If you have been reading about Aib substitution and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2025-10-06. Where a claim depends on a specific study, the study is described rather than over-claimed.
Pharmacological activity arises from agonism at the glucagon-like peptide-1 receptor, a G protein-coupled receptor expressed in the pancreas, the gastrointestinal tract, and the brainstem. Receptor activation raises intracellular cyclic adenosine monophosphate and enhances insulin release in a glucose-dependent manner, an effect that diminishes when blood glucose concentration is low. Other effects include slowed gastric emptying and hypothalamic satiety signalling. These pathways are described well. Receptor desensitisation rates across tissues, relative to the endogenous hormone, are still under investigation, and reported findings differ between laboratories.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
The outer chloroplast membrane is a semi-porous membrane that small molecules and ions can easily diffuse across. However, it is not permeable to larger proteins, so chloroplast polypeptides being synthesized in the cell cytoplasm must be transported across the outer chloroplast membrane by the TOC complex, or translocon on the outer chloroplast membrane. The chloroplast membranes sometimes protrude out into the cytoplasm, forming a stromule, or stroma-containing tubule. Stromules are very rare in chloroplasts, and are much more common in other plastids like chromoplasts and amyloplasts in petals and roots, respectively. They may exist to increase the chloroplast's surface area for cross-membrane transport, because they are often branched and tangled with the endoplasmic reticulum. When they were first observed in 1962, some plant biologists dismissed the structures as artifactual, claiming that stromules were just oddly shaped chloroplasts with constricted regions or dividing chloroplasts. However, there is a growing body of evidence that stromules are functional, integral features of plant cell plastids, not merely artifacts.
This disagreement led to the 1865 Gastein Convention, which, despite its casus belli being the defence of the German-speaking Schleswig-Holsteiners' wish to remain unified, granted Schleswig and Lauenburg to Prussia and Holstein to Austria. However, this situation did not last long.
In April 2018, Boston Market announced that it was expanding its menu to offer rotisserie prime rib nationwide, three days a week. In 2019, the chain closed 45 locations, with one report noting competition with rotisserie chickens sold at regular supermarket chains. In 2020, it introduced baby back ribs paired with Sweet Baby Ray's sauce. In April 2020, Sun Capital Partners sold Boston Market to Engage Brands, LLC, a company of Rohan Group, owned by Jignesh "Jay" Pandya. This started a difficult period in which the company stopped paying its suppliers, rent, and some employees. This resulted in over 150 lawsuits. In 2023, New Jersey shut down 27 locations when it was determined employees were owed hundreds of thousands of dollars. The chain started with about 300 locations at the start of 2023, but was down to 79 locations later that year, and by early 2024 there were fewer than 30 locations even though the chain opened a new location in India.
Sources: en.wikipedia.org
As of 2016, challenges including optimizing sample treatment, optimizing disk surfaces, developing readers that can deploy multiple colors of light delivery and sensing for multiplexing, and for clinical use, obtaining regulatory approvals. The field is similar to lab-on-a-chip platforms. As of 2010 companies including Gyros AB, Tecan, and Burstein Technologies were working on bringing CD/DVD based immunoassays and equipment to market. Bioanalysis Microanalysis Immunoscreening List of chemical analysis methods
Immunity is determined genetically. Genomes in humans and animals encode the antibodies and numerous other immune response genes. While many of these genes are generally required for active and passive immune responses (see sections above), there are also many genes that appear to be required for very specific immune responses. For instance, Tumor Necrosis Factor (TNF) is required for defense of tuberculosis in humans. Individuals with genetic defects in TNF may get recurrent and life-threatening infections with tuberculosis bacteria (Mycobacterium tuberculosis) but are otherwise healthy. They also seem to respond to other infections more or less normally. The condition is therefore called Mendelian susceptibility to mycobacterial disease (MSMD) and variants of it can be caused by other genes related to interferon production or signaling (e.g. by mutations in the genes IFNG, IL12B, IL12RB1, IL12RB2, IL23R, ISG15, MCTS1, RORC, TBX21, TYK2, CYBB, JAK1, IFNGR1, IFNGR2, STAT1, USP18, IRF1, IRF8, NEMO, SPPL2A). The Center for Modeling Immunity to Enteric Pathogens (MIEP)
The price for pure bismuth metal was relatively stable through most of the 20th century, except for a spike in the 1970s. Bismuth has always been produced mainly as a byproduct of lead refining, thus the price usually reflected the cost of recovery and the balance between production and demand. Before World War II, demand for bismuth was small and mainly pharmaceutical—bismuth compounds were used to treat such conditions as digestive disorders, sexually transmitted diseases, and burns. Minor amounts of bismuth metal were consumed in fusible alloys for fire sprinkler systems and fuse wire. During World War II, bismuth was considered a strategic material, used for solders, fusible alloys, medications, and atomic research. To stabilize the market, the producers set the price at $1.25 per pound ($2.75 /kg) during the war and at $2.25 per pound ($4.96 /kg) from 1950 until 1964. In the early 1970s, the price rose rapidly due to increasing demand for bismuth as a metallurgical additive to aluminium, iron, and steel. This was followed by a decline owing to increased world production, stabilized consumption, and the recessions of 1980 and 1981–1982. In 1984, the price began to climb as consumption increased worldwide, especially in the United States and Japan. In the early 1990s, research began on the evaluation of bismuth as a nontoxic replacement for lead in ceramic glazes, fishing sinkers, food-processing equipment, free-machining brasses for plumbing applications, lubricating greases, and shot for waterfowl hunting.
== Drug targeting == Certain antibiotics, such as tetracyclines, prevent the aminoacyl-tRNA from binding to the ribosomal subunit in prokaryotes. It is understood that tetracyclines inhibit the attachment of aa-tRNA within the acceptor (A) site of prokaryotic ribosomes during translation. Tetracyclines are considered broad-spectrum antibiotic agents; these drugs exhibit capabilities of inhibiting the growth of both gram-positive and gram-negative bacteria, as well as other atypical microorganisms. Furthermore, the TetM protein (P21598) is found to allow aminoacyl-tRNA molecules to bind to the ribosomal acceptor site, despite being concentrated with tetracyclines that would typically inhibit such actions. The TetM protein is regarded as a ribosomal protection protein, exhibiting GTPase activity that is dependent upon ribosomes. Research has demonstrated that in the presence of TetM proteins, tetracyclines are released from ribosomes. Thus, this allows for aa-tRNA binding to the A site of ribosomes, as it is no longer precluded by tetracycline molecules. TetO is 75% similar to TetM, and both have some 45% similarity with EF-G. The structure of TetM in complex with E. coli ribosome has been resolved.
Sources: en.wikipedia.org
Amifostine (ethiofos) is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by Clinigen Group under the trade name Ethyol.
== History == The calcium channel experiments that led to the discovery of P-type calcium channels were initially completed by Llinás and Sugimori in 1980. P type calcium channels were named in 1989 because they were discovered within mammalian Purkinje neurons. They were able to use an in vitro preparation to examine the ionic currents that account for Purkinje cells' electrophysiological properties. They found that there are calcium dependent action potentials which rise slowly and fall quickly then undergo hyperpolarization. The action potentials were voltage dependent and the afterhyperpolarizing potentials were connected to the spike bursts, located within the dendrites of the Purkinje cells. Without calcium flux in the Purkinje cells, action potentials fire sporadically at a high frequency.
In certain areas of the world, like Ethiopia where this was studied extensively, as the cows needed to intake more nutrition to balance out their milk production, there was also an increased level of chemical fertilizers and heavy metal traces found in the milk due to increased exposure to agricultural chemicals. These chemicals can then easily be passed on to humans and lead to a contaminated milk supply. BST increases the longevity or the activity of the mammary cell leading to higher milk production and some other non-desirable side effects. Despite public controversy of the use of growth hormones in food-producing animals, the number of violations has decreased substantially in the past two decades. For comparison, the level of antibiotic-residue detected in bulk milk tank trucks in 2012 was one fifth the level that it was in 1996. As reported by the USDA, the US pattern for milk BTSCC declined steadily from 316,000 cells per mL of milk in 2001 to 224,000 cells/mL in 2010 and 206,000 cells/mL in 2011 (USDA, 2013). Mammary health in the animals themselves has improved over this time period as well as the overall health of the dairy herd in general. This is mostly attributed to better application methods of rBST and a better understanding of how the hormone affects the animals.
=== Manual === The earliest polarimeters, which date back to the 1830s, required the user to physically rotate one polarizing element (the analyzer) whilst viewing through another static element (the detector). The detector was positioned at the opposite end of a tube containing the optically active sample, and the user used his/her eye to judge the "alignment" when least light was observed. The angle of rotation was then read from a simple fixed to the moving polariser to within a degree or so. Although most manual polarimeters produced today still adopt this basic principle, the many developments applied to the original opto-mechanical design over the years have significantly improved measurement performance. The introduction of a half-wave plate increased "distinction sensitivity", whilst a precision glass scale with vernier drum facilitated the final reading to within ca. ±0.05º. Most modern manual polarimeters also incorporate a long-life yellow LED in place of the more costly sodium arc lamp as a light source.
Bitcoin (abbreviation: BTC; sign: ₿) is the first decentralized cryptocurrency. Based on a free-market ideology, bitcoin was invented in 2008 when an unknown person published a white paper under the pseudonym of Satoshi Nakamoto. Use of bitcoin as a currency began in 2009, with the release of its open-source implementation. From 2021 to 2025, El Salvador adopted it as legal tender currency before revoking it. As bitcoin is pseudonymous, its use by criminals has attracted the attention of regulators, leading to its ban by several countries. Bitcoin works through the collaboration of computers, each of which acts as a node in the peer-to-peer bitcoin network. Each node maintains an independent copy of a public distributed ledger of transactions, called a blockchain, without central oversight. Transactions are validated through the use of cryptography, preventing one person from spending another person's bitcoin, as long as the owner of the bitcoin keeps certain sensitive data secret. Consensus between nodes about the content of the blockchain is achieved using a computationally intensive process based on proof of work, called mining, which is performed by purpose-built computers. Mining consumes large quantities of electricity, with surveyed miners reporting that 52% of their electricity use came from sustainable energy sources, and has been criticized for its environmental impact.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。