Everything below concerns Aib substitution. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-12-24. Numbers and descriptions here follow the published literature rather than marketing material.
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 signing of the Protocol of Rio de Janeiro in January 1942 was processed in the consciousness of the urban masses -stricto sensu-, not only as a historical fact of territorial confinement, but as a psychic and physical mutilation also assumed in individual terms. The painful saying that for decades has been repeated in school classrooms would already say: "Yellow, blue and red: the flag of the patojo." From 1941, being Ecuadorian would imply being handicapped and a loser, which will deepen the identity conflict of the Ecuadorian mestizo: if before he was incomplete, imperfect or chulla because he fled from his roots, now he was incomplete or patojo because he was facing reality." In addition, Peruvian historians, such as Germán Leguía and Martínez, have accused Ecuadorian historians of a well-documented and marked anti-Peruvianism when trying to minimize the role of the pro-Peruvian party in Guayaquil, headed by Gregorio Escobedo, during the Independence of Ecuador. Between Them would be included Pio Jaramillo Alvarado, Óscar Efrén Reyes (who would criticize the Peruvians of Saraguro, Cuenca, Loja and Guayaquil, provinces with populations that sought to annex Peru at the beginning of the 21st century, as hindrances to the national unification of Ecuador in Gran Colombia of Bolívar) and Pedro Fermín Cevallos.
== Awards and honours == The HGSA honours one eminent member annually by inviting them to present the HGSA Oration at the Annual Scientific Meeting. Additionally, one outstanding mid-career researcher is invited to deliver a presentation at the Annual Scientific Meeting to showcase their work in the Sutherland Lecture, named in honour of Prof Grant Sutherland. Each year, the membership is invited to nominate eminent retiring members to Emeritus Membership of the Society. Nominations are called for members who have contributed significantly to the running and welfare of the Society for a Service Award. HGSA Council scrutinizes and considers these nominations before awarding.
== See also == Cryoscopy and cryoscopic constant Ebullioscopy and ebullioscopic constant Dumas method of molecular weight determination François-Marie Raoult Standard atomic weight Mass number Absolute molar mass Molar mass distribution Dalton (unit) SDS-PAGE
Sources: en.wikipedia.org
== Background == Descriptions of rejuvenation and immortality remedies are often found in the writings of alchemists. But all those remedies did not allow even alchemists themselves to live longer than a hundred years. Though the average lifespan of people through the past millennia increased significantly, maximum lifespan almost did not change - even in ancient times there were fairly well and unbiasedly documented cases when some people lived for more than a hundred years (for example, Terentia who lived 103 or 104 years). While among the billions of people of the modern world, there is only one case of life over 120 years (Jeanne Calment, 122 years). The super-long lives of people that are mentioned in ancient books, apparently, are highly exaggerated, since archaeological data show that even the oldest of the ancient people lived no more than modern supercentenarians. In some cases the exaggeration, possibly, is not intentional but occurs due to errors in translation between languages and synchronization of chronological systems. The species limit of human life is estimated by scientists at 125–127 years, and even in the most ideal conditions a person will not live longer due to aging of the body. Some scientists believe that, even if medicine learns how to treat all major diseases, that will increase the average lifespan of people in developed countries by only about 10 years. For example, biogerontologist Leonard Hayflick stated that the natural average lifespan for humans is 92 years.
vacuole Any of a class of enclosed, fluid-filled compartments present in many eukaryotic cells as well as bacteria, often large and conspicuous under the microscope and serving any of a huge variety of functions, including acting as a resizable reservoir for the storage of water, metabolic waste, toxins, or foreign material; maintaining cellular homeostasis and hydrostatic pressure; supporting immune functions; housing symbiotic bacteria; and assisting in the degradation and recycling of old cellular components.
Mixing red, green, and blue sources to produce white light needs electronic circuits to control the blending of the colors. Since LEDs have slightly different emission patterns, the color balance may change depending on the angle of view, even if the RGB sources are in a single package, so RGB diodes are seldom used to produce white lighting. Nonetheless, this method has many applications because of the flexibility of mixing different colors, and in principle, this mechanism also has higher quantum efficiency in producing white light. There are several types of multicolor white LEDs: di-, tri-, and tetrachromatic white LEDs. Several key factors that play among these different methods include color stability, color rendering capability, and luminous efficacy. Often, higher efficiency means lower color rendering, presenting a trade-off between the luminous efficacy and color rendering. For example, the dichromatic white LEDs have the best luminous efficacy (120 lm/W), but the lowest color rendering capability. Although tetrachromatic white LEDs have excellent color rendering capability, they often have poor luminous efficacy. Trichromatic white LEDs are in between, having both good luminous efficacy (>70 lm/W) and fair color rendering capability. One of the challenges is the development of more efficient green LEDs. The theoretical maximum for green LEDs is 683 lumens per watt, but as of 2010 few green LEDs exceed even 100 lumens per watt. The blue and red LEDs approach their theoretical limits. Multicolor LEDs offer a means to form light of different colors.
For services to Business and to the UK Film Industry. Catherine Anne Goodman, LVO. Artist and Educator. For services to Art. Professor Roger James Goodman. Nissan Professor of Modern Japanese Studies and Warden, St. Antony's College, University of Oxford. For services to Social Science. Gayle Jean Margaret Gorman. Lately HM Chief Inspector and Chief Executive, Education Scotland. For services to Education and Charity. Gerard Arthur Georges Grech. Founder, Tech Nation and Managing Director, Founders at the University of Cambridge. For services to the Technology Sector. The Reverend Nicholas Glyn Paul Gumbel. Lately Vicar, Holy Trinity Brompton, London. For services to the Church of England. Paul Harris. Deputy Chief Executive Officer and Operations Director, HM Courts and Tribunals Service. For Public and Voluntary Service. Martin James Hewitt, QPM. Lately Chair, National Police Chiefs Council. For services to Policing. Professor Peter Michael Hollingsworth. Director of Science and Deputy Keeper, Royal Botanic Garden, Edinburgh. For services to Botanical Science. Karl James Hoods. Chief Digital and Information Officer, Department for Science, Innovation and Technology and Department for Energy Security and Net Zero. For services to Technology and to Education. Professor Andrew Lee Hopkins, FRS, FMedSci, FRSE. Chief Executive Officer, Exscientia. For services to Science and to Innovation. Christian Edward Johnston Horner, OBE. Team Principal and Chief Executive Officer, Red Bull Racing. For services to Motor Sport. Pauline Jean Howie, OBE.
Sources: en.wikipedia.org
== Background == KEZAD Group was launched in September 2022 through the consolidation of Khalifa Industrial Zone Abu Dhabi (KIZAD) and ZonesCorp. It was established to expand Abu Dhabi’s economic cities and free zones, offering and streamlining infrastructure development, regulatory frameworks, and investment facilitation.
=== Elevation and pinecone production === Some growers claim that the elevation of the pinyon pine is an important determinant of the quantity of pine cone production and, therefore, will largely determine the number of pine nuts the tree will yield. The US Department of Agriculture notes that variation in cone production between trees growing on identical sites is often observed. American pinyon pine cone production is most commonly found at an elevation between 1,800 and 2,600 m (6,000 and 8,500 ft), and ideally at 2,100 m (7,000 ft). This is due to higher temperatures at elevations lower than 1,800 m (6,000 ft) during the spring, which dry up humidity and moisture content (particularly snow packs) that provide for the tree throughout the spring and summer, causing little nourishment for pine cone maturity. Although several other environmental factors determine the conditions of the ecosystem (such as clouds and rain), the trees tend to abort cones without sufficient water. High humidity encourages cone development. There are certain topographical areas found in lower elevations, such as shaded canyons, where the humidity remains constant throughout the spring and summer, allowing pine cones to fully mature and produce seed. At elevations above 2,600 m (8,500 ft), the temperature substantially drops, drastically affecting the state of the dormant cone. During the winter, frequent dramatic changes in temperature, drying, and gusty winds make the cones susceptible to freeze-drying that permanently damages them; in this case, growth is stunted, and the seeds deteriorate.
Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight or at least 8 hours before the test. Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT) Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).
Wenzel Model was developed to calculate the dependence that surface roughness has on the observed contact angle. Surfaces that are not atomically smooth will exhibit an observed contact angle that varies from the actual contact angle of the surface. The equation is expressed as:
In the late 1970s, the Peruvian communist party Shining Path developed and synthesised Mao Zedong Thought into Marxism–Leninism–Maoism, a contemporary variety of Marxism–Leninism that is a supposed higher level of Marxism–Leninism that can be applied universally.
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。