Building Materials While most modern homes must adhere to very strict environmental regulations, many older homes were built with highly toxic materials. If your home is more than a decade or two old, then you might want to spend some time figuring out if there are any dangerous materials in the walls or roof. To locate those materials, you can contact a home inspector who will look over every inch of your property. It might be tempting to get rid of those materials on your home, but you should call a company that specializes in removing those contaminants if any are found. Dangerous Cleaning Supplies One of the easiest ways to make your home more eco-friendly is to remove all of the dangerous cleaning supplies that are in your cupboards. Even many of the seemingly safe cleaning supplies are filled with harsh chemicals or CFCs. To safely get rid of those products, you can call your local waste management company to see if they have a hazardous materials drop-off site. While you can find safe cleaning products at most stores, many people are now making their own cleaners with harmless ingredients, such as baking soda, white vinegar, and lemon juice. In addition to taking care of these few problems, you should also make sure that you practice eco-friendly habits at home. Taking shorter showers, turning off unused electronics, and other minor changes to your daily habits could end up having a huge impact on the environment.
  21. Almost half of the lakes in the United States are polluted to the point that they are considered unsafe for swimming, fishing and supporting marine life. Keeping the lakes clean is a great way to help the planet. Use these tips to help clean up local lakes around the country. Use Less Salt in the Winter While salting sidewalks and roadways helps melt snow that can cause icy accidents to occur, it is also becoming a big problem in lakes. The chloride from the salt eventually makes its way to lakes and rivers. This chloride builds up in lakes and aquifers, killing marine ecosystems. Use only as much salt as necessary to melt the ice and let local officials know that you support efforts to reduce salt usage on highways and roadways. Use Natural Pesticides and Herbicides Pesticides and herbicides used to keep bugs and weeds out of gardens leech into the ground and make its way into the water that goes into the lakes. Pesticides and herbicides are high in phosphorous and nitrogen that pollute lakes and kill wildlife. Natural pesticides and herbicides can help reduce dangerous levels in the water. Biological nutrient removal also aids in the reduction of phosphorus and nitrogen in lake water. Switch to Non-toxic Tackle Those who enjoy fishing may want to look at their tackle. Toxic tackle, such as lead jigs and sinkers, leach lead into the water. Additionally, waterfowl such as trumpeter swans and loons pick at the tackle that is left on the sides of the lake or in the water. These animals may contract lead poisoning and die, which disrupts the entire ecosystem of the lake. Pack it In, Pack it Out There is nothing that makes summer memories like spending a warm day on the boat out on the lake. Keep water clean by making sure nothing is left around the lake or dumped into the lake after a day of fun. Trash, leftover food and supplies that are brought to the lake need to be disposed of properly at home. These items pollute the lake and harm fish and wildlife that live around the water. Keeping the lakes clean is the responsibility of everyone. Lakes are the biggest reservoirs of water in the country. Making the lakes clean keeps the water that everyone drinks free from pollutants and dangerous chemicals. Clean water means a healthier, happier life for everyone.
  22. Recycling is more than just a way to help the environment - it's also a fantastic business tool. If you own a business, you might want to look at recycling as a way to thrive in an increasing competitive market. Below are just four methods you can use to help your business through recycling and recycled materials. Sell Scrap and Old Equipment for Recycling If you're looking for a good way to turn your extra materials and old equipment into cash, you'll definitely want to take a look at recycling. While many businesses think that recycling is limited to some extra copper wiring or maybe even some old boxes, the truth is that there are buyers for virtually everything you use. If you want to sell electrical equipment that you no longer need, for example, you'll almost certainly be able to find a buyer who can meet your price. Buy Discount Recycled Materials Recycled materials are often a great alternative to buying new. Not only is doing so is a good way to reduce waste and to help out the environment, but recycled materials also tend to cost a great deal less. If you buy recycled, you'll get all the benefits that you would typically get from buying top-shelf materials without having to deal with the significantly higher price tag. Buying recycled is simply a smart move for any budget-conscious business. Make a Great Public Impression If you look at many of the major corporations around the world, you'll notice that they have very conspicuous green initiatives. While many might do this because they truly care about the planet, the truth is that doing so is just as much a public relations ploy as anything else. If you choose to use recycled materials, do so conspicuously. It will help to get an increasingly environmentally conscious public on your side. Show Investors Resourcefulness Finally, remember that all of these actions tend to look good to investors. Investors who know that you're dedicated to making a good public impression, cutting costs, and creating new revenue streams are also investors who are eager to buy into your business. If you're looking for new ways to bring in partners or to increase the size of your operation, using recycling as a point of pride can be a great choice. Don't be afraid of recycled products or materials. They can save or make you money, but they can also become a cornerstone of your business' reputation. When you're ready to grow, start looking to recycled materials.
  23. Construction can have a large impact on the environment. The use of heavy machinery and invasion of wildlife habitat are just a few of the more common problems when it comes to the construction industry. Here are some of the ways that construction companies can work to reduce their impact on the environment. Use Sustainable Products Sustainable building products work to reduce the amount of natural resources that are being used up. For example, you can reduce the impact on the environment that’s caused through the use of concrete by switching to timbercrete. This is the combination of some concrete being mixed with sawdust. The sawdust comes from the waste products of the lumber industry. Other sustainable products include the use of bamboo, ferrock, and other renewable wood products. Reduce Energy Consumption The type of heavy machinery that’s typically used on a construction site produces large amounts of pollution and noise. Replacing this type of equipment with more energy efficient models, or even their electric counterparts help make your construction site better for the environment. Another thing to consider is your fuel usage. For example, not leaving your equipment idling when it’s not needed will reduce the amount of fuel that’s required for the job. Focus Recycling Efforts The amount of waste that’s generated on your construction site can be reduced. Using industrial scrap metal recycling services will ensure that your leftover metal can be put to good use. It will also give you the benefit of not having so much to clean up on your jobsite. This will work to reduce the amount of materials that are transported to the landfill and can make for a greener worksite. You may even be able to recycle some of the other construction debris. Low Impact Solutions The manner in which you go about the building process plays a large part on the amount of impact that the environment experiences. For example, minimizing your impact on the natural habitat around you starts with site planning. You may be able to keep larger trees and build around them. Reducing the amount of dust that’s generated on your site is another solution. You could use recycled water or rain water instead of fresh water when you’re spraying down the dirt. Construction companies can change the way that people think about the building process. Use these solutions so that you can reduce your environmental impact when it comes time to erect a new development.
  24. 1.1.2 Drug Ion Electrical Properties and Drug Loading Capacity The interaction between the drug and the phospholipid layer molecule has an important effect on the structure and load of the liposome, and the effect of the charge effect is particularly significant. Generally, when the charge properties of the drug and the phospholipid molecular layer are the same, it is not easy to be encapsulated. By adding appropriate excipients during the preparation of the liposome to make it a charged liposome opposite to the charge of the encapsulated drug, the drug encapsulation rate can be improved. For example, in the preparation process, octadecylamine is added to obtain positively charged liposomes, and phosphatidic acid is added to obtain negatively charged liposomes. The antiviral drug cidofovir is negatively charged under normal physiological conditions. It is found that liposomes made with positively charged phospholipids composed of DOTAP and DC have a significantly higher encapsulation rate than liposomes made with electrically neutral phospholipids. However, other studies have shown that when the positively charged drug sumatriptan uses a neutral phospholipid as the membrane material, the encapsulation rate is low, and when the positively charged material stearylamide is added to the membrane material, the phospholipid membrane is significantly strengthened, thereby t lop09he leakage of the drug is prevented, and the drug load is increased. However, the encapsulation efficiency was lower than that of positively charged membranes after the addition of negatively charged membrane dicetyl phosphate, indicating that in some drug encapsulation processes, charge is not the main factor influencing. 1.1.3 Decoration and Encapsulation Rate of Medicinal Chemical Structure The chemical structure of a drug determines its physical and chemical properties. By modifying the structure of a drug to some extent, the hydrophilic and hydrophobic properties of the drug can be improved, thereby improving the encapsulation efficiency of the drug. Researchers reacted the anticancer drug cyclocytidine with palmitic acid to obtain two derivatives of monopalmitate and dipalmitate, which were separately encapsulated to prepare liposomes. As a result, the encapsulation rates of the two derivatives were found. It rose to 86.5% and 93.7% respectively, while the original drug was only 21%. The HLB value shows that on the one hand, the original drug is converted from hydrophilic to lipophilic after esterification, and the encapsulation position of the drug is correspondingly transferred from the aqueous phase to the external lipid phase. On the other hand, the long ester chain obtained by structural modification can be embedded in the lipid membrane. In addition, the fluidity of the lipid membrane is reduced, thereby increasing the liposome stability and encapsulation efficiency. Liposomal particle size design Particle size is an important evaluation index of liposomes, and its size and degree of uniform dispersion directly affect the in vivo behavior of liposomes. Large particle size liposomes are easily endocytosed by macrophages and concentrated in the liver. Smaller particle size liposomes can effectively prolong the circulation time of the drug and play a long-lasting effect. When the particle size is less than 50nm, liposomes can penetrate the liver endothelium and enter the spleen, bone marrow and tumor tissues. Duan Yisong et al etc. used long-circulating material polyethylene glycol to prepare mitoxantrone long-circulating liposomes with an average particle size of 60nm. Compared with ordinary liposomes, the average residence time in rabbits was prolonged by 6.2h, reflecting Its long cycle advantage. Awasthi et al. Investigated the particle size on the circulation time of PEG-modified liposomes in rabbits and found that the optimal particle size is 160-220 nm. Large particle size liposomes (400-530nm) are highly targeted to liver and spleen-enriched reticular macrophages. When the liposome particle size increases to 1-12 μm, it is easily taken up by the lungs. After azithromycin was prepared into cationic liposomes, the mice were administered tail vein to study the distribution of azithromycin in mouse whole blood and various tissues. AUC increased by 7.4 times. This is because liposomes larger than 6 μm will be mechanically filtered by pulmonary capillaries and then taken up by monocytes into lung tissue. Preparation method selection The preparation method of liposomes greatly affects the structure and particle size of liposomes, so it is generally selected according to the nature of the drug and the purpose of the drug. For fat-soluble drugs, mechanical dispersion methods such as film dispersion method and freeze-drying method can be selected to prepare multilayer liposomes with large particle diameters, so that the drug is slowly released in the target tissue. If you need to increase the drug's transport speed, you can choose to prepare small single-compartment liposomes. The main methods include ethanol injection, surfactant treatment, film-ultrasonic method, and so on. The drug loading of water-soluble components is generally not high. The key is to increase the volume of the aqueous phase in the liposome. Therefore, large monolayer or polycystic liposomes are generally selected for preparation. The reverse thin film dispersion method and the double emulsion method and the freeze-thaw method are suitable for the preparation of large particle size aqueous drug-loaded liposomes. Among them, the reverse thin film dispersion method is mostly large monolayer liposomes, including The sealing rate can reach 60-65%, and some studies have shown that for the hydrophilic drug salvianolic acid B, the large monolayer liposomes (LUV) prepared by the reverse evaporation method, the ethanol injection method, and the double emulsion method are used. Compared with liposomes, the encapsulation rate is the highest. The repeated freeze-thaw process in the freeze-thaw method will be accompanied by the formation of ice crystals, which will cause mechanical damage to the phospholipid bilayer, thereby increasing the chance of water-soluble drugs entering the phospholipid bilayer and increasing the encapsulation rate. At the same time, multi-compartment liposomes can be prepared into small single-compartment liposomes by repeated extrusion and freeze-thaw methods, which increases the drug loading space and drug loading. In addition, the microencapsulation method is suitable for preparation Small-particle-size drug-loaded liposomes in aqueous phase. For amphiphilic drugs such as weak base and weak acid, they can be encapsulated by active drug loading methods, such as PH gradient method, ammonium sulfate gradient method metal ion gradient method, and so on. In some cases, a single method alone cannot meet the requirements of encapsulation efficiency and particle size, especially for compound drugs with different properties in the co-loading concentration, so it is often combined with several methods.
  25. Mesenchymal stem cells have the characteristics of low immunogenicity and homing to ischemic or injured tissues. After entering into the host body, they can homing to specific sites and be differentiated into endoderm, mesoderm, and ectoderm under the influence of microenvironment cells derived from individual germ layers, such as bone, cartilage, tendon, fat, liver, kidney, skin, muscle, nerve, and even pancreas, are more than 10 kinds of mature cells, thus becoming ideal seed cells for organ repair in regenerative medicine. Initially, mesenchymal stem cells were found in the bone marrow, but highly invasive bone marrow donation experiments were needed. In addition, the number and differentiation potential of mesenchymal stem cells decreased with age. Recently, umbilical cord blood has been less damaged due to acquisition methods and has been used as an alternative source of mesenchymal stem cells. Another promising source of mesenchymal stem cells is adipose tissue. This review compares these three mesenchymal stem cell sources from aspects such as morphology, success rate of isolation of mesenchymal stem cells, frequency of clonal colony formation, expansion potential, multi-directional differentiation ability, and immune phenotype. Adipose tissue can be used as an alternative source of bone marrow tissue for the isolation of mesenchymal stem cells. In addition, people have also found that mesenchymal stem cells are also found in cord blood, periodontal ligaments, amniotic fluid, dermis, periosteum, skeletal muscle, fetal lung, fetal liver, placenta and pancreas. Mesenchymal stem cells have broad clinical application prospects and can be used to treat diseases of the nervous system, liver and kidney injury, autoimmune disease, heart disease, bone disease, cartilage disease, ischemic vascular disease, diabetic complications and tumors. They can also be used in tissue engineering and facial shaping. In addition, they can be co-transplanted with hematopoietic stem cells to treat blood diseases. Based on this, the article made an inventory of the research progress made by mesenchymal stem cells in recent years. 1.TEPCM: magnetic mesenchymal stem cells promise to improve cartilage repair doi: 10.1089 / ten.tec.2019.0001 Cells carrying superparamagnetic iron oxide nanoparticles (SPIOs) can be directed to a specific location by an external magnetic field, which is beneficial for tissue repair. Recently, a research report entitled "In Vitro Safety and Quality of Magnetically Labeled Human Mesenchymal Stem Cells Preparation for Cartilage Repair" was published in an international magazine Tissue Engineering Part C: Methods. The safety and effectiveness of this magnetically labeled mesenchymal stem cells (MSCs) in repairing cartilage defects. Researcher Dr. Naosuke Kamei said that “in this study, we demonstrated the safety of magnetically labeled MSCs through karyotyping, clone formation experiments, and total proliferation experiments. After labeling, we found only small differences in mesenchymal stem cells”. Researchers can evaluate the quality of stem cells by the differentiation of chondrocytes and their reactivity to magnetic forces. The results show that the appropriate concentration of superparamagnetic iron oxide nanoparticles can help optimize the mesenchyme while ensuring magnetic attractiveness and differentiation ability of plastid stem cells. Nat Commun: Identify key proteins that regulate angiogenesis in tumors doi: 10.1038 / s41467-019-10946-y Recently, in a research report published in the international journal Nature Communications, scientists from the Barcelona Institute of Biomedicine found that inhibiting the function of p38 protein or inhibiting angiogenesis in human and mouse colon cancer. This process is called angiogenesis, which is essential for cancer cell growth and can promote cancer progression and metastasis. Researcher Dr. Angel R. Nebreda said that we found that p38 activity is very important for mesenchymal stem cells (MSCs). These stem cells have high plasticity and can be concentrated around blood vessels. It participates and plays a role in many key processes, such as tumor formation. This study clarifies the molecular mechanism of tumor angiogenesis. Researchers have now described the activity of p38 in cancer cells, but until now they did not know the key role that the protein plays in MSCs, and very little is known about how the protein is involved in tumor angiogenesis. In this study, researchers clarified the key role of the protein p38 in the cardiovascular process during tumor angiogenesis, especially how it promotes the development of MSCs. The researchers said that p38 can play a role in MSCs cells. The effect is to inhibit angiogenesis. Using genetically modified mouse models, researchers have found that inhibiting p38 may stimulate cardiovascular production in tumors, and this situation also occurs during the repair process of damaged tissues in the body. 3.EBioMedicine: researchers develop cancer treatments that target bone metastasis while retaining bone tissue doi: 10.1016 / j.ebiom.2019.06.047 Researchers at the University of California, Irvine (Irvine, UCI) have developed a treatment and tested it on mice using engineered stem cells to target and kill cancerous metastases in bone tissue while preserving bone. The new method, published in the journal EBioMedicine, equips engineered mesenchymal stem cells to target them, prompting them to transfer to bone metastases, where they release therapeutic drugs. "The power of this strategy is that we provide a combination of anti-tumor and anti-bone resorption agents so that we can effectively block the vicious circle between cancer and its bones," said the study's lead author Weian Zhao, associate professor of pharmaceutical sciences and biomedical engineering, said. "Compared to chemotherapy, this is a safe and almost non-toxic treatment, and chemotherapy often causes lifelong problems for patients." To be continued in Part Two…
  26. While many of us can easily recycle our paper, glass and plastic waste, recycling electronics and batteries is not as easy. However, recycling these items might be even more important than recycling more common household waste. You may not know this, but both old electronic items and batteries can leach harmful chemicals into the soil and groundwater. Recycling Electronics According to the Environmental Protection Agency, 2.84 million tons of electronics were thrown away in 2017, with little more than 1 million tons recycled. The rest mostly ended up in county landfills. Unfortunately, electronic devices often contain hazardous heavy metals, including barium, lead, silver, chromium, cadmium, and mercury. These can easily leech into the soil and groundwater, poisoning the environment. The good news is, recycled electronics can often be refurbished and resold or donated to people in need. Likewise, some of the valuable metals, such as copper, silver, and gold, can be recovered and reused. Battery Recycling Batteries contain large amounts of toxic heavy metals and chemicals and simply tossing batteries in the trash can easily contaminate the soil pollute the water. The good news is, the Environmental Protection Agency reports that 99.1% of lead-acid vehicle batteries are recycled. This is because when you get a new battery for your vehicle, the auto shop already has a line to recycle all of the old batteries. Unfortunately, batteries from our electronic devices are not responsibly recycled. More often than not, people don’t know how to recycle such batteries and simply toss them. However, many electronics retailers have battery recycling drop-offs, and there are battery recycling services that collect batteries from your business or office. Reclaiming Valuable Metals Both electronics and batteries contain valuable metals that can be recovered. Recovering these metals not only keeps them out of our landfills and our environment, but it also reduces the need for strip mining. It’s a sad fact, but many of the metals used in batteries, such as lithium, are mined in third-world countries, often using child labor. To prevent future shortages of lithium, cobalt, nickel, and other rare earth metals, recycling for lithium batteries is essential. Recycling retrieves not only nickel, cobalt, copper, lithium, and aluminum from old batteries, but also valuable graphite and manganese. The good news is, recycling can recover anywhere from 25% to 95% of the materials from a lithium-ion battery. Putting paper, plastic, and glass out on the curb for recycling is easy. However, with a little bit of forethought, recycling electronics and batteries will take very little effort.
  27. Exosomes are nano-scale vesicles secreted by cells. These microvesicles are usually about 30-150 nanometers in diameter and contain important cellular molecules such as proteins and RNA. Previous studies have shown that exosomes can be used as diagnostic markers for cancer, neurodegenerative disease, and kidney disease. In recent years, exosomes isolation technology has made significant progress and development. Ultracentrifugation Ultracentrifugation is the most commonly used exosomal purification method. After removing dead cells and cell debris by low speed centrifugation, high-speed centrifugation is used to precipitate vesicle particles of the same size from soluble molecules such as free proteins and protein complexes purified. It is important that the exosomes be subsequently washed at least once with PBS or fresh growth medium to reduce free residual proteins therein. In addition, all centrifugation steps must be performed at 4 ° C to keep the proteases, DNase and RNases inactive. Usually ultracentrifugation is also used in combination with a sucrose density gradient (its continuous distribution from low to high density) or a sucrose cushion (30% sucrose cushion), that is, centrifuged at 100,000-200,000 xg in a centrifuge (containing exosomes) In 120 minutes, the exosomes in the sample should be enriched in a sucrose density range of 1.13-1.19 g / mL. Although this powerful method can obtain highly purified exosomes, there are some disadvantages. Indeed, the process of ultracentrifugation is time-consuming and labor-intensive, and requires a lot of raw materials. The biggest drawback is that repeated centrifugation operations are likely to cause damage to exosomal vesicles and reduce their quality, or soluble proteins in the sample may form aggregates and clumps with exosomes to cause contamination. Ultrafiltration centrifugation Considering that exosomes are cystic bodies with a size of several tens of nanometers, which are larger than ordinary proteins, exosomes can also be separated according to their size, such as ultrafiltration and size exclusion chromatography (SEC). Ultrafiltration is the selective separation of samples using ultrafiltration membranes with different retention molecular weight (MWCO). That is, the solvent, ie, some small molecular substances, is filtered to the other side of the membrane, while high relative molecular mass substances larger than the membrane pore size are retained On the ultrafiltration membrane, the purpose of separating exosomes is achieved. This method is simple and efficient, and does not affect the biological activity of exosomes. It is the best method for studying exosomal RNA because it produces greater RNA production than ultrafiltration and precipitation methods. It is also possible to pass a nanofiltration concentrator. However, the main disadvantage of ultrafiltration is that exosomes may block the filter pores, resulting in shorter membrane life and lower separation efficiency. Exosome membranes also adhere to each other, resulting in low separation yields and even erroneous test results. In addition, there is another interference that needs to be resolved in the method of separating exosomes based on the size of the exosomes, which is the existence of a large number of non-exosomal nanovesicles that are similar in size to the exosomes. In SEC, the porous phase fixed in the column can also be selectively separated based on the molecular size using the principle of gravity flow. Small molecules can pass through the pores and cause later elution, while larger components (including exosomes) can be eluted early, bypassing the pores. This method can greatly maintain the integrity and biological activity of exosomes, and combine with differential centrifugation to obtain highly purified exosomes. PEG-base precipitation method Polyethylene glycol (PEG, 8000 kDa) can competitively bind free water molecules, so that less soluble molecules or exosomes are precipitated from the solution. Earlier this method was used to collect virus from samples such as serum, and now it is also used to precipitate exosomes. Samples are usually incubated overnight at 4 ° C with PEG, and exosomes are then recovered by low-speed centrifugation or filtration. However, this method also has some problems: for example, the purity and recovery of exosomes are low, false positives (more proteins or some polymers that are difficult to remove), and mechanical or chemical additives that damage the exosomes. Alternatively, if you know the sugar chain composition of the exosomes, you can use lectins to enrich the exosomes. Lectin is a protein that binds to carbohydrates and can be centrifuged at low speed after agglutinating exosomes. In recent years, exosomes have been separated based on the principle of precipitation. Various commercial exosomal extraction kits have also been developed on the market. The operation is simple, and high-purity and high-recovery exosomes can be obtained without ultracentrifugation. Magnetic bead immunoassay Exosomes are available because they are rich in protein and have many specific marker receptors on their surface, such as CD9, CD81, CD63, CD82, Hsp70, Ras-related protein Rab-5b, cytoskeleton protein actin, and TSG101. Anti-marker antibody-coated magnetic beads can be captured after incubation with exosomes. Because the heterogeneity of exosomes is consistent with their origin, the abundance of these markers on different exosomes is also different. Therefore, you can capture different types of exosomes from a sample by using specific antibody combinations, and select these exosomes by immobilizing these antibodies on ELISA plates, magnetic or chromatography beads, or microfluidic devices. Although immunoaffinity technology has the advantages of high specificity, high purity exosomes can be obtained without affecting the morphological integrity of exosomes, it is the preferred method for enriching and characterizing unique exosomes. However, this method is low in efficiency, and the biological activity of exosomal contents is easily affected by pH and salt concentration, which is not conducive to the downstream experiments. Phosphatidylserine affinity This method combines PS (phosphatidylserine) with magnetic beads and uses the principle of affinity to capture PS outside exosomal vesicles. This method is similar to the immunomagnetic bead method, and the exosomes obtained are complete in morphology and highest in purity. Since no denaturant is used and the biological activity of exosomes is not affected, exosomes can be used for cell co-culture and in vivo injection. 2016.9 "Scientific Reports" magazine published the latest data of this method, showing that PS method can extract relatively high purity exosomes. Chromatography The exosomes isolated by this method are uniform in size under electron microscopy, but require special equipment and are not widely used. Exosome isolation is the first step for exosome characterization. The quality of exosome separation directly affects the subsequent researches of exosome qualitative and quantitative as well as applications in disease diagnosis and therapy. With the extensive experience in exosome isolation, Creative Biolabs provides a portfolio of exosome isolation products which can help you with the high-quality exosome isolation from many types of biofluids in an efficient, faster and cheaper way.
  28. Vitamin E is a fat-soluble vitamin that was discovered as early as the 1920s. Vitamin E includes tocopherols and triene tocopherols, a total of 8 compounds. Alpha-tocopherol is the most widely distributed and most abundant form of vitamin E in nature. Tocopherol is a hydrolysis product of Vitamin E and is one of the most important antioxidants. How does Vitamin E help the human body? Vitamin E helps delay aging Vitamin E is a strong oxidant and is not weaker than lycopene and astaxanthin. After entering the body, vitamin E can help fight free radical Oxylipin peroxidation, eliminate free radicals, and delay aging. Vitamin E helps boost immunity If vitamin E is lacking, it will reduce the body's humoral immunity and cellular immunity, and increase the possibility of human diseases. Proper vitamin E supplementation will help to strengthen the body's ability to resist disease and enhance its physique. Vitamin E helps eliminate pigmentation Pigmentation is caused by the deposition of lipofuscin in skin cells. Lipofuscin is the product of cells being oxidized by free radicals. This substance not only produces stains and hinders aesthetic appearance, but also deposits in the internal organs and brain cells, causing cardiovascular and cerebrovascular diseases, and endangering health. Vitamin E as a strong oxidant can eliminate these free radicals, help prevent the generation of pigmentation, and at the same time tenderly expand peripheral blood vessels, reduce blood viscosity, and prevent cardiovascular and cerebrovascular diseases. Vitamin E can stabilize the protein active structure of the cell membrane, promote the normal development of muscles and maintain the elasticity of the skin, so that the skin and the body remain active; Vitamin E entering the skin cells can directly help the skin fight against the damage of free radicals, ultraviolet rays and pollutants, preventing The skin loses its elasticity due to some chronic or hidden injuries until it ages. Because of these effects of vitamin E, it is believed that vitamin E helps beauty. Vitamin E helps protect eyesight Vitamin E can inhibit the lipid peroxide response in the lens of the eye, expand the peripheral blood vessels, improve blood circulation, and prevent the occurrence and development of myopia. Vitamin E helps relieve stomach ulcers The poor gastric mucosal resistance in patients with ulcer disease is related to the disturbance of fat peroxidation. Vitamin E can regulate fat oxidation and scavenge oxidative free radicals, while protecting cells from oxidant damage. At the same time, a large amount of vitamin E can promote the proliferation of capillaries and small blood vessels, improve the surrounding blood circulation, increase the supply of oxygen in the tissue, thereby creating good nutritional conditions for healing of the ulcer surface. In addition, it can still inhibit the growth of H. pylori and reduce the recurrence rate of ulcer disease after healing. Vitamin E helps promote sex hormone secretion Vitamin E can increase men's sperm vitality and quantity; increase women's estrogen concentration, improve fertility, and prevent miscarriage. Is it okay to take a lot of vitamin E for a long time? Vitamin E is found in edible oils, fruits, vegetables and grains. The recommended daily intake for adults is 8 to 10 IU. Vitamin E in the general diet can completely meet the needs of the human body. Therefore, the general population does not need to take vitamin E for a long time. Long-term use is not only unsafe, but also has side effects. Taking large doses of vitamin E for a long time may cause various diseases. The more serious ones are: Intake of low-dose vitamin E has anti-oxidant effect, but it may no longer have antioxidant activity when ingested in large doses. At this time, vitamin E becomes a pro-oxidant; Thrombophlebitis or pulmonary embolism, or both, is due to the high dose of vitamin E that can cause platelet aggregation and formation, which may trigger the risk of stroke; Headache, dizziness, dizziness, blurred vision, muscle weakness; skin cracking, cheilitis, angular cheilitis, urticaria;
  29. In recent years, studies have found that the incidence of primary malignant brain tumors has increased significantly, and the current prognosis is poor. Therefore, studying the mechanism of brain tumor recurrence, improving the prognosis of patients, and prolonging their survival time is an important research direction and a major problem faced by experts: due to the vague understanding of the source of brain tumor cells and its mechanism. Although a large number of related experimental studies have been done on the pathogenesis of malignant brain tumors, but no satisfactory results have been achieved. Currently, only a small percentage of cells in surgical tissues of brain tumors have been found to have infinite proliferation, self-renewal, multi-directional differentiation potential, and tumorigenicity. These cells are called brain tumor stem cells (BTSCs), and others tumor cells have no or only short-term proliferation ability. Igntova and other scholars first reported that brain tumor stem cells (BTSC) existed in brain tumor surgical specimens, and isolated precursor neurons that can form neurospheres from glioblastomas, which are called neural stem cells in brain tumors. At present, each brain tumor stem cell has been successfully cultured and isolated from surgical specimens such as medulloblastoma, different grades of astrocytoma, ependymal tumor, and ganglioglioma. Since Singh et al. First isolated CD133-positive tumor stem cells from malignant brain tumors, research on brain tumor stem cells has gradually become a hot topic in neuroscience and related fields. Preliminary studies have found that the occurrence, development, metastasis, and recurrence of brain tumors may be closely related to brain tumor stem cells. Therefore, further in-depth discussion of the biological characteristics of brain tumor stem cells and the mechanism in the occurrence and recurrence of malignant brain tumors will definitely be very important for the future of radical treatment and prevention of malignant brain tumors. Here in this article, we will introduce three important biomarkers. One of the most prominent one is TSGF, namely a group of tumor-related substances. It is a collective term for several internationally recognized carbohydrates and metabolites (lipoproteins, enzymes, amino acids) related to the growth of malignant tumors. TSGF is an effective, convenient and valuable tumor marker for the diagnosis and judgment of brain malignant tumors. In addition, studies have shown that the expression specificity of tumor markers such as nestin, BEHAB, YKL-40, EphA2, glial fibrillary acidic protein, CD133, fatty acid binding protein, and MMP-9 is more obvious in gliomas. 1. BTSC There are many hypotheses about the source of BTSC, but currently they tend to be derived from mature neural stem cells (NSCs). The accumulation of multiple mutations leads to tumorigenicity and becomes BTSC. The source is discussed from the following two aspects: ① The origin of the tumor is consistent with the NSC distribution area. Studies have shown that the origin of brain tumors may originate in a part of the subventricular area, and BTSCs with high proliferation and differentiation potential are constantly produced in this area, which leads to tumorigenesis, and these areas coincide with the main locations of NSCs. ② BTSC and NSC have many similarities in genetics. The main manifestation is that BTSC does not express markers of differentiated cells, but instead has NSC markers, such as Nestin or CD133. In summary, both theory and experiments support that BTSC is likely to be derived from mutant NSCs that are constantly dividing and proliferating. Although BTSC and NSC have many similarities, there are also obvious differences between them: first, BTSC has stronger self-renewal and proliferation capabilities than NSC, and the number of passages in vitro culture has increased significantly, with an immortalization trend. Its self-renewal and differentiation have become imbalanced; secondly, BTSC differentiates into the same phenotype as the parent tumor under the conditions that induce NSC differentiation and does not differentiate into neurons and glial cells in the same proportion as NSC. These differences provide new research directions and ideas on how to transform NSC into BTSC and whether the two are at the same level of differentiation. 2. CD133 protein, nestin, Sox2 protein In recent years, Rath et al. have successfully cultured and isolated meningioma stem cell spheres with spherical focus growth through serum-free suspension culture. At present, most scholars use CD133 and Nestin as specific markers of brain tumor stem cells. CD133 is a transmembrane protein with a relative molecular weight of 120,000. Studies have shown that both solid tumors and brain tumor cell spheres obtained from in vitro cell line cultures show CD133 positive staining; and CD133 positive cells isolated from glioma cell lines in serum-free culture, they all grew spheroidally, had infinite proliferation, self-renewal, and multi-directional differentiation. Singh et al. compared the biological characteristics of CD133-positive and negative tumor cells and found that the former has a strong ability to self-renew and proliferate, while the latter adheres to growth, does not divide, and does not proliferate. In vivo tumorigenicity tests showed that 100 CD133-positive tumor cells were tumorigenic, while 1 × 105 CD133-negative tumor cells formed only one glial scar at the transplant site. For these reasons, CD133 is considered to be the most important marker of brain tumor stem cells. However, recent studies have shown that CD133-negative cells in some brain tumors also have the characteristics of tumor stem cells. Therefore, CD133 is not a reliable marker for brain tumor stem cells. Nestin, which belongs to the intermediate microfilament, is expressed in undifferentiated neural pluripotent stem cells and was once considered a marker of brain tumor stem cells. However, the study found that the same group of tumor cells, Nestin-positive ratio is much higher than CD133-positive ratio, which indicates that Nestin is also expressed in progenitor cells that have just begun to differentiate, and is not a reliable brain tumor stem cell marker. Sox-2 belongs to the Sox (Sry-related HMG Box) gene family and is located at 3q26.3-q27 of the chromosome. It is a highly conserved transcription factor that can regulate the self-renewal of embryonic stem cells. It is the only Sox gene found in current research that plays an important role in maintaining the differentiation potential of embryonic stem cells. It is also a key to induce adult cells to become pluripotent stem cells. 3. Brain tumor stem cells The research of brain tumor stem cells has become a new hot spot in the field of brain tumor research. Although great achievements have been made in the successful isolation and culture of brain tumor stem cells, no complete theoretical system has been formed so far. Therefore, it is of great significance to study the pathogenesis and biological behavior of brain tumors and to find new treatment options for malignant brain tumors that target tumor stem cells in the future. It can be imagined that the detection of tumor stem cells will become a new classification and judgment of brain tumors in the future. It is possible to use various treatment schemes for brain tumor stem cells to specifically kill brain tumor stem cells, instead of killing all tumor tissues, in order to achieve radical cure and prevent tumor recurrence and metastasis. With the continuous research on brain tumor stem cells, it will inevitably have a profound impact on the pathogenesis, pathological grading, prevention of recurrence and treatment options of brain tumors, making the radical cure of malignant brain tumors possible.
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