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  1. Yesterday
  2. Ways to reduce water waste is something that every homeowner should consider, to save you money, reduce your carbon footprint, and to maintain your property. Water waste is often something that goes unnoticed for a period of time because it happens in areas where we are not easily able to access. With just a couple adjustments and the help of a plumber, you can easily reduce the water waste in your home. These are a few plumbing upgrades to make in your home for reducing water waste. Install Low Flow Shower Heads Low flow shower heads are easy upgrades to make on your own and affordable too. An average shower uses over fifteen gallons of water, but when you switch to a low flow shower head you end up using about seventy percent less water during the average shower. Reduce the Water Pressure Reducing the water pressure to your household is a great way to reduce the amount of water you use at any one time. Most homeowners are huge fans of high water pressure, which is often used as an indicator of good plumbing. However, by reducing the water pressure you become more conscious of how much water you are using and the amount wasted is significantly reduced. Check for Leaks A huge part of water waste happens out of sight, in areas where we don't even know water is being lost. Check your home and property for water leaks which occur over time as plumbing decays. A plumber is able to perform this role and can end up saving you both money and prevent damage that is being done to your property. Replace Older Appliances and Fixtures Older appliances and fixtures are often sources of leaks and water waste. Not only are these new appliances more energy efficient, but they are better put together and require less resources to operate. Older fixtures are also known to become damaged after time and spring leaks within the mechanisms. Insulate Your Pipes As colder weather sets in, it takes longer for hot water to reach the faucet and this is often made longer when the pipes in your home are not insulated. Insulating your pipes is easy and cheap, and it can mean the difference between a significant or a small amount of water waste occurring every single day. Reducing water waste in your home is much easier than you think and should each of these tips should be reassessed every year.
  3. Last week
  4. The pathogen that causes new coronary pneumonia is a new type of coronavirus, which is closely related to the previously familiar severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Infected patients will have fever, fatigue, and dry cough as the main clinical manifestations. In severe cases, acute respiratory distress syndrome will progress rapidly, or even die. So far, no specific drugs and vaccines have been approved for marketing. After the new type of coronavirus (SARS-CoV-2) invades host cells, it begins to replicate in large numbers. The two processes of transcription and replication of the genetic material RNA genome are the core. The transcription of genetic material will finally be translated into the structural constituent protein of the new virus, and its replication will form the RNA genome of the new virus. RNA-dependent RNA polymerases (RdRp), also known as non-structural protein 12 (nsp12), can be assembled with multiple other non-structural proteins to form an efficient RNA synthesis "machine". As the core component of this transcriptional replication machine, RNA polymerase is one of the most important antiviral drug targets. Disrupting its function is expected to prevent virus replication and ultimately achieve the goal of treatment. The research on the drug targets of the new coronavirus, especially RNA polymerase, is very important for the research and development of such targeted drugs and the verification of the pharmacodynamic mechanism. The structure of the complex analyzed shows that the RNA polymerase of the new coronavirus has the conservative characteristics of other viral RNA polymerases, and contains the NiRAN (Nidovirus RdRp-associated nucleotidyltransferase) characteristic domain of the Nidovirus; at the same time, viral RNA polymerization enzymes and virus non-structural proteins nsp7 and nsp8 constitute the core unit of transcription and replication machinery. Excitingly, the researchers also discovered for the first time a unique "β hairpin" domain at the N-terminus of the RNA polymerase of the new coronavirus. The discovery of this domain is to clarify the biology of the new coronavirus RNA polymerase. Through in-depth analysis of the atomic resolution structure, the research team discovered the key amino acid residues for the function of the new coronavirus RNA polymerase, and through the "hepatitis C virus polymerase ns5b-Sofosbuvir" effect. The structure of the “molecular” complex was compared, and the possible mode of action of the effector molecules (that is, the final product after metabolism) of remdesivir and fapilavir in inhibiting the new coronavirus RNA polymerase was proposed. This study is the first to finely describe the internal structure of the transcription and replication machinery of the new coronavirus "RdRp-nsp7-nsp8", and shows how the effector molecules of drug candidates such as Radixivir and fapilavir can precisely target and inhibit viral RNA synthesis. Furthermore, a reasonable mechanism explanation was put forward for exerting pharmacodynamic activity, which laid an important theoretical foundation for the in-depth study of the molecular mechanism of the new coronavirus replication, and opened up a new way for the development of specific drugs against new coronary pneumonia. In addition, the "Anti-Coronavirus Research Alliance" formed by the research team of Shanghai University of Science and Technology and its collaborators also jointly published the important research results of the new coronavirus on Nature "Structure of Mpro from COVID-19 virus and discovery of its inhibitors" "It is the first to successfully analyze the high-resolution three-dimensional structure of the main protease (Mpro), the key drug target of the new coronavirus, and to use three different drug discovery strategies to find inhibitors against the new coronavirus. In the research strategy designed from scratch, the "Alliance" found that the Michael receptor N3 is a potent inhibitor of the main protease, and was the first to analyze the 2.1Å high-resolution complex structure of the main protease-N3 (and later Increase to 1.7Å), which is also the world's first three-dimensional structure of the new coronavirus protein to be resolved. In order to facilitate relevant scientific and technological workers to develop antiviral drugs targeting this enzyme as soon as possible, the "Alliance" for the key research issue published the research results for the first time and published the structure in the Protein Data Bank (PDB). Since January 26, the team has directly provided data to the laboratories of more than 300 universities, research institutions and enterprises. This structure was selected as the February Molecule of the Month by PDB protein structure database, and was reported by PDB. Since then, the "Alliance" has continued to jointly use virtual screening and high-throughput screening strategies to screen more than 10,000 old drugs, clinical drugs, and natural active products, and found several species that have significant inhibitory effects on the main protease. Lead drugs, including disulfiram, carmofur, ebselen, shikonin, Tideglusib and PX-12. Subsequent anti-coronavirus experiments showed that both ebselen and N3 can significantly inhibit the replication of the neocoronavirus at the cellular level. It is worth mentioning that ebselen has been used in clinical trials for the treatment of various diseases such as hearing impairment (completed the second clinical phase), and has a good safety performance. The above-mentioned research results have laid an important foundation for the rapid development of anti-coronary pneumonia drugs with clinical potential.
  5. Abstract: Similar to SARS-CoV, SARS-CoV-2 is also a family member of coronavirus. But why is it leading to such a serious situation and when can we get rid of it? This article will explain the details about the development and future trends of SARS-CoV-2. As of July 1, 2020, the number of people diagnosed with COVID-19 worldwide has reached 11,669,259, and the death toll is as high as 539,906. On the frontal battlefield, there are still many doctors and nurses around the world struggling and working hard to save more lives. You may still remember the SARS epidemic caused by SARS-CoV in 2013. The virus started in Guangdong, China and a total of 5327 clinically diagnosed cases and 349 deaths have been reported in Mainland China. It also belongs to coronavirus, but why is this novel coronavirus caused by SARS-CoV-2 more serious than the similar virus of 2013? Coronavirus is a kind of pathogen that mainly causes respiratory and intestinal diseases, which mainly comes from domestic animals, poultry and wild animals (such as civet cats, bats). SARS-CoV can cause infection of the lower respiratory tract and induce pneumonia. The onset is rapid and highly contagious, with fever as the first symptom, with chills, headache, muscle aches, general fatigue and diarrhea gradually developed. Patients who are seriously ill may suffer from respiratory distress syndrome. The novel coronavirus, SARS-CoV-2, will infect the upper and lower respiratory tracts at the same time, which also allows it to spread like flu. A difference is that after the first symptoms of the patient, there are a large amount of viruses in the nose and throat of the upper respiratory tract, and the virus level in the nasal cavity is higher. At present, the most difficult challenge is those who are infected without symptoms. Although they do not show any symptoms, the virus levels in their bodies are comparable to those of symptomatic patients. Therefore, they not only have hidden characteristics, but also have the ability to be contagious, which makes it difficult to control the epidemic. In addition, SARS-CoV-2 has the characteristics of strong contagion, high population susceptibility, long incubation period, and diversified clinical manifestations, posing a huge threat to people's health and seriously affecting people's normal work and life. Experts of respiratory diseases said that the pneumonia caused by SARS-CoV-2 is likely to turn into a chronic, long-term human disease like the flu. As SARS-CoV is highly transmissible and pathogenic with the main attack organ the lungs, it is not easy to survive for a long time, and it cannot continue to spread. However, SARS-CoV-2 can also attack the kidneys, heart and other organs, thus is more difficult to cure. Scientists from Creative Biolabs, a CRO service provider once did a lot of research on SARS-CoV and MERS said, "We still know very little about SARS-CoV-2, but every study is a small piece of this huge virus puzzle." One thing is clear, protection against infections will most likely not stop the virus from spreading, but it will slow its spread. Many countries are currently conducting many antiviral drug tests for patients infected by SARS-CoV-2. And the vaccine may be available by next fall. Therefore, the more we slow down the spread, the better we can deal with this virus. In this long historical process, vaccination can be said to be the only more effective preventive measure. During the influenza epidemic season, comprehensive measures such as influenza vaccination are taken to prevent it, which has shown being very effective in controlling the influenza epidemic. In response to SARS-CoV-2, more and more vaccine candidates are currently undergoing evaluation and clinical trials worldwide and this number will increase substantially in the future. What distinguishes humans from other creatures is that humans have sufficient wisdom, courage, and perseverance. It’s believed that with global efforts, a safe and effective vaccine can be available as soon as possible.
  6. When we want to help the environment, it’s important to make the most of every opportunity. One major opportunity to live a greener life is to upgrade to a new green-tech car. Unfortunately, a car like this may currently be out of your price range. The good news is that there is plenty you can do to upgrade and change your lifestyle that will let you get a newer, greener car as soon as possible. Here are a few ways to upgrade to a new green tech car. Make Room in Your Budget If your budget is stretched to the max, it’s time for a budget review. Building margin into your budget will allow you to set some money aside each month until you finally have enough for a down payment on your dream car. If you look hard enough, you’ll likely find plenty of fat that you can trim. Just keep your end goal in mind, and you’ll be surprised at how much you’re willing to change. Sell Your Current Car If you’re almost over the hump when it comes to being able to afford a new car, all that you may need to do is sell your current car. If your car has seen better days, there are still companies that offer cash for junk cars to help give you the financial jolt you need to succeed. You can also try selling your vehicle yourself, although that may take longer, which would delay your timeline for getting a new car. Look for Rebates Since you’re interested in an eco-friendly car, you may find that your local or state government has rebates to help you offset the cost of your new car. Since cities and states benefit when their citizens produce less pollution, there is a vested interest in steering people toward cars that sip instead of guzzle gas. Seek A Loan Although not everyone can obtain a car loan, these types of loans are far easier to obtain than more restrictive loans such as mortgages. As long as you have the money to make the monthly payments during the term of the loan, then this could be your best option. Typically, you’ll want to check with local lenders to get their rates before you head to the dealership, as this will provide the most options to ensure you’re getting the best deal. Take Care of It Once you finally have the means to pay for your new car, it’s important that you take good care of it. After all, you don’t want your financial investment to end in financial ruin because your car breaks down after only a few years. For most vehicles, though, as long as you give them care on the proper schedule, you can expect to get several years and tens of thousands of miles of use before it’s time for a replacement.
  7. When it comes to living a sustainable lifestyle, it's the activities you do every day that tend to be more important than the big and impressive things you do. That's why it's important to find ways to make your everyday activities more sustainable. The good news is that making your lifestyle more sustainable doesn't have to cause major inconveniences. In fact, there are many aspects of sustainable living that are more enjoyable than their non-sustainable counterparts. Compost If you have the space, composting is an excellent way to live a sustainable lifestyle. Rather than sending organic waste to the dump, you can keep it on your property and turn it into rich fertilizer for your garden. Even if you live in a city, you can use a desktop composting bin to create smaller amounts of compost that you can use in a window box or herb garden. Buy Products Made From Recycled Materials Recycling is a key component of creating a healthier planet for future generations. In order to support recycling efforts, though, it's important to buy products made from recycled materials as often as possible. Without a solid market for products made from recycled materials, companies will be forced to use virgin materials, which typically have a more significant impact on the environment. You can find ways to buy recycled materials, like dog toys or yarn from a site like Combine Errands Although vehicles make everyday tasks much more convenient, they add a significant amount of pollution to the atmosphere. While the best response to this problem is to buy a car that gets better gas mileage, that isn't always feasible. A more simple solution is to be more careful about planning your errands so that you can reduce the amount you drive, thus reducing your carbon footprint. Collect Rainwater Water is one of the most vital resources in terms of completing everyday activities around your home. Since water is a limited resource, though, it's important to conserve it whenever possible. One great way to overcome this problem is to collect rainwater as it leaves your home's gutters. Using rain collection barrels, you can ensure that you always have water available to water your plants and do other outdoor tasks. This will help lower your water bill and ensure that there's water available for future generations. One reason that people pollute more than they should is that they simply fall into a rut and don't think through their actions. By continuing to do things the way you've always done them, you will likely use more energy and create more pollution than you would if you took some time to observe your actions. By thinking through the things you do every day, you can begin to search for new ways to do these things so that you can help make the world a better place.
  8. Earlier
  9. You already do your part for the environment by choosing energy-efficient appliances and reusable household goods, but have you considered the environmental footprint of your home's plumbing system? The top four plumbing issues that can wreak havoc on the ecosystem include water wastage, overuse of water, chemical pollution and garbage accumulation from discarded plumbing materials. If you want to green up your pipes, here are four simple ways to counteract these problems. Lower Your Flow One of the easiest and most effective ways to curb water wastage in your home is to install low-flow faucets, showerheads and toilets. Are you worried about getting all the shampoo out of your hair? Today's low-flow technology is miles ahead of those trickling faucets you remember, so you won't even notice the difference. The best part is that reducing water wastage not only helps save the environment but also saves money on your monthly utility bills. Recycle Greywater Overusing water resources is a growing problem, and outdoor usage, such as watering your lawn or garden, accounts for between 30 and 60 percent of household water usage. However, you don't have to say goodbye to your lush lawn if you want to save water. Use water that would have otherwise been discarded to water your grass or garden with a greywater recycling system. Avoid Chemical Drain Cleaners What do you do when your drain is clogged? If you're like most people, you reach for a bottle of drain cleaner. Although drain cleaners can bust up clogs quickly, the harsh chemicals they contain end up in lakes and streams where they can upset the PH balance and poison wildlife. Most plumbers recommend trying natural methods like baking soda or a plastic pipe snake to bust up a clog and calling in the professionals if that doesn't work. Choose Eco-friendly Materials The pipes that carry water to your faucets and fixtures can also cause a problem for Mother Nature when they wear out and get discarded. If you're installing new plumbing, choose materials that are durable and recyclable. Although the price tag is high, you can't do better than copper pipe. Not only does copper last forever, but it's also recyclable and better for your health than plastics, which often contain potentially harmful chemicals like BPA. Remember, keeping your plumbing in good condition is also essential for protecting the ecosystem. Poorly maintained pipes can leak and waste water or contaminate important water sources like groundwater, lakes and streams. Most importantly, be aware of how much water you are using as well as what you are flushing down your drains.
  10. The early success rate of establishing the PDX model is extremely low, which is largely due to the rejection of the transplanted material by the host immune system. Although methods such as X-ray irradiation and thymectomy have been used to suppress the host's immune system, the development of the PDX model has largely benefited from the production of immunodeficient host mice. The first breakthrough was the development of nude mice. In 1962, Scottish doctor Issacso and others first discovered individual hairless mice in non-inbred albino mice, but did not conduct an in-depth analysis of them. In 1966, Flanagan from the Institute of Animal Genetics in Edinburgh confirmed that this hairless mouse was caused by allelic mutations on the chromosomes. He believed that it was a new spontaneous mutant and named it "Nude" mouse. Flanagan also found that female nude mice had extremely low fertility and could not raise their offspring due to poor breast development, but unfortunately he did not find the most important feature of nude mice, athymic glands. In 1968, Pantelouris from the University of Strathclyde in Scotland discovered athymic glands in nude mice obtained from the Institute of Animal Genetics in Edinburgh, which aroused great interest among medical biologists around the world. Nude mice are congenital hairless, athymic, and completely lacking in T lymphocyte function, and do not produce rejection response to xenotransplantation. Therefore, they are especially suitable for xenotransplantation of xenogeneic animal tissues and human tumor xenotransplantation, and are expected to replace thymectomy mice. In 1969, Danish scholar Rygaard successfully transplanted human colon cancer tumors into three nude mice for the first time. Six days after tumor transplantation, tumor tissue was found at the transplanted site. On the 40th day of tumor transplantation, the original 2×2×2mm tumor tissue had grown to 10×20×25mm in two of the nude mice, and 5×5×20mm in the other nude mouse. No signs of tumor growth were found in normal mice in the control group. As a result, scholars have established many PDX tumor models by transplanting various types of tumor tissues into nude mice. In 1983, Bosma, GC and others discovered a severe combined immunodeficiency CB17-SCID mouse, which lacks mature T cells and B cells, but the innate immune system retained in the body such as normal NK cells is not good for humans. Long-term colonization of source cells. In 1995, Jackson Lab used non-obese diabetic mice NOD/Lt to cross with SCID mice, and NOD-SCID mice were produced. This hybrid breed inhibits the activity of NK cells and is accompanied by defects in the innate immune system. Therefore, it is an animal model with more severe immunodeficiency, easier xenotransplantation success and stable application. However, NOD-SCID develops thymoma in an average of 8.5 months, so long-term models are not suitable. In 2002, the Japan Institute of Experimental Animals (CIEA) bred NOG mice. They successfully established a severely insufficiency immune system by crossing NOD/scid mice and γ-chain IL-2 receptor knockout (IL2rγKO) mice. Compared with NOD-scid mice, the survival rate of human cell and tissue transplantation in NOG mice is significantly improved. At the same time, it can implant a higher proportion of normal or cancerous human cells and tissues. In 2005, Jackson Lab in the United States developed NOD-scid gamma (NSG) mice. Due to genetic mutations, these mice have defects in T and B lymphocytes and the gamma chain gene of IL2 receptor, which has important immunoregulatory functions, was knocked out. In addition, NK cells also lose their function and can be used to transplant human cells and tissues without causing traditional immune responses. They are currently the most ideal recipient mice for humanized tissue transplantation. Subsequently, some scholars transplanted human hematopoietic stem cells (HSC) into these mice to form humanized hematopoietic and immune system reconstruction mice, which proved to be very effective human-derived mice. In addition, there are PBMC models in which human peripheral blood mononuclear cells are directly injected into severe immunodeficiency mice for immune reconstitution; human embryonic liver and thymus are co-transplanted under the kidney capsule of immunodeficiency mice, and at the same time BLT models are established by injecting hepatic hematopoietic stem cells from the same embryo into mice. These models are also widely used in the research and construction of PDX models and are effective tools for studying human diseases. In recent decades, with the widespread use of immunodeficient mice, a large number of PDX tumor models have been successfully established. These models retain the histopathology, molecular characteristics and drug response of their parent tumors, can reproduce tumor heterogeneity that cell line systems have not captured, and show potential clinical trial response prediction capabilities at the population level. In view of this, the PDX model provides a powerful tool and has been widely used to study cancer biology and assist in the preclinical setting of personalized cancer treatment and drug screening.
  11. An environmentally friendly car is society’s attempt to reduce air pollution and decrease everyone’s dependence on gasoline. However, buying a brand-new hybrid or electric car is not an option for everyone. Sometimes, it works to compromise by looking at the features that make a car green and the features that don’t make it green. Here are 4 tips to consider as you look for green used vehicles. Compare the Gas Mileage Gas mileage, also known as fuel efficiency, determines how far the car goes without needing to be refueled. This rate is the most important factor to consider when looking at an energy-efficient vehicle. You should not automatically choose the vehicle with the highest mpg ratio, though. You also need to consider other design features, such as the car’s engine, tires, weight and type of oil, that affect its energy efficiency. Compare the Toxic Emissions Rate A great deal of a city’s air, soil and water pollution comes from cars. In major cities, much of the toxic air pollution is caused by vehicle emissions. The U.S. Environmental Protection Agency sets Tier 2 and Tier 3 standards to limit the amount of emissions that are released by certain types of vehicle. People who want used vehicles should review the general toxic emissions ratings that are available. Compare Hybrid vs Non-Hybrid Vehicles When people hear of energy-efficient cars, they often hear of hybrids that run on petroleum and electricity. It’s not necessary to buy a hybrid to drive an environmentally friendly car. It is necessary to learn the similarities and differences between hybrid vehicles and non-hybrid electric or gas-powered vehicles. Compare the Repair Rates When buying a green used vehicle, avoid the one that requires a lot of repairs. It may be cheaper, but it consumes more energy than a healthy vehicle. A damaged car emits more toxic gases into the air as it struggles to work properly and becomes overheated. Make sure that your chosen car is built well with a long lifespan, and have it maintained at least once year. Green used car buying is not always straightforward. Sometimes, it takes learning the basics of hybrid and electric vehicles that you’ve heard of but know nothing about. But your efforts of trying to save energy and the environment will pay off in the end. Continue to review the tips and tricks of finding the best deal for your used vehicle.
  12. Antibody-drug conjugate (ADC) is a humanized or human monoclonal antibody that is conjugated to a highly cytotoxic small molecule (payload) through a chemical linker. It is a novel form of treatment and is used in cancer chemotherapy. This new antibody-based molecular platform can selectively deliver effective cytotoxic payloads to target cancer cells compared with traditional chemotherapy, thereby improving efficacy, reducing systemic toxicity, and having better pharmacokinetics (PK)/Pharmacodynamics (PD) and bio-distribution. Driven by the success of Adcetris® and Kadcyla® approved by the FDA, this drug class is developing rapidly along with approximately 60 ADCs currently in clinical trials. In this article, we briefly reviewed the molecular aspects of each ADC component (antibody, payload, and linker), and then mainly discussed traditional and new technologies for successfully constructing clinically effective ADC coupling and linker chemistry. From the point of view of medicinal chemistry and pharmacology, current efforts in conjugation and connection chemistry will provide deeper insights into the molecular design and strategies of clinically effective ADCs. The development of site-specific conjugation methods for the construction of homogeneous ADCs, especially ways to improve ADC design will open the way for new cancer treatment methods. An introduction In the past half century, with the development of chemotherapy, the treatment of cancer has improved significantly. In addition to surgical resection, radiotherapy, targeted therapy using small molecules or monoclonal antibodies, and recent immunotherapy, chemotherapy using cytotoxic agents is the main treatment option. Chemotherapy is perfected by screening and developing small molecules that can selectively cause cancer cell death by inhibiting microtubule function, DNA synthesis or protein function. Although chemotherapy has achieved great success in the treatment of cancer, especially leukemia, there are still difficult problems, such as the development of drug resistance mechanisms. Serious adverse reactions caused by off-target cytotoxicity may worsen the patient’s quality of life, leading to drug withdrawal. This fact makes clinicians and medicinal chemists reluctant to pursue more potent cytotoxic drugs to treat cancer. In this case, the use of highly cytotoxic agents combined with cell targeting molecules has become a potential clinical strategy. In particular, antibody-drug conjugates (ADC), humanized or human monoclonal antibodies conjugated to cytotoxic small molecules via chemical linkers, may undergo fundamental changes in the design and administration of cancer chemotherapy. The platform can target cancer cells and selectively deliver highly cytotoxic drugs, thereby creating a broad therapeutic Indeed, successful clinical results using ADCs have inspired scientists in the biomedical research community to further advance this new platform to the next generation of cancer treatments. In this article, we reviewed the molecular aspects of ADCs, the latest developments in ADCs that have been successfully used in clinical applications, and the coupling and connection technologies used to successfully construct ADCs. A brief history In 1913, German physician and scientist Paul Ehrlich first proposed the concept of selectively delivering toxic drugs to target cells. Forty-five years later, his targeted therapy concept was proved for the first time in the form of ADC, where methotrexate was conjugated with a leukemia cell targeting antibody. In early research, polyclonal antibodies were the main targeting agent. In 1983, the first use of anti-carcinoembryonic antigen antibody-vinblastine conjugate for ADC human clinical trials, and reported promising results. Advances in antibody engineering technology, including the production of humanized antibodies, have promoted ADC research. The first-generation ADC consisting of chimeric or humanized antibodies was tested in the 1990s. Finally, further major efforts on practical therapies led to the FDA-approved ADC: Gimumab ozogamicin (Mylotarg®) for CD33-positive acute myeloid leukemia in 2000, and for CD30-positive relapsed or refractory Hodgkin’s lymphoma in 2011 brentuximab vedotin (Adcetris®). Anaplastic large cell lymphoma and trastuzumab Emtansine (Kadcyla®) were used in HER2-positive breast cancer in 2013. However, Mylotarg® was withdrawn from the market in 2010 due to lack of clinical benefit and lethal high toxicity compared to standard chemotherapy. Despite this setback, ADC technology is still developing rapidly, and about 60 ADCs are currently in clinical trials. In addition to immunotherapy using checkpoint inhibitors, this emerging chemotherapeutic molecular platform is expected to significantly increase its market share as one of its largest markets. The most effective anti-cancer therapy in the near future. The structure and mechanism of ADC Another important consideration is the limited number of payload molecules that can be effectively delivered to target cells. If it is assumed that the efficiency of each step in the ADC mechanism is 50% (biodistribution, binding to antigen, internalization, release of payload, intracellular stability of payload, and binding of payload to target), then only 1.56% administered drug molecules can enter the target cell. In fact, the estimated actual intake is much lower than this assumption (less than 0.01% per gram of tumor injection). Therefore, in order to maximize the therapeutic efficiency of using ADC, the cytotoxicity of the payload must be high enough to effectively eradicate target cells, and ideally should be in the picomolar range. It is very important to choose important toxic drugs as payloads, and ideal drugs have inherent selectivity to target cancer cells. Certain types of non-cancer cells may be able to internalize ADC through non-specific pinocytosis or crystallizable fragmentation (Fc) region receptor-mediated endocytosis. In addition, the payload can be released when it degrades into circulating blood. Therefore, the payload is mainly selected based on the above considerations; anti-mitotic agents are usually less toxic to non-cancer cells than to cancer cells, and are payloads that are mainly used in FDA-approved ADC and ADC clinical trials. In addition to calicheamicin (for Mylotarg®), auristatin (for Adcetris®) and maytansinoid (for Kadcyla®), a new type of highly effective anti-mitotic compound has been explored for ADC loading: Carmycin, pyrrolobenzodiazepine dimer (PBD) mannosides, mannosins, and tubulolysin analogs are such examples. To be continued in Part II…
  13. More people are opting to install a solar panel in their home. A solar panel can help you save a lot of money. However, there are several things that you need to do in order to ensure that you get the most out of your solar panel. Have Your Solar Panel Installed by a Professional You may be able to install your residential solar panel yourself. However, it is best for you to have it installed by a professional. They will be able to safely install your solar panel. Proper placement will also ensure that your solar panel gets maximum sun exposure. Additionally, proper placement will help you protect your property. Sell Your Extra Energy Back Many solar companies have an option to sell back the energy you don’t use. This not only cuts down your energy bill immensely, but it supplies green energy to be recycled for other uses by the company. Once you pay off your solar panels entirely, you’ll be able to completely bank off of your extra solar energy with no offsetting costs. Make the Most of Your Energy Use During the Day Because solar panels can only generate energy during the day, it is best for you to make the most of your energy during the day. For example, it is best for you to charge your appliances during the day. You can also set a timer to where your appliances power down after a certain time. Of course, just because it only absorbs energy during the day doesn’t mean that you won’t have energy at night, as solar panels store the energy they collect for later use. Using your energy during the day, however, will allow for extra storage to be used in the evening so you won’t be using energy while your panels aren’t pulling in more. Clean Your Solar Panels on a Regular Basis Your solar panel will not work as efficiently if it is not clean. That is why you will need to have your solar panels cleaned once every six to 12 months. Bird droppings, debris, and mold can reduce the amount of sunlight that your solar panel receives. You will also need to make sure that trees and not blocking the solar panel. A solar panel can help you save a lot of money on energy. However, in order to get the most out of it, you will need to have it installed by a professional. You should also use one appliance at a time and make the most of your energy during the day. Additionally, you should clean the solar panels regularly.
  14. Pests invading your homestead garden can ruin not only entire crops but also your plans to live off-grid. Managing garden pests is especially frustrating when you don’t know what type of pest is eating up your garden. Identifying your pests is an important first step, before you can take action to protect your crops. Large Animals Animals such as deer, raccoons, rabbits, and birds will all find the vegetables growing in your garden irresistible. The good news is, these larger animals can be easier to control than insects. A 6-foot tall fence should keep out deer and even raccoons. Digging a trench a few feet deep around the garden, and embedding chicken wire can also help discourage burrowing animals, such as rabbits, from getting into your veggies. Finally, adopting an outdoor cat will help keep rodents under control. Insect Pests On the other hand, insects are nearly impossible to keep out with a simple barrier. Identifying the culprits is the first step. First, take note of the type of damage. If there are holes chewed through the leaves, you have some type of chewing insects, such as caterpillars or locusts. Sickly, yellow leaves could indicate aphids; look under the leaves for this sap-sucking pest. If you see squiggly lines on the leaves, you have leaf miners, which are likely the larvae of many different types of flies, beetles, and moths. Natural Pest Control Natural pest control methods include fostering beneficial insects to eat the bad insects munching your veggies. For example, ladybugs love to eat aphids, and praying mantises will capture and eat all sorts of pests, such as grasshoppers. Nematodes are another type of insect that kills other insects. Another way to help control insect pests is to plant bug-repelling plants, such as marigolds, geraniums, or chrysanthemums. You can also plant herbs like basil, garlic, onion, parsley, and peppermint to repel insect pests. Plant these among your vegetables. Insecticides Finally, insecticides can be used. For example, you can mix one part garlic juice with four parts water, and spray it onto your plants. You can also dust your plants with diatomaceous earth. This a fine, white powder made of fossilized phytoplankton. It’s harmless to people and animals, but will cause insects to dry out and die. If your garden is infested with snails and slugs, place a few shallow bowls of beer around the garden; snails love beer, and they’ll crawl in, get drunk, and drown. If these natural solutions aren’t working, you’ll want to contact a pest control service. They can help you identify your pests and understand why your solutions haven’t worked yet. They can also recommend alternative pesticide solutions. Pests are a pain, and they can do a lot of damage to your food supply if they’re not caught and removed quickly. Do some research to learn what kind of pests you’re dealing with and how to keep them out.
  15. Conducting business in an environmentally friendly way is becoming increasingly important for consumers. Environmental safety refers to practices that create a safe workplace and that have as little impact as possible on the world at large. As a company owner or manager, finding ways to avoid environmental hazards with your business is not just a sound ethical choice. Many prospective clients appreciate a company that shows care and consideration for the environment. Some of your customers may be happy to reward your efforts with regular orders or requests for your services. Here are just a few ways to avoid creating environmental hazards with your business. Use Appropriate Storage and Labels Some businesses have to deal with dangerous, toxic chemicals in their daily operations. There are already guidelines in place that you can use to educate workers about the potential dangers of the chemicals you might use or move. Proper labels on storage tanks are a basic yet essential part of the regulations here. It is also important to make sure that any employees that need to handle these things will have access to the appropriate protective gear. Consider a Specialist Agency As a company owner or manager, you probably familiarized yourself with standard safety regulations for your industry when you were getting the business up and running. However, you might not be aware of all the technical details that go into environmental safety in the workplace. Think about using an outside source or environmental safety company like Element Building Sciences to help you. They can assist your workers in the testing of materials, proper health and safety training, or preparations for a disaster. Don’t Forget Unseen Issues Not every potential problem that could pose a threat is obvious. If workers need to spend long hours around extreme heat, cold, or loud noises, there is potential for damage without coming into contact with anything dangerous. Many workers find out over time that some of these conditions have caused great harm. This often results in worker’s injuries that require large payouts in compensation. Check for less visible threats to protect yourself and your employees. Guard Against Personal Hazards Personal hazards can be similar to some of the unseen ones. However, there is a greater focus on manual labor that could directly affect a worker as part of his or her job. A heavy load that isn’t labeled properly or tools that malfunction could cause serious personal injuries that make a workplace environment unsafe. These are some of the most common workplace hazards, and proper training is a big part of avoiding them. The prevention of environmental hazards inside and out of a workplace is becoming a more crucial step in the success of any company today. In addition to helping you gain loyal customers and repeat business, it’s also a requirement by law. Using some of these tips, you can comply with OSHA standards and create a safe, welcoming workplace for your employees.
  16. The amount of energy used in your home can be reduced significantly through energy proofing. This process involves repairing and replacing broken components and sections in your home that cause energy wastage. It may sound easy for a technician, but it can be problematic for untrained homeowners. These are the main repairs around your home that can lead to efficient use of energy: HVAC System Repairs Heating and cooling your home may contribute to the high use of energy. The primary system used in the heating and cooling of a house is the HVAC system. Proper maintenance of the system helps in conserving energy. The main repairs that should be done include cleaning the vents and air ducts, maintaining the thermostat, and lubricating any moving part. Collectively, this will ensure that the system does not use a lot of energy to operate. When the furnace and heat pump have performance issues, they are likely to use a lot of energy. To reduce the wastage of energy, you should replace air filters, seal any leaks in the air ducts, and install a programmable thermostat. You also need to ensure that the heating and cooling system is working optimally. Windows and Doors Repairs As a homeowner, you should ensure that your windows and doors are opening and closing effectively. If the frames of these structures are broken, you may experience high energy bills. They will let cold air into your house during the cold seasons, making your heating and cooling system overwork. You should hire an expert to rectify the broken doors and windows to enhance energy efficiency. Thermostat Repairs Many gadgets at home use a thermostat, which regulates the energy used by a system. When a thermostat is malfunctioning, it stops regulating the energy used by a unit. You should check to ensure that all the thermostats are working effectively. Also, it is imperative to replace manual thermostats with smart thermostats that automatically schedule a system. Siding Repairs The defective sidings of your house can cause energy inefficiency. Therefore, it is advisable to regularly inspect your house to identify gaps in the home's sidings. Leaky sidings may increase energy consumption in your house and lead to high monthly bills. The energy used in your house is influenced by how well energy-consuming systems are working. The repair of each of these systems leads to efficient use of energy. Also, the home must be kept in excellent condition to ensure that airflow is easily regulated.
  17. Businesses and homeowners are turning to solar energy to power their lives more than any other time in US history. Factors behind this include the falling cost of solar panels and rebates and incentives offered by the government and utility companies. However, saving money is just one factor that has encouraged people to choose solar power. Other factors include a desire to improve their health and protect the environment by reducing the use of fossil fuels. How Do Solar Panels Work? Solar panels make it possible for photons or particulates of light to release electrons from atoms. This is used to generate a flow of electricity. When you look closely at a solar panel, you see that it is made of several smaller units called photovoltaic cells. When several of these photovoltaic cells are put together, they create one solar panel. How Does Solar Energy Impact the Environment? Solar energy is renewable. It is a clean resource. It reduces harmful emissions that can affect the atmosphere. Since it minimizes greenhouse gases around the world, solar energy has a favorable impact on the environment. Traditionally, energy used in the United States is produced from fossil fuels, including coal and natural gas. The process by which fossil fuels are extracted is expensive and detrimental to the environment. If mankind could capture the sun’s energy for just one hour, you would be able to power the entire planet for one year. Using solar panels is one step toward eliminating mankind’s reliance on fossil fuel for the most consistent and abundant source of energy available. How Solar Energy Impacts Health Solar energy leads to fewer air pollutants. According to the National Renewable Energy Laboratory, sulfur dioxide, nitrous oxides, and particulate matter, emissions would drastically drop around the world if everyone adopted solar use. This could lead to a reduction in chronic bronchitis, cardiovascular problems, and respiratory issues. As a side benefit, there would be fewer missed days from work related to these health issues. The Benefits of Solar Energy The benefits of solar energy are easy to see. It can lower your electric bill. Solar energy reduces a person’s or company’s carbon footprint. This improves the health of the building’s occupants and of those around them. The sunlight used to produce solar energy is free and available in abundance. Fossil fuels are quickly running out. Reducing reliance on a finite resource, like fossil fuel, and taking advantage of an infinite power supply, like the sun, has wide-ranging benefits for the planet.
  18. When many people think about things that they can do to make their homes energy-efficient, they think about their appliances. You can also make your plumbing more energy-efficient. There are several things that you can do to increase the energy efficiency of plumbing. Energy-Saving Water Pipes The type of pipes that you have will determine how energy efficient they are. The right pipes will also improve water pressure, reduce leakage, and minimize heat loss. The best types of pipes for you to buy are PEX pipes or steel pipes. These types of pipes will also last longer. If you are not ready to replace your pipes, then there are still things that you can do to help them save energy. You can add pipe insulators to copper and plastic pipes. The pipe insulators can cut heat loss by 80 percent. Water-Saving Toilets Water-saving toilets are designed to use less water. There are some toilets that use 20 to 60 percent less water than your average toilet. The water-saving toilets work just as well as regular toilets. There are also some toilets that allow you to adjust the amount of water that your toilet uses. Energy-Efficient Water Heater Water heaters have a tendency to use more energy as they get older. Poor insulation can also your water heater to not work as efficiently as it should. If your water heater is over the age of 10, then it is a good idea for you to get a new water heater. New water heaters are not only more energy-efficient, but they also use less water. Additionally, you may want to install a tankless water heater if you live in an apartment or a small home. A tankless water heater only heats water when you need it. This can help you save even more energy and water. Replace Faucets and Showerheads One of the easiest things that you can to make your plumbing more energy efficient is to replace the faucets and showerheads. New faucets and showerheads can reduce water usage by 30 percent. They are also inexpensive and easy to install. Making your plumbing more eco-friendly can help you save a lot of money. You can save money by installing energy-saving water pipes and toilets. You can also install an energy-efficient water heater. Furthermore, you can save a lot of energy by replacing faucets and showerheads.
  19. Did you know that many of the metals used to produce everyday objects are recycled rather than mined from the earth? Collecting and selling scrap metal for recycling is a great way to earn money for hobbyists and professionals alike. Whether you’re looking to make a little extra cash on the side or recycle scrap metal as a full-time job, here are some tips to help you get started. Know Your Metals When it comes to scrap metal, copper is the reigning king. The energy and expense required for copper recycling is much less than creating copper from ore, which makes any existing copper extremely valuable. Precious metals like gold and silver fetch an even higher price than copper, but they are difficult to find in large quantities. Other metals that can earn you a pretty penny include aluminum, brass, iron and steel. Seek Out Sources Now you know what metals to look for, but where do you find them? Construction waste is a great source of scrap copper from plumbing and wiring. You can also find copper wiring inside old electronics and appliances. Check pawn shops, thrift stores and estate sales for precious metal jewelry that can be sold for scrap. One of the most accessible sources of scrap metal is discarded aluminum cans, but you will need a lot of them to earn a significant amount of money. Have a Collection and Storage System The trunk of your car might be sufficient for scrap metal hobbyists, but you’ll need a more sophisticated setup if you’re serious about recycling. Get a truck or van for hauling your scrap around and a warehouse to store it. Use tall shelves and labeled bins to keep everything organized. Find the Best Price After all the effort you put into finding and collecting scrap metal, you don’t want to let it go for nothing. Search around for buyers who can give you the best price for your recyclable metal and keep an eye on the markets because the price of many metals fluctuates over time. Having a good storage system can help you hang onto your scrap until you find the best price. Remember, metal recycling isn’t a get rich quick scheme. It takes a lot of work and perseverance to earn a living with scrap metal, but your efforts will pay off eventually if you stick with it. Don’t forget to keep careful track of your business so you can identify trends and maximize your profits.
  20. In the past few decades, home improvement has taken on more and more of an emphasis on green remodeling. To help protect the environment, these remodeling strategies are focused on lowering energy consumption and improving resource management. Here are four of the most popular green home updates and how they benefit the environment. Purchased Reclaimed Supplies The materials that you need for your home improvement project, such as wood and tiles, are likely available as reclaimed components of previous construction projects. Even your countertops and insulation can be made from recycled materials. Reclaimed materials are becoming all the rage with homeowners who want to minimize their environmental footprint. In addition to being a healthier alternative from an environmental perspective, these reclaimed materials are often more affordable than new ones. Plug the Leaks With Better Insulation One of the biggest environmental burdens that American homes pose is the energy that is lost around poorly insulated windows and doorways. In the summertime, too much precious air-conditioned air can escape through cracks around the windows and doors, and in the wintertime, warm air can seep out. You can cut down on your energy consumption and save substantial money on your heating and cooling bills by filling the cracks around windows and doors and by checking the insulation in these areas. Update Your Windows In addition to the heat lost through worn or poorly sealed door and window frames, you may also be losing warmth through your old windows. Traditional windows are single-paned, which provides very little insulation against summer’s heat or winter’s cold. When it’s time to update your home, choosing replacement windows with two panes of glass can go a long way in helping you lower your energy usage. Use Eco-Friendly Paint Volatile Organic Compounds (VOCs) are fumes that are commonly found in commercial paints. They can be dangerous for humans as they can cause nausea and difficulty breathing as well as many other health problems. They can also cause ozone pollution as well as other environmental hazards. However, the trend is reversing as many manufacturers now produce low or no-VOC paints for the environmentally-conscious consumer. Low and no-VOC paints represent a superior alternative to paints containing VOCs because the compounds can leak into the nearby soil and water supplies, endangering both human and animal life alike. Solar Energy The sun is indisputably the greatest source of energy that we have. Until now, though, harnessing the power of the sun to power our homes was overly expensive and just not feasible for most homeowners. However, that is rapidly changing as more and more tech companies pour money into developing solar technologies into viable consumer products. Now, more solar-powered home appliances are available than ever before, at prices that can fit even a modest budget. You don’t have to do a complete overhaul of your home all at once to make it more eco-friendly. However, when it comes time to make normal repairs or renovations, consider choosing the greener option. The great thing about making these changes is that, in addition to doing your part to conserve resources, they also come with significant cost-savings that make good economic sense as well.
  21. Home decor is the latest industry to include sustainable materials. When it comes to home decor, it is generally about aesthetics and less about whether a product or materials are sustainable. But, there are plenty of options that are both beautiful and functional as well as green. Everything from the paint on your walls to the natural stone tiles on your floor can be sourced with sustainability in mind. The ease of finding these products means that you don't even need to make many changes to your personal style or worry about a huge expense in order to easily use sustainable materials. These are a few easy changes to consider and ways in which you can easily make your home more sustainable. Select Furnishings Made From Sustainable Materials Anytime you need to update or redecorate items in your home, focus on options that are made from sustainable materials. Fabrics, wallpaper, cabinetry, flooring, and furniture are all choices that help establish a room and make a great backdrop for smaller decor pieces. More brands continue to offer sustainable options with each year as options become available and consumers show interest in swapping out less earth friendly choices. Choose Quality Over Fast Decor Like fast fashion, decor is available cheap and on trend. Stop buying items that fall into the category of fast decor and instead choose quality pieces that will last a lifetime and can be incorporated into your decor scheme year to year and season to season. Quality pieces will include those that are made from reclaimed wood, covered in organic natural fabrics, sourced from natural stone outcroppings, and from brands that have earth friendly manufacturing processes. Repair and Purchase Second Hand In addition to purchasing quality decor and furnishings, consider purchasing secondhand or repairing those items you already own to breathe life into old items. Along with overbuying fast decor or purchasing pieces that will not last, buying secondhand is a great way to keep items out of the landfill. You can quickly reupholster a chair or couch with sustainable fabric, making it as good as new. Small home furnishings from lamps to shelving to art pieces can be purchased secondhand or repurposed in a way that suits your personal style. DIY projects are also a great way to use up sustainable materials in a way that coordinates with the decor in your home. All of these ideas can help you create the home of your dreams.
  22. Everyone likes to see custom-made wood furniture. You may not realize that an aged door can be removed, taken apart and rebuilt into a brand-new piece of woodwork. You can decorate your entire home with customized pieces. The following are four popular ideas to consider for this craft. Coffee Table Turn your old door into a wooden coffee table. Replace an old coffee table or put it in a room that has no table at all. An old, unattractive door can look like an elegant, polished table if it’s made correctly. And for many people, building a table by hand is more fulfilling than hiring a professional to do all of the work. There are many different types of materials that can be incorporated with wood, such as metal, glass or porcelain. Some tables are made with wooden frames and legs and an elaborate glass centerpiece. In the end, a badly scratched door can be built into a luxurious, polished table. Shelves In some rooms, there can never be enough shelves. Your garage or attic could use more shelves if it’s overflowing with old books, appliances, storage bins, etc. Compared to coffee tables, shelves are easier to create and install. Restored Doors Old doors can be made into brand-new ones with different designs. Install replacement doors that have been freshly sandblasted to remove the scratches and cracks. Have the door polished to prevent new damage and painted a different color. This door will look brand new, even if it’s been used for decades. Bench or Chair People can learn to make furniture by hand using old doors. A bench or chair is not too difficult to make with a few power tools. It’s also interesting to see how one useful creation can transform into another. Build a simple wooden bench for your backyard or a loveseat swing for your front yard. Use the old wood to build a tree house for children. Another option is to build a rocking chair for the living room or bedroom. There are a million items that you can make out of an old door. Start by building items that you use on a regular basis, such as tables and shelves. Then, consider using old doors to craft other items like bedposts, bar tables or picture frames. Know that a door of any age and condition still has value and can be used for good.
  23. Just because the weather is heating up doesn’t mean that you need to accept huge water bills. With a little bit of hard work and a few simple upgrades, you should be able to save a huge amount of water during the sweltering summer months. Adjust Your Irrigation Many people don’t realize just how much water is needed to keep their lawns and plants alive during the hottest months of the year. As soon as the weather starts to warm up, you will need to adjust your sprinkler system so that the water doesn’t evaporate before it is absorbed. In most areas, homeowners should have their sprinklers turn on a few hours before the sun comes so that the ground can become fully saturated. Double-Check for Leaks Slow leaks are another problem that many homeowners struggle with, and this issue could have a huge impact on your water usage. To check for a slow leak, you will need to turn off all of your appliances and faucets and then check the water meter. If the numbers on your water meter continue to move even though no one is using any water, then you probably have a leak. Reuse Your Water You might be surprised to hear that you can actually reuse much of your water as long as it doesn’t have too many contaminants. The average wastewater treatment system is very easy to install, and one of those systems will allow you to use old water to keep your lawn and plants alive. Those types of systems are also perfect for families that would like to grow their own food in a garden or small farm. Collect Rain Even if you don’t live in an area that gets a lot of rain, rain barrels could still be very beneficial. During a single rainstorm, your rain barrels might fill up in a matter of minutes, and that water can be used in many different ways. Before you install any rain barrels, you will need to figure out exactly where all of the water on your roof goes during a rainstorm so that you can collect as much as possible. In addition to these few tips, you should also make sure that your family is being sensible with water usage. That includes steps such as taking shorter showers, turning off faucets when they aren’t needed, and properly using all of the appliances.
  24. CD Genomics, an innovative sequencing and genotyping company, recently announced the launch of its new website with brand new product and service ranges and easy-access custom design. Gene Panel is an invaluable tool to analyze parallel gene expression for disease-associated mutations. Among them, next-generation sequencing (NGS) technologies are perhaps the most widely used approaches, which can analyze genetic mutations of large sample-size projects and facilitate research on human well-being. In the meantime, some non-NGS technologies may offer alternations for gene panel with a much more affordable price. CD Genomics Disease Panel is a one-stop destination for kinds of sequencing and reagents needs. Their catalog features hundreds of products such as Ready-to-Use NGS Panel for oncology, genetic disorder, genotyping, pathogen infections, Custom Panel Product and Non-NGS Panel, which can promote researchers’ disease research, biomarker discovery, molecular diagnostic application and targeted drug development. The newly launched website also features updated service descriptions and details, and a new Resource page. The services range from Predesigned NGS Panel for cancer, inherited disease, pathogens and pharmacogenomics testing, Tumor Mutational Burden Analysis, Custom NGS Panel, to Non-NGS Panel, for example, MassARRAY, Multiplex SNaPshot, Multiplex Ligation-Dependent Probe Amplification and ARMS-PCR for Sequence Variation Analysis. Moreover, customers searching for a new addition to the backyard can decide between the listed items and others. “CD Genomics can quickly respond to customers’ primers design or probes determination requirements. The accumulation of each measurement ensures a shorter turnaround time. Their comprehensive quality control and verification ensure the accuracy of results. I’d like to recommend the appropriate technology for gene-targeted detection to other researchers or institutions.” Said by a client, Jonson Smith. The company has an Illumina platform for variant detection. Multiple disease-related genes and regions of interest can be detected in a single assay. CD Genomics is a professional sequencing company with extensive experience in detecting genetic mutations such as SNPs, indels, copy number variations, and DNA methylation. About CD Genomics CD Genomics enjoys a high reputation for sequencing, microarray analysis, library construction and genotyping, providing reliable services to pharmaceutical and biotechnology companies as well as academia and government agencies. Based on rich experience in targeted sequencing, CD Genomics has developed a specialized platform for targeted sequencing of disease-related genes to accelerate research on disease pathogenesis, disease identification, biomarker discovery, targeted drug development, etc. CD Genomics offers predesigend NGS panels, which include a designed library of targeted sequencing, as well as a custom panel that allows customers to select genes of interest to design their own sequencing panels.
  25. In 1991, Lynne Burek published a brief commentary in the 75th anniversary issue of the American Journal of Epidemiology entitled, “The Interaction of Basic Science and Population-Based Research: Autoimmune Thyroiditis as a Case History” (1). He traced the pathways that led us from fundamental investigations in the laboratory to population studies designed to determine the factors that predict the risk of autoimmune thyroid disease before the onset of diagnostic clinical signs. In the present article, He will especially comment on the changes in the field that mark the transition into the 21st century, which reflect a combination of broadly based systematic research. The autoimmune diseases, which collectively affect more than 20 million Americans, are clinically diverse but share a fundamental etiology: a self-reactive adaptive immune response. By definition, these diseases are distinguished by the presence of B cells and T cells that recognize antigens present in the body of the host, in the form of self-reactive antibodies or T cells. In recent years, a related group of diseases has been described as sharing many of the same inflammatory mediators but lacking self-reactive lymphocytes, which are often to referred as “auto-inflammatory responses,” and these disorders usually have a clear genetic component and evidence of activation of innate immune system. According to epidemiologic studies, the incidence rates of autoimmune disorders is increasing in industrialized countries, which probably reflects some environmental changes. In addition, greater attention has been directed to these diseases because of improved diagnostic procedures and therapeutic interventions. However, for any of them, there is essentially no definitive cure. A common feature of most autoimmune diseases, is that they develop gradually, so serious tissue damage might occur before the clinical diagnosis diseases. This observation strengthens the efforts to diagnose autoimmune diseases earlier in their courses before irreversible damage occurs. These studies are interdisciplinary in nature and require the combined efforts of immunologists, epidemiologists, environmental scientists, geneticists, and clinicians. In the past decades, such collaborative teams have conducted many researches on autoimmune diseases. The primary early risk factors for induction of an autoimmune response have been identified in the genes of the major histocompatibility complex (MHC) (2). Heightened susceptibility depends on potent activation of self-antigen–specific T lymphocytes by antigen-presenting cells bearing the same MHC. In sub-sequent studies of thyroiditis in humans, an autoimmune response to particular epitopes of the thyroglobulin molecule predicted progression of disease. Other genes, inside and outside of the MHC, modify the initial autoimmune response. These immune-regulatory genes are often expressed through particular cytokines and other inflammatory media- tors and enhance or limit the disease of genetically susceptible animals selected on the basis of their MHC haplotype (3). Beyond these genetic risk factors, many internal variables can shift autoimmune responses to clinical disease that are less likely to occur. These variables include such factors as gender, age, pregnancy, and even neurologic and emotional signals. Combined with genetic factors, characteristic autoimmune antibodies are the best predictors of impending autoimmune diseases. On the basis of the earlier decades of fundamental research, the practical application of this knowledge in human susceptibility predictors is described. Because of the high genetic susceptibility of thyroiditis in their family members, children with high genetic predisposition to thyroiditis were studied, and the onset of autoantibody formation and occurrence of clinical signs in normal children were tracked. Through years of follow-up research, children with a high risk of autoimmune thyroiditis can be identified. For example, among the 19 siblings who share the MHC haplotypes with a brother or sister who has been clinically diagnosed with autoimmune thyroiditis, 17 (89%) have thyroid antibodies, and 6 of these 17 (35%) showed biochemical or physical evidence of thyroid dysfunction during the first decade of observation. Since the beginning of this study, researchers have revisited these children in disease- susceptible families on several occasions and have proposed a gradual “natural history” of autoimmune thyroiditis. The step 1 in the "natural history" begins with a combination of genetic traits, and then the step 2 is environmental exposure, such as excessive dietary iodine (5). Step 3 is marked by the production of characteristic autoantibodies to specific determinants of thyroglobulin, as well as the production of antibodies against additional thyroid-specific antigens, such as thyroid peroxidase. In step 4, subclinical thyroiditis is evidenced by a decrease in thyroxine levels. Then in step 5, thyroid-stimulating hormone is compensatoryly increased, and thyroxine is rised to normal level. Finally, step 6 is characterized by overt hypothyroidism in which the thyroxine level cannot rise, the level of thyroid-stimulating hormone is increased, and there is pathologic and clinical evidence of thyroid goiter or an atrophic thyroid gland. Because this series of steps can take many months or years, there is an opportunity to identify individuals at highest risk of developing autoimmune disorders by using genetic and functional markers and to intervene with preventive measures. The Autoimmune disease model Childhood Asthma Asthma is a chronic airway inflammatory disease. Due to the persistence of this chronic inflammatory reaction, the airway is highly reactive, and the symptoms recur when exposed to the cause. The study of the pathogenesis of asthma has evolved from the theory of sputum to the theory of chronic inflammation of the airways, and has now developed into a parallel theory of smooth muscle dysfunction and airway inflammation. Clinical treatment can also be done by repeated treatment, with emphasis on anti-inflammatory and relief of smooth muscle spasm. In the 1950s, non-selective adrenaline was used as an antispasmodic agent to treat asthma. In 1956, a selective strong short-acting β2 agonist (Short Acting Beta 2 Agonist, SABA) was introduced. In 1971, a β2 agonist (Long Acting Beta2 Agonist, LABA) came out. Oral glucocorticoids were used in the 1960s to antagonize airway inflammation, which is effective but has many side effects. In 1972, beclomethasone dipropionate (BDP) was successfully developed. In the 1980s, budesonide (BUD) and fluticasone propionate (FP) were developed. By analogy, these inhaled corticosteroids have a stronger anti-inflammatory effect on the airway, and their side effects are significantly reduced. When children are stimulated by allergens, cold air or other incentives, they often first manifest as symptoms of upper respiratory tract allergy, such as itchy eyes, itchy nose, sneezing, etc. Because infants and young children are difficult to express itching, their symptoms often only express as blinking, blowing nose, etc, and further manifest as itching, dry cough and expectoration. These symptoms usually last for hours or days before the onset of asthma. Sudden onset of wheezing is a major feature of childhood asthma. The wheezing symptoms of asthma in children vary greatly depending on the severity of asthma. Children may have high-pitched wheezing that can be heard without a stethoscope or at a distance. Due to frequent breathing or difficulty breathing, asthma symptoms in infants and young children can be expressed as mouth breathing and nose flapping, and many children may be accompanied by a cough. Under normal circumstances, dry cough will appear at the beginning of the disease. When the seizure subsides, a white mucus-like phlegm will be coughed out. In severe cases, the symptoms of asthma can be expressed as irritability, purpura, pale, and cold sweat. Physical examination revealed an increase in heart rate and wheezing in both lungs. Symptoms of heart failure may be further aggravated with jugular vein engorgement, edema, middle lung, small blisters, and enlarged liver. Signs of emphysema can be seen in children with chronic asthma, such as barrel chest and chest percussion. In the remission period, children with asthma may have no symptoms or signs, have no effect on activities, or only manifest as symptoms of allergic rhinitis and pharyngitis. A small number of children may have chest discomfort, with or without wheezing in the lungs. To be continued in Part II…
  26. To develop drugs that target specific cell surface proteins, it is helpful to understand other proteins in its vicinity. The pathology of many diseases can be understood by elucidating local biomolecular networks or microenvironments. To this end, the enzymatic proximity labeling platform is widely used to map a wider range of spatial relationships in subcellular structures. However, there has long been a search for techniques that can map the microenvironment more precisely. Geri et al describe a microenvironmental profiling platform that uses photocatalytic carbon ene generation to selectively identify protein interactions on cell membranes, a method called MicroMap (μMap). A light-triggered labeling technique that improves the spatial resolution of this type of mapping. Specifically, they relied on a photocatalyst with a very short range of energy transfer to activate a carbine-based tag that could only diffuse a small distance in water before the reaction. Using photocatalytic-antibody conjugates to spatially localize carbene generation, they demonstrated selective labeling of antibody-bound targets and their microenvironment protein neighbors. They used this technique to identify the constituent proteins of the programmed death ligand 1 (PD-L1) microenvironment in living lymphocytes and selectively label them in immune synaptic junctions. Therefore, it its a valuable system in cancer immunotherapy. About author Creative Biostructure, founded in 2005, is specialized in providing cost-effective contract services to both academia and biotech/pharmaceutical industries in the field of structural biology and membrane protein technologies. The company has developed all-in-one, gene-to-structure pipelines for the structure determination of macromolecules. With a team of experienced professionals, Creative Biostructure is able to solve the structure of many challenging proteins including GPCRs, ion channels, transporters, enzymes and viral targets. The company also provides a comprehensive list of products and other related services to facilitate research in structural biology. Creative Biostructure has also built up a unique and comprehensive Membrane Protein Screening Platform. Aiming at elucidating the fundamentals of membrane protein systems, the company provides gene-to-structure services on the purification, crystallization, structure determination and analysis of various membrane proteins.
  27. Abstract: Since SARS-CoV-2 is similar to SARS-CoV, the research of 2003 that ACE2 is an essential receptor for SARS-CoV infection can be further explored for unveiling the secret of SARS-CoV-2. An ongoing outbreak of a novel coronavirus (SARS-CoV-2) has raised global concerns. It is identified as the cause of pneumonia with unknown etiology. Since the early outbreak in Wuhan, China, it has subsequently spread to all provinces of China and many other countries. In fact, coronavirus is a relatively common human virus, which causes 10% of the common colds. However, some coronaviruses are more harmful, such as SARS-CoV and MERS- CoV and the novel coronavirus, named SARS-CoV-2. How does SARS-CoV-2 infect patients? Spike protein (including S1 and S2 subunits) is the most important pathogenic protein of coronavirus, which helps the virus to bind to the transmembrane receptor protein on the human cell membrane, thereby helping itself to enter the cell. The latest research shows that the Spike proteins of SARS-CoV-2 and SARS-CoV are more conserved, and in vitro experiments have proved that as long as the cell expresses ACE2, SARS-CoV-2 can infect cells; on the contrary, if there is no ACE2 on the cell protein, it will not be infected. Therefore, it is believed that SARS-CoV-2 is mediated into the interior of cells through the binding of Spike proteins to ACE2 proteins, which may become a breakthrough in the study of SARS-CoV-2. What is ACE2 protein? The ACE2 gene is located on the X chromosome, which encodes a type I transmembrane glycoprotein with a single extracellular catalytic domain. ACE2 has a well-known homologous gene, ACE, which is also an angiotensin-converting enzyme. ACE and ACE2 both have two domains: the amino-terminal catalytic domain and the carboxy-terminal domain). Despite similarities, ACE2 and ACE function differently. ACE's role is to convert angiotensin I (AngI) to active angiotensin II (AngII), thereby increasing hypertension. The role of ACE2 is to convert AngII to heptapeptide angiotensin 1-7 (Ang1-7), and then antagonize the blood pressure-increasing effect of AngII, which has a negative regulatory effect on the RAS system. Therefore, ACE2 functions completely differently from ACE and the two work together to balance blood pressure. Lessons from SARS Due to the function of ACE2, previous basic clinical studies have linked it with hypertension and cardiovascular disease, but in 2003, after ACE2 was identified as an essential receptor for SARS coronavirus infection, its research in this area has been carried out. And because the pathogenic mechanism of SARS-CoV-2 is highly similar to SARS of 2003, the current research of SARS is extremely informative. In 2003, researchers identified ACE2 as a functional SARS-CoV receptor by co-immunoprecipitation technology. Subsequently, ACE2 was identified as an essential receptor for SARS infection in vivo in the ACE2-knockout mouse model. However, previous studies have found that ACE2-knockout mice with lung injury have a more severe acute injury and higher mortality than the wild-type mice, suggesting that ACE2 deficiency may worsen the symptoms of acute lung injury. Therefore, ACE2-mediated degradation of AngII is important for lung protection against the pathogenesis of pneumonia causing by SARS-CoV infection. To unveil the secret of SARS-CoV-2, more research is needed, and at the same time, scientists worldwide are dedicated to finding methods of more accurate diagnosis and more efficient treatment.
  28. Despite the widespread use of radiological techniques in diagnosis and treatment, there is still no material that can protect people from radiation. Recently, researchers at the Nanoparticle Research Center at the Korea Institute of Basic Science, in collaboration with colleagues at Seoul National University, the College of Dentistry, and the Institute of Dentistry, reported an efficient and safe nanocrystal that is effective against dangerous dose radiation. By growing manganese oxide (Mn3O4) nanocrystals on cerium oxide (CeO2) nanocrystals, the group improved the catalytic activity of CeO2/Mn3O4 nanocrystals, thus avoiding the side effects of lethal radiation. HYEON Taeghwan, director of the IBS Nanoparticle Research Center (Seoul National University), said: "Reactive oxygen species (ROS) are found in many major diseases, including sepsis, cancer, cardiovascular disease and Parkinson's disease. When our body is exposed to high levels of radiation, large amounts of ROS are generated within milliseconds due to the breakdown of water molecules. These ROS severely destroy cells and eventually lead to their death." The research team used CeO2 and Mn3O4 nanoparticles for their excellent ROS scavenging ability. The challenge is how to use these antioxidant nanomaterials in a safe and economical way: although effective, CeO2 and Mn3O4 nanoparticles can only act to remove ROS at high doses, which is not only difficult to apply but also very wasteful. In recent studies, researchers have borrowed from methods commonly employed in the field of catalysis: stacking nanoparticles with different lattice parameters results in surface strain and increases oxygen vacancies on the surface of nanocrystals. "The synergistic effect of the strains produced on Mn3O4 and the increase in oxygen vacancies on the CeO2 surface improve the surface-binding affinity of ROS, thereby enhancing the catalytic activity of nanocrystals," said Han Shangen, lead author of this study. "Strain engineering of nanocrystals, which are mainly studied in the catalyst field, has now been extended to the medical field to protect cells from ROS-related diseases," said CHO Min Gee, co-first author of the study. The team examined the safety and efficacy of this novel antioxidant nanocrystal. Molecular dynamics were analyzed using an acute radiation model of human intestinal organoids. "Genes expressed by organics pretreated with CeO2/Mn3O4 nanocrystals were associated with the proliferation and maintenance of intestinal stem cells compared with the group without pretreatment, while fewer genes were associated with cell death," explained Sang-woo Lee. In a mouse study, with only a very small dose (1/360 of the amifostine injection dose), CeO2/Mn3O4 nanocrystals significantly increased the survival rate of animals to 67% and reduced oxidative stress to internal organs, circulatory system and bone marrow cells without obvious signs of toxicity. "To ensure the safe and widespread use of radioprotectants in clinical practice, it is critical to maintain high catalytic efficacy at low doses." PARK Kyungpyo, a professor in the Department of Dentistry at Seoul University, said: "This CeO2/Mn3O4 nanocrystal demonstrates its strong antioxidant effect and effectively protects our entire body even in small doses." About the Author Collected by Matexcel. At Matexcel, many surface modification techniques have been developed so that our expertise in surface chemistry made post-synthesis functionalization possible, conveniently incorporating polymers, proteins, DNA, and antibodies to synthetic nanoparticles and other nanostructured surfaces.
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