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  1. Today
  2. Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with “two-target” functionality can interfere with multiple surface receptors or ligands associated. 1. Development history of three generations of bispecific antibodies The advent of hybridoma technology in the 1970s reminded people whether the same antibody could be used to target two different targets, namely Bispecific Antibody (bsAb). Most of the earliest bispecific antibodies are developed by chemical coupling methods. Although the method is much simple, the resulting products are complex and heterogeneous and difficult to use in industrial production. Until the 1980s, scFv-based recombinant bispecific antibodies appeared and gradually became the focus of research with the popularization of recombinant DNA technology. Amgen/Micromet’s BiTE (Bispecific T cell Engager) is the archetype of the first generation of bispecific antibodies, characterized by a simple structure and two scFvs connection. But it also has obvious disadvantages such as short half-life and low expression. A pump for continuous administration is clinically necessary due to the short half-life with only two hours. Fortunately, the clinical dose of BiTE is less than one tenth of the amount of common antibodies, which virtually solves the problem of mass production. The first recombinant bispecific antibody Blinatumomab (CD3-CD19 BiTE) was finally approved by the FDA in December 2014 for marketing in the United States after various difficulties. Genentech’s Paul Carter team invented the knob-into-holes bispecific antibody in the 1990s as the second-generation bispecific antibodies, with a structure and stability similar to that of natural IgG. Roche/Chugai’s Emicizumab (factor IX and factor X bsAb) using the knob-into-hole technology was approved by the FDA in November 2017 as the second bispecific antibody marketed in the United States. There are currently about 120 bispecific antibodies in different clinical development stages around the world, including third generation bispecific antibodies. If taking T cell-targeted therapy as an example, Roche’s CEA-TCB (CD3-CEA bispecific antibody) is a typical representative of third-generation bispecific antibodies, which utilizes the knob-into-hole technology of second-generation bispecific antibodies, and Roche engineers invented CrossMab technology shortly after the acquisition of Genentech and successfully solved the bottleneck of knob-into-hole in common light chain. In addition, CEA-TCB achieves bivalent binding of tumor antigens and monovalent binding of CD3, enabling the bispecific antibody to produce avidity effects when combined with tumor antigens while reducing CD3 antibody binding toxicity. At present, CEA-TCB has completed Phase 1 clinical trials and achieved satisfactory results. 2. The challenges for bispecific antibodies development Since 1986, the first antibody drug, Muromonab (OKT3), has been approved for marketing, the FDA has approved the listing of 73 antibody drugs by the end of 2017, and there are only two bispecific antibodies listed above. The development of bispecific antibodies lags significantly behind therapeutic monoclonal antibodies, which mainly results from the following reasons: Early bispecific antibody has a difficult expression and poor stability, as well as a complicated production process; The early development cost of bispecific antibodies is significantly higher than that of monoclonal antibodies; Bispecific antibody project involves target biology, structural biology, antibody engineering, and screening strategies. In 2017, the market capacity of antibody drugs broke through the $100 billion mark for the first time. Antibody drugs have become one of the fastest growing areas in the pharmaceutical industry. Bispecific antibodies at the forefront of antibody drug development have long been the development direction of major pharmaceutical companies around the world. It is believed that bispecific antibody will have a considerable market share in the field of solid tumor treatment. Compared with CAR-T, bispecific antibody drugs have the advantages of dose controllable and flexible drug administration period. At the same time, bispecific antibody drugs can also target other immune cells, such as NK, Macrophage, etc. Author Bio Creative Biolabs was established in 2004 by scientists who are dedicated to conquering of cancer. Over the past 10 years, Creative Biolabs has grown into a recognized world leader in antibody (rAb) discovery, engineering, production, and analysis. Standing on the shoulder of a giant, the bispecific antibody (BsAb) team has a collective of experienced scientists committed to providing high-quality services to customers all over the world. Now, with the cutting-edge platforms and methods (quadroma development, chemical conjugation, and genetic engineering), a comprehensive list of bispecific antibody products is available to customers in academia and industry fields.
  3. Yesterday
  4. Brief Introduction to Short Tandem Repeats Microsatellite DNA, also known as short tandem repeats (STR) or simple repeat sequences (SRS or SSR), is widely found in prokaryotic and eukaryotic genomes, consisting of a unit of two to thirteen nucleotides repeated hundreds of times in a row on the DNA strand which is about 5% of the eukaryotic genome, the basic unit (core sequence) is 1-6bp. The most common of these is (CA) n and (TG) n, and the human genome has about 5 × 104 ~ 1 × 105 (CA) n repeats which take 10% of the genome. Each microsatellite DNA has the same core sequence structure, the number of repeating units is about 10 to 60 times, and its length is generally not more than 300bp, mostly located in the non-coding region of the gene, intron or untranslated region. which may be present in the Alu sequence or Satellite sequence, but in the coding sequence and exon also can find the presence of microsatellite DNA. The high polymorphism of microsatellite DNA is mainly due to the difference in the number of tandem numbers. There is a big difference in the distribution for microsatellite DNA in different races and populations due to the number of repeat units and repetition, which constituted STR genetic polymorphism. And the number of repetitions between different individuals at a homologous STR site is also different so that STR loci analysis can identify individuals that are similar to fingerprint recognition. It is possible to create a personal gene file by identifying a specific sequence of genomes at particular loci. Currently, there are more than 10,000 STR loci are available. STR analysis has become an important analytical method for individual identification and paternity testing in the field of forensic science. It can be applied to judicial case investigation, that is, genetic fingerprint analysis. The Causes of STR The replication slip caused by mismatches between DNA strands during the mitotic process is considered to be the most common cause of the occurrence of STR, and in general, there will be an average of one-thousandths of microsatellite DNA will undergo replication slippage. The study showed that the rate of tandem duplication at repeat sequences was higher than the probability of point mutations occurring elsewhere in the genome. Most of the replication slides only cause a change in the repeat unit, and the probability of replication slip is different due to the size of the different copy units and different species. STR Detection Method STR analysis is one of the most useful methods in molecular biology which is used to compare specific loci on DNA from two or more samples. There are two common methods for STR detection: capillary electrophoresis (CE) and gel electrophoresis, which can be used to determine the specific amount of microbes Satellite sequence and draw the STR map. Typically, each allele is shared by about 5-20% of people. And the advantages of STR analysis will be reflected in the simultaneous identification of multiple STR loci. Each individual can be identified accurately by the resulting STR map. In theory, if there were 16 STR loci being used in combination, the recognition rate will be 0.999999999998. The Importance of STR Analysis It is still common for cell lines to be misidentified and cross-contamination, although scientists use a variety of traditional methods to identify cells, there are still dozens of cross-contamination happened. And even some researchers found that cell lines were misidentified or cross-contamination while cell identification reports for the higher score study articles publication, resulting in erroneous conclusions. All of which will lead to the waste of research funding and time, and resulting in a large number of invalid or erroneous data that will mislead other researchers. Based on the statistics data, around 20% of the cell lines were misidentified and cross-contamination in the labs so that it is a serious concern for researchers to provide accurate cell line identification and prevent cell lines from cross-contamination. Currently, several STR loci have been developed to analyze cross-contamination and cell types at the same time, that can detect up to 0.1 ng of DNA (about 15 Diploid genomes) with high sensitivity for the trace pollution. All the mentioned above is the complete guide for the Short Tandem Repeat and its importance!
  5. Last week
  6. Not only does caring for the environment help the planet, learning how to reduce your emissions and utilize energy more efficiently will help defray costs and wear on your trucks. A big rig has more demands on it than a standard truck. Some of the same techniques that work on smaller trucks still apply when you’re trying to make your rigs more energy efficient, though. The nature of trucking means that massive amounts of fuel and paper are used, but this doesn’t mean that you can’t do anything to cut back. Here are some of the methods that you can employ in order to improve your fleet’s energy efficiency while they’re on the road. Save the Trees Even though the ELD mandate deadline hasn’t arrived yet, it’s still time to start having your drivers track their hours on the road on their phones instead of on paper. You can massively reduce the paper waste created by truckers by simply switching to electronic documentation. Also, you can encourage your drivers to carry a bag in their trucks to throw away paper and plastic products. These can be dropped off at gas stations and truck stops with recycling areas. Drivers should also be encouraged to bring reusable containers for your food. You’d be surprised at the amount of trash from snacks and waste products your fleet can go through in a year. You will also be eligible for tax breaks and discounts for recycling products, so it will be putting money back into your pocket as well. Pay Attention to Mileage Fuel prices and maintenance costs continue to climb in the industry, so finding ways to increase your fuel mileage is paramount. Selecting the right octane of fuel in order to maximize your engine’s efficiency is the first place to start. It can also help to look into the best and worst truck engines. This is what your big rigs are going to need to keep it going for all of those miles. Plan your routes in advance to maximize fuel efficiency, and have your drivers practice consistent acceleration. Braking and accelerating suddenly wastes more gas than maintaining a steady speed. And of course, keep careful tracks of fuel usage and expenses. What you find can help you determine where you can pinch to cut excess fuel usage. Conserve electricity All of the accessories and electricity used on engine startup can work to drain a truck’s battery. The problem with causing this level of stress to a truck battery is that it can wear down faster over time. This is definitely not good for the environment over the long run, or for your efficiency. Choose a battery that can last for as long as possible. Select a commercial battery supplier that sells top-rated brands so that you can find the right battery to keep your truck running. Try to reduce idling time and turn your trucks off when they don’t need to be running. If your routes are not too far, you can even consider integrating electric vehicles into your fleet, or another form of fuel-efficient rig. Perform Maintenance Keeping up with maintenance will also help to improve your fleet’s efficiency. Replacing air filters and changing the oil on a regular schedule ensures that your engines can operate at an optimal level. Regular tune-ups will need to be performed so that wear and tear doesn’t start to break down your engine’s ability to function properly over time. Make sure your drivers check the engines after each trip so that you can stay on top of any issues before they can develop into a problem. Using some common-sense approaches will work to improve your fleet’s energy efficiency. Use these tips to help you navigate the green trucking world.
  7. Firstly, let us see two antibodies: 4G2 antibody This product is a mouse monoclonal antibody that specifically recognizes E protein from DENV-2. The E protein-binding antibody 4G2 is an epitope-specific antibody that can be used in ELISA. A11 antibody Recombinant Human Antibody (EDE2 A11) is capable of binding to DENV E proteins, expressed in HEK 293 cells as the combination of a heavy chain (HC) containing VH from anti-DENV E proteins mAb and CH1-3 region of human IgG1 and a light chain (LC) encoding VL from anti-DENV E proteins mAb and CL of human kappa light chain. So, what is DENV? Figure1. Dengue virus Dengue virus (DENV) belongs to a serotype subgroup of flaviviridae. Its morphological structure is similar to that of Japanese encephalitis virus (JEV), but its size is small, about 17-25 nm. It can be divided into four serotypes according to antigenicity, 1, 2, 3 and 4 serotypes. There are antigenic differences among different viral strains in the same type. Viral characteristics and physicochemical properties DENV has a capsule and is a single positive strand RNA virus without segments. The viral genome is about 11 KB long. It encodes three structural proteins (C-prM-E) and seven non-structural proteins (NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5). Among them, E protein is the main structural protein of the virus, which determines the histophilicity of the virus and mediates the binding of the virus to cell receptors. At the same time, it is also an important component of influencing virulence, causing protective immune response and immunopathological damage. The virus is sensitive to heat and can be inactivated at 56 ℃ for 30 minutes. Lipid solvents such as chloroform, acetone, lipase or sodium deoxycholate can inactivate the virus by destroying its envelope. Viruses are sensitive to gastric acid, bile and protease, and to ultraviolet and gamma rays. Antigenicity and serotype According to the antigenicity of virus E protein, it can be divided into four serotypes: DENV1, DENV2, DENV3 and DENV4. The antigenicity of these viruses was cross-linked, but not with other antigens of flaviviridae. Antigenic determinants of viral envelope protein E can induce protective neutralizing antibodies and hemagglutination inhibitory antibodies, and may be involved in the occurrence of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). NS1 and NS3 are both immunoreactive and immunogenic, which can induce protective immunity against dengue virus homology in mice. Clinical symptoms Dengue virus often causes asymptomatic recessive infection. The main clinical manifestations of the patients are dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The main clinical manifestations of DF include protruding fever, severe headache (mostly frontal pain), post-ocular pain (aggravation of eyeball movement), general pain and joint pain, nausea and vomiting, lymphadenopathy, leukopenia and thrombocytopenia. DF not only causes heart, liver, lung, kidney, brain and other system damage, but also leads to myocardial damage. The clinical manifestations of DHF/DSS are more serious. In addition to the above DF symptoms, severe and persistent abdominal pain, nasal, oral and gingival bleeding, skin bleeding and ecchymosis, black stool, extreme thirst, pale skin and mucosa, chills, restlessness or sleepiness, hematocrit > 35% and other manifestations can occur. Serious cases can cause death. DENV infection can also cause encephalitis. Pathogenesis The pathogenesis of dengue fever and dengue haemorrhagic fever has not been fully elucidated so far. It is generally believed that the complex interaction between virus and host causes severe risk factors, including patient's age, virus serotype and genotype, and host's genetic background. Recent studies have shown that there are several hypotheses about the pathogenesis: viral affinity, viral toxicology, host susceptibility, antibody-dependent enhancement (ADE), cross-reactive T cell response and cytokine storm. This paper briefly introduces ADE and cytokine storm. Scholars believe that there are group-specific determinants and type-specific determinants on the surface of DENV. The antibodies produced by the former have a strong enhancement effect on DENV infection, called enhanced antibodies, while the antibodies produced by the latter are called neutralizing antibodies. When the body is re-infected with different types of DENV, serum neutralizing antibodies cannot completely neutralize the virus. Enhanced antibodies can bind with the virus to form immune complexes. These immune complexes promote the replication of the virus in these cells through Fc receptors on the membrane of monocytes or macrophages, resulting in ADE effect, leading to clinical outcomes in patients. Symptoms worsen, blood concentration and shock occur, resulting in DHF/DSS. However, DHF/DSS can also occur in many patients with primary infection, indicating that there are other pathogenic factors. Cytokines are small molecular weight soluble proteins or polypeptides secreted by immune cells and other types of cells. They have the functions of transmitting information between cells, regulating immune response, and participating in inflammatory damage and other pathological processes. However, excessive inflammation can cause systemic inflammatory response syndrome and make the body in a state of hypermetabolism and hyperdynamic circulation. Over-release of inflammatory cytokines may lead to multiple organ dysfunction syndrome and even death. The control of inflammation is essential in the treatment of many diseases. It was found that the levels of IL-1, IL-4, IL-6, IL-13 and TNF-alpha were significantly increased in severe patients with dengue fever. There is a significant correlation between TNF-alpha and thrombocytopenia. Studies have shown that the transition from Th1-type response to Th2-type response is an important mechanism of DHF/DSS. Cytokines in severe patients are mostly Th2-type cytokines. After virus infection, excessive release of cytokines and inflammatory factors increases vascular permeability, leading to hemorrhage and shock. Diagnosis The diagnosis of dengue virus is mainly a combination of clinical symptoms and laboratory diagnosis. Laboratory diagnosis of dengue virus includes virus isolation, antigen and antibody detection, gene detection and so on. Virus isolation Virus isolation is the golden standard for the diagnosis of viral diseases. The duration of dengue viremia is relatively short. Samples should be collected within 4 to 5 days of the onset of fever. Virus isolation and culture can be carried out by living mosquitoes, cells or animals. Antigen detection NS1 protein is the main marker antigen of dengue virus infection. NS1 protein appears earlier than IgM antibody and can be used for early diagnosis. At present, several commercial kits have been used to detect the NS1 antigen of dengue virus. Serological detection The serological method is more convenient because the humoral immune response of patients infected with dengue virus lasts for at least several weeks after the onset of the disease and the sample can be collected for a relatively long time. Detection of IgM, IgG capture ELISA, IgM, IgG indirect ELISA and hemagglutination inhibition test are the most commonly used serological methods for diagnosis of dengue virus infection. Gene diagnosis In recent years, the molecular biology diagnostic methods of dengue virus have been enhanced. Nucleic acid amplification has become the most important method for rapid diagnosis of dengue virus. Various RT-PCR methods try to detect the RNA of dengue virus. The nucleic acid amplification technique can be used to identify the serotype of dengue virus as well as to detect the virus. Owing to its high throughput and parallel processing, gene chip technology can detect and analyze pathogens comprehensively. Its simple and fast operation, low cost and small size provide wide application prospects in the fields of molecular biology, disease diagnosis and treatment. Scientists used PCR to amplify the nearly full-length dengue virus 2 gene, digested the amplified products by enzyme-digestion-PCR, and constructed the dengue virus 2 DNA library to obtain microarray probes. The probe was fabricated into a DNA chip for detection of type 2 dengue virus by dot analyzer. The results showed that the hybridization of the sample with type 2 dengue virus gene chip was highly sensitive and specific. Dengue fever, as an important vector-borne infectious disease, has been increasing year by year, seriously endangering human health. Although some achievements have been made in the related research, there are still many problems to be solved urgently. There is still no consensus on the pathogenesis of dengue fever, especially in severe cases. There is no effective prevention and treatment measures. Future work should start with the mechanism of virus and host, obtain effective treatment of dengue fever as soon as possible, and todevelop a protective multivalent vaccine.
  8. Who protects us day and night, all our life without days off and holidays? Of course our Guardian angel. But if we want more, it’s enough just to ask our “chefs” about it. Let’s talk about how to properly communicate with them. Who will you be like that? All angels, like people, are different, therefore, in order to find an approach to them, you need to find out who exactly takes care of you. For this some time you need to watch … yourself. Dresses and decorations. Do you adore all sorts of trinkets — bracelets, large beads and hoop earrings, although you don’t wear jewelry yourself? It is possible that your second angel is not indifferent to them — a beautiful woman with golden hair, blue eyes and melodious laughter. From her you have a passion for light flowing fabrics of bright colors and Indian sari. Again, you don’t wear anything like that, but you always enjoy admiring such things. Of course, your angels may well be not so exotic, all of the above is just a vivid example that allows you to understand what you need to pay attention to in this case. In addition, it is only a small part of those signs by which you can recognize your guardian angels. But if you understand the principle by which this can be done, their “identification” will no longer be difficult for you. Of course, you can also refer to the sites that provide Free Angel Reading More and more people around the world are beginning to notice such an interesting phenomenon as repeating sequences of numbers — the so-called “angel numbers” (angelic numerology). Thousands of people talk about the “same time” on clocks, timers, billboards, mobile phones and other places surrounding modern man. 3333 has its own characteristics and the value of the number is interpreted as an angel’s help. The appearance of this combination suggests that the person is in difficulty, but next to him is the divine power, which is ready to support. Your guardian angel is near, and he will certainly help. The secret meaning of the number 255 is the growth of the soul and the choice of the direction of its development. Spirituality is your priority. You are constantly in touch with the higher mind that leads you. At some point, you begin to understand that the higher intelligence is you yourself, but who has reached the opportunity to telepathically tune your lower selves to rise to a new level of development. By the way, if you find this article useful, you might like the Protective Zodiac Jewelry they have. Check it
  9. When cleaning the household, we often don’t place as much emphasis as we should on our product selections. What does it matter anyway? Cleaning is cleaning, right? What if I told you that the emissions from the various chemicals used within a multitude of household products are at the equivalent level of automobile emissions when it comes to air quality? It is a discomforting fact unless you enjoy simulating what it is like to huff exhaust fumes. Product selection should be important to you. Keep reading as the experts at Safe Green Cleaning educate more. Making the Right Choice So how do we go about making the safest choice for cleaning the home? The trick is to keep an eye out for volatile organic compounds, or VOC’s. VOC’s are tiny particles that can travel and take force themselves inside your lungs. These same microbial chemicals cause a plethora of nasty issues, such as eye irritation, nose irritation, wheezing, asthma attacks and respiratory infections. Even more disturbingly, there exists a link to possible long-term effects to kidneys, liver, the central nervous system and cancer. With all these hazards, it is imperative to make the correct selection. Sadly, it is not as easy as taking a quick glance at the back of the product container. In many cases, the label on the product is devoid of such a list. Federal law does not require companies to provide such a warning. Fortunately, California legislated SB 258: The Cleaning Product Right to Know Act. This law did create a nationwide directive that forced the organizations manufacturing cleaning supplies to provide ingredients contained within the fragrance. Deciphering the Bad Labels It doesn’t take a specialized degree to filter through the nuance surrounding the complicated language referencing the ingredients printed on the labels. We’re going to teach you what terms to look out for when making a selection. Listed below are common terms you’ll find on cleaning supplies. Active Ingredients These are actively bad for your health. Generally, these are antibacterial pesticides used to kill bacteria, viruses and mold. There are far safer alternatives to utilize. Anything with the above listing is not required to clean your house. Enzymes These are proteins, often mixed in with cleaners to break down soils and stains. These are natural, so it is easy to disregard them as safe. For example, a toxigenic chemical, boric acid, is commonly added to stabilize the enzymes. This combo is most hazardous when the reproductive system is exposed to it. Optical Brightener As the name implies, it can make fabrics appear brighter to the naked eye. Laundry detergent will utilize optical brightener. It can blanket the clothing being run through the washing machine. Optical brightener can also cling to the clothing even after a rinsing. This fact is relevant because the brightener chemical can also cause skin irritation. Organic Okay, something labelled organic has to be a safe pick, right? Sadly, this idea is not foolproof. Given there are no legal restrictions regarding the term organic, it pays to be skeptical. It is a loaded term which can mean a whole lot of nothing; a USDA Organic logo is the only safeguard to go off of when making a selection. The logo does create a legal imperative that makes the company bound to honor their claim of the item being organic. If the logo is absent, pick the product at your own risk. Surfactant A surfactant is a chemical compound used to loosen dirt and grease. They are necessary for cleaning. It is also true that some surfactants are safer than others. Certain surfactants are toxic to aquatic life, like nonylphenol ethoxylates, and are slow to decompose. What Labels are Safe? Given the list has been all negative, this question is inevitable. Fortunately, there exist safe selections. The terms you want to look for will say biodegradable, Green Seal / Ecologo, essential oils and free and clear of perfumes and dyes. Looking for these labels will help you make a safe selection for your household cleaning and avoid hazardous VOC’s.
  10. August 16, 2019, as a leading supplier and manufacturer in antibody field, Creative Biolabs recently has updated its new product types for therapeutic antibody, which has at least three types of mechanisms. For instance, the neutralizing effect of the therapeutic antibody on its ligand directly binds its ligand, so that its ligand does not act on the target tissue and cells to trigger an undesired reaction; antibody-mediated cytotoxicity of the antibody binds to the target cell, Cytotoxicity that triggers immune cells; complement-mediated cytotoxicity antibodies have a complement-binding site that, upon binding of the antibody to the target cell, triggers the complement effect and kills the target cell. These new items of Creative Biolabs are including but not limited to: Anti-CD34 Therapeutic Antibody Anti-CD55 Therapeutic Antibody Anti-CD81 Therapeutic Antibody ... “those newly-updated products in therapeutic antibodies will bring a lot to our customers in their research programs. Our experienced scientists can guarantee the high quality of them and they can perform well during all kind of research items to assist researchers to achieve success. The anti-34 therapeutic antibody is a kind of recombinant humanized monoclonal antibody expressed in CHO binding to human CD34. It can recognize the human cd34 antibody membrane-protein in the cell membrane and perform well in the clinical treatment of hematologic malignancies and solid tumors, etc. The anti-CD55 therapeutic antibody is binding to human CD55. cd55 antibody is built with strong potential to be applied as an additive agent to treat gastric cancers. Studies show that a single 20mg dose can induce the cell killing in human primary gastric tumors, which results to tumour cell regression in over half of PAT-SC1-treated patients. And we do believe patients with gastric cancers can be totally free in the nearly future. The target of anti cd81 antibody is human CD81, which is generated by genetic immunization. It is very promising in the virus-host interactions. All in all, newly-updated products will bring Creative Biolabs another shine.” Dr. Carlose Smith explained, a senior scientist in R&D of Creative Biolabs. “with the faith of providing high-quality products and professional services, Creative Biolabs is always trying its best to develop products and services needed by our customers. And we do offer the custom services and products for some specified items. Of course, Creative Biolabs has gained a good fame among our customers and other biological companies.”Dr. Carlose added. We do believe that Creative Biolabs will be much more better in the near future due to its dutiful spirit of enterprise. Now, it has been well received among customers. About Creative Biolabs With more than ten-year corporate history, Creative Biolabs has accommodated many excellent researchers at home and abroad to develop high-quality and professional products and services belonging to the antibody field, which is now getting more and more popular and needed by clinical researches. The future for Creative Biolabs is getting more and more promising due to its professional scientists and research staff.
  11. Relapsing fever is transmitted via arthropod vectors. The human body louse (Pediculus humanus corporis) transmits Borrelia recurrentis, the causative organism of louse-borne relapsing fever (LBRF), while Ornithodoros ticks are vectors for the at least 15 different species of Borrelia that cause endemic or tick-borne relapsing fever (TBRF). While humans are the only known host for the LBRF spirochete, the TBRF-causing Borrelia species (with the exception of B. duttonii) have their reservoirs in small rodents and have been found in several locations worldwide. In North America, three species of Borrelia cause TBRF, and several outbreaks of the disease have been described. In East Africa, B. duttonii is the principal cause of TBRF. Antibody responses against relapsing fever Borrelia species are primarily directed against outer surface lipoproteins. Two major protein groups have been identified, namely, variable small proteins (approximately 22 kDa) and variable large proteins (approximately 38 kDa). These proteins have been studied most thoroughly for B. hermsii and B. turicatae. It is probable that all of the relapsing fever Borrelia species share the same antigenic variation scheme as that described in detail for these two species. When spirochetes are present in blood, they must evade the immune defense systems. Before the acquired immune responses lead to the production of antibodies, the alternative pathway of complement operates as a major innate immune defense system against the invading organisms. In the presence of antibodies, complement acts as an effector system, mainly via the classical pathway (CP). Both pathways lead to coating of the target surface with C3b. Together with their cleavage products, such as iC3b, the C3b molecules opsonize the target for phagocytosis. Further activation can lead to the formation of lytic membrane attack complexes. To avoid overconsumption of the components of the complement cascade and to protect self-cells from harmful attacks, complement activation must be tightly regulated. This is mediated by regulatory proteins in plasma and on cell surfaces. The major fluid-phase regulators of complement are factor H (FH), for antibody-independent alternative pathway activation, and C4b-binding protein (C4BP), for antibody-dependent CP activation. These regulators accelerate decay of the C3 convertases (C3bBb and C4b2a, respectively) and act as cofactors for the irreversible inactivation of C3b and C4b, respectively. As a net effect, these functions prevent complement-mediated destruction of the target in both the absence and presence of antibodies. Acquisition of the host plasma complement regulator FH has been shown to be beneficial for complement evasion among other spirochetes, such as Borrelia burgdorferi sensu stricto and B. afzelii, which express at least two FH binding proteins. Also, the relapsing fever agents B. hermsii and B. parkeriihave been shown to bind FH, while no binding has been observed for B. turicatae. B. hermsiiexpresses a unique 20kDa outer surface protein (FhbA) responsible for FH binding. The bacteria that cause human Lyme disease belong to a group of at least 15 species, referred to as Borrelia burgdorferi sensu lato, or the Lyme disease agent bacterial group. Among these, B.burgdorferi sensu stricto causes Lyme disease in North America, while in Europe and eastern Asia Borrelia afzelii, Borrelia garinii, and Borrelia bavariensis sp. nov. are the best-known causes. However, more recently, Borrelia bissettii, Borrelia lusitaniae, Borrelia spielmanii, and Borrelia valaisiana have been isolated from Lyme disease patients. Other species in this bacterial group, such as Borrelia japonica and Borrelia sincia in Asia, have not been associated with human disease. To date, genome sequences have been reported for 14 B. burgdorferi isolates, two B. afzelii isolates, two B. garinii isolates, one B. bavariensis sp. nov. isolate and 1 isolate of unassigned species. The complete genome sequences for three additional Borrelia species: B. valaisiana isolate VS116, B. bissettii isolate DN127 clone 9, and B. spielmanii isolate A14S. DNA samples from low-passage isolates were sequenced to minimize plasmid loss, and genomes are sequenced to about 8-fold coverage as previously described. Genome annotation is performed using the JCVI Prokaryotic Annotation Pipeline . The DN127 chromosome and 35 of 39 plasmid sequence contigs are closed, but in order to maximize the use of available funds, the sequences of a few replicons are not closed and some gaps remained in these sequences (two chromosomes and one cp9 and three cp32 plasmids, because they are much less variable than the other plasmids). These three genome sequences include 3,914,891 bp in total (1,258,865, 1,403,466, and 1,252,560 bp for strains VS116, DN127, and A14S, respectively), with an average of 1,304,497 bp/genome. Like the sequences of other Borrelia species, they include numerous linear plasmids (6, 7, and 7, respectively) and circular plasmids (2, 2, and 2, respectively). Plasmid numbers in these three strains range from 11 in VS116 and 12 in A14S to 16 in DN127. Plasmids that are very similar to B. burgdorferi sensu stricto cp26, cp32 (7 in DN127, versus 3 in the other two strains analyzed), and lp54 plasmids are present in each of these isolates, and DN127 also contains an unusual fusion of four partial cp32 plasmids. Plasmids with predicted lp17 compatibility are also present in all three genomes, making it the only other plasmid type, in addition to cp26 and lp54, to be found in all 23 B. burgdorferi sensu lato sequenced genomes. However, the gene contents of the lp17s are much more variable than the other universally present plasmids. The detailed analyses of these genome sequences will be a major step forward in attaining a complete understanding of B. burgdorferi sensu lato diversity. They will contribute to the development of species- and group-specific vaccines and diagnostic tools, as well as inform us whether these species are in genetic contact with the more-common Lyme disease-associated agents. Reference [1] Barbour A G, Hayes S F. Biology of Borrelia species. [J]. Microbiological Reviews, 1986, 50(4):381-400. [2] Van H C, Comberbach M, De G D, et al. Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults [J]. Vaccine, 1996, 14(17–18):1620-1626. [3] Kraiczy P. Whole-genome sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii. [J]. Journal of Bacteriology, 2012, 194(2):545-6. [4] Cutler S J, Moss J, Fukunaga M, et al. Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp.[J]. International Journal of Systematic Bacteriology, 1997, 47(4):958-68.
  12. Going eco-friendly seems to be the next big trend. Big companies, small businesses and individuals altogether have teamed up to reduce the impact that human life has on the planet. Sustainable homes have increased in popularity, not only because they leave a much smaller footprint on the environment, but because they are a far better investment in the long run. The list of benefits you get by living in a green house is long and constantly updated, but the most important ones still remain the same: Low maintenance costs The main purpose of eco-friendly homes is to be built from materials that are both less invasive for the environment, but also more durable, so that you don’t have to constantly fix or rebuild things and waste more resources. This way, even though some green materials cost more than traditional ones, you will end up saving more in the future. When you buy or build a new house, don’t think only about the initial investment, but also about the impact it will have on your wallet in the next 10 or 15 years. For example, building a house that has lots of big windows, which allow sunlight to pass through, will help you save tremendously on energy costs. At the same time, the materials used have a much smaller impact on your health. Conventional construction materials give off chemical emissions that, although small, can affect the air you breathe. This is why lots of people recur to humidifiers or other appliances to help get rid of the dry, unbreathable air. Eco-friendly materials are not only safer, but help with air circulation and ventilation. Energy efficiency Possibly one of the first reasons people decide to move into eco-friendly houses is that they are extremely energy efficient, which means you utility bills will be much lower. One of the prime sources for energy is coal. But coal is a non-renewable resource, not to mention that mining coal is extremely polluting for the environment. A sustainable home is designed is such way that it takes advantage of as many natural resources as possible. For example, when setting up the layout of the house, rooms that are the most used, such as kitchen or living room are placed on the side of the house that receives the most natural light throughout the day, to avoid having to use artificial light. Big windows are also a part of the design, for the same reason. On top of that, green building constructors also recommend installing solar panels, so you can make use of the energy from the sun as much as possible. It makes for a good long-term investment The popularity of green buildings is increasing tremendously, which means that, in 10 years, traditional homes are going to become less and less desirable. Investing in an eco-friendly home now means staying ahead of the market and laying the ground for profit in the future. Even owners of luxurious homes are looking to make adjustments so that their houses are more environmentally friendly. Those adjustments help increase house value and turn their properties into mines of gold. The reason that people are looking to spend more on a sustainable home precisely because they will get more out of it in the future. Eco-friendly houses are also easier to sell and retail for more than traditional ones. Better living conditions Less invasive materials and more use of natural resources are what make a sustainable house better to live in. When you take advantage of natural light all day long, you are more prone to be productive, feel relaxed and enjoy living in your house. The materials used have a lower emission of chemicals, lowering the risks for asthma or allergies that may occur due to mold. Thus, the air inside is more breathable and makes for a healthier indoor environment. Temperature regulation is also one of the key elements that constructors take into consideration when building eco-friendly homes. Eco-friendly materials are designed in such way that they help with insulation and temperature fluctuation much more than traditional ones. Smaller environmental footprint Last, but not least, you will help the planet. By using materials that are not damaging the environment, you will become an active part of the movement that is trying to make Earth a better place. Meeting your needs does not mean you have to endanger the world around you and it is entirely possible to live comfortably, while at the same time thinking about nature. All processes of traditional building are affecting the environment in one way or another. Be it because constructors are not disposing of materials in a conscious way, or because traditional energy systems are leaving a huge carbon footprint. Green buildings contribute to reducing the greenhouse effect and lay out a better world for future generations to live in.
  13. There are many residential and commercial property owners who extol the virtues of either artificial turf with its complete landscape system or a real grass lawn, and they have good reasons for their strong opinions. However, which type of lawn is best for you? If you’ve got blank patches of yard yearning to breathe green, read on to learn which type of lawn best suits your needs and preferences. Artificial Turf Benefits Artificial turf is eco-friendly and has the feel and look of real grass. The ground and drainage are prepared, the material used keeps the artificial blades erect, and there is a special “yarn” that creates the “soft-grass” realistic blades that come in a variety of textures, lengths, designs, and colors. This means that you get a soft, always-green lawn without all the many hassles of real grass and all its upkeep, mowing, fertilizing, weeding, re-seeding, and most importantly, watering. Although expensive, the artificial turf life expectancy could possibly be 15 or 25 years or more, which actually makes it less costly than real grass over its life span. Artificial Turf Drawbacks It is often made at least partially with recycled materials, so it is not biodegradable. While it doesn’t have the same watering needs as a real lawn, it cannot be so easily disposed of as a grass lawn. Another drawback is that artificial turf absorbs heat in the direct sun and feels hot when you touch it. The temperature in 80-90 degree weather can actually exceed 160 degrees, making it hazardous in the heat of summer for children and pets. An additional problem for dog owners is that it does not absorb an animal's waste, although liquids can pass through to the ground underneath. Real Grass Lawn Benefits Real grass, in the right climate, can make more sense than artificial turf by its entirely organic nature. Grass is bio-degradable and produces oxygen just like any other plant, and when only organic fertilizers are used, it can even be a beneficial snack to help the digestion of cats and dogs alike. While it does retain heat, it does not do so to the degree of artificial turf and is generally safe to walk on as long as there are no hazardous weeds growing with it. Organically sustained grass can also increase the bio-diversity in your neighborhood by providing food and refuge to a variety of animals and insects. Real Grass Lawn Drawbacks Immaculately maintained grass lawns come with a cost to the environment and account for one-third of residential water use. Use of toxic fertilizers and weed killers can pollute the groundwater and pose a serious health risk to children and animals that are exposed to it. Mowing, trimming, and blowing with gas and electric power tools also consumes energy and produces air pollution that otherwise wouldn’t be necessary. While a natural lawn can potentially be environmentally sustainable, it’s important to note that it likely will not be soft and green for a majority of the year. The type of lawn you choose is a personal preference. Both have pros and cons regarding cost, care, and the environment that must be considered on an individual basis. The climate you live in, your home, and your ability to care for and use a lawn of either kind must be considered. You must decide which benefits and drawbacks make the most sense to you and your lifestyle.
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  15. When heavy toxic metals build up in the air, water, and land, it’s more difficult for the contaminated site to support life. Environmental pollution is the main cause of morbidity and mortality in the world. It’s a problem that affects both developing countries and not only. Even if developed countries have the necessary resources and technology to combat the introduction of harmful or poisonous substances into the environment, they prefer to encourage over-energy consumption, waste and inefficiency. Industrialisation, which has a great impact on economic growth, isn’t a good thing for the environment. Factories use chemicals and fuels that contribute to air and water pollution. And let’s not forget about the excessive use of fossil fuels. Companies need to understand once and for all that they have a responsibility toward the environment. Business activities should be bringing benefits instead of causing irreparable losses. Make sure you do your bit for the environment. Implement environmental pollution control measures in the nick of time. Promote air quality Air pollution is so dangerous that it damages crops and kills people. According to the World Health Organization, about 7 million people die each year due to exposure to fine particles in the polluted air. Any solid or liquid particle that gets into the air affects its quality. Manufacturing industries are mostly responsible for polluting the atmosphere. If you’re engaged in the industry by the manufacture of products, you contribute to air pollution. One way to promote air quality is to install a fume extraction system. In addition to protecting the environment, this system reduces noise levels and minimises running costs. It’s essential to create a fume extraction maintenance strategy. It’s necessary to install a new filter every now and then. Fortunately, there are companies that can take over this operation for you. Good ventilation is important. The design of the ventilation system will take into account air quality, energy efficiency, and environmental impact. Write an environmental pollution policy People are inclined to comply with the rules, so if you wish to reduce environmental pollution, write a policy that promotes environmental protection. You’ll support the preservation of the physical, chemical, and biological integrity of the ecosystem, not to mention there are many advantages to be gained for your business. Highlight how you’ll manage the environmental effects of business operations. You may need to demonstrate to customers or your commitment to Mother Earth and having such a policy in place will turn out to be useful. An environmental policy is necessary because, more often than not, environmental pollution isn’t taken into consideration when it comes down to decision-making. As an entrepreneur, you must think about the consequences of your actions and keep in mind that the negative effects take place somewhere in the future. This means that they’re not visible right away. Choose the right format for your environmental policy and don’t forget the fact that it’s personal to your business. You can craft any kind of content, but all policies must feature the same themes. Dispose of non-combustible solid waste As the name clearly suggests, non-combustible waste doesn’t ignite or burn when subjected to fire. Examples of such waste materials include rubbish, pieces of glass, and ash. These hazardous substances should be transported in transparent bags so that the content can be easily identified. Non-combustible solid waste can be recycled, which is the reason why it should end up in specialised recycling centres and not in the landfills. You may be under the impression that your organisation doesn’t produce a high amount of garbage. Well, you’re wrong. Non-combustible waste is generated by handling and treatment. It’s recommended to have a waste management system in place. Determine how many by-products your company produces, reduce the amount of waste that goes to the landfills, and identify collectors of non-combustible solid waste. Useless or unwanted products derived from industrial activities should be discarded in an adequate manner. It’s important to adopt a responsible attitude at all stages of production and consumption. Support actions to reduce water pollution Excessive water usage is threatening not only the economy but also the environment. What could be worse? Polluting drinkable water, of course. Unsafe water kills a high number of people each year and, needless to say, water pollution is the result of human activity. What happens is that pollutants are dumped into creeks, rivers, and swamps, which represent the main sources of water and sanitation. The good news is that many businesses are taking strict measures in an attempt to minimise water pollution. What can you do? Well, don’t dispose of chemicals or cleaning solutions as you please. Set up hazardous and non-hazardous waste disposal before getting started. If you discharge anything, make sure you have authorisation to do so. The solids, liquids, and gaseous substances that you’re getting rid of can possibly affect the quality of the groundwater. Finally yet importantly, tour the facility and gather background information. find out everything you can and identify prevention strategies. Eliminate automobiles that use gasoline or diesel fuel It’s no secret that vehicles that run on gasoline or diesel pose a threat to the environment. They emit far too much nitrogen compounds and particulate matter. Cars of this type have become subject to negative publicity and it’s not hard to understand why. If you’re serious on minimising pollution, offer employees different company cars. There’s no reason to withdraw this incentive. All you have to do is to make a few adjustments. A better strategy, at least from an environmentalist standpoint, is to offer employees green cars. Better yet, offer incentives for hybrids and alternative cars. The employees can use the sum of money receive to purchase an eco-friendly automobile like a Tesla Model 3. You’re not going to change the world through this initiative, but you’ll get people to think about change, and that’s more important. Implement this program and reap the benefits. You’ll be able to recruit and maintain the best employees if you offer incentives to purchase hybrid and alternative cars.
  16. Going green has become a major focus for homeowners. Not only does going green decrease your carbon footprint, but it also saves you green (as in dollars). Below are four ways that today’s modern homeowner can help make their home more eco-friendly. Get an Energy Audit By now, nearly every energy provider offers a free home energy audit. If you haven’t had one yet, call your energy provider and they will send someone out to check your power use, AC service and advise you on how to go green and save energy. Go Native with Your Landscaping One of the latest trends in going green is native landscaping. This type of landscaping is tailored to the natural climate rather than the cookie-cutter style of landscaping reminiscent of the ‘50s. This helps homeowners go green by using little to no pesticides, cultivating the natural foliage, relying mostly on natural rainfall rather than consistently using a sprinkler, and allowing natural plants and flowers to thrive. Water is a precious resource, especially in drier climates, and natural landscaping is an excellent way to go green. Consider Solar Panels While solar panels may not be feasible for every homeowner (depending on the roof layout) it is one of the best ways to go green in your home. Yes, it is an investment. However, you’d be blown away at how much money you can save as well as how much energy. If you’re curious about solar panels, Google has created an ingenious way to check your roof for how many sunlight hours your home received per year called project sunroof. Enter your address and check it out! Get Smart (Home Tech) One of the biggest ways you can decrease your carbon footprint is by letting the latest technology do it for you. Sure, leaving the bathroom light on now and then may not seem like a big deal, but it does solidly increase the size of your home’s carbon footprint (not to mention your energy bill). Smart home tech is specifically designed to help you go green, including turning off lights, controlling the heat and AC, and turning off TVs and radios. Investing in this tech will help you go green and save some green on your energy bill. Going green as a homeowner isn’t just about saving money, it’s about doing your part to be a responsible homeowner and lowering your home’s personal carbon footprint. If every homeowner did their part to be more eco-friendly and have a greener home, imagine the difference that could be made in the overall environment!
  17. These days, everyone worries about the environment and what we can do to lessen our environmental impact. It can be hard to be environmentally friendly all the time and do the right thing at every hour of the day, but there are a lot of things that we can do to have more of a positive impact on the environment. If we stop and think about where the things that we use each day come from, how they are made and how they are disposed of, we can see just how much our lives have an impact on the environment, and how important it is to be conscious of how our actions are affecting the world that we live in. Rent your clothing Keeping up with the latest fashion trends can be hard when you are trying to lessen your environmental impact. Buying items that are made of sustainable materials that can last for several years is a great way to combat the environmental issues that go with fast fashions, but it can be costly to buy these sorts of pieces. Renting your clothing instead of buying is another great way to have a positive impact on the environment through fashion, because it allows people to recycle clothing that others no longer want, by giving it them a new purpose. Clothing rental companies like The Volte are great for people that are looking to rent their clothing, because it allows customers to pick and choose from several designer items available, so you can be trendy and environmentally conscious. Start a compost heap If you want to do something about some of the scraps of fruit and vegetables that you are throwing away each day when you cook, you should start a compost heap in your garden. Starting a compost heap is easy, and it only requires a large bin or tub for you to put your waste into. You can put your clippings from the garden into the compost bin as well, so it too can be used again. The only things that you should not put in your compost bin are citrus and onion scraps because they do not break down easily like other natural foods, so try to leave them out of your compost bin. Having a compost heap is great for people that garden because you can use the broken down scraps and liquids to feed your plants, rather than letting them go into the garbage and ending up in landfill. Think about your transport If you are worried about your carbon footprint and want to make some changes to be more environmentally friendly, you might need to look at your current mode of transport. If you own a car that you drive by yourself regularly, you might want to consider walking or riding a bike instead, by you will not be creating any unnecessary emissions on your journey from A to B. Walking or cycling to work is also great for people who are looking to get fit, because you can fit some exercise into your day without changing your schedule too much. If you live far away from the place that you need to get to, you should consider using public transport instead of driving a car, because buses and trains are more environmentally friendly per person, compared to a car. Shop locally If you are concerned about how the things you buy each day are affecting the environment, you should start buying from local vendors to lower your impact. Shopping locally is not only great for the local economy, but it is great for the environment, too. Items that are bought locally do not need to be transported to get to the shop that you are buying them from, so the carbon emission created by locally sourced items would be much lower. Also, if you are buying local produce, you may find that it tastes better than foreign produce because it is fresher and has fewer chemicals added to it to keep it fresh. This means that you will reap the rewards yourself if you buy locally sourced food. Being environmentally friendly these days is not as hard as it used to be, now that we know how some of our actions can have a serious effect. Making a few changes here and there to your everyday life can significantly decrease your environmental impact, and a lot of the things you can do not require a lot of effort to make a difference. Starting with some small changes like turning the tap off when you brush your teeth is a great place to start because they are things that you can do easily. Then, you can move onto the bigger ones like walking to work instead of driving, which can have a big impact if a few people get on board. If all of us did this, we would see some big changes to the environment in no time at all.
  18. Water is a scarce resource in many places around the country. A few cities in drought-stricken areas have implemented watering rations. They give fines to homeowners who violate these regulations, and this has caused many of these homeowners to search for alternative materials for landscaping, ones that help conserve water. You’ll find four of those materials below. Rocks and Gravel Rocks come in many sizes and types; you can even buy multi-ton boulders. Nothing drinks less water than a rock, so that’s a plus for the environment, and landscaping stores have truckloads of them in all different sizes, colors, and shapes. Gravel may not sound like the most beautiful landscaping material, but it works great. You can buy it in different colors and sizes, and maintaining it won’t cost you any water at all. Drought Resistant Plants When water’s tight, there’s no better choice of a plant than one that has low water needs. Many of these hearty plants can go weeks without water yet still retain their beauty. When introducing drought-resistant plants to your area, make sure they’re not invasive, or they might cause you some headaches. Also, after planting them, contact someone local that offers residential mulch services to mulch and maintain the mulch around the plants. Artificial Turf Artificial turf has come a long way and is no longer the surface of years ago. Today’s various artificial lawns are much softer than those in the past. They are also more heat-resistant today. There has been some controversy surrounding some of the chemicals that make up certain artificial turfs and their risk to human health. The way to avoid this risk is to purchase non-toxic turf. Concrete Pavement and Pavers Putting down concrete pavement will cost you some water upfront, but after that, it’s water-free forever. If you have a piece of lawn that’s drinking too much H2O, you might consider throwing a small slab down and turning it into a patio or sitting area. Concrete pavers don’t need any water at all and come in an array of different sizes, shapes, and colors. They make an excellent replacement for the areas of your yard that are too water-intensive and are easy to install. The materials listed above may not be the first landscaping choices of many. However, they are a great option if you are wanting and needing to conserve water. Remember, water conservation can lead to a beautiful landscape and a healthier environment.
  19. There is no doubt in accepting the fact that solar energy yields a lot of advantages, and this is the prime reason why people in today’s age are opting for this option for saving the environment. Solar energy Long Island has received huge popularity for several reasons. However, protecting the environment is not the only factor. There are many other benefits associated with the use of solar energy such as cost-benefit, low maintenance, energy independence etc. whether you are interested about protecting the environment from global warming or you are more attracted towards the low-cost factor, going green is remarkably a smart idea. Here, in this article, you will come to know about a number of reasons why using solar energy panels is the most beneficial option. Knowing these reasons will let you understand why it is the most viable and attractive alternative fossil fuel energy. So, now, let’s have a look at those reasons below so you can take an informed and wise decision. Why is solar energy Long Island the most demanding option? 1. Protect the environment The most important and prominent factor is the environmental benefit. The overuse or overexploitation of the non-renewable resources leadsto some burning problems such as extreme level of pollution, higher costs, paucity, and so on. We, people, should not depend on fossil fuel for creating energy because the resources will gradually disappear over the years. Above all, depending on fossil fuel continuously will lead to even more pollution, and this will eventually affect people’s health and the climate. Therefore, opting for a safe, clean, healthy and renewable source of energy is imperative. 2. Solar energy is renewable One of the most important advantages is that it is a renewable form of energy which we can use for billions of years. The sun will shine forever, and thus, using its power will never diminish, unlike those fossil fuel energy sources. When fossil fuel energy will not be available on the earth anymore, the Sun will still be there and provide enough power to the world. 3. Solar energy is clean Unlike fossil fuel energy, solar energy is clean and harmless. There is no unpleasant smell, no gas emission, no smoke – it is completely clean. Considering the harmful green-house effect and climate changes, finding a clean source of energy like solar energy is the best way to protect the environment and reduce the negative effects that fossil fuel releases in the environment. Using solar energy is like protecting ourselves and our generation to come. Living in a safe and healthy environment is everyone’s right, and it is our responsibility to protect it from harmful gaseous effect. 4. Low-cost factor Solar energy is associated with the low-cost factor, and it is environment-friendly. As its main source of energy is the Sun, once you install a solar panel, you can use free energy as long as you want. It is for everybody, and you don’t need to spend a penny on availing this. You can relish its benefits. While for using fossil fuels, you need to pay a certain amount as it is brought from different sources and suppliers, and thus, it is not free like solar energy. Therefore, these are the above-mentioned reasons why solar energy Long Island has received so much acceptance from the people. It is the best means of energy which you can use for a long time without bearing any harmful effect.
  20. Energy consumption without a doubt is a hot topic in this day and age. It’s been a big topic for quite some time now, too, and with good reason. People are becoming more and more thoughtful with regard to their approaches to energy use. If you want to minimize your consumption of energy in a big way, there are all sorts of intelligent things that you can try right now. Unplug, Unplug, Unplug Unplugging may seem like a simple thing. It can actually be a game-changing strategy for people who are passionate about decreasing their energy consumption substantially, however. If you want to do the planet a massive favor, you should take the time to unplug your household appliances any time you do not require them. Doing so only takes a couple of seconds or so. Learn All About Electric Water Heating Electric water heating is often the answer for people who want to lower energy consumption dramatically. You can work with a capable electrician who can point you into the right direction regarding electric water heater selection. Try to find out about electric water heaters that are known for superior energy efficiency. Your electrician should be able to provide you with fantastic recommendations. Take Advantage of the Gift of Daylight Lighting should be one of your focal points. If you want to take charge of your use of energy, you should contemplate your lighting strategy at home in great detail. It can be a wonderful idea to buy lighting products that are associated with energy efficiency. It can be just as wonderful an idea to prioritize daylight. Skylights and windows make taking advantage of daylight a possibility. They’re both highly energy-efficient as well. Invest in Residential Insulation Residential insulation can go an incredibly long way for all households that are keen on the concept of lowering energy consumption significantly. If you insulate your living space well, then you can stop the frustrating loss of heat from taking place. Basement, attic and wall insulation can all do a lot to lower wintertime electricity use dramatically. Don’t forget that insulation can even aid you in times of higher temperatures. People these days have more concerns about the world than ever before. If you’re in that camp, then you don’t have to feel helpless in any sense. If you want to aid the planet, you can do your part by minimizing your energy consumption.
  21. More people are becoming more environmentally friendly. More of us are realizing how important it is to use various measures for a cleaner, healthier air for our families. And while many eco-friendly measures have been adopted in our homes, we can also implement these practices in our businesses. Sustainability is often ignored in businesses, and as a result, there are more toxins released in the air which can cause different health ailments, ranging from allergies to even cancer. Because of this, it is vital to implement the sustainability of resources in your business, and the following includes four ways to implement sustainable usage of resources in your business: Change Your Light Bulbs Changing to LED lighting is great. These lightings utilize much lower energy than regular light bulbs. Also, these bulbs don’t have toxic gases, like mercury, that are contained by fluorescent and incandescent lights. And even though they are more expensive than other bulbs, they last five times longer than other bulbs as well. Stop Using Plastic Bottles There are millions of plastic waste bottle generated in the US every year even though some of these bottles were recycled. To reduce this ecosystem burden, installing a water filtration system is a good idea for your office. The water will be clean and fresh, and you will save money and time by eliminating the package water buying routine. Use Green Vendors From septic tanks to recycled paper for your printer, you can do business with reputable companies. Perform your due diligence in researching which companies are serious about their sustainability efforts. Doing this is key to finding the right vendors. Search for businesses that use energy-efficient manufacturing plants and vehicles. Conserving Human Energy An energetic, healthy staff is more productive and creative. To help keep your team healthy, you can serve healthy snacks at meetings, such as nuts, dark chocolate, and organic fruits and vegetables. You should also maintain a safe, non-toxic environment. There are more toxins released in the air which can cause different health issues. In some cases, health issues can be dangerous. Nevertheless, we all can join the movement to sustain a healthier environment even at our companies. Using these sustainable ways will help businesses significantly in this movement. Not only are more homes participating, but businesses are doing their part as well to make a difference.
  22. You already know the importance of recycling paper, aluminum cans, plastic bottles and other common household items. However, you might not be aware of the many other materials that might be around your home that can be recycled. Here are four surprising household items that you can recycle. Plant Pots If you’re tempted to discard old plant pots that you no longer need in the trash, you should think again. Most plant pots are made from plastic and other recyclable materials that can be used to make new pots or other items. Many municipal curbside recycling programs allow plant pots to be included in recycle bins for pickup. Another option is to take old pots to a hardware store that accepts them for recycling. Mattresses The mattresses that you use on the beds in your home can also be recycled when you’re ready to replace them. Some mattresses contain chemicals that are potentially harmful to the environment, so giving them to a recycler that accepts old mattresses will be a good idea. The springs in mattresses along with old bed frames can be recycled as well. Refrigerators Even though it may initially seem easier to have an old refrigerator hauled away to the dump, you should be aware of the chemicals that are found in refrigerators that can negatively impact delicate ecosystems if they’re released into the environment. Many of the metals that refrigerators contain can be given to scrap metal services for recycling. Other components of a refrigerator can be recycled at a recycling center. You’ll want to make sure that any recycler you’re thinking of giving your old refrigerator to removes Freon. If they don’t remove Freon, you’ll need to have a professional remove it first before your refrigerator can be recycled. Crayons Coloring crayons that children often use can be recycled by either giving them away to other children who are in need or using old bits to make new crayons. In certain recycling facilities, old crayon bits are divided into smaller pieces and placed in an oven with high heat. The heat from the oven melts the wax into a liquid substance, which is then poured into molds to make new crayons. There are many ways to do your part for the planet by recycling. Making yourself aware of all the items and other materials around your home that are recyclable can help you adopt better green living habits.
  23. 4 Eco-Friendly Garden Projects

    What better way to bring out your creativity and care for the environment at the same time than by creating a backyard garden? The use of recycled items to embellish the backyard garden space helps to add some touch to the project. It also assists in highlighting your fun personality as you seek out new ways of using readily available materials to garden. As you continue looking for new ideas and new methods to spruce up your garden project, consider the projects listed below: Bring Out Your Old Boots and Fill Them with Flowers The old rain boots that you outgrew or a member of your family outgrew in the past year should not have to end up in a landfill or in your trash bag. Take a few pairs of old boots and use some scissors to make drain holes in their soles. Proceed to fill the boots using potting soil. You can then use these boots to plant your preferred seasonal blooms. The boots will look adorable when you line them up along the length of your entryway. Alternatively, you can also place them in your vegetable garden to help you add a touch of color. Use Artificial Grass to Create a Walking Path Gardening is a fun activity, but it can easily turn messy, especially when wet soil gets into your pristine looking shoes. Using recycled artificial grass will help you maintain that lush green look in the garden while getting rid of the mess that comes with gardening. Use the grass to come up with walkways between the sections present in your garden. Taking into account that this grass will never require watering, it means that you can now focus your attention to tending to your plants. Lawn maintenance should not interfere with your gardening activities. The good thing about the artificial grass is that you can place it with ease on your preferred location. Create a Raised Bed Garden Using Old Tractor Tires The good thing with home gardens is that you are at liberty to innovate as much as you would like. And as it is, old tires tend to easily clutter landfills as they take ages before they can start biodegrading. So why not keep the tires from the landfill by giving them an all-new purpose? By collecting a few old tires, you can easily create a raised bed garden while at the same time getting to extend the purpose of these rubber items. You can choose to stack up these tires to help you add interest. Or you can also paint them using whimsical colors as a way of brightening the space available in your backyard. Use Old Silverware as Your Plant Markers Old silverware can easily be put into use by decoupage to help transform them into suitable plant markers. All you need to do is to print a photo of each plant type present in your garden. Proceed to use the decoupage media to affix the printed photo to the back of your silverware. You could also label the silverware making sure to give each spoon a name of the plant you are growing. While at it, make sure that you have a place to store all your garden tools and supplies. An EasyShed for instance, helps you to store gardening essentials away from the elements. It also ensures that your tools are within easy reach whenever you need to tend to your plants. Turning the items in your trash bin into great gardening treasures is not complicated when you choose to adopt a new outlook to life. You do not have to look farther than your home for you to create the ideal backyard garden.
  24. The Impacts of Littering

    Nobody likes a litterbug. However, studies show that out of everyone across the country, people from Queensland and New South Wales are responsible for disposing of the most waste improperly. Because of this, the achievements of others around the country who are trying to dispose of their waste properly has been overshadowed. However, if we can teach people just how much their littering impacts the rest of the world, we may see some improvements sooner than we think. It can kill animals We’ve all seen the advertisements and posters about how disposing of our rubbish in the wrong places can kill animals. However, most of us don’t realise that even getting rid of something small like a gum wrapper or a bottle cap can have a big impact later on. And even though it can be hard to clean up on land, it can be even harder to keep the oceans clean, and plastic rubbish is the main form of litter floating in our oceans. It is estimated that about 88% of the ocean’s surface across the world is covered in plastic debris, with about 8 million metric tons of plastic being thrown into the ocean annually. These numbers will continue to grow if we don’t do something about it and the animals that live in the ocean will feel this impact the most because many animals will either ingest this rubbish by accident or get caught in it because it has no idea what it is. This also means that humans that consume marine animals that have plastic inside them will be impacted because the plastic can not be fully digested by any living creature. It pollutes the soil, water and air When you litter, some of the toxins in the products that you are throwing away can actually leach out into the ground and pollute the soil around it. Because soil is absorbent and it can take on a bit of any substance that you add to it, when you add things like plastic or rubbish that contain chemicals to it, the soil will absorb some of the toxins in the litter. Now you may be thinking that there is no way that this can affect you, but you have to remember that most of the things that you eat are grown and raised in soil. So this is another way that littering can directly impact your diet in a negative way. These toxins from plastics and litter that absorbs into the soil can also seep into the water from the ground so that even the water that we drink can be impacted. It costs the economy Littering is not just about the environmental impacts, there are terrible social impacts that littering has as well. For example, it has been noted that areas, where littering is more common, are places where people are most likely to litter, because they may subconsciously follow what other people are doing or have done before. It can also impact other attitudes in the area towards things like crime and graffiti because the atmosphere in these areas is different from those that are cleaner and well looked after. Because littering is such a big problem in city and suburban areas, local, state and federal governments have had to start allocating funds to combat the problem by paying for more people and organisations to clean up litter on the streets. If more people reduced their amount of waste they produce, reused items that can be reused and recycled things that can be made into something new, there would be a lot less rubbish on our streets that has to be disposed of. There are a number of ways that littering can impact our everyday lives. Littering can affect the water you drink, the food that you eat and the streets that you live on and it is something that can be easily fixed if all of us work together to do the right thing. If you are interested in limiting the litter in your area and making a positive change to help the environment, you should join a group in your local area that is focused on conservation and limiting the waste in your area. Littering is not a problem that can be solved quickly and easily, but every little bit counts, so doing what you can when you can, will make a big impact. Author Bio: Susie is a content manager at 1300 Rubbish, a rubbish removal company that can help you to dispose of any residential, commercial, construction or green waste that you want to get rid of in a responsible way. 1300 Rubbish is based in Australia and offers rubbish removal services to people across the country in all of the major towns and cities.
  25. Perhaps the most important factor in choosing the insulation for your new home is its ability to reduce energy costs. In the winter, insulation should keep warm air in, and in the summer, it should keep hot air out. Choosing the right insulation can reduce your energy bill by as much as 30 percent. For decades, most homes were constructed using fiberglass insulation; however, fiberglass can cause many health issues. Whether you’re building a new home or remodeling, consider an eco-friendly insulation alternative to make your home both comfortable and safe. Consider removing your ceiling insulation and replacing it with one of the following upgraded, eco-friendly options. Recycled Cotton Since cotton is both natural and a renewable resource, it’s among the most eco-friendly insulation options. Scraps from old blue jeans and other used clothing are shredded and produced into heavy batts that fit between your wall studs just like fiberglass insulation. To make cotton insulation non-flammable, it’s treated with a borate solution. Cotton does not contain harmful formaldehyde and does not cause respiratory problems. Likewise, cotton insulation is a natural insect repellent. Cork This option is made from the outer bark of cork trees. It’s free of toxins, renewable, biodegradable, and recyclable. It also helps to deaden noise. Cork is among the most versatile materials, and can be used for a wide variety of products. Although cork has been used for more than a century as a building material, it’s eco-friendly value has only recently become widely known. Cellulose Cellulose insulation is made from recycled paper; it’s toxin-free and safe to install. Modern cellulose insulation is often made from recycled newspaper with an added fire retardant, made from a combination of ammonium sulfate and borate. The insulating performance of loose cellulose insulation compares well to other types of affordable insulation. Sheep’s Wool Sheep’s wool is a natural fire retardant, and in recent years, the insulating qualities of sheep’s wool have been applied to home construction. The wool fiber’s outer layers are water-resistant while the inner layers absorb moisture. This insulates your home while preventing condensation within the walls. When you insulate with sheep’s wool, you will save both energy and money in the long run. There is no right or wrong choice when it comes to green options for insulating your home. Just do your own research, weighing the pros and cons of each type of insulation to find the one that works best for your home.
  26. Jute bags and their promotional aspect

    Jute is a super fiber that has been around since ancient times. It is a natural fiber that is derived from a mix of different vegetable fibers. The main plant is generally the jute plant. It has a rustic yellowish brown look to it. Jute hessian bags changes its strong personality to somewhat beautiful as these bags are great to look at as well. Companies often make promotional jute bags due to the strength and durability of this material. This signifies the feeling of generosity and care towards customers. In the current time when people are stressed over ecological issues, jute can be a promising answer as it is totally natural and is easily biodegraded. Mentioned below are some types of jute bags used for promotional purposes by a lot of businesses and especially retail and wholesale stores: 1) Jute vine Bags A lot of small businesses specially retail and wholesale firms have been using these for promotional purposes for a long time now as they order custom vine bags with their logo and contacts mentioned there. These accessories have a very positive impact on customers as it makes them feel special and they will always remember your business whenever they buy vine due to the bag. This increases the number of returning customers. 2) Carry bags Jute is an eco-friendly material and with governments around the world restricting the use of plastic bags, this is a great way to earn some loyal customers by providing them jute carry bags for their daily shopping. Stores have been doing this for a long time and it allows them to please both customers and the government with one blow. These bags can have your stores name and details printed on it which will act as a source of advertising whenever that bag is out in public. 3) Jute handbags There are a lot of designer jute handbags which can be gifted to loyal customers. Make sure you don’t overdo the advertisement on the bag as handbags can be used daily. It is human nature to talk about their belonging hence by giving customers beautiful handbags you are advertising yourself at a large scale as whenever someone asks them about the bag, the name of your business will surely pop-up and you will have a high chance of gathering potential new customers. Customizations available for jute bags When you decide to do promotional giveaways of jute bags there are certain things that the agency will offer you, they are as follows- 1) High quality image printing As a business you can print the services you offer on these bags along with your name and images of your products. All this is done in high quality and acts as a source of advertisement. 2) Print your logo Printing your log on the promotional bag is optional but somewhat important as you can make your presence felt without disturbing the overall looks. This is a great way for maintaining goodwill among costumers. 3) Customize the color scheme You can customize the color scheme of the bag and can make it more matching to the color scheme of your logo or you can do this to simply improve the looks of the bags.
  27. Antibody drugs are one of the fastest growing biopharmaceuticals, which bring huge benefits to the innovative drug market, with anti-tumor antibody drugs predominating. Since rituximab, the first antibody drug for cancer treatment, was approved by the US FDA in 1979, 17 antibody drugs have been approved for cancer treatment, but the gemtuzumab has withdrawn from the market. According to statistics from 2013, there are about 350 antibody drugs currently in clinical research, most of which are in the early evaluation stage. Therapeutic antibodies in Phase III clinical studies include 28 monoclonal antibodies and a mixture of monoclonal antibodies mainly used for cancer, inflammation or immune diseases, Alzheimer's disease and infectious diseases, 10 of which are cancer therapeutic antibodies.There are also many antibody drugs in preclinical studies, and their research trends are mainly focused on the following aspects, including: the discovery and confirmation of new antibody targets, new strategies to reduce antibody immunogenicity, conjugates of antibodies and drugs, and research on bispecific antibodies as well as other novel antibody drugs. 1.Discover new antibody target molecules At present, the target molecules of antibody drugs are mainly divided into three categories: 1. Clinically validated target molecules, the efficacy of which has been confirmed, for example: CD20, HER2, EpCAM and CTLA-4; 2. Experimentally verified target molecules, the efficacy of this type of target molecule has been confirmed in cells and animals, such as IGF-1R, CD19, CD80, CXCR4 and ICAM-1; 3. New functional target molecules, newly discovered target molecules with certain efficacy, such as RAAG12, CD151, TSN-1, etc. To date, only a few target molecules for anti-tumor antibody drugs have been approved for marketing, and currently only nine. Many tumor-associated biomarker molecules have been reported, and thus so many target molecules for antibody therapy can be excavated. Even if the same target molecule has been developed, different molecular epitopes exist, and antibody drugs against different epitopes can be developed. For example, 5. Anti-CD20 antibody drugs have been marketed, and the 5 are now in clinical research. In addition, many tumor cell transmembrane receptors and extracellular matrix-related genes can be spliced by differential splicing, which can generate new editing sequences and form new differential receptors and substrates as new antibody target molecules. The differentially spliced gene variants have been reported to be: FGFR variants, EGFR variants, EpCAM variants, L1CAM variants, Claudin18 and CD44 variants, and splicing of versican VN, fibronectin F and prion protein T Variants, etc. In recent years, many tumor-associated antibody target molecules have been studied, including EpCAM, PSMA and folate-binding proteins, as well as gangliosides, αVβ3, TRAILR2, FAP and toughlin. Recently, glypican proteoglycan has also been reported as a new target molecule for the treatment of liver cancer antibodies. Reduce antibody immunogenicity Many antibody drugs are murine antibodies, which produce human anti-mouse antibody (HAMA) responses in clinical treatment. Therefore, for long-term treatment, an antibody drug that requires repeated administration is likely to produce a HAMA reaction, which requires humanization to reduce its immunogenicity. Humanized antibodies include chimeric antibodies, modified antibodies, and the like, which have biological properties such as reduced HAMA response and prolonged half-life in blood. In contrast to murine antibodies, the functional effector portion of the humanized antibody drug can be engineered as needed, and the humanized constant region of the antibody prevents the production of anti-isotype antibodies during treatment. The modified antibody further reduces the proportion of the murine fraction in the antibody compared to the chimeric antibody, and significantly reduces the HAMA response. In addition, the study of fully human antibodies has also received great attention and is one of the important development directions of antibody drug research. Fully human antibodies can be obtained by phage display technology, antibody library screening technology and transgenic animal technology. The anti-tumor antibody drugs produced by this technology have obvious inhibitory effects on cancer growth. The immunogenicity of antibody drugs is one of its major toxic side effects, but there is no reliable prediction method for the frequency and timing of immunogenicity and antibody aggregation. If these problems are solved, new antibody detection techniques need to be developed. The results of studying the immunogenicity of human-derived antibodies, humanized antibodies and murine antibodies in humans indicate that: 1. More than 20% of mouse-derived antibodies induce tolerable immunogenicity, or negligible. These mouse antibodies do not need to be humanized; 2. Humanized antibodies can reduce immunogenicity, but their clinical therapeutic effects are also significantly reduced; 3. The immunogenicity of antibodies from different sources is not completely consistent with the law. A small number of humanized antibodies and fully human antibodies also produce significant immune responses; 4. Not only do we need to evaluate the utility of fully human and humanized antibodies item by item, but we also need to consider cost-effectiveness, while considering biochemical characteristics and targeted treatment indications. To date, there is no good way to completely eliminate the risk of antibodies binding to host cells. But classical research suggests that monomeric immunoglobulins are inherently tolerable if we are able to create methods to prevent antibody aggregation or immune complex formation. To be continued in Section Two…
  28. Antibody Engineering comprises in vitro selection and modification of human antibodies, including humanization of mouse antibodies for therapy, diagnosis, and research. It holds the potential for creating antibodies with multiple specificities, greater affinity for their targets, and fewer side effects. In this article, the development history and types of antibody engineering drugs are talked. Antibodies as therapeutic agents An antibody is an immunoglobulin molecule with a specific amino acid sequence induced by an antigen, synthesized and secreted by lymphocytes (plasma cells). An antibody can bind to an antigen such as a bacterium, a virus or a toxin, and neutralize and remove the harmful substance by the following three or one of the following methods: a. directly inactivates the antigen; b. the immune effector cells phagocytose and destroy it; c. it is weakened by the surface of the antigen and thus be easily damaged by complement. The study of antibodies as therapeutic agents has been going on for a century. The lateral chain theory proposed by Ehrlich laid the foundation for immunology and immunotherapy. He believes that the surface of the cell has specific receptor molecules (or side chains) that bind only to specific groups in the toxin molecule; if the cells survive with the toxin, they will produce excess side chains. Some of the side chains are released into the blood, which is an anti-toxin. This is what is now called an antibody. Ehrlich uses organic arsenic compounds to treat syphilis and introduces the term "magic bullet" in the field of chemotherapy to strengthen the strategies and goals of specific therapies. As early as 1895, it was reported that Hericourt and Richet injected cancer cells into animals to produce antiserum for the treatment of cancer patients, and the symptoms of the patients were significantly improved. In the early 20th century, many researchers repeated the above tests, but failed to obtain a definite therapeutic effect, and sometimes even produced serious side effects. Later studies have found that antisera contain a large number of different kinds of antibodies, which are directed against different antigens on the surface of cancer cells, and these antigens are also present in normal tissue cells. Therefore, the cross-reactivity of antibodies with normal tissues may lead to serious consequences. Antiserum has long been effective in neutralizing exogenous toxins such as snake venom, but has not been effective in the treatment of tumors and other diseases. Monoclonal antibody In 1975, Köhler and Milstein used B lymphocyte hybridoma technology to prepare monoclonal antibodies (MAb). Monoclonal antibodies have high specificity, uniform properties and are easy to mass produce. A variety of monoclonal antibodies can be prepared in vitro by cell engineering, which is an epoch-making advance in antibody production. It is especially important that monoclonal antibodies have high specificity for the corresponding antigens and homogeneity of the antibody molecules, which can greatly reduce cross-reactivity with normal tissues in vivo, and bring new hope for the treatment of diseases by using antibodies, especially for treating tumors. At that time, some people called it "magic bullet", and it is expected that monoclonal antibodies can specifically attack pathogenic cells or pathogens without causing toxic side effects. In the past 20 years, monoclonal antibodies have been widely used in the diagnosis of diseases, and make much breakthroughs have despite many obstacles. To distinguish, an antibody previously prepared by immunizing an animal with an antiserum pathway is referred to as a polyclonal antibody, or a conventional antibody. Genetically engineered antibodies Since the monoclonal antibodies prepared by the B lymphocyte hybridoma technique are mostly murine, the human anti-mouse antibody (HAMA) reaction can be induced in the human body, which limits the application of the monoclonal antibody as a therapeutic agent in humans. In order to overcome the heterologous reaction of murine monoclonal antibodies, in the mid-1980s, researchers explored the genetic engineering of mouse-derived monoclonal antibodies to prepare humanized antibodies. For example, they spliced the variable region of mouse Ig to the constant region of human Ig or modified the CDR region of the murine Ig to the human Ig. At the same time, considering the treatment of solid tumors with intact antibodies, the molecules are too large to penetrate the extracellular space into the deep tumor, so genetic engineering methods are used to miniaturize antibody molecules, such as single-chain antibodies (scFv), diabody, minibody, etc. The establishment and development of antibody library technology can directly clone the gene of specific antibody in the prokaryotic cell system by genetic engineering method, which greatly promotes the preparation and research and development of novel genetic engineering antibodies. Antibody engineering has become a key technology to promote the development of antibody drugs. Immunoconjugates and fusion proteins The molecular structure and function of the antibody has two sides. One is the specific binding to the antigen and is completed by the variable region. The second is the effect function triggered by binding to the antigen, which is completed by the constant region. In order to enhance the effector function of antibody drugs, especially tumor antibody drugs, and to enhance their killing effect on tumor cells, an effector molecule or a "warhead" substance is commonly used to chemically connect with an antibody to prepare an immunoconjugate. The specificity of the antibody is utilized as a targeting vector; the "target" is used to kill tumor target cells. There are three main types of substances used as "warheads", namely radionuclides, chemotherapeutics and toxins. These "warhead" substances are linked to antibodies, which constitute radioimmunoconjugates, chemical immunoconjugates and immunotoxins, respectively. A fusion protein can be produced by a genetic engineering method, and the antibody portion of the fusion protein is generally a single-chain antibody scFv; the portion corresponding to the "warhead" is generally a toxin fragment, a cytokine or a peptide drug. The monoclonal antibodies, antibody fragments, genetically engineered antibodies, and immunoconjugates described above can be collectively referred to as antibody-based drugs, also known as monoclonal antibody therapeutics. Such antibody drugs are prepared by a cell engineering method or a genetic engineering method or a combination of two methods, and may also be referred to as an antibody engineering drug. Antibody drugs for clinical application The development of antibody drugs has a prominent position in the field of biotechnology drugs. The number of antibody drugs currently in preclinical and clinical research stages is among the highest in biotechnology drugs. The variety of antibody drugs in research and development is versatile, and the diseases that may be used for treatment include cancer, viruses and other infectious diseases, cardiovascular diseases and immune system diseases, among which cancer treatment is the first.
  29. Bridging cells (in-transbinding)—bridging cell method The most commonly used bridging cells are bridging effector T cells and tumor cells, also known as T cell-engaging bsAb (bsTCE). In addition, NK cells, stem cells, and tumor cells etc. are also used. bsTCE directly couples T cells and tumor cells to form immune synapses, activates in TCR, releases granzymes and perforin, and finally lyses tumor cells. BsTCEs bind to CD3ε in the CD3ε-TCR complex and activate T cells without antigen presentation. Although this mechanism was proven to be highly effective in the laboratory by co-culture experiments, it caused rapid uncontrolled cytokine release syndrome (CRS), including the earliest marketed CD3×EpCAM bsTCE catumaxomab, via the Fc segment binding to FCγR expressing Kupffer cells in the liver and causes uncontrolled hepatotoxicity. Targeting bsTCEs by CD3 requires complete inhibition of Fc-mediated effector function to reduce non-target toxicity and maximize therapeutic effects. Tumor target—Target expression and efficacy The activity of some bsTCE is positively correlated with the expression level of tumor targets, such as CEA, CD33, HER2. There are also some no significant correlations with expression levels, such as EPHA2, PSMA. However, there is also a minimum required tumor target expression, such as RG6106 requires at least 50 bsTCE binds to the myeloma surface FCRL5, while Roche cibisatamab requires 10,000 CEA in combination with bsTCE to be activated. Structural design Bivalent tumor targets can increase drug binding activity and enhance drug efficacy. Some tetravalent bsTCEs are under development, including Adaptir and TandAb, which have two CD3 and two TAA binding units. In addition, trivalent bsTCEs are under development, in which CD3 is monovalent and TAA is bivalent. For example, RG6026 (also known as RO7082859; Roche). Immune checkpoint Clinically administration of monoclonal antibody against CTLA-4, PD1/PD-L1 immunological checkpoints have been quite successful. More than 10 corresponding bispecific antibodies have entered the early clinical stage worldwide, involving PD1/PD-L, CTLA4, lymphocyte activation Gene 3 (LAG3) or T cell immunoglobulin mucin protein 3 (TIM3; also known as HAVCR2) Previously, two checkpoint antibodies were combined to improve efficacy. For example, treatment of melanoma patients with ipilimumab (anti-CTLA4) + nivolumab (anti-PD1) improves survival compared with ipilimumab alone. However, clinical immune-related side effects have also multiplied. In order to improve the safety of the combined targeting of PD-1 and CTLA 4, an Fc-silencing bsAb, a high affinity inhibition of PD-1, and a low affinity binding inhibition of CTLA 4 were designed to inhibit the PD-1 pathway. This design is beneficial for inhibiting PD-1-CTLA 4 double positive tumor infiltrating lymphocytes, and at the same time reducing the binding of CTLA 4 expressing peripheral T cells, thereby providing better safety. Currently, the safety and early efficacy of the four PD-1×CTLA4 bsAbs are being evaluated in early clinical trials. The concept of blocking two immunological checkpoint inhibitors is also clinically used for other target combinations, such as PD-1 x LAG 3, PD-1 x TIM3, and PD-L1 x CTLA 4. Bridging receptors (in-cisbinding)—bridge acceptor inhibitory activity Targeting inhibition of tumor receptor tyrosine kinases (RTKs) such as EGFR and HER 2 is a successful anticancer approach, but the development of drug resistance is one of the major limiting factors for such treatment. Drug resistance typically involves up-regulation of other RTKs that bypass specific receptor inhibition to activate parallel signaling pathways. For example, in the tyrosine protein kinase MET pathway, non-small cell lung cancer (NSCLC) tumors are resistant to EGFR tyrosine kinase inhibitors. JNJ-61186372 (Janssen Pharmaceuticals) is an EGFR x MET bsA that blocks EGFR and MET signaling by inhibiting ligand-induced activation and receptor degradation by cFAE. JNJ-61186372 has antibody-dependent cytotoxic activity (ADCC) which is produced by Fc containing low fucose. The glycotypic analysis in the quality control of such bispecific antibodies should be noted. Bridging receptors (in-cisbinding)—bridge acceptor agonist receptor activity In contrast to blocking pathogenic signals with inhibitory antibodies, some therapeutic concepts require receptor signals to be activated by agonistic antibodies. Specific bsAbs are also particularly suitable for activating multi-component receptor complexes because they require simultaneous binding of the receptor and the co-receptor to activate. Activation of the fibroblast growth factor 21 (FGF 21) pathway has been reported to improve obesity and diabetes. However, the pharmacokinetic properties of recombinant FGF21 are poor, and chronic treatment has a risk of adverse reactions. Thus, the agonist bFKB8488A (Roche) was designed to activate this metabolic pathway by selectively targeting the fibroblast growth factor receptor 1C (FGFR1C)-β-Klotho (KLB) receptor complex. KLB is selectively expressed in liver, fat, and pancreatic tissues, while FGFR1C is widely distributed in liver, fat, and pancreatic tissues. Thus, co-targeting of these receptors may limit signal activation to only tissues that co-express KLB and FGFR1C and limit the adverse consequences of extensive FGFR activation, such as induction of cell proliferation. Preliminary results from an ongoing human first trial showed an improvement in cardiac metabolism in obese patients with insulin resistance. Cofactor mimetics Sampi and his colleagues began producing a bsAb to replace FVIII as a potential treatment for hemophilia A to prevent bleeding from FVIII dysfunction. The role of bsAb is to mimic the activated form of FVIII, FVIIIa, which binds FX and FIXa to enhance the catalytic activity of FIXa. In a wide range of screening efforts, a dual-characteristic antibody called AE 910 or emicizumab was finally selected and finally approved by the FDA for routine prevention to reduce bleeding in patients with hemophilia A using FVIII inhibitors. Further approval in October 2018 also included the use of emicizumab for prevention in patients without FVIII inhibitors. Emicizumab was first approved in Europe in March 2018. Piggyback approaches The first target-specific transport of a second specific target using the bsAb is referred to as a "piggyback transport" or "hijacking" method for accessing a restricted cell chamber. Raso and colleagues described the first case of the use of hijacking concept-specific transport proteins, which linked bispecific receptors to ricin A, mediating toxin internalization and toxicity. A recent example is the hijacking of the transferrin transport pathway to cross the blood-brain barrier and enter the immune-immunized brain region. The researchers targeted the transferrin receptor (Tfr) by using a binding arm of the bsAb, and the second binding arm carries β-secretase 1 (BACE 1), which transports BACE1 into the brain, and TfR×BACE 1 bsAb can reduce amyloid (Aβ, Aβ) peptide levels in brain tissue and cerebrospinal fluid. Psl×pcrvbsAb MEDI3902 is a full-length IgG 1 antibody inserted between Fabs and fc to form a symmetrical 2+2 format. This antibody enhances P. aeruginosa killing effect by neutrophils using a similar piggyback mechanism. Reference Oberst, .mAbs 6, 1571–1584 (2014). Laszlo, GS et al. Blood 123, 554–561 (2014). Lopez-Albaitero, A. et al. . Oncoimmunology 6, e1267891 (2017) Wolchok, J. D. et al. N.Engl. J. Med. 377, 1345–1356 (2017). Dovedi, S. J. et al. Cancer Res. 78,2776(2018). Hedvat, M. et al.Presented at the 2018 Society for ImmunotherapyofCancer (SITC) (2018). Xu, J. et al. . Am. J. Physiol. Endocrinol. Metab. 297,E1105–E1114(2009).Wu, A. L. et al.Sci. Transl Med. 3, 113ra126 Xu, J. et al. . Am. J. Physiol. Endocrinol. Metab. 297, E1105–E1114 (2009). Wu, A. L. et al. Sci. Transl Med. 3, 113ra126 Sampei, Z. et al. PLOS ONE 8, e57479 (2013)
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