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  1. Yesterday
  2. IL is short for interleukin. Interleukin is a kind of cytokines produced by many kinds of cells and used in many kinds of cells. It belongs to the same family of cytokines as hemocyte growth factor. They coordinate and interact with each other to complete hematopoiesis and immune regulation. Lnterleukin plays an important role in signaling, activating and regulating immune cells, mediating T and B cell activation, proliferation and differentiation, as well as inflammatory responses. The function of interleukin is related to the expression and regulation of immune response, which is involved by many factors such as lymphocytes or macrophages. In the process of studying the immune response, many molecules with biological activity were found in the cell culture supernatant stimulated by mitogen. Researchers named each molecule after their measured activity, and reported nearly 100 kinds of factors for more than ten years. A comparative study using molecular biology techniques later found that many of the factors previously named for biological activity were actually the same substance with pleiotropic properties. In 1979, to avoid the confusion of naming, the second international symposium on lymphokines uniformly named the leukocyte interaction cytokines during the immune response as interleukin (IL). At present, at least 38 interleukins, named IL1 ~IL38 respectively, have been found, with complex functions, network formation and overlap. They play important roles in the maturation, activation, proliferation and immunomodulation of immune cells. In addition, they also participate in a variety of physiological and pathological reactions of the body. Here to introduce 5 kinds of interleukin below. 1. IL2 IL2 is also called T cell growth factor (TCGF). It is mainly produced by T cells and exerts its effects in the form of autocrine and paracrine. It can activate T cells and promote cytokine production, stimulate NK cell proliferation, enhance NK killing activity and generate cytokines, induce LAK cell production, promote B cell proliferation and secrete antibodies, and activate macrophages. Its receptor IL2R is composed of IL2Rα, IL2Rβ and IL2Rγ. 2. IL11 IL11 was initially found in the culture supernatant of primate bone marrow stromal cell line pu-34. It mainly generated by mesenchymal-derived adherent cell, such as bone marrow stromal cells, matrix fibroblasts, human embryonic lung fibroblasts and trophoblast cells. The function of IL11 is similar to that of IL1, IL6, G-CSF and SCF: 1. To promote the production of B cell antibodies. 2. To promote the growth of some IL6-dependent cell lines such as TF-1. 3. Synergistic effect with IL3 and IL4 on bone marrow hematopoietic stem cells, to shorten the Go phase of stem cells. 4. Synergism with IL3 can promote the colony formation, growth and maturation of megakaryocytes in vitro, increase cell volume and the number of peripheral blood platelets. 5. IL11 can stimulate erythrocyte progenitor cells at different differentiation stages of mouse bone marrow and fetal liver. 6. To induce acute phase protein synthesis in hepatocytes. 7. It can inhibit lipoprotein lipase (LPL) activity and adipocyte differentiation, hence, it is also known as an AGIF. 3. IL12 Interleukin-12 (IL12) is a cytokine with extensive biological activity, mainly produced by activated inflammatory cells. Its main functions are: 1. To synergize IL2 to promote differentiation of CTL, NK and LAK. 2. To promote the proliferation of PHA activated T cells. 3. To promote Ig production and type conversion of B cells. 4. IL18 IL18 belongs to IL1 ligand family and its structure is similar to IL1 protein family. It is a powerful pro-inflammatory cytokine with the most characteristic function of regulating cell proliferation, differentiation and extracellular matrix formation. Therefore, IL18 plays an important role in the occurrence and development of diabetic nephropathy (DN). It can be combined with IL18BP to inhibit its biological activity. Therefore, IL18 BP is called a natural antagonist of IL18. 5. IL22 Interleukin-22 (IL22) is a member of the IL10 cytokine family discovered in recent years, originally known as IL10-related T cell differentiation induction factor (IL-TIF). IL22 was found to be highly expressed in a variety of malignant tumors of the digestive system, and the increased expression of it was associated with tumor progression and poor prognosis of patients. Interleukins are clinically used as indicators of the state of the immune system. It also acts as a cellular signal to regulate immune system function and treat immune diseases. The study of interleukins can deepen the understanding of physiological functions of human body, deepen the understanding of the occurrence and development of diseases, and deepen the understanding of the origin of life processes.
  3. Last week
  4. Definition of toxicology Toxicology is the science of studying the harmful effects of toxic substances on body and its mechanisms, outcomes, and hazards. It is mainly used for safety evaluation and risk assessment of exogenous substances. The tasks of drug toxicology include clinical toxicology, new drug clinical trials, and the task of drug epidemiology research. Its basic purpose is to understand and master the toxic effects of drugs, to provide a scientific basis for clinical safe medication and to avoid or mitigate the occurrence of these toxic effects in the course of medication. There are many types of toxic effects, including adverse drug reactions, side reactions, allergies, idiosyncratic reactions, and carcinogenicity. The importance of preclinical reproductive toxicology research for new drugs Preclinical safety evaluation is one of the key links in the development of new drugs. The main purpose is to determine the safety characteristics of drug candidates through evaluation, so as to provide experimental basis for further development. However, with the intensification of market competition and the rapid growth of investment in new drug research and development, the current routine safety evaluation methods are no longer sufficient. In addition, due to the increase in the number of new drugs, the country's requirements for drug safety are also gradually increasing. These phenomena suggest the necessity of preclinical toxicology studies (e.g., vaccine reproductive toxicology study). Preclinical drug toxicology is a new discipline that studies the toxic effects of drugs and its mechanisms, and evaluates the safety of new drugs, including acute toxicity, repeated drug toxicity, safety pharmacology, special toxicity (genotoxicity, reproductive toxicity, carcinogenicity), toxicokinetics and other research. The purpose of the study was to find the symptoms of the toxic reaction of the drug, the duration of the onset and the end, the dose level of non-toxic reaction, the safe range of the dose and the dose of the toxic reaction, the nature and reversibility of the toxic reaction, and the like. The information obtained by the Institute of Drug Toxicology is an important basis for ensuring the safe use of drugs by patients. Therefore, preclinical drug toxicology research is a very important part of the development of new drugs. What are the preclinical toxicology tests in vaccine development? A vaccine is a general term for a variety of biological products containing antigenic substances that can induce specific active immunity in the human body. In preclinical studies of new vaccines, it is important to examine the safety of vaccines by conducting preclinical safety assessments of relevant animals. The drug safety evaluation in the preclinical study of new drugs refers to the use of drugs larger than the clinical dose, or longer than the clinical use time, to find and evaluate the potential toxic effects, toxicity performance, and reversibility of target organ damage. This study helps to identify toxic doses, detect toxic effects, determine safe dose ranges, find toxic target organs, and determine the reversibility of toxicity. The difficulty in drug safety evaluation in preclinical studies of new vaccine drugs is that the vaccine itself does not directly exert its preventive or therapeutic effect, but acts by inducing the immune system to produce antibodies or activate T cells.
  5. Therapeutic antibodies have a broad development potential. According to relevant data, the market for therapeutic antibody drugs in the world can reach 320 billion US dollars by 2021. The therapeutic antibody drugs have huge market possibility. For innovative antibody research organizations and development enterprises, the success development of antibody drugs is an important goal, and a direction for antibody developers to work on. But where to start with for a successful development of antibody drugs? The first thing you might think of is the efficacy and side effects of antibody drugs. While as a medicine, unmet clinical needs are also an important factor that should be considered initially by antibody drug research and development companies and personnel. It is also the starting factor and the foothold of the development of therapeutic antibody drugs. How do we measure unmet clinical needs? In short, it can be summarized as the following two aspects: (1) There is currently no treatment for a certain disease; (2) The current curative effect is not satisfactory or there are side effects that some patients cannot tolerate for the drugs. Of course, the two aspects can be further refined, and the confirmation of true clinical needs is obtained through a large number of investigations and data analysis. In some extent, it is a huge innovation if antibody drug R&D companies can make differentiated products that truly satisfy and solve clinical needs. If so, it is more likely to be successful in the development of antibody drugs and in the commercialization of later stages. Whether it is a real clinical need is a comprehensive judgment by the first-line of doctors, patients and others. Some companies have not experienced the above interviews, research and analysis. Based on the investigation of individual doctors and data, they have determined that the products they develop can meet the clinical needs and solve practical problems. In fact, the conclusion is very unobjective. Why is this important? Because it is a directional problem for innovative pharmaceutical companies, including innovative antibody drug R&D companies. It involves subsequent project strategies and target selection. If the direction is wrong, it is like driving a car to a wrong destination. It is also difficult for the drug development to achieve the final value. The antibody drug development strategy analyzed above is to address unmet clinical needs, which is a strategic issue. Then how to achieve this goal? Make some differentiated antibody drugs is a tactical problem. After analyzing the FDA approved listing (more than 70 therapeutic antibody drugs) and hundreds of antibody drugs currently in the late stages of clinical development, we can find two important changes in the development: (1) The side effects of antibody drugs are controllable, and the functions and effects are continuously improved; (2) The continuous expansion of the target of monoclonal antibody action has expanded to new disease treatment areas and new indications. Therapeutic antibody drug R&D companies can develop differentiated products that can solve and meet actual clinical needs in the above two aspects. These two aspects are also the key factors to analyze the value of antibody drug R&D companies and related products. Generate Therapeutic Antibodies with support from the leading global biotech company—Creative Biolabs. From custom bioreagents to antibody drug developments, Creative Biolabs offers a comprehensive range of services to aid in basic and translational biomedical research as well pharmaceutical research & development.
  6. So many things to do, so little energy. If these words sound familiar to you, then you are not alone. “Let food be thy medicine, and medicine be thy food” There is truth in what Hippocrates, the “Father of Modern Medicine”, once said. Let what you eat be your medicine because if you choose healthy food, then you are already taking steps in protecting your body from ailments. In this busy world, there are so many things that demand your attention. However, there are times when you easily feel exhausted. Sometimes it does get too hard to deal with your things-to-do when you’re already tired in the middle of the day. That is why it would be good to make a habit of choosing to lead a healthy lifestyle that includes exercise and proper diet. Here are some of the healthier choices when you want to bulletproof yourself from sickness: Health Bars If you are living an on-the-go lifestyle, you really do not have much time to spend poring over recipe books and cooking up healthy food. As much as you’d want to, you simply do not have the luxury to leisurely eat at home. For those who have to usually dine and dash (or for those who just want to have a quick healthy snack), health bars are heaven-sent solutions. These quick energy foods provide a much-needed boost of power that helps keep you stay full and focused. For example, Bulletproof’s Fudge Brownie Collagen Protein Bars are made from carefully sourced ingredients that make this handy treat power-packed with protein. This versatile snack can also be a good ingredient in quick treats like a Fudge Brownie Berry Crumble. What’s more, it has collagen that helps in giving you smoother and more hydrated skin, stronger joints, and aids in faster recovery. These bars also contain quality fats like Brain Octane® which is a brain-powering, high-octane fat extracted from a coconut’s most potent parts. Other flavor choices are Choco Chip Cookie Dough, Vanilla Shortbread, and Lemon Cookie. There are also chocolate fuel bars that come in Original Dark and Himalayan Sea Salt. Cold Brews Some people cannot get on their day without having their cup of coffee. Hot or cold, they must have a cuppa to fuel the day ahead. Some prefer the convenience of cold brews, however, as there is no waiting to brew. Simply open and pour, and they get the daily dose of their power drink. However, unknown to many, good old coffee can also contain energy-sapping mold toxins. This robs you of mental agility, which is the opposite of what you need. With Bulletproof Coffee Cold Brews, you get clean coffee that has gone through small-batch brewing. The brewing process also uses triple-filtered water and low-temperature extraction so you can enjoy a smooth and bold drink with low acidity and almost no bitterness. Aside from containing Brain Octane® oil, this delicious cold brew also has butter sourced from grass-fed cows. It is rich in omega-3 fatty acids like ALA and EPA which are good for your heart, muscles, and other organs. They serve as building blocks for cell membranes as well as your body’s energy storage. It also has zero sugar so there’s no worry about having a sugar crash. Best drink when chilled, these cold brews come in dark chocolate, mocha, vanilla, vanilla latte, and original flavors. FATwater Water is said to be one of the best drinks you can take to hydrate your body. Bulletproof takes it a step further by coming up with FATwater, a refreshing drink that powers you up. When you want to have a cool, tasty, and refreshing thirst quencher, grab a bottle of grapefruit, lemon, or pineapple FATwater. This bottle of pure, deionized water has micro-droplets of Brain Octane® oil for fast energy production. It is easily absorbed by the body and is converted into a unique energy source called “ketone bodies”, that, unlike excess energy from most fuels, cannot be stored as fat. FATwater is also fortified with B vitamins, nutrients that support energy production at the cellular level. It is also sugar-free and has only 20 calories per bottle. Keep It Up With the responsibly sourced ingredients, nutrients, proteins, and healthy fats in these bars and beverages, you can eat and drink without feeling guilty. If you are pressed for time, keep in mind that there are handy snacks and drinks that can keep you fueled throughout the day. Even better, with all the healthy ingredients they contain, you can be confident that you are, indeed, bulletproof from sickness.
  7. If you run a business that needs a new location built or own a company that manages commercial construction projects, there are some ways that you can help ensure the work is done in the most ethical way possible. Sticking to a strong code of ethics throughout the construction project can be good for both you and the world around you. Here are four tips for ethical management of new company construction projects. Recycle Materials Many of the materials that are used in construction projects can be recycled. All too often, leftover materials that could have been recycled end up in the trash that goes to landfills and creates additional environmental hazards. Most types of plastics and metals are recyclable. Glass and wood can also be repurposed for future use. Another great way to show environmental responsibility is by purchasing construction materials that are made from recycled products. Hire Local-Based Labor Hiring locally instead of bringing in staff members from other cities, states or countries can be better for the local economy and provide more people with jobs. Hiring locally also makes it easier for you to find the most qualified and ethical staff members and run the appropriate background checks on them. Labor Works is just one of many staffing companies that can supply you with the employees you need to complete your construction project. Go Above and Beyond Safety Measures In addition to meeting the standard safety measures, you can put in more effort to ensure that everyone at the construction site stays safe. This includes providing extra safety for your construction workers along with any other employees who might be working at the site. A great way to learn about the proper safety measures that you should be taking and the extra things that you can do to keep everyone safe is to read the guidelines set forth by the Occupational Safety and Health Administration (OSHA). Use High-Quality, Low-Emission Machinery There are many types of construction machinery that emit low amounts of pollutants while still being excellent in quality. Other types of machinery often emit more pollutants that can diminish air quality and contribute to more harmful effects of greenhouse gases. Making sure that high-quality, low-emission machinery is used in your construction can help your business reduce its carbon footprint. Tractors, forklifts and generators are just a few types of construction machinery that come in low-emission models. Ethical construction management is possible with the right planning, equipment and staff. You’re sure to see many benefits when you maintain an ethical commercial construction project.
  8. Endothelial cells cover the inner surface of the blood vessel, and epithelial cells cover the inner surface of the internal organs. The epithelial cells also cover the outer surface of the human body. If a large number of epithelial cells are found in the urine during urine testing, it indicates a urinary tract infection. The endothelial cells and epithelial cells that make up the tissue are derived from the epithelium, but the two are different in location, structure, and function (as the table). In addition, both cells form the interface between the inner and outer environments. Endothelial cells are located "inside" the body, such as the interior of blood vessels, while epithelial cells are often described as covering the "outside" of the body, such as the outer layer of the skin (epidermis, epidermis). Comparison of endothelia cells and epithelial cells: Items Endothelial cells Epithelial Cells Location Endothelial cells form endothelium, a thin layer that covers the inner surface of the blood vessel. Briefly, the cells cling to the blood vessel wall. Therefore, the inner wall of the entire circulatory system is covered by endothelial cells. These cells form the interface between the blood vessel wall and the blood. They close to the inner surface of the heart. They are a thick layer of single cells. The epithelial cells that make up the epithelial tissue cover not only the outer surface of the body, but also the outer surface of all internal organs of the body. For example, the epidermis of the outermost layer of the skin is the epithelial cell. The skin on the surface is thus covered by epithelial cells, which provide a protection for the body. Epithelial cells also cover the surface of internal organs, such as the liver, stomach, intestines, lungs, urethra, bladder, and the like. In other words, epithelial cells cover the surface and internal tissues of the body. functions Endothelial cells covering the vessel wall regulate blood flow in the blood vessels, which release NO. NO is a vasodilator that promotes blood circulation and helps control blood pressure. Endothelial cells can also secrete a variety of proteins that cause blood disorders, but they also stop bleeding. The inside of the glomerulus contains endothelial cells, which act to filter blood. The epithelial cells that make up the skin protect the subcutaneous tissue from damage, bacterial intrusion, dangerous chemicals, and avoid excessive loss of moisture. When necessary, the skin's epithelial cells also secrete sweat to regulate body temperature. Epithelial cells covering the pancreas secrete enzymes to promote digestion. In addition, epithelial cells on the surface of the small intestine absorb nutrients from the digested food. Epithelial cells on the surface of the respiratory tract form mucous membranes that secrete mucus to prevent inhaled bacteria and viruses from entering the lungs. Specialized epithelial cells are secreted on organs that are in contact with nerve endings such as skin, nose, tongue, eyes, etc., which recognize sensory stimuli. In summary, the main functions of epithelial cells involve secretion, absorption, and protection. Features The endothelial cells that make up the endothelial tissue are monolayer structures, and water molecules and oxygen molecules easily pass through the endothelial cells and enter the tissues surrounding the endothelial cells. In addition, endothelial cells lack a packed epithelial morphology, and there are gaps between endothelial cells, which contribute to the passage of liquids and the diffusion of substances. The epithelial cells that make up the epithelial tissue have a variety of structures to protect the body from the external environment. Epithelial cells are tightly bound, similar to bricks, with few gaps between cells. Intermediate Filaments Some proteins, referred to herein as intermediate filaments, support the cells and form the shape of the cells. Simply speaking, the intermediate filaments provide the cellular structure. Endothelial cells contain vimentin filaments. Keratin filaments provide the structure of epithelial cells. Surface layer The surface of endothelial cells is a non-thrombogenic, soft surface that does not coagulate during normal blood circulation. Epithelial tissues composed of different types of epithelial cells exhibit irregular papillary projections. Schematic diagram of endothelial cells (Figure 1) and epithelial cells (Figure 2): Endothelium is a kind of epithelium. The endothelial cells are distributed on the inner surface of the blood vessels. In the lumen, the endothelial tissues form the interface between the circulatory system or the lymphatic system and other parts of the blood vessels. The structure is as follows: Figure 1. Schematic diagram of endothelial cells Figure 2 shows the morphology of epithelial cells. Epithelial cells can be arranged in a single layer of cell structure, or in two layers, or even a multi-layered cell structure. As shown in Figure 2, all glands are composed of epithelial cells. The function of epithelial cells includes secretion, absorption, protection, and transmembrane transport. Figure 2. Morphology of epithelial cells
  9. Earlier
  10. Are you using too much toothpaste?

    New research from the Centres for Disease Control and Prevention (CDC) in the United States has found children are using far too much toothpaste. The Australian Dental Association (ADA) agrees, saying less is more for both adults and children. So how much is too much and what are the risks? Here’s what the home doctor team at House Call Doctor recommends. What happens when you use too much toothpaste? If a child ingests too much toothpaste containing fluoride, a compound that helps strengthen teeth and prevent tooth decay, their risk of developing a dental condition known as dental fluorosis increases. "Fluoride in too higher concentration mixes with the other minerals that are trying to develop in our teeth. We have multiple minerals that make up our teeth and it basically changes the ratios," Senior Vice-President of the Australian Dental Association Queensland, Norah Ayad said. Fluorosis can cause a chemical imbalance which causes teeth to become stained or discoloured, and in severe cases, affect the quality of their surface. "Because the mineral content of the teeth is changing, it can make the surface of the teeth not as smooth," Mr Ayad said. "It's much easier to brush and clean a smooth surface — things are going to wipe off it easier — compared to a really rough and raggedy surface which is what you get with quite severe fluorosis." So how much toothpaste should I use? While most people will squeeze a ribbon of toothpaste along the length of their brush, experts say that adults only need one, pea-sized blob of fluoridated toothpaste when brushing. "I think the reason we're used to smearing the length of the toothbrush is advertising from the companies," Mr Ayad said. "[As adults], it's not going to cause any damage because our teeth are already developed, it's just going to waste toothpaste."
  11. From the medical point of view, extract are generally divided into plant extract (including herbal extract), animal extract. In general, the extracts we talk about can be understood as plant extract, herbal extract and animal extract. Animal extracts are extracted from animal bodies, some animal tissues or organs by mild enzymatic hydrolysis or boiling, then concentrated and dried by spray to become meat extracts. It is a new industry corresponding to plant extracts. Formerly commonly referred to as biochemical products, biochemical API. Its main categories are: amino acid, peptide, protein, enzyme and coenzyme, polysaccharide, lipid, nucleic acids and their derivatives. The biggest characteristic is that it can dissolve into water. Here we will introduce two promising animal extracts below: 1. Carboxypeptidase Carboxypeptidases (CPs) are exopeptidases that degrade and release free amino acids one by one from the C end of the peptide chain. Commonly used are A, B, C and Y, 4 kinds of carboxypeptidase. Carboxypeptidase exists in the organism in the form of proenzyme and plays an important physiological function in the tissues and organs of animals and plants. Carboxypeptidase A and B are digestive enzymes, such as pancreatic carboxypeptidase A and B can be used to digest food. In addition, carboxypeptidase y(CPC) can act on any c-terminal residue, carboxypeptidase M(CPM) selectively participates in peptide hormone processing, carboxypeptidase D(CPD) and carboxypeptidase N(CPN) participate in peptide and protein processing, etc. Carboxypeptidase is widely used in medicine, food and other industrial fields. In the field of medicine, since carboxypeptidase is widely involved in the biochemical reactions of the body, the detection of carboxypeptidase in the body can achieve the purpose of diagnosis and treatment of diseases. In addition, it can also be used for the degradation of undesirable substances (toxins, etc.) in the body. In the food industry, it can be used to prepare oligopeptides with high F value, remove ochratoxin from food and feed, and be used as a bitter reliever. In the field of biotechnology, carboxypeptidase can be used for the synthesis of polypeptides and the determination of polypeptide amino acid sequence. It can also be used as a model enzyme to help the research of other enzymes. The carboxypeptidase of animal origin mainly exists in the pancreas of pigs and cows, such as carboxypeptidase A/B, whose quantity is very limited and the price is very high, resulting in its limited application. Carboxypeptidase from microorganism exists in the vacuoles of yeast, aspergillus and other fungi, and has broad application prospect. Therefore, with the help of genetic engineering strategy, recombinant carboxypeptidase can be produced in large quantities with microorganism as the host, which is expected to overcome the limitations of animal and plant raw material sources encountered in the production process of carboxypeptidase, so as to further reduce the production cost, improve product quality, deepen the study of enzymatic properties and expand the application range. 2. Hyaluronidase Hyaluronidase is a kind of enzyme that can degrade hyaluronic acid. It is widely distributed in nature and exists in mammals, insects, leeches and bacteria. In recent years, the research on hyaluronidase has been increasing gradually, and its application in medicine, plastic surgery and other fields has attracted people's attention. Hyaluronidase was first discovered in 1928, when extracts from testicles and other tissues were discovered to act as a "diffusive factor" by promoting the penetration of other harmful venom components and enhancing their immobility in the bloodstream. Hyaluronidase from different sources has some differences, but since its discovery, it has gradually gained people's attention and has been widely used in medicine and other fields. Based on this, the properties of hyaluronidase and other related research has become a field worthy of attention. It is widely distributed in various vertebrates (their testicles, animal venom, etc.) and invertebrates (insects, leeches, duodenal worms, etc.). It also exists in microorganisms (streptomyces, staphylococcus, clostridium, etc.). It has different substrate specificity, a wide range of pH values, different catalytic mechanisms and a variety of functions. Although much work has been done in this area, much remains to be done in the field of enzymology, particularly three-dimensional structures, site-directed mutants and enzymatic kinetics, to enhance understanding of binding sites, substrate recognition and catalytic mechanisms. Cloning more recombinases can determine the classification and association of these hyaluronidases. Further study the structure of purified hyaluronidase substrate to improve the understanding of the synergism of the enzyme. There are many unanswered questions regarding the regulation of expression, including complete gene sequences, the degree of regulatory coordination and the molecular mechanisms underlying the response to putative inducers. With the deepening of research, the characteristics of hyaluronidase from different sources have been gradually explored, which provides a new approach and theoretical basis for the prevention and treatment of hyaluronidase-related diseases.
  12. People are rapidly becoming more environmentally conscious, and most want to see that reflected in the businesses with which they choose to work. If you run a construction business, it's wise from both an environmental and business standpoint to look into ways to become more eco-friendly. Below are a handful of changes you can make that will have a positive impact on the environment. Recycle Your Materials Your first step in becoming eco-friendly has to do not with what you will use, but with what you've already used. Take a look at what you've got left after a job and then determine the best way to deal with that material. In some cases, you can hold onto it and use it for another job. In others, a trip down to the scrap yard or recycling center might be more environmentally friendly. The goal is to avoid throwing away anything that can be reused. Use Recycled Products There are plenty of other companies that are working just as hard as you to be eco-friendly, so why not contribute by using their recycled products? Reclaimed wood, recycled construction materials, and even second-hand materials can be just as good as buying new but they have far less of an environmental impact. Whenever safety and budget allow, make sure that you use recycled materials in your projects. Go Energy Efficient The equipment you use can be a major cause of environmental damage, so take some time to figure out how to reduce that impact. Using equipment that is more energy friendly is great for the environment and it can actually save you money over the course of several jobs. While you might need to make an investment in new, more efficient tools, you'll end up saving money once you look at how much your fuel costs have dropped. Consult an Expert Environmental engineers will not only be able to give you a better idea of the environmental impact of your current projects, but they can also help you to figure out ways to be more eco-friendly with future builds. Taking some time to look for environmental consulting can help you to ensure that your plans for environmental responsibility get a professional seal of approval. Becoming more ecologically friendly means taking some time to examine your current practices and to figure out what needs to be changed. Adapt where you can, but don't be afraid to try something entirely new if that will make an impact. If you're willing to make radical changes, you can do your part to help the environment.
  13. immunodiagnosis, an important component of in vitro diagnosis, is used for the diagnosis of various diseases and the determination of immune status. In medicine, it is an important method to determine the cause of disease and lesion site, or to determine whether the immune status of the body is normal. In addition, it is also used in forensic blood stain identification, biochemical serum composition identification and research of species evolution. In addition, it has also been used in forensic medicine for the identification of blood stains, the identification of biochemical serum components and the study of species evolution, etc., which can be carried out in vivo and in vitro. Immunodiagnostic reagents are the most widely used in diagnostic kits and are widely used in hospitals, blood stations and physical examination centers. They are mainly used for hepatitis detection, venereal disease detection, tumor detection and pregnancy detection. Among them, immunodiagnosis includes radioimmunoassay, enzyme-linked immunoassay, chemiluminescence, etc. Enzyme-linked immunity: ELISA has the advantages of low cost and large-scale operation. Meanwhile chemiluminescence immunoassay: CLIA has the advantages of sensitive, rapid, stable, selective, reproducible, easy to operate, flexible and diverse methods. In medicine, it is an important method to determine the cause of disease and lesion site, or to determine whether the immune status of the body is normal. Western blot theory is a hybridization technique that combines high-resolution gel electrophoresis with immunodiagnostic methods. Western blotting is also called enzyme linked immunoelectrotransfer blot (EITB) It has the advantages of high capacity, high sensitivity and high specificity, and is the most commonly used method for the detection of protein characteristics, expression and distribution, such as qualitative and quantitative detection of tissue antigens, mass determination of polypeptide molecules and antibody or antigen detection of viruses, etc. Ria (radioimmunoassay) is a method to study the occurrence, development and transformation of the body's reaction to antigens by competitive inhibition reaction between isotopically labeled and unlabeled antigens. Radioimmunoassay involves two techniques: the first is biological. It USES the response of specific antibodies to identify a given organic substance; The second is physics. It introduces radioactive atoms into organic matter and marks them. It can measure almost any substance in the organism, including various hormones secreted by the organism itself, various drugs taken orally or injected by the patient, some virus antigens, etc., and has been widely used in clinical routine tests. Latex enhanced immunoturbidimetric assay is a method based on the immunological precipitation reaction principle. Its basic principle is to combine the substance to be tested (antigen) in the sample with the human IgG(antibody) coated on polystyrene particles in the reagent to form insoluble immune complex. Compared with the traditional turbidimetric method, the turbidity of the immune complex is further amplified due to the coated polystyrene particles, which overcomes the disadvantage that it is difficult to form turbidity when the amount of antigen-antibody complex is small, improves the sensitivity of detection, meets the requirements of rapid reaction and micro quantization, and is suitable for automatic biochemical instrument detection. Latex immunoassay is not only simple and rapid, but also can be automated, suitable for batch detection, and the reagent cost is relatively low, is one of the best choice of laboratories with automatic biochemical instrument to carry out PCT detection, has a wide range of application prospects. Lateral flow test principle is in the 1990 s in monoclonal antibody technology, colloidal gold immune chromatography technology and new materials technology developed on the basis of a new type of in vitro diagnostic technology, is fast, simple, single copy detection and economic advantages, has been widely used in medical tests, food quality monitoring, environmental monitoring, agriculture and animal husbandry, entry-exit inspection and quarantine, forensic finalized and other fields. With the rapid development of immune detection technology, quantitative, high-sensitivity, multivariate detection and system integration have become a new research focus in the field of IVD. Compared with traditional ELISA and colloidal gold qualitative lateral chromatography, lateral flow test has many advantages, such as good stability, wide linear range and high sensitivity. Immunological detection method is a series of experimental methods for the determination of antigens, antibodies and immune cells. With the interdisciplinary infiltration, the scope of immunology is expanding, and new immunological detection methods are emerging one after another. The application of IVD assay is also expanding, which not only becomes an important method for the diagnosis of a variety of clinical diseases, but also will continue to provide convenience for the research of many disciplines.
  14. There is a large demand for Chinese goods especially in the electronics sector and one can find many options when it comes to choosing the right dropship Chinese wholesaler for obtaining these goods. From digital devices like cameras, picture frames and watches to audio and video systems, solar gadgets, and appliances related to health and lifestyle, a dropship Chinese wholesaler can be the one stop shop to get everything at very reasonable prices. A dropship Chinese wholesaler usually ensures shipping of the goods within 3 -5 days and the delivery is through UPS, DHL or EMS. These dealers like BigBoxStore and Ownta, are secure and certified dealers. Such dealers will have most of the personal information of the consumer and it is good to check if they are PayPal verified sites with SSL encryption. The other advantage in buying goods from a dropship Chinese wholesaler is the customer service, which is usually available round the clock. The dealers also give warranty for their goods which in sometimes is coupled with the product company's extended warranty. The dealers for the sake of their own business ensure that the customer gets to know the best prices for various stock like cell phones, dvd players etc. Unlike most wholesale stores, one can get good prices even when they buy in small quantities from a dropship Chinese wholesaler. The dropship Chinese wholesaler would package the goods at attractive prices and usually for the sake of reputation ensures that they are not damaged. Many sites like Chinavasion offer products with a 12 month warranty which is a decent time period to test the quality of a product. The sites are also advanced and give the customer a real-time peek into the supplies, so customers do not have to go through the disappointment of trying to book an article only to know later that the stock is not available. Importers also do not have to worry about the paper work and clearance required for the items as it is usually taken care of by the courier companies most of the times. As a dropship Chinese wholesaler deals in constant shipping of goods, one can ensure the best prices in shipping which sometimes might not be charged on the customers at all. This comes as stark contrast to buying from individual stores where customers usually pay the shipping charges which could be substantial if you are from a different part of the globe altogether. Import Express is a wholesale online site from China. Find cheap import products at wholesale price, including Clothing, Mobile Phone, Computers, Jewelry, Beauty, Sports, Home decor and so on, Shopping on Import-express For Small Businesses now. Import Express is supposed to be the first priority for new comers. They have global reach servicing customers in more than over 200 countries. Import Express, a B2B based wholesale website. Since 2005, Import express has played a critical role in helping more retailers grow faster around the world. As an experienced end-to-end wholesale solution company, Import-express provides professional wholesale and drop ship service. The website continue to provide high-quality wholesale business service that empowers retailers to do more business all over the world. It offers full catalogs, including children's boutique clothing, sunglasses, shoes, clothes, jewelry and accessories, beauty, 3C products, household necessaries and so on that totally more than 500,000+ SKU. Also, new and trendy arrivals added every day. See More:Wholesale Clothing from China, Wholesale Children's Clothing, Wholesale Shoes China, Wholesale Pet Supplies Business Benefits for Customers: 1). Ideal for small business---Low minimum order & lower price 2). Combine Shipping---( We collect all products you buy from China in one box then ship it to you!) Save shipping cost from China 3). One-Stop Business Services---Quality testing before shipping 4). 40$ coupons for the new users 5). Up to 20% OFF
  15. Ah, summer. The sky is blue and bright, the days are longer, the grass is higher, and everyone wants to spend all their time outside. With this kind of summer fever in the air, it’s hard to keep your kiddos from getting covered in bug bites of every kind, and even more so if you’re worried about the chemicals they might be running into. If you want to keep your babies bug and chemical free, these tips are for you. Smell Ya Later Don’t like strong smells? Neither do mosquitos. Fortunately, the scents that mosquitos and other bugs dislike tend to be ones that are alright for us human beings. Scents like lemon eucalyptus, citronella, and lemongrass are huge no-no’s for insects, and if those aren’t for you either, you can always go for something like grapefruit, clove, or even peppermint. You can even look into garage door repair if you want. Find a skin-safe product or look around for baby-safe items that include these scents and oils. It’s Lit If you’re having a little trouble keeping baby still long enough to get covered in anti-bug ointment, there are other alternatives. Take the time to light a citronella candle, especially when you’re in a space small enough that it’ll keep the bugs away, or break out the incense to burn and ward them off. For those of you with tiki torches, there’s citronella fuel available to fill those with, too. Keep an eye out for all of your options. Plant it Baby Want to stop the bugs at the garden gate? Rearrange some of your plantings this season to include useful greenery that keeps the bugs at bay. Some common kitchen herbs, like basil and rosemary, can put the kibosh on mosquitos before they bite, while sweet scented ones like rosemary and mint keep other biting bugs far away. Designing your garden with potential bad bugs in mind can help you seriously cut down on the number of bug bites you’ll need to treat over the course of an average summer day. While we might have our beefs with nature on certain points—like bee stings, bug bites, and the entire general concept of mosquitos—the more natural we can keep things, the better it is for our kids. In this case, the little things can add up to big benefits. You can easily combine some oil of lemon eucalyptus on exposed skin with a bed of geraniums and a citronella candle to cover as many bases as possible, or change up the items you use to keep your kids safe in a scent-sensitive way. Have a good summer.
  16. Ah, summer. The sky is blue and bright, the days are longer, the grass is higher, and everyone wants to spend all their time outside. With this kind of summer fever in the air, it’s hard to keep your kiddos from getting covered in bug bites of every kind, and even more so if you’re worried about the chemicals they might be running into. If you want to keep your babies bug and chemical free, these tips are for you. Smell Ya Later Don’t like strong smells? Neither do mosquitos. Fortunately, the scents that mosquitos and other bugs dislike tend to be ones that are alright for us human beings. Scents like lemon eucalyptus, citronella, and lemongrass are huge no-no’s for insects, and if those aren’t for you either, you can always go for something like grapefruit, clove, or even peppermint. You can even look into garage door repair if you want. Find a skin-safe product or look around for baby-safe items that include these scents and oils. It’s Lit If you’re having a little trouble keeping baby still long enough to get covered in anti-bug ointment, there are other alternatives. Take the time to light a citronella candle, especially when you’re in a space small enough that it’ll keep the bugs away, or break out the incense to burn and ward them off. For those of you with tiki torches, there’s citronella fuel available to fill those with, too. Keep an eye out for all of your options. Plant it Baby Want to stop the bugs at the garden gate? Rearrange some of your plantings this season to include useful greenery that keeps the bugs at bay. Some common kitchen herbs, like basil and rosemary, can put the kibosh on mosquitos before they bite, while sweet scented ones like rosemary and mint keep other biting bugs far away. Designing your garden with potential bad bugs in mind can help you seriously cut down on the number of bug bites you’ll need to treat over the course of an average summer day. While we might have our beefs with nature on certain points—like bee stings, bug bites, and the entire general concept of mosquitos—the more natural we can keep things, the better it is for our kids. In this case, the little things can add up to big benefits. You can easily combine some oil of lemon eucalyptus on exposed skin with a bed of geraniums and a citronella candle to cover as many bases as possible, or change up the items you use to keep your kids safe in a scent-sensitive way. Have a good summer.
  17. There are so many businesses around the United States and planet that, simply put, do not take green and eco-friendly approaches to going about things. If that fact upsets you, then you can go ahead and take action. You can do so by being a positive role model to all of these wasteful and unmindful businesses. Remember, your aim should be to get others to do the right thing. Conserve Energy Any Time You Can Energy conservation can do a lot for people who care about green approaches. If you want to conserve invaluable energy, there are all sorts of things you can daily. You can employ light bulbs that do not consume substantial amounts of energy. You can depend on decreased laundry temperatures. You can even turn off your television any time you’re not sitting directly in front of it. Learn about Carbon Taxes and other Benefits Learning can be a powerful tool for people who want to be role models to companies that aren’t exactly savvy in the eco-friendly sector. You should learn about carbon taxes that apply to vehicle fossil fuels. These kinds of taxes strive to decrease emissions of greenhouse gases. They promote alternative energy choices as well. Carbon tax benefits abound if you know how to look for them. Focus on Your Water Consumption People who care about the planet should not use water mindlessly. If you want to get American businesses to do their part to aid the planet and environment, then you should try to think at length about your household and its water consumption. Employ short cycling any time you take on your laundry duties. Prioritize showers that are on the brief side. Take care of annoying household leaks without any hesitation, too. Leak water can get out of hand before you know it. Make Carpooling a Priority Gasoline consumption isn’t ever a laughing matter. If you want to prompt businesses in America to take on green methods, then you should aim to carpool any time the option is accessible to you. Try to carpool with people who work with you each morning. Try to carpool with them on the way back from work in the evenings as well. There are so many companies in America and around the globe that aren’t exactly environmentally-friendly. If you want to change that permanently, then you need to take action and lead a green existence yourself. You can do so pretty easily nowadays, too.
  18. With awareness increasing around the topic of sustainability, more organizations have appeared that are focused on green practices. If you are currently thinking about opening your own business, one that benefits from eco-friendly characteristics, the main issue that is probably holding you back is lack of capital. Getting the necessary funding isn’t an easy process, considering you are competing against numerous other entrepreneurs with the same financial needs. If you believe you have a solid business plan, and your business idea could appeal to others, you should start revising your funding options. You have a leaping advantage from the start, green businesses becoming more appealing in recent years, with the rise of sustainable actions on a global scale. Here are some of the ways you might be able to get capital: Governmental grants You should first start by looking into how the government supports sustainable organizations. In various countries, eco-friendly business ideas are backed up by the state through different forms of grants. The amount can vary here, and so do eligibility requirements. Funding programs designed for green initiatives are available, and depending on the specifics of your business concept, applying for one could provide you with your wanted results. Do some research, and see how the government can assist you in getting your green business on its feet. Crowdfunding When federal funding isn’t an option – perhaps you don’t qualify for it – you’ll need to explore other solutions. One of the options that have become quite popular in recent years, and a method used by many entrepreneurs to enter the business world is crowdfunding. Crowdfunding gives you the chance to raise capital (usually a limited amount) with financial support from different individuals. Almost any business can be eligible for this type of funding, as long as the guidelines of the said crowdfunding platform. The reason why this is an option worth your attention is that in recent years, people have become more eager to encourage green initiatives. If you are able to highlight the eco-friendly nature of your future organization, you are likely to gather your needed capital mount rapidly. There are several crowdfunding platforms out there, each coming with its own set of requirements and benefits. It’S up to you choose GoFundMe, Kickstarter or Indiegogo. Remember that usually, people will contribute to strong projects, projects they are actually passionate about, so you need to perfect your pitch and have an excellent presentation for your business plan. Get in contact with investors Drawing the interest of investors is another option worth your thought. Private funding can work great in various situations, and if you are willing to share the stocks of your organization, this possibility can be advantageous from various points of view. Investors are always on the hunt for a great opportunity, and those who are showing an interest in green initiatives themselves, will likely take your proposition into account. Private equity investors or peer-to-peer investors aren’t our only choices here. You can access the necessary funding from anyone who has the net worth and income required to help you, and wishes to see your concept brought to life. Successful Forex market investors, stock investors, angel investors – the list of possibilities isn’t at all limited, you just need to get in touch with someone who actually wants and has the finances to support you. Online lending platforms Society’s digitalization has come with quite a lot of appealing prospects. Getting a hold of a certain amount of money, with minimal requirements involved, is possible nowadays through online lending platforms. This is an easy solution if you only require a small amount of money, are able to return it short-term. If you have already self-funded your business, and just need a bit of extra support until getting your business on track, you should research this particular option more and find out what requirement you have to meet. Contests Last but not least, you should look into contest funds. Although not as easy to access as the other options above-mentioned, entering a funding contest is worth a shot. This way of raising capital for green businesses has been developed from the desire of increasing the number of sustainable businesses. More entrepreneurs have worked towards developing green startup concepts instead of traditional business formats due to the monetary appeal of this type of funding possibility. The competition is of course steep, so you shouldn’t make this your primary choice. However, if you have an innovative idea in mind, and can support it accordingly, you do have a chance at winning. If you have a great green business concept you would want to bring into the market, but you currently lack the necessary capital, discovering the right means of funding becomes a priority. Options are several, you just need to find one that works best for your situation. The solutions found here should be explored first.
  19. If you have decided to remodel your house, you probably know that a shift is taking place in the remodelling industry. Eco-friendly renovations were too expensive in the past, for homeowners to consider them an option, but nowadays they come at a more affordable price, so they’ve become a trend. Green remodelling is not a trend only because the cost of the project is more affordable, but also because nowadays homeowners are more concerned with the way they affect the planet. By deciding to remodel your house, you have already chosen the sustainable solution. Building a house from scratch would require using new resources, but remodelling implies reusing some of the materials you already have in your house. So your big question may be how do you make an eco-friendly house happen? Here are our suggestions. Reuse as much as possible An essential part of living sustainably recycling. The entire purpose of the remodelling project is to purchase as few things as possible, and to repurpose the materials and items you already have. It will serve the planet by reducing the emissions during the manufacturing and transportation processes, and it will save natural resources from being used to create new items. If you have to buy some new items, make sure you purchase eco-friendly ones because they are more effective and durable in contrast with the standard ones. Choose sustainable materials If this is your first remodelling project, you may find challengeable to choose materials. You need to know what you are looking for before visiting the local store. Because there are no regulations around the terms sustainable, organic or natural, you may have difficulties in identifying the right material. Also, you should keep in mind that not all green products are designed equally, certain certifications state the level of sustainability every material and item has. The golden rule when choosing materials is to buy the ones that don’t emit toxic chemicals into the air. Stay away from the ones that contain voltaic organic compounds because they are causing long-term health issues. Natural products have a longer life than synthetic ones. Let’s take the example of a rug, the same model made from wool will last 50 years longer than the ones made from synthetic fibres. Granite is a top choice when remodelling kitchens, it can last for generations. Update to environmentally-safe windows When the windows are taking a toll on your air and heating systems, it’s the moment to replace them with new ones. Search the market for energy-efficient ones made from sustainably sourced materials. For example, UPVC is a popular choice because it’s an energy efficient material, and it’s obtained during a process that doesn’t cause toxins release. Here are some pieces of advice if you don’t know how to choose high-quality windows. - Steel and aluminium windows are inefficient even if they are made from recyclable materials. - Double and triple-pane glass windows are more expensive than other models but they provide better insulation. - Fiberglass window frames are a green choice because they are made from sand, a limitless resource. - Wooden frames are also a green solution if you buy them from a manufacturer that harvests the material from a sustainable forest. Go solar You should use the power of the sun in your advantage, it’s one of the few renewable sources of energy humans can use to transform their homes into green sanctuaries. You can install solar panels to collect the power of the sun and to generate electricity. By making this choice, you will have lower electricity bills and you will help the planet save energy. It will also reduce your carbon footprint because there’s nothing in the power of the sun that can pollute the environment. Your energy system will not release greenhouse gases, it will only need a source of clean water to operate. Install bamboo flooring Many people ask themselves what makes bamboo a better choice than other types of materials. Well, it’s more durable, it grows faster than other types of wood, it’s moisture resistant, and fewer pesticides are required to grow it. Bamboo can be harvested without harming or destroying its roots, it’s a greener option in comparison with wood. By installing bamboo flooring you save the trees that can grow into forests that provide oxygen for people to breathe cleaner air. Buy used household items Just because you want to change the way your house looks, it doesn’t mean you have to buy only new and shiny things. Pre-owned items can make your house as stylish and comfortable as new ones. You should visit second-hand and antique shops, and check the items that seem to have a good condition. Many of them have a rustic look that makes your house feel cosier and welcoming. And where do you count that you can save money this way?
  20. Introduction Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis worldwide; with an estimated 35,000 to 50,000 cases and 10,000 deaths annually. Approximately 25% of encephalitis patients die while about 50% of the survivors develop permanent neurologic and/or psychiatric sequelae, including memory loss, impaired cognition, behavioral disturbances, convulsions, motor weakness or paralysis, and abnormalities of tone and coordination. The virus is a member of the JE serogroup of the genus Flavivirus, family Flaviviridae, and is transmitted between vertebrate hosts by mosquitoes, principally by Culex tritaeniorhynchus. Flaviviruses are known to cause many diseases in humans. Japanese encephalitis virus (JEV), West Nile Virus (WNV), Dengue Virus (DENV), Yellow Fever Virus (YFV) and Zika Virus (ZIKV) are the most common flaviviral infections. Japanese encephalitis was recognized in horses and humans as early as 1871. In 1924 a severe epidemic was reported from Japan. In 1934, Hyashi reproduced the disease in monkey by intra-cerebral inoculation. In 1935, JE virus was isolated from human brain in Tokyo, Japan, and its virological and serological prototype, Nakayama strain, was established. Five genotypes of JEV are known at present. Different genotypes of JEV (associated with different virulence patterns) thrive in a particular climatic condition: genotypes IV (the oldest) and V are isolated in the tropical endemic region of Indonesia–Malaysia, whereas genotypes III and I are found in the epidemic region. Signs and Symptoms Most JEV infections are mild (fever and headache) or without apparent symptoms, but approximately 1 in 250 infections results in severe clinical illness. Severe disease is characterized by rapid onset of high fever, headache, neck stiffness, disorientation, coma, seizures, spastic paralysis and ultimately death (Figure 1). The case-fatality rate can be as high as 30% among those with disease symptoms. Of those who survive, 20%–30% suffer permanent intellectual, behavioural or neurological problems such as paralysis, recurrent seizures or the inability to speak. Figure 1. Common symptoms of Japanese encephalitis. The incubation period of JEV is about 10-15 days. Most of the infected patients have no symptom or mild symptom, only a few with central nervous system symptoms, such as high fever, headache, cachexia, disturbance of consciousness and convulsions, etc. The manifestation can be divided into four levels according to the severity of the disease: a. Mild symptoms. Patients remain conscious, but with cachexia in different degrees. Usually with no convulsions except several child patient caused by high fever. The temperature of the patient could between 38~39℃. Most mild symptom patient recovery within one week. The infection usually needs CSF or serological test to confirm. b. Common symptoms. Patients with conscious disturbance such as lethargy or mild coma, abdominal reflex and cremasteric reflex disappearing, may have sort term convulsion. The temperature of the patient could be about 40℃ last for 10 day, no sequela. c. Severe symptom. The temperature keep above 40℃, patients become unconscious and with repeated or continuous convulsion. Usually have localizing symptom and sign. Central respiratory failure could also appear. The progress could last for more than two weeks. Patients could have mental disorder and paralysis among recovery phase, some would have sequela after recovery. d. Burst symptom. The temperature rising quickly, patient become high or over fever, and with repeated or continuous strong convulsion. Could be die due to the respiratory failure if not rescue in time. Survival usually suffer serious sequela. Viral Structure JEV is an enveloped virus about 50 nm in diameter with a single stranded (ss), plus sense, RNA genome of ~11 kb in length. The genome is organized into a capsid formed by multiple copies of capsid C protein; which is covered by a host derived lipid bilayer. The genome has one open reading frame (ORF) encoding for a single polyprotein, which is cleaved into 3 structural proteins e capsid C, precursor to membrane (prM), envelope E and 7 non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5, by viral proteases and host signalases, post translationally. C protein has w120 amino acids and forms homodimers. It is involved in packaging of the viral genome and formation of the nucleocapsid. prM (~165 aa) and E (~495 aa) are glycoproteins having two transmembrane helices. They are released from the nascent polyprotein following co-translational cleavage by signal peptidases. In the immature virions, prM protein might serve as a chaperone for folding and assembly of the E protein. The prM gets cleaved by cellular furin-like protease to form M (~75 aa) and the protein peptide during the maturation of the flaviviruses in the Golgi complex. Ninety homodimers of E protein present in the host derived lipid bilayer form the major mature virion component. The E protein is the main target of neutralizing antibodies and contains a cellular receptor-binding site(s) and a fusion peptide. Figure 2. Viral structure of Japanese encephalitis virus. The viral particle (A), the E protein structure (B) and the cross-section profile of JEV (C). Diagnosis, Treatment and Prevention Diagnosis: Individuals who live in or have travelled to a JE-endemic area and experience encephalitis are considered a suspected JE case. To confirm JEV infection and to rule out other causes of encephalitis requires a laboratory testing of serum or, preferentially, cerebrospinal fluid. Surveillance of the disease is mostly syndromic for acute encephalitis. Laboratory diagnosis of JE is generally accomplished by testing of serum or cerebrospinal fluid (CSF) to detect virus-specific IgM antibodies. JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed. In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of autopsy tissues can also be useful. Treatment: There is no antiviral treatment for patients with JE. Treatment is supportive to relieve symptoms and stabilize the patient. Prevention: Safe and effective JE vaccines are available to prevent disease. There are 4 main types of JE vaccines currently in use: inactivated mouse brain-derived vaccines, inactivated Vero cell-derived vaccines, live attenuated vaccines, and live recombinant vaccines. Over the past years, the live attenuated SA14-14-2 vaccine manufactured in China has become the most widely used vaccine in endemic countries, and it was prequalified by WHO in October 2013. All travelers to Japanese encephalitis-endemic areas should take precautions to avoid mosquito bites to reduce the risk for JE. Personal preventive measures include the use of repellents, long-sleeved clothes, coils and vaporizers. Travelers spending extensive time in JE endemic areas are recommended to get vaccinated. Article source: References: 1. Misra U K, Kalita J. Overview: japanese encephalitis[J]. Progress in neurobiology, 2010, 91(2): 108-120. 2. Johri; Sunit K. Singh S. Japanese encephalitis virus: from genome to infectome[J]. Microbes and Infection, 2011 (4). 3. Solomon T, Ni H, Beasley D W C, et al. Origin and evolution of Japanese encephalitis virus in southeast Asia[J]. Journal of virology, 2003, 77(5): 3091-3098. 4. Luca V C, AbiMansour J, Nelson C A, et al. Crystal structure of the Japanese encephalitis virus envelope protein[J]. Journal of virology, 2012, 86(4): 2337-2346. 5. Ghosh D, Basu A. Japanese encephalitis—a pathological and clinical perspective[J]. PLoS negl trop dis, 2009, 3(9): e437.
  21. Antibody-drug conjugates (ADCs) consist of recombinant monoclonal antibodies (mAbs) that are covalently bound to cytotoxic chemicals (called warheads) through synthetic linkers. ADCs not only have the anti-tumor efficacy of highly cytotoxic small molecule drugs, but also combine the high selectivity, stability and favorable pharmacokinetic characteristics of the mAb. In this article, the selection of antigen targets in ADC development, the warheads used in ADCs in clinical stages, the design and optimization of linkers, antibody selection and optimization, site-specific and alternative conjugate chemistry, and strategies to enhance potency are discussed. Non-oncology ADCs are also included. Antigen target selection A major problem in the development of cancer ADCs is the identification and validation of sufficient antigenic targets for the mAb. Several factors need to be considered in antigen selection. First, an ideal antigen of interest has a high level of expression in a tumor, but little or no expression in normal tissues, or at least expression is limited to a given tissue type to reduce ADC target toxicity and result in an acceptable therapeutic index. Second, the target antigen should be present on the cell surface so that circulating mAbs can enter. Third, the target antigen should be an intrinsic antigen, so that after binding, the ADC is transported into the cell, and the cytotoxic agent can exert its function. However, non-internal ADCs may show significant toxicity in some cases and often cause a strong "bystander effect." Future designs should consider the relative role of cytotoxic drugs and antibodies in the antitumor activity and toxicity profile of the entire ADC. Warhead for clinical ADC ADCs currently undergoing clinical trials, most targeting DNA or microtubules, have been efficiently optimized. Since the number of antigens on the surface of tumor cells is limited (about 5,000-106 antigens per cell) and the average drug-to-antibody ratio (DAR) of ADC is limited to 3.5-4, that is, the amount of ADC transferred to tumor cells is very low, and the cells that are combined with cell toxicity may cause clinical failure. Auristatin and maytansin, which act by inhibiting tubulin assembly, are the most commonly used warheads for ADCs today. Other warheads used are based on pyrrolobenzoquinazoline (PBD), dihydroindolothiazepine, Tubulysins, calicheamicin, irinotecan derivatives, docamomycin, camptothecin analog, adrenaline and doxorubicin and so on. In fact, due to fierce competition, more and more ADCs in early clinical trial studies did not disclose the chemical structure of antigen targets and/or warheads and linkers. Linker design and optimization Premature release of the drug in the circulation can lead to systemic toxicity and lower therapeutic indicators. An effective linker design must balance good stability over a few days in the cycle as well as efficient lysis when delivered to target cells. To enhance the solubility and DAR of ADCs and overcome the resistance induced by extracellular proteins (such as MDR1) delivered by chemotherapeutic agents, several strategies are being investigated: conditional release of drugs in the cytoplasm of target cells (removable and non-removable cleavage of the linker); the enhancement and limitation of the bypass effect is achieved by the ability to cross the biofilm-linker-drug metabolite; the polar linker increases solubility and reduces MDR. Antibody selection and optimization Both antibody and ADC are forced to increase the homogeneity and developability of the antibody to reduce the rate of drug loss. Analytical techniques such as liquid chromatography, electrophoresis and mass spectrometry not only help to select clones of the best antibodies with suitable glycosylation characteristics, but also for the comprehensive structural identification of research fields and potential clinical candidates, as well as for identification "Hot spots" on antibodies that are detrimental to stability and pharmacokinetic and pharmacological properties. Mass spectrometry also helps to optimize the structure of next-generation mAbs from a pharmaceutical perspective, allowing the development of drug candidates (OptimAbs) and ADCs (OptimADCs) with reduced CMC loading and better drug properties. Selection of antibodies includes chimeric, humanization and selection of human antibodies as well as isotype selection. New coupling strategy The second-generation of ADCs are controlled mixtures of different drug loading materials with a typical average DAR of 3.5 or 4. Species with DAR greater than 4 show lower tolerance, higher plasma clearance and reduced in vivo efficacy. Most ADCs today have a common structural feature, such as a thiosuccinimide linkage formed by a maleimide reaction of a thiol and an alkyl group. However, most ADCs cause measurable removal of maleimide during long-term circulation, which can be solved by site-specific coupling and alternative conjugate chemistry: for example, engineering cysteine, unnatural amino acid engineering, enzymes auxiliary ligation, sugar recombination and sugar binding, amino-terminal engineered serine, ligation to the Fab nucleotide binding site, re-bridging of native cysteine, avoiding retro-Michael disintegration and high load of ADC. Improve the performance of the ADC Additional strategies to improve ADC performance can be designed to avoid potential resistance to warheads, by using smaller protein scaffolds to enhance tumor penetration, or by combining ADCs with recently approved mAb-based immune checkpoint inhibitors. ADC for non-oncological indications There are few studies on ADCs for non-cytotoxic drugs. For example, an ADC directed against C-X-C chemokine receptor type 4 is an antigen that is selectively expressed on serum cells; antibody-antibiotic conjugates (AAC) against S. aureus in cells. Conclusions and future development The development of ADCs has benefited from general improvements in the design of therapeutic mAbs, as well as specific improvements in conjugate synthesis methods that enhance homogeneity. The linker strategy and the diversity of warheads provide new opportunities to improve drug delivery in tumors, while also reducing the chances of drug exposure to normal tissues. In fact, it is important to better understand the toxicity determinants of ADC, whether it is used as a single drug or in combination with other therapies. To increase the therapeutic index, the ADC needs to reduce the minimum effective dose under the potency of the cytotoxic agent, or increase the maximum tolerated dose in terms of tumor selectivity. The next generation of ADCs relies on the synthesis and characterization of more homogenous and stable ADCs with macromolecular structures with medicinal chemical-like control. Recent ADC developments have revived interest in cytotoxic natural products, and in the future, the breakthrough in ADC performance may involve warheads with new combat mechanisms. In addition, alternative forms of new mAbs have emerged, but must be compared to full mAb in terms of therapeutic indicators such as toxicity, efficacy, and pharmacokinetics.
  22. 7. The remaining kit materials should be properly preserved After the standard product is packed, it can be stored according to the temperature required by the manual. This can avoid contamination. It can avoid repeated freezing and thawing of the standard products that require cryopreservation. The enzyme label plate is put back into the foil paper bag, desiccant is added, the sealing is sealed, and stored at 4 ° C. Do not completely balance the enzyme plate to room temperature, then put it back into the foil paper bag, because at this time due to the temperature difference, there will be water vapor on the microplate, which is not conducive to stable storage. 8. Add samples in a fast and accurate way, avoiding air bubbles The loading time should be controlled within 15 minutes. Mix the sample before loading, especially the sample that is thawed after cryopreservation (the sample that is naturally melted will have stratification), and mix it upside down, but pay attention to the movement and avoid bubbles. If the frozen sample is precipitated, it can be centrifuged again. Care should be taken to avoid air bubbles throughout the loading process. Air bubbles affect the mutual binding of proteins and affect the reaction. 9. Ensure uniform temperature during incubation to prevent evaporation and drying The sealing film is compressed during incubation. When multiple plates are tested together, lay the plates flat and do not stack them to avoid drift or edge effects due to uneven temperature. 10. Application of the plate washer The use of a plate washer not only reduces labor intensity, but also helps to ensure the stability of the ELISA test. At present, the automatic plate washer not only has many practical washing actions, such as bottom flushing, two-point aspiration, vibration, and cross-priming; it can also adjust parameters such as flushing pressure, flushing distance, and flushing time as needed. By optimizing these parameters, a good washing effect can be ensured. The performance of the plate washer has a great influence on the accuracy of the results. A good plate washer should ensure that the residual liquid after washing is as small as possible, generally not exceeding 2 μL, and the artificial clapper paper is not wet after washing. The suction needle should be checked regularly for blockage. 11. Manual washing instruction Add lotion quickly. The lotion should be freshly prepared to avoid contamination by other reagents or bacterial. Soak it for 30s-1min. The pouring of the seesaw should be quick and easy. After pouring, draw the board on the absorbent paper and use high-quality absorbent paper without dust or debris. It is necessary to force the plate so that there is no visible liquid hanging in the hole; but it should not be too heavy to allow the sample to dry for too long. Immediately do the subsequent dosing after the ELISA plate is patted. 12. Key points of color reaction The ELISA assay is an enzymatic substrate color reaction, which increases with time and darkens, so choosing the optimal time to terminate the reaction is an important factor in obtaining an accurate standard curve and sample concentration. The termination process should be complete. When using the TMB substrate, the complete termination point is yellow, and there will be no blue or green color. If necessary, the 96-well plate can be oscillated if necessary during the termination process, or mixed with a pipette tip (the stop solution contains strong acid to avoid corrosion). 13. Data analysis Perform curve fitting and analysis according to the data analysis method recommended in the manual. The standard curve in the specification is the result obtained by a very experienced operator in the manufacturer's laboratory. The customer's standard curve and the standard curve in the specification may differ, but it’s not means bad. Generally, the criteria for judging the standard curve are: background OD value <0.2; highest point OD value>1.0; correlation coefficient R2 is close to or equal to 1. As long as the standard curve that meets these conditions is available. Summary When you understand and master these unique tips for ELISA, you are very close to make an excellent ELISA experiment. Creative Diagnostics provides a wide range of enzyme-linked immunosorbent assay (ELISA) kits for the detection of hundreds of different proteins and molecules, including cytokines, growth factors, markers for infectious diseases, diabetes and tumor, drugs and small molecules, etc. You can search for the ELISA kit you need by target name, species, etc. on their website. Should you need any assistance, the company’s experienced scientists are more than happy to provide optimized protocols and helpful technical support to accelerate your research.
  23. Contrary to what many people believe, making a home eco-friendly doesn’t need to be a time-consuming or expensive process. The average homeowner could actually save quite a bit of money over the years by going green. Here is a look at three simple steps that you can take to make your household as eco-friendly as possible. Cut out the Single-Use Products Single-use plastic products are incredibly bad for the environment, and you might be using dozens of those items every single day without even realizing it. One of the easiest ways to limit your impact on the environment is to remove most of the single-use products from your home. Some of the worst offenders include straws, plastic cutlery, plastic bags, paper coffee cups, single-use water bottles, and plastic bags. While many of those items can be recycled, the recycling process isn’t completely efficient, and some of the materials will never be used again. Upgrade Your Light Bulbs Swapping out your light bulbs might not seem like a significant upgrade, but this simple project could end up saving you a few hundred dollars per year. Older CFL bulbs tend to be very inefficient because much of the energy is turned into heat instead of light. LED bulbs, on the other hand, turn almost all of the electricity into visible light. Replacing all of the older CFL bulbs in your home with LED bulbs is going to have a major impact on your monthly energy bills. You might also want to invest in “smart” LED bulbs that can be controlled with an app. With a single tap of your smartphone screen, you will be able to turn off or dim all of your lights. Install Solar Panels The solar market is growing at an astonishing rate, and more homeowners are investing in solar panel installation every year. From the moment that your solar system is connected, you are going to notice a drop in your energy bills. Depending on where you live and what type of system you have installed, you might even be able to sell excess electricity back to your energy company. These systems have become quite advanced over the last few years, and they work perfectly in most climates. To help homeowners cover the upfront costs, many states offer financing programs to those who connect their solar systems to the electrical grid. In addition to these three tips, you should also make sure that your family sticks to eco-friendly habits around your home. That includes limiting the length of your showers, turning off the lights when you leave a room, and unplugging any electronic devices that aren’t being used.
  24. An overview of several commonly used antibodies for neurological and neuroendocrine tumors 1. Neuron-specific enolase (NSE) It has been found that there are three kinds of the same enzymes in the brain tissue, namely dd.dr and rr. NSE belongs to the rr shape. It exists not only in nerve cells and their axons, but also in various endocrine cells and their associated tumor cells. Previous experiments detected 69 cases of APUD system tumors by NSE, and all of the results were positive; while only 2 of the 16 cases of secretory glands such as pancreatic cancer were positive. It can be seen that NSE is a very useful antibody for detecting tumors in the APUD system. It is suitable for a variety of tissue sections, with monoclonal and polyclonal antibodies, and better results can be obtained with antigen retrieval. 2. Chromogranin A Chromogranin A antibody detects neuronal and neuroendocrine cells and its related tumors, such as pheochromocytoma, medullary thyroid carcinoma, islet cell tumor, pituitary tumor, carcinoid and so on. Monoclonal antibodies and polyclonal antibodies are available, which are suitable for various types of slices and antigen retrieval is required. 3. Glial fibrilary acidic protein (GFAP), clone 6F2 GFAP is one of the intermediate filament proteins and is an effective marker for astrocytes and ependymal cells and their derived tumors. According to the immunohistochemistry of 60 astrocytomas cases, the results were all positive. Therefore, it is the prior antibody choice for astrocytoma and ependymoma. Polyclonal antibodies have been used in the early stage, and monoclonal antibodies have been recently used, which do not require any treatment and are suitable for various sections. 4.S-100 S-100 is a protein isolated from bovine brain. Three sub-shapes of S-100 have been discovered through extensive research, i.e. S-100ao, S-100a and S-100b. It can be detected in human Schwann cells, ependymal cells, astrocytes, nerve fibers, nerve sheaths, skin melanocytes, and the like. Therefore, it can be used to detect tumors of the above tissues and their sources. The antibody is suitable for various sections and does not require any treatment. The dilution should be 1:200 and the background should be controlled as much as possible. Other antibodies for cancers 1. Thyroglobulin (TG), clone 2H11 TG is a glycoprotein synthesized by thyroid follicular cells. It is an antibody with high specificity among many antibodies. It is only used to detect thyroid tissue and tumors derived from it, without any treatment and good results can be obtained. It adapts to a variety of slices, but background control should be noted. 2. Bovine Dapiuomavirus (BPV) The antibody is mainly used for detecting infectious diseases of the reproductive system such as condyloma acuminata. The virus is present in the hollowed cells of the epithelium. According to experiments, not all the hollow cells contain virus after color development detecting, which may be due to loss of cells on slices in the process of production. In the markers of 50 cases, viruses of varying contents were found. The antibody is a polyclonal antibody, and the dilution can be 1:400 when vacuum negative pressure detection is used. The background control should be noted, and good results can be obtained without any treatment, and are suitable for various slices. 3. Proliferation cell nuclear antigen (PCNA) PCNA is an acidic protein with a molecular weight of 36 kD, which is an aid to DNA polymerase when DNA is replicated. This protein appears when the cell enters the proliferative cycle. It is a marker of the cell proliferation cycle, especially the "S" phase. Suitable for all kinds of slices. 4. Cow calf alkaline phosphatase (CAP) The antibody detects normal osteoblasts, small intestinal cells, prostate epithelial cells, and cells containing CAP throughout the body. However, it is commonly used in clinical tests to detect the content of CAP in bone tumors and prostate tumors. The antibody does not require any treatment and is suitable for various sections. 5.Estrogen receptor (ER) ER is an acidic protein with a specific function. It transmits hormone information. The study found that this substance is present in the nucleus of cancer cells, such as breast cancer, endometrial adenocarcinoma, cervical cancer and other cancer. At present, in the treatment of these cancer patients, it is first necessary to detect whether the ER is positive. If positive, anti-hormone therapy will be taken, if negative, hormone therapy will be taken. In conclusion, the positive or negative result of ER test is directly related to the choice of treatment plan, and is a hard indicator to judge the prognosis of patients. At present, when detecting ER, it is necessary to perform thorough and complete antigen retrieval. According to experiments, in order to obtain satisfactory results, it is necessary to perform long-time bath-type antigen retrieval, that is, immersing the slices in the container of the antigen repair solution, and then put it together in the pot and boil for forty minutes. If the antigen retrieval time is not enough, the slice can also be negative. In addition, high pressure retrieval, vacuum negative pressure and microwave retrieval can also be used. 6. Progesterone receptor (PR) PR, like ER, is listed as a mandatory test in the treatment of breast cancer, cervical cancer, endometrial adenocarcinoma, etc. In order to develop a medical plan and judge the prognosis hard indicator, the general test is performed simultaneously with ER and PR.
  25. When making a reclaimed office space, keep in mind that you’ll be using recycled materials, or leftover materials from various places. You can get these type of materials for cheaper that new ones in some cases. Reclaimed office spaces are basically recycled, refurbished spaces that use all used materials so there is less waste. In this way, reclaimed spaces keep the environment safe. Here are some of the essential items that will come in handy when you’re creating a reclaimed office space. Air Compressor An air compressor has so many different uses on a construction site. Using a nail gun on walls made of pallets can help the process go much faster. You might have to adjust the PSI, so keep that in mind as you work. Framing and trimming will go much faster if you use a nail gun instead of trying to do everything by hand. In some office spaces, certain aspects of the design are left unfinished, to save on costs and keep the aesthetic you’re looking for. It all depends on what you want your finished product to be. Make sure that your air compressor is oil-less so that you don’t get your new space messy before you even complete the project. An air compressor can also help with the cleanup tasks at the end of the day. Telescoping Forklift Even reclaimed office spaces require heavy lifting. Some projects may require even more heavy lifting, depending on the reclaimed material being used. For all of those heavy reclaimed materials that need to be moved from one part of the site to another, a forklift is absolutely essential. This can make exterior reclaimed spaces safer to complete. Using an equipment rental company for your reclaimed office space construction project will allow you to obtain the tools that you require for the individual job without having to purchase them on your own. Laser Level A lot can be said for ensuring that all surfaces in your project are level from start to finish. Doing this will limit the frustration you may experience when having to do level things over and over again, such as reclaimed windows, if they aren’t right the first time. A laser level will also help you keep your line level across a larger area of floor. Even reclaimed office spaces need advanced technology to help them come to fruition. Using a laser level is especially important for reclaimed spaces, as some materials may be irregular and may have inconsistencies. Many tools have laser levels to ensure that you can make a level cut or so that you can keep those holes centered up throughout the process. Miter Saw A good miter saw is essential to any construction project. You want to ensure that you aren’t wasting good wood making cuts that aren’t up to par. Select one that will allow you to make a variety of angle cuts so that your finishing tasks can be as accurate as possible. Many times, you need to make many of these type of cuts when dealing with recycled and reclaimed materials. Depending on the type of blade that you install in the saw, it can also help you with some of your plumbing projects. There are other tools that can come in handy when you’re constructing your reclaimed office. Select tools that are highly rated and easy to use in order to make things as simple as possible on you.
  26. Abstract: In recent years, the development of immunology research has brought many exciting breakthroughs in the innovation of cancer diagnosis and treatment strategies. Immunotherapy has become the fourth tumor treatment mode after surgery, radiotherapy and chemotherapy, and has been successfully used in the treatment of various tumors. Among them, adoptive immunotherapy has received great attention in the past few decades. In vitro cultured tumor infiltrating lymphocytes or lymphocyte-activated killer cells can affect tumor regression in a specific cancer. However, adoptive immunotherapy is not a first-line treatment in clinical practice as adjunctive therapy due to certain limitations. With the development of genetic engineering, immunotherapy using genetically modified T cells is more attractive in the treatment of human tumors. Chimeric antigen receptor is one of the strategies for genetically modified T cells. CAR-T cell therapy is a method of combining the high specificity of antibodies to antigens and the cytotoxic activity of T cells to target cells. T cells expressing a chimeric antigen receptor are obtained by genetic recombination, purified, expanded and activated in vitro, and infused into a patient to perform the function of killing tumor cells. In the past 25 years, CAR-T has shown good targeting, killing activity and persistence in both in vivo and clinical trials, in the treatment of malignant tumors such as leukemia, lymphoma, glioma and lung cancer. A delightful effect has been achieved. Through artificial genetic modification, T cells express single-chain antibodies that recognize tumor-specific antigens and signals that activate T cells, thereby achieving targeted killing of tumor cells. At present, clinical studies have confirmed that CAR-expressing T cells can be effectively used to treat refractory or relapsed acute B-lymphocytic leukemia, and thus promote the use of CAR-T for the treatment of other hematological malignancies and solid tumors. This article mainly introduces the research progress and broad prospects of chimeric antigen receptors. Keywords: chimeric antigen receptor, T cell, tumor, immunotherapy Car-T cell structure and preparation Car is located on the surface of T cell membrane and is a Tran’s membrane structure composed of extracellular binding domain, hinge region, Tran’s membrane region and intracellular signal region. Although the adverse effects of CAR-T treatment have not been fully resolved, the success of anti-CD19CAR-T has pushed the treatment of CAR to industrialization. Currently, most CAR-T production processes are cumbersome and expensive. Production procedures include isolation, activation, transduction, proliferation, and reinfusion of T cells: 1 Acquisition of peripheral blood T cells from patients using apheresis: 2 Activated T cells: Activated T cells typically use anti-CD3 and anti-CD8 immunomagnetic beads, Cytokines such as interleukins can also be added to enhance the activation effect; 3 CARs synthesized by genetic engineering are transduced into T cells, and the transduction methods can be divided into viral transductionand non-viral Transduction (electroporation, transposon-based or gene editing system transduction methods) 4CAR-T will be placed in medium with IL-2 and other cytokines for 2 weeks; 5CAR-T is washed and concentrated, And quality inspection, only after the quality inspection, CAR-T can be returned to the patient. How does CAR-T work? T cells are specific anti-tumor effector cells in humans, but their function is MHC-restricted. The construction of a specific chimeric antigen receptor was first proposed in 1989. This process first combines the T cell receptor (TCR) subunit with both single-chain variable regions of tumor antigen monoclonal antibodies, and then transfects by retroviral, lent viral vector or transposon gene transduction methods. T cells are stained, and the finally modified T cells are expanded and purified in vitro and then returned to the body. The constructed CAR-T cells can specifically recognize and bind tumor antigens in vivo, and have the ability of T cells to self-renew and kill. T cells are genetically modified to obtain targeted killing activity, which is not inhibited by the local immune microenvironment of the tumor, thereby breaking the host's immune tolerance state, and allowing T cells to specifically recognize specific antigens on the surface of tumor cells in a non-MHC-restricted manner. Enhance its ability to recognize and kill tumor cells. Application of Car-T cells in tumor therapy Traditional radiotherapy, chemotherapy, surgery and other cancer treatment methods still have great limitations in the treatment of refractory and recurrent tumors. Cellular immunotherapy has pointed out a new direction for cancer treatment. Among them, the therapeutic effect of Car-T cells is particularly prominent. Since the birth of Car-T cells, with the continuous improvement of its functions, it has gradually moved from scientific research to clinical practice. It has been widely used in hematological tumors, lymphomas, melanomas, ovarian cancers, neuroblastomas, kidney cancers, etc. In the treatment of malignant tumors, CD19 is the initial and most studied target of Car-T cells, and has outstanding clinical efficacy in the treatment of leukemia and lymphoma. CD19 is only expressed on the surface of B lymphocytes, so CD19Car-T cells input into the body do not damage normal cells of the body. It has been reported that CD19Car-T cells in patients with refractory relapsed chronic lymphocytic leukemia, acute lymphocytic leukemia, and non-Hodgkin's lymphoma have achieved satisfactory response to complete remission and no recurrence. Several security issues that cannot be ignored Off-target effect What is the off-target effect? Most CAR-targeted target antigens are not tumor-specific and have varying degrees of expression in normal tissues, so CAR-modified immune cells can also damage normal tissues while attacking tumor tissue. Therefore, the chimeric antigen receptors expressed by CAR-T cells can be two or more, and generally normal tissue cells expressing only one antigen can be prevented from being damaged by CAR-T, or can be selected only for tumor cells. The target antigen on the surface is specifically bound to tumor cells without binding to normal tissue cells. Cytokine release syndrome (CRS) CRS is a syndrome in which CAR-T cells are proliferated in a large amountafter exposure to cells with tumor antigens, and a large number of tumor cells are killed. In this process, a series of cytokines are formed, which form a cytokine storm and cause serial damage to the patient's body. It is the most common and most adverse reaction in the treatment of CAR-T cells. In response to this problem, not only the design of safe CAR-T cells, but also the number of cells injected into the patient each time is strictly limited, thereby reducing the occurrence of such adverse reactions. Prospects of chimeric antigen receptors In the field of tumor immune cell therapy, chimeric antigen receptor T cell therapy (CAR-T) represents the most advanced technology of today. With the development of modern biological science, CAR-T has received more and more attention. In terms of tumor immunotherapy, CAR-T clinical trial results show that it has unparalleled advantages, but in the technical improvement and large-scale clinical application, CAR-T still has many challenges. How to improve the ability of CAR-T cells to specifically kill tumors and the safety and effectiveness of clinical treatment is an urgent problem to be solved in CAR-T treatment. With the deepening of research and the increasing technology, it is believed that CAR-T therapy will play an increasingly important role in the immunotherapy of tumors for the benefit of medical development and human health. References [1]Mo Z, Du P, Wang G, et al. The Multi-Purpose Toll of Tumor Immunotherapy: Gene-Engineered T cells [J]. Journal of Cancer, 2017, 8(9): 1688-1705. [2] Olbrich H, Slabik C, Stripecke R. Reconstructing the immune system with lentiviral vectors [J]. Virus Genes, 2017, 53(5):722-728
  27. What are the glyconegineering and glycosylation? Glycoengineering, as well as protein engineering and gene engineering, belongs to the category of biotechnology, and its basic research is also called glycobiology. The research of glycoengineering is still in the stage of basic and applied basic research. glycoengineering, which was born in 1990s, is a discipline to study the structure, function, metabolic regulation and application of glycoconjugates.With the research and elucidation of the biological functions of sugar chains, a variety of glycan antibodies are being developed, some of which have gone into clinical practice. Among many post-translational modifications of proteins, glycosylation modification is one of the most important and complex modifications, and also one of the key quality attributes for evaluating antibodies. The function of monoclonal antibodies is closely related to glycosylation modification. Glycosylation modification can affect the properties of proteins, such as conformation, stability, solubility, pharmacokinetics, activity and immunogenicity. Figure1.Types of glycosylation Different glycosylation modifications have different effects on the stability, half-life, safety and biological activity of the antagonists, which are described below. Stability and half-life The most obvious effect of glycosylation modification is that it can increase the stability and solubility of protein. Studies have shown that glycosylation protects proteins by hiding binding sites between proteins and proteases. Rudd et al found that the steric protection of N-glycosylation on adjacent polypeptides was due to the formation of hydrogen bonds between glycosylation and hydrophilic amino acids. Glycosylation modification can also hinder the binding of protease and antibody, thereby increasing the stability of antibody. Sialic acid glycosylation can prolong the existence time of glycoprotein in serum. When the glycoprotein chains are terminated by galactose modification or desalicitated, they can be recognized by the sialic glycoprotein receptor (ASGPR), resulting in a significant reduction in half-life. The ASGPR located on the surface of hepatocytes can not recognize the glycoprotein of total sialic acid, but it will be desalibrated by the non-specific sialidase in the blood as the blood circulates. The galactose glycosyl group of bare can be recognized by ASGPR, and the glycoprotein is degraded. Other studies suggest that high levels of mannose reduce the half-life of antibodies in serum. In general, the more stable the drug is in the body and the longer its half-life, the more effective it will be. As for antineoplastic drugs, if the stability of drugs is high and the half-life is long, the dosage can be reduced appropriately and the interval between doses can be designed longer, and the effect is the same. However, with the increase of drug stability and half-life in human body, drug safety will become one of the factors to be considered because of potential miss-target. Safety The key quality attributes of antibodies (CQAs) are the criteria to judge whether they are qualified or not. CQAs must be within an appropriate range to ensure the effectiveness of drugs and, more importantly, the safety of drugs. By influencing the effect function of Fc terminal, glycosylation modification of Fc terminal can affect the safety of antibodies in the form of immunogenicity, PK/PD. The development of antibodies has experienced the development of murine primordial antibody, chimeric antibody, humanized antibody, and finally the whole human antibody. The immunogenicity of antibodies has been continuously decreasing.Antibodies have developed into human antibodies, and the immunogenicity caused by different glycosylation modifications should not be considered. However, in order to increase the efficacy of antibodies or prolong their half-life, some amino acid mutations and glycosylation modifications are often introduced artificially, and their potential immunogenicity should be considered when making such modifications. Moreover, immunogenicity is not only caused by internal factors, but also by external factors such as materials, formation of polymers and introduction of surfactants. The main consideration of PK/PD is the minimum dose and time of drug action in vivo. It is particularly important to minimize the immunogenicity of antibodies that can not completely eliminate the immunogenicity. Glycosylation affects PK mainly by affecting the stability and half-life of antibodies. The effect of glycosylation on the activity of antibodies acts on PD, which will be discussed in the following sections. The clearance of antibodies that bind strongly to Fc receptor is low, and glycosylation can affect the binding strength of antibodies to Fc receptor or C1q complement. If the clearance rate of antibody is low, antibodies bound to Fc receptor or C1q complement may cause the immune system to attack normal cells, resulting in serious miss-target effect. Biological activity Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are two important pathways for the efficacy of antibodies in cancer therapy. The glycosylation modification sites of Fc end of antibody are usually the binding sites of Fc receptor (ADCC mechanism) and C1q (CDC mechanism). By adjusting glycosylation, the binding of Fc receptor and C1q with antibody can be increased, thus the activity of antibody ADCC and CDC can be increased.It has been reported in many studies that glycosylation of sialic acid can affect the binding of antibody to FcγRIIa, thus reducing the activity of ADCC. Figure2.Mechanisms of action of ADCC and CDC Conformation determines performance. The effects of glycosylation modification on the stability, half-life, safety and biological activity of antibiotics are cross-cutting. It is the best choice to control the glycosylation modification of antibodies within an appropriate range so as to balance the three. Expectation Drug glycosylation is a unique post-translational modification. Their synthesis is not a mode-driven process, so it is a difficult task to obtain a consistent glycosylation. Sugar forms are known to regulate a range of complex functions, and it is pertinent to invent strategies that are easy to monitor sugars in real time. In addition to significant progress in process analysis, glycosylation level control remains an unrealized goal. Biopharmaceutical industry and academic researchers have made great efforts to bridge this gap, and have made great progress in understanding the complexity of post-translational modification. They have also understood the effects of process variables on sugar types and the effects of polysaccharide types on the efficacy of biopharmaceuticals. This also clearly implies that in the development of bio-analogue drugs, similar drug manufacturers can not obtain information about the original research and development of drugs.
  28. Carbon emissions are a significant threat because they contribute to climate change. Climate change causes rising sea levels, extreme weather, and other problems that are currently facing our society. Many governments recognize this impact and are combating carbon emissions as a result. Here are just a few ways that world governments are taking a stand to reduce global emissions. The Paris Agreement This landmark decision was organized by the United Nations. It came into effect in December 2015. Simply put, this was a decision to hold governments responsible for reducing climate change. The goal is to keep the global temperature from rising to 2 degrees Celsius (35 degrees Farenheit) during this century. Ideally, it would even be below 1.5 Celsius (34 degrees Farenheit). This would be achieved through pooling together resources and improving technology to reduce industrial emissions. The Agreement will be revisited and updated every 5 years. While the United States has since pulled out of the agreement, other countries continue to stay in and work hard to lower their emissions for the safety of the planet. Carbon Taxes A carbon tax brings climate change responsibility closer to home. Carbon tax benefits include involving ordinary citizens in the effort against global warming. Each citizen (and, on a broader scale, industry) would be taxed according to the amount of carbon they produce on a regular basis. New York City is getting in on the game by imposing a "congestion pricing" plan. Taxi rates would go up the longer they sit in traffic. The money would then be returned equally among citizens through dividends, meaning that those who produced the least amount of carbon emissions would profit the greatest in the end. While there are concerns on how this would affect lower-income demographics, those working on the plan continue to change their approach to better suit the needs of modern citizens. Rewards for Clean Energy Efforts This financial benefit goes hand-in-hand with carbon taxes. In the United States, as well as other westernized countries, businesses can offset their carbon emissions by purchasing clean energy credits. Incentives include greater reliance on solar energy or wind power. Many rewards can come down on the local level as well. Some states provide tax reductions for installing solar panels. People who use solar panels can "sell" the electricity they generate back to the grid. Doing this gives profit to those individuals and companies who invest in renewable energy sources and works as a strong incentive toward more responsible business practices. Public Transportation Initiatives Not all cities are well known for having a good public transportation infrastructure. There are a few that are working to change that. For example, Indianapolis has instituted their Red Line Bus Service. It is a rapid-transit line that runs entirely on electricity. Other initiatives include making Denver, Colorado, a more walkable city by putting in parks. The city also wants to ensure a majority of residents live closer to public transportation in order to cut down on automobile emissions. Individuals can support their governments in these efforts as well. Installing solar panels in your home and using carbon calculators are great ways to inspire grassroots-level change. Recycling and supporting environmentally-conscious companies can also be a major step in the right direction. Climate change affects us all and it's important to get involved in whatever way we can.
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