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  1. Yesterday
  2. 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."
  3. Last week
  4. 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.
  5. 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.
  6. 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.
  7. Earlier
  8. 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
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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?
  14. 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: https://www.creative-diagnostics.com/Japanese-Encephalitis-Virus.htm. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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
  21. 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.
  22. 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.
  23. Tumors are high-risk and high-mortality diseases that pose a serious threat to human health. A large number of studies and prevention data confirm that early diagnosis and early treatment are the most effective ways to prevent and treat cancer and reduce mortality. Therefore, the search for cancer markers that can be used for early diagnosis has become the focus of attention. However, in addition to poor differentiation, easy metastasis and high-speed proliferation, malignant tumor cells are completely equivalent to normal cells in cytological behavior. No specific expression products or shedding components have been found so far, or various malignant cancer markers have not yet been discovered. This brings problems to tumor diagnosis and immunotherapy.The ideal specific cancer markers must meet the following requirements: (1) unique to a certain tumor; (2) related to tumor size and stage; (3) therapeutic monitoring; (4) prognosis; (5) Does not intersect with healthy people and other diseases. Cancer markers that meet these criteria have not been discovered so far and may never be found. In recent years, all cancer markers used in clinical practice are mostly tumor-associated antigens, or some normal people also have trace amounts, but the amount is different. In any case, finding tumor-specific antigens is still a hot spot for cancer research because of the refractory tumors and the need for biotherapy. Classification of common cancer markers: 1. Cancer Antigen 19-9 (CA19-9) The carbohydrate antigen CA19-9 is a monoclonal antibody numbered 1116NS19-9 obtained by Koprowski et al. in 1979 using a human colon cancer cell line to immunize BALB/c pure mice and hybridize with myeloma. A class of tumor-associated carbohydrate antigens, the antigen recognized by the monoclonal antibody is named the carbohydrate antigen CA19-9. CA19-9 is a tumor-associated antigen, which is related to Lewis blood group components and can be present on normal tissue cells. It is not unique to tumor cells. It is mainly found in epithelial cells such as the stomach, intestine and pancreas of the fetus. The biliary cells and the stomach, colon, endometrium and salivary gland epithelium can also be synthesized. In certain malignant tumors, CA19-9 in body fluids is often at a high level. Observing the changes of CA19-9 in vivo is conducive to early detection of the above-mentioned malignant tumors of organs, and has certain differential significance for the benign and malignant tumors. CA19-9 is detectable in serum, tumors, non-neoplastic diseases, and normal humans, but there are significant differences in CA19-9 levels in benign and malignant diseases. In benign diseases, normal people, serum CA19-9 elevation is usually low or transient, mostly below 100U/ml.In malignant tumors, the detection rate of different organs is different. At present, the increase of serum CA19-9 is more common in digestive tract tumors, especially pancreatic tumors, followed by biliary tract, colon, liver and stomach. In lung cancer, breast cancer and ovarian cancer. There is also a certain detection rate. The concentration of CA19-9 and the positive detection rate in the same organ tumor are related to the pathological type. For example, the CA19-9 concentration of colorectal cancer is higher in adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma, but in papillary gland. Cancer and phosphorus cancer are lower. There are many clinical reports on the sensitivity and specificity of serum CA19-9 in various tumors, which are different from the disease and the number of cases in the selected cases, but the general trend is consistent. In the pancreatic cancer, the detection rate of serum CA19-9 is the highest. The sensitivity of each family is about 79%, even as high as 90.2%, and the specificity is between 70% and 90%. It has been used as a test for pancreatic cancer. Preferred serological indicators. The sensitivity in cholangiocarcinoma, gastric cancer, colon cancer, and liver cancer was 67% to 86%, 31.5% to 68%, 50%, and 49% to 60.9%, respectively. The sensitivity in lung cancer and breast cancer is low, about 10%. Many studies have shown that the concentration of CA19-9 is related to tumor size, especially in pancreatic cancer and colon cancer. A large number of studies have shown that preoperative detection of CA19-9 levels can help to determine the prognosis of patients with cancer, especially for patients with pancreatic cancer, colon cancer, hepatobiliary tumors, and gastric cancer. Preoperative high CA19-9 is a prognostic factor. The chances of recurrence and metastasis are high and the survival time is often short. The tumor marker CA19-9 is a tumor-associated antigen. This index has important significance in the diagnosis, curative effect, prognosis and postoperative monitoring of malignant tumors such as pancreatic cancer, cholangiocarcinoma, liver cancer, gastric cancer and colon cancer. However, its specificity is still low, and the detection rate varies from place to place. How to improve the clinical value of this marker remains to be further studied. The detection rate of CA19-9 varies from one report to another, and it is related to the selected method and the sensitivity of the selected kit, in addition to the difference in the condition and number of cases in the selected case. With the deepening of research, the emergence of more sensitive, more reliable, more reproducible, more convenient, more environmentally friendly and economical assays, the development of highly specific CA19-9 antibody will increase the value in tumor diagnosis. 2.Cancer Antigen 125 (CA 125) CA125 is a heterogeneous high molecular weight mucin-like glycoprotein containing mainly galactose, N-acetylglucosamine and N-acetylaminogalactose chains. The protein is partially rich in serine and can be recognized as an antigen by the monoclonal antibody OC125, hence the name CA125. Although the CA125 antigen is a glycoprotein, it has both membrane-bound and episomal states. CA125 in plasma and body fluids binds to glycoproteins of different relative molecular masses, respectively, and has the smallest subunit of CA125 immunoreactivity. CA125 is present in the body cavity epithelial cells of embryonic development and disappears several hours after birth, but reappears in ovarian cancer cells. Immunohistochemistry revealed that CA125 was found in fetal digestive tract epithelial cells, amnion, adult pleura, peritoneal mesothelial cells, fallopian tube endothelium, uterus and cervix, but no CA125 was found in adult and fetal ovarian epithelial cells. Under normal circumstances, CA125 does not enter the blood circulation, so the quality of CA125 is very low in healthy people and most benign diseases. CA125 can enter the blood circulation and various body fluids and exhibit high expression during the growth and metastasis of malignant tumors and when some non-tumor diseases progress. Elevated serum CA125 marker is a direct contact between the shed tumor cells and the systemic circulation when the "natural barrier" in the human body is destroyed, resulting in elevated serum CA125 levels. If the tumor is confined, CA125 has not yet reached the systemic circulation, and the level of CA125 in the blood is not high. Serum CA125 has been widely used in ovarian cancer screening, diagnosis, disease monitoring, prognosis and treatment. Serum CA125 combined with a variety of tumor markers can greatly improve the diagnosis and differential diagnosis of ovarian cancer. The half-life of CA125 used during chemotherapy can better predict the patient's response to treatment and monitor disease. The quality of serum CA125 can predict the trend of the subject to develop ovarian cancer. Serum CA125 detection combined with CT for the follow-up examination of patients with ovarian epithelial cancer is more valuable for detecting tumor recurrence. In addition, the current experimental and clinical studies on the treatment of ovarian cancer with CA125 monoclonal antibody have made great progress, and may bring new hope for the treatment of ovarian cancer. Examining the test results of elevated serum CA125 to patients can greatly improve the rate of return visits and improve the enthusiasm of women for regular gynaecological examinations. 3. Cancer Antigen 27.29 Breast carcinoma-associated antigen CA27.29 is a glycoprotein antigen produced by the MUC-1 gene. The product of the MUC-1 gene is MUC-1, which is a transmembrane glycoprotein expressed by glandular epithelia. The function of MUC-1 is associated with anti-pathogens and cell signaling. While overexpressed MUC-1, glycosylation changes, and abnormally intracellular localization have been related to cancers. Besides, MUC-1 was found in many types of malignant cells such as breast, ovarian, pancreatic, lung and prostate carcinomas. It can be shed into the circulation of the patients who have breast cancer. Hence CA27-29 is a part of MUC-1 and it can be detected by specific antibodies. Alterations in glycosylation of MUC-1 have great influence on its physiological and pathophysiological activity by affecting the interaction between the MUC-1 and other target proteins. It has been reported that the abnormal glycosylation of MUC-1 induces novel protein-protein interaction and increases the expression of phospho-IκB kinase (IKK)-β and phospho-inhibitor of nuclear factor kappa-B (IκB)-α which are the membranes of NF-κB family. By stimulation with inflammatory factors such as TNF-α, the cancer form MUC-1 induces activation of NF-κB members and interact with phopsho-p65, then moves to the nucleus to regulate the production of pro-inflammatory factors such as IL-6 and TNF-α. Then, the inflammatory cells like myeloid cells and neutrophils are recruited to the tumor site by the inflammatory cytokines. Moreover, the inflammatory cells are capable of enhancing tumor growth and progression by producing pro-inflammatory and pro-tumorigenic cytokines. For patients with breast cancer and ovarian cancer metastasis, especially those who have no clinical symptoms after treatment, when the serum CA27.29 is checked regularly, it is found that patients with CA27.29 measured value greater than 40 U/mL are less than the measured value. Patients with 40 U/m L or 40 U/m L have a much lower survival rate. Serum C A27.29 levels can also be used as a predictor of cancer recurrence in other adenocarcinomas, such as metastatic colorectal cancer and pancreatic cancer patients, and tumor metastasis can be found significantly earlier than other imaging techniques. This method is of little significance for the diagnosis and diagnosis of breast cancer patients during the construction period. In addition, in some diseases or physiological conditions, such as benign tumors, serum CA 27.29 values may also increase in the first 3 months of pregnancy, so attention should be paid to differential diagnosis. 4. Cyclin D3 (CCND 3) Encoded by CCND3 gene, CCND3 protein belongs to the highly conserved cyclin family. All the cyclin members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins act as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns. Different expressions contribute to the temporal coordination of each mitotic event. CCND3 forms a complex with CDK4 or CDK6, and functions as a regulatory subunit of those two proteins. A number of reports have revealed that CCND3 are involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with CCND3 was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants of CCND3 have been found so far. CDKs promote cell cycle transitions in mammalian cells by phosphorylating key substrates cyclins. Abnormal expression of cyclins was reported to be involved in many cancers progression. Highly expression of Cyclin D3 was reported in a number of tumor cells. Cyclin D3 gene is amplified in bladder carcinoma in situ. Genomic changes disrupting the expression of Cyclin D3 are involved in the aberrant growth of several human B-lymphoid malignancies. Targeting Cyclin D3 by miR-138 induces cell cycle arrest in hepatocellular carcinoma. Furthermore, Cyclin D3 is selectively required for proliferative expansion of germinal center B cells. For breast cancer, CCND3 is overexpressed in human breast cancer cell lines and primary invasive breast cancers. In addition, E1AF promotes breast cancer cell cycle progression via upregulation of CCND3 transcription. All the studies reveal that CCND3 is the marker of many tumor cells. Research and development of highly specific CCND3 antibody widely used in disease screening and therapeutic monitoring, providing key products to the research market and providing the highest value for the diagnosis and prognosis of many tumor cells Reference [1] Ni X G, Bai X F, Mao Y L, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer [J]. Eur J Surg Oncol, 2005, 31(2):164-169. [2] Gorp T V, Cadron I, Despierre E, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm[J]. 2011. [3] Cen P, Duvic M P, Kurzrock R. Increased cancer antigen 27.29 (CA27.29) level in patients with mycosis fungoides[J]. Journal of the American Academy of Dermatology, 2008, 58(3):382-386. [4] Büschges R, Weber R G, Actor B, et al. Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas.[J]. Brain Pathology, 2010, 9(3):435-442. [5] Zheng G, Patolsky F, Yi C, et al. Multiplexed electrical detection of cancer markers with nanowire sensor arrays[J]. Nature Biotechnology, 2005, 23(10):1294.
  24. Simple Introduction First of all, let’s start with its definition: Peptide mapping is the main method for the analysis and identification of protein products and preparations. In addition, there are some other core techniques such as peptide mass mapping and peptide mapping ms. The following are functions of Peptide mapping: To confirm that a protein primary structure (amino acid sequence) including the N and C terminals. To provide protein loci and the proportion of modified groups, such as glycosylation, acetylation, sulphates a00nd phosphorylation. To provide qualitative and quantitative information on protein degradation products To get information on protein oxidation and deamination directly. According to these useful features above, peptide mapping has already gained in popularity in biological field. After getting numerous data from peptide mapping, the next step is deeper analysis. A sample graph of peptide mapping Peptide Mapping Analysis Based on graphs of peptide mapping and also peptide mass mapping, scientists can get a lot of useful information. According to the size of molecular weight of proteins, peptides and amino acid composition characteristics, the use of strong specificity of proteolytic enzyme [is commonly endopeptidase] on the special peptide chain site will peptide fragment into smaller fragments, through the separation of a certain form characteristic fingerprint detection methods. eolytic enzyme [is commonly endopeptidase] on the special peptide chain site will peptide fragment into smaller fragments, through th The picture below shows the steps of peptide mapping method: Step 1: Protein digestion: Immobilized trypsin provides rapid and simple protein digestion with high reproducibility, high sensitivity and excellent data quality in a format that is compatible with automated operations. Step 2: Peptide separation: this technique provides a complete set of chromatographic tools for all development applications requiring peptide separation and analysis Step 3: Biological mass spectrometer: It provides a fast and easy to solve multicomponent analysis method, Used for sequence determination, structural analysis, molecular weight determination and component content determination of polypeptides. What’s more, it has the characteristics of high sensitivity, strong selectivity and good accuracy. Step 4: Peptide analysis software: Integrated software can save time and identify more materials. Simple software workflows can guide biotherapy, characterization pathways, and provide comprehensive coverage, including peptide sequence validation and identification of all variants and modifications. So peptide mapping analysis is quite effective and important in some specific aspect of research. Let’s take an example here: Study on quality control of impurities and harmful substances in Genetic Recombinant Drug is a crucial project., in particular, when the recombinants are used in the production of genetically engineered drugs undergo mutations. Probably, they would bring some mutations into drugs. Besides strengthen control of original material and process of production, peptide mapping analysis is necessary method to ensure safety and consistency. As a result, peptide mapping analysis has given rise to a number of new things. For instance, HPCE, A new electrical technology for separation which emerged in 1980s. Because of its relatively high resolution, HPCE has started a wider road for structural analysis and quality control of protein drugs. At present, in addition to the routine analysis of amino acid sequence of some small peptides, the peptide graph analysis is one of the important conventional indicators to control the consistency of most gene engineering products. All in all, technologies on peptide mapping have already penetrated into every corner of our everyday life.
  25. We all know the pressures of living green that have been thrown on our society for the last couple of decades. While we know it’s great for us, it’s not always great for our wallet. Things like installing solar panels are very costly to do. However, there are many green living practices you can do that can help pad your wallet instead of empty it. Get Rid of Old Scrap Metal There are scrap metal buyers literally everywhere across the country. Many will come to your doorstep and load up your old scrap metal for you. They’ll even pay you for the metal that they collect. While you may not be hoarding tons of scrap metal, small quantities can bring you some good money. Think about old appliances, piping, and other metal that you may have which accumulated over the years. Round it all up and give a scrap buyer a call to cash in on your old junk. Install Aerators for Low-Flow Water Sources Do you realize how much water you use on a daily basis? The United States Geological Survey Agency’s research shows that the average American uses 80 to 100 gallons of water per day. Do a little math for an entire month’s worth of water use and you’ll understand why your water bill is so much. You can help to curb the amount of water you use by installing water aerators and low-flow systems. For example, a water aerator in your sink will put in extra oxygen when you run the sink to help reduce the amount of water flow. In addition, low-flow showerheads can easily reduce the amount of water coming out of the showerhead while you’re enjoying a bath. Line Dry Your Clothes We all need to have dry, clean clothes each day. Running your dryer requires constant use of electricity for about 45 minutes to 1 hour depending on the size of the load and its materials. You can save running your dryer by simply hanging up your clothes outside. Clotheslines have been used by society for ages. They use the natural elements, like the wind and the sun, that wick away the water from your clothes. Going green is a revolution that requires a lot of small habits done consistently over time. You can do your part in going green by selling old scrap metal, installing water aerators, and line drying your clothes. All of these options will not only help the green initiative but they will also end up putting more money back into your wallet.
  26. What is an autoantibody? Autoantibodies are antibodies that target tissues, organs, cells, and cellular components. The growth, development and survival of the human body have the maintenance of a complete autoimmune tolerance mechanism. The normal immune response has a protective defense effect, that is, it does not react to its own tissues and components. Once the integrity of self-tolerance is destroyed, the body regards its own tissues and components as "foreign substances", and an autoimmune reaction occurs to produce autoantibodies. Normal human blood may have low titers of autoantibodies, but no disease occurs. However, if the titer of autoantibodies exceeds a certain level, it may cause damage to the body and induce disease. There are many kinds of autoimmune diseases antibodies , the most important of which are antinuclear antibodies. In addition, anticardiolipin antibodies, neutrophil cytoplasmic antibodies, anti-mitochondrial antibodies, anti-erythrocyte antibodies, anti-platelet antibodies, anti-endothelial cells antibodies, anti-neurovirus antibodies, rheumatoid factor, anti-thyroglobulin antibodies, anti-insulin bodies Antibodies and the like are also autoantibodies. Reasons for autoantibody production: Antibodies are generally produced by the immune system by foreign proteins or other substances (especially pathogenic bacteria) that enter the body and are used in immune reactions to eliminate harmful foreign substances. Usually, the immune system can recognize and ignore the body's own cells, and does not produce antibodies to it; at the same time, the immune system does not overreact to substances (such as food) that are not threatened in the environment. However, under certain circumstances, the immune system recognizes the body's own substances and treats them as foreign invaders, thereby producing antibodies (ie, autoantibodies) against these substances, triggering autoimmunity. These autoantibodies attack the cells, tissues, and organs of the body, causing an inflammatory reaction and causing damage to the body. The production of autoantibodies may be due to the presence of some of the same molecular structures between pathogenic antigens (bacteria, viruses, etc.) and their own components: an immune response that cross-reacts with autoantigens; or some infectious agents that cause autoantigens Denatured, the immune system produces autoantibodies to these exposed new antigens. The pathogenic effect of autoantibodies is still unclear. Whether it is the "cause" or "consequence" of autoimmune diseases has different opinions. For patients with high titers of autoantibodies, those without clinical symptoms may not need treatment, but should go to the hospital regularly. Review and review. In tumors, inflammation, autoimmune diseases (such as lupus erythematosus, genital warts, Crohn's disease, multiple sclerosis), neurodegenerative diseases, infectious diseases, etc., a large number of autoantibodies are produced and accumulated in patients. Some autoantibodies have emerged in the early stages of a specific disease, even before the onset of symptoms of the disease, providing a reliable disease biomarker for the early diagnosis; some autoantibodies are the body's own protection against disease. Sexual antibodies, which provide new ideas for the treatment of the disease, as data from the world-renowned pharmaceutical giants show that 60% of the profits of large pharmaceutical companies have come from drugs that belong to antibodies. So how do you discover these potential autoantibodies? Methods for screening for autoantibodies: At present, the most suitable method for screening autoantibodies is the protein chip method. A protein chip often has thousands of protein spots, which can screen one autoantibody that can interact with these proteins at one time, and then pass fluorescent These autoantibodies can be found by incubation of the marker against the anti-Human IgG secondary antibody and fluorescence detection. The principle is simple, but it is very difficult to do, why? This has to say about the binding process of antibodies to antigens. In short, the corresponding antibody recognizes a specific epitope on the antigen and then binds it. The epitopes are divided into two types, linear epitopes and non-continuous epitopes. A linear epitope consists of a contiguous sequence of amino acids. An antibody that recognizes a linear epitope recognizes this amino acid sequence and produces an antigen-antibody binding reaction; a non-contiguous epitope is composed of a discontinuous amino acid, which is correct by the antigenic protein. After folding, they are close together and recognized by the corresponding antibody, producing an antigen-antibody binding reaction. In the body, most autoantibodies are non-continuous epitopes that recognize antigens. Correct identification and screening of these autoantibodies requires that the proteins on the protein chip be full-length, correctly folded, and biologically functional. However, the traditional protein chip can only guarantee that the protein synthesized on the chip is full-length (some can not be guaranteed), can not guarantee the correct folding of the protein, and can not guarantee the normal biological function of the corresponding protein. Other problems affecting the screening of autoantibodies by traditional protein chips include high CV values (>30%), poor reproducibility, low resolution, high background signal, and inability to distinguish autoantibodies with low expression levels. Screening for autoantibodies with such protein chips is like fishing with a large network full of loopholes. Screening of autoantibodies with such protein chips has brought great resistance to researchers and companies in the research of antibody screen. Sengenics' ImmunomeTM Protein Chip Research Platform, invented by Professor Jonathan Blackburn at the University of Cambridge in 1996, is a collaboration between Oxford and Cambridge. It is the only one in the world that is fully-length, correctly folded and functionally validated. Protein chip platform. Autoantibodies that recognize non-contiguous epitopes can be screened for advantages that cannot be replaced by other protein chip products. The ImmunomeTM Protein Microarray Research Platform contains 1631 full-length, correctly folded and functionally validated human proteins, covering cancer antigens, transcription factors, kinases, signaling pathway molecules, etc., to meet the research needs of users in different directions. Daban's low autoantibodies provide strong technical support as biomarkers. Compared to traditional protein chip products in the screening of autoantibody applications, Sengenics ImmunomeTM protein chip products can be described as "Skynet is restored, not leaking", full-length, correct folding, functional verification, wide coverage, low coverage CV low background signal, high-resolution full-generation protein chip platform technology helps researchers and business users to "capture big fish" in the field of autoantibody research, and return home.
  27. Everyone says that the grass is greener on the other side of the fence, but green doesn’t always mean environmentally friendly. Those homeowners who want to be conscious of their impact on the environment can start with their own yard care practices and what they grow. Doing so can ensure that both your yard and the natural landscape beyond stay green and healthy, and here are a few ways you can accomplish that. Use Native Plants When you use plant life that is common to the community, it helps provide food and resources for native animals. You can ensure local species survive with trees, shrubs, and plants that offer food and nesting material. Growing native plants also prevents the spread of aggressive foreign plants that could overtake the local native plants in your area. Plus, local plants are easier to grow and care for because they thrive in your climate. If you want a low-maintenance yard, then the garden center can show you which plants are easiest to care for and hardy plants for your climate. Feed Pollinators Bees help pollinate crops and flowers. Martha Stewart says 80 million pounds of pesticides are put on crops and communities across the United States annually. These chemicals kill bees and other animals that are susceptible to small environmental changes and displace others. Something as simple as planting flowers and fruits to provide nectars for pollinators can do a great deal of good in giving your local bees, butterflies, hummingbirds, and other pollinators a place to refuel. Anything that flowers can work, so when you’re considering plants to grow in your yard and garden, keep that in mind. Plant Trees You can help the environment by planting trees. Not only do trees help clean the air, but they also offer valuable shelter to birds and animals. Fruit trees especially can be a source of nourishment for the local wildlife. Not only do the flower buds provide nectar for pollinators, as previously mentioned, but they also give fruits and seeds to birds, squirrels, and other animals that are now running out of healthy food sources and shelter. To encourage birds to return to your yard, planting oak trees for shelter is a great idea, and the acorns they grow make for great food for animals. Cardinals and bluebirds are partial to dogwood trees, and pine trees are excellent for most bird species, as well as for animals. Use Organic Fertilizers Another tip is to work with gardening centers and landscaping companies that offer organic fertilizers as opposed to the more toxic varieties. These organic fertilizers are safe for pets and any birds, bees, or animals that visit your yard while still creating a green lawn. If you want to attract specific species, then the landscaper can also give you ideas about what bushes or flowers you can plant to attract them to your yard. Make sure that the fertilizers you get work well with your intended plants and lawn, as different plants and regions require different nutrients to thrive properly. You can make sure your side of the fence is greenest by adding local plants and trees. Organic fertilizer will protect your pets and ensure bees and birds are safe on your property. Whether you are familiar with the area or you want to know more about specific plants, the local garden center or landscape provider can help you discover the right ways to help the Earth in your little corner of the world.
  28. Your home’s features and condition play a major role on the impact you make on the planet. Many people assume that they need to make huge, expensive home improvements to create a green living environment. While installing solar panels and a rainwater collection and purification system are some of the many expensive projects that you could invest in, proper home maintenance can have a beneficial impact as well. These are some of the maintenance tasks to complete regularly to create a greener home environment. Schedule HVAC Service Regularly Living without an HVAC service would be miserable for most people. While this system understandably uses a significant amount of energy, it may currently be using more than it needs to. For example, when the system is dirty or developing signs of damage, the equipment may run more frequently or for longer periods of time than it otherwise would. This directly wastes energy and creates pollution in the process. When you schedule regular HVAC maintenance service, the components will be clean so that the system can work efficiently. In addition, developing repair issues can be identified and addressed quickly before they become major issues. Maintain Your Plumbing Features Fresh water is in short supply, so water conservation is a primary concern. In some homes, hidden water leaks waste tons of water before they are identified and repaired. In other homes, a huge leak spews hundreds of gallons of water or more into the home in a very short period of time. While not all leaks can be prevented, you can take steps to prevent some of these issues. For example, you can reduce your water pressure to minimize strain on the pipes. You can also invest in a water softener and reinforce pipe joints. Re-Seal Doors and Windows Periodically Energy loss also occurs through damaged window and door seals. These seals tend to deteriorate rapidly, and they may need to be replaced at least once per year. By doing so, you can keep climate-controlled air in the home and help your HVAC system to work more efficiently. You may also consider installing solar film over your windows for additional benefit. Each of these maintenance tasks should be included in your regular home care schedule. However, it is easy to overlook or delay working on them. Now that you know that they affect your property’s condition as well as your impact on the environment, you can see that these tasks deserve your regular attention.
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