Everything below concerns Adsorption. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-04-17. Numbers and descriptions here follow the published literature rather than marketing material.
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。
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
Reverse-phase high-performance liquid chromatography is the standard method for purity assessment, separating the peptide from truncated or oxidized variants. Mass spectrometry confirms molecular mass and detects modifications, while ultraviolet absorbance near 280 nanometers supports concentration measurement through tryptophan and tyrosine residues. Circular dichroism can indicate secondary structure, though the peptide is largely helical in solution, and ion-exchange chromatography resolves charge variants. Purity values above 95 percent are typical for research-grade material. Stability studies track degradation over time under defined conditions.
Lyophilized semaglutide is typically stored at temperatures between minus 20 and minus 80 degrees Celsius for long-term preservation. Short-term storage at 2 to 8 degrees Celsius is common for working aliquots. Repeated freeze-thaw cycles can degrade the peptide and are usually avoided. The molecule is hygroscopic in its solid form, so containers should remain sealed with desiccant. Solutions are less stable than powders and are generally prepared fresh. Light exposure is limited because aromatic residues can undergo photo-oxidation.
| Property | Value | Notes |
|---|---|---|
| 分子式 | C187H291N45O59 | 按主链与 C18 二酸侧链计算 |
| 分子量 | 约 4113.6 道尔顿 | 游离碱形式，随反离子略有差异 |
| 外观 | 白色至类白色冻干粉末 | 具吸湿性，需干燥保存 |
| 溶解性 | 微溶于水，易溶于碱性缓冲液 | 溶解性随 pH 升高而改善 |
| 等电点 | 约 5.4 | 影响缓冲液选择与聚集倾向 |
Stability studies examine how temperature, pH, and moisture influence degradation rates over time. In aqueous solution, hydrolysis and deamidation accelerate as pH moves away from mildly acidic conditions. Light exposure and residual metal ions can also trigger oxidation of susceptible residues. Accelerated aging at elevated temperature is used to estimate shelf life, though extrapolation to room temperature carries uncertainty because individual degradation pathways do not always scale predictably.
Lyophilized semaglutide powder is typically held at minus twenty degrees Celsius for long-term storage. At that temperature, solid-state degradation reactions proceed slowly and the peptide remains intact for extended periods. Repeated freeze-thaw cycles are best avoided because they promote aggregation and can shift the proportion of monomeric peptide present. Working aliquots are often prepared so that each portion is thawed only once, and desiccant is placed inside the vial to limit moisture uptake.
Storage at minus 20 degrees Celsius or lower in a desiccated container preserves the peptide for extended periods, while working solutions are commonly held at two to eight degrees Celsius for short intervals. Light exposure and repeated freeze-thaw cycles accelerate degradation, so dividing material into single-use aliquots is generally recommended. Adsorption to glass and plastic surfaces can lower the measured concentration of dilute solutions, particularly below one milligram per millilitre. The degradation routes most often reported for GLP-1 analogues are deamidation, methionine oxidation, and backbone hydrolysis. Relative rates under specific conditions are frequently described only for individual formulations.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 or 280 nanometres is widely used to assess purity and to resolve related impurities. Liquid chromatography coupled to mass spectrometry confirms identity through the protonated molecular ion and fragment ions formed in tandem experiments. Capillary electrophoresis and peptide mapping after enzymatic digestion supply complementary information on charge variants and modification sites. Circular dichroism and nuclear magnetic resonance can report on secondary structure in solution. Absolute quantification usually depends on an external standard, and reported purity depends on the detection wavelength and integration parameters chosen.
Lyophilised material appears as a white to off-white cake or powder that is hygroscopic, and containers are usually equilibrated to room temperature before opening to limit condensation. Dissolution is performed in water, phosphate-buffered saline, or a mildly alkaline buffer, since solubility rises above neutral pH. Gentle inversion or low-speed mixing is preferred, because vigorous vortexing can promote surface denaturation and aggregation. Complete dissolution may require several minutes, and brief sonication is sometimes applied. Passing the solution through a 0.22 micrometre membrane removes particulates but does not by itself sterilise the liquid.
The distinction between established facts and open questions matters here. That the peptide binds the GLP-1 receptor and stimulates insulin release in a glucose-dependent manner is well documented. How individual variability in receptor density, gastric emptying rate, and gut microbiome composition shapes response remains an active research area. Long-term outcomes beyond five years of continuous use are not yet fully characterized in published trials, and several extension studies are ongoing.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L cells after food intake. The molecule is a 31-amino-acid backbone modified at three positions to resist cleavage by dipeptidyl peptidase-4, the enzyme that degrades native GLP-1 within minutes. A lysine residue at position 26 carries a linker and a C18 fatty diacid, which promotes binding to serum albumin and slows renal clearance. These changes extend the circulating half-life from roughly two minutes to about one week in humans.
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.
Alcohol dehydrogenase class-3 is an enzyme that in humans is encoded by the ADH5 gene. This gene encodes glutathione-dependent formaldehyde dehydrogenase or the class III alcohol dehydrogenase chi subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class III alcohol dehydrogenase is a homodimer composed of 2 chi subunits. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis.
==== United States ==== As of 2023, 38 states, four territories, and the District of Columbia allow medical use of cannabis (in which THC is the primary psychoactive component), with the exception of Georgia, Idaho, Indiana, Iowa, Kansas, Nebraska, North Carolina, South Carolina, Tennessee, Texas, Wisconsin, and Wyoming. As of 2022, the federal government maintains cannabis as a schedule I controlled substance, while dronabinol is classified as Schedule III in capsule form (Marinol) and Schedule II in liquid oral form (Syndros). On 18 December 2025, President Donald Trump issued an Executive Order titled "Increasing Medical Marijuana and Cannabidiol Research", directing the DEA and FDA to reclassify medical marijuana. To that end, on 23 April 2026, the Department of Justice issued an order to immediately reclassify medical cannabis as a Schedule III controlled substance when dispensed by state-licensed cannabis dispensaries to individuals with a state issued medical marijuana card. The DEA is in the process of conducting expedited public hearings to address the broader rescheduling of all cannabis from Schedule I to Schedule III, with the hearings scheduled to begin 29 June 2026. This rescheduling makes medical marijuana legal for medicinal use when obtained from licensed dispensaries, and once the broader rescheduling is complete, should allow it to be prescribed by licensed physicians who are also licensed by the DEA to prescribed controlled substances. However, as it is still a controlled substance, diversion for recreational use will still be illegal under federal law.
Since then, many more antibiotics and other secondary metabolites have been isolated and manufactured by microbial fermentation on a large scale. Some important antibiotics, other than penicillin, are cephalosporins, azithromycin, bacitracin, gentamicin, rifamycin, streptomycin, tetracycline, and vancomycin. Animal or plant cells, removed from tissues, will continue to grow if cultivated under the appropriate nutrients and conditions. When carried out outside the natural habitat, the process is called cell culture. Mammalian cell culture fermentation, also known as recombinant DNA technology, is used mainly for the production of complex big molecule therapeutic proteins, or biopharmaceuticals. The first products made were interferon (discovered in 1957), insulin, and somatropin. Commonly used cell lines are Chinese hamster ovary (CHO) cells and plant cell cultures. The production volumes are very small. They exceed 100 kg (220 lb) per year for only three products: Rituxan (Roche-Genentech), Enbrel (Amgen and Merck & Co.), and Remicade (Johnson & Johnson). Fine chemical production by mammalian cell culture is a much more demanding operation than conventional biocatalysis and biosynthesis. The bioreactor batch requires more stringent controls of operating parameters, since mammalian cells are heat and shear sensitive. In addition, the growth rate of mammalian cells is very slow, lasting from days to several months.
=== Teflon (polytef) === This was the original material used as a bulking agent, first used to treat urinary incontinence in 1964, and then about 20 years later it was the first material used as a bulking agent to treat FI. Polytef paste is polytetrafluoroethylene, glycerin and polysorbide. The particles are mostly very small in size (4–40-μm). Research in animals has shown that these particles migrate and may be found in lymph nodes, lungs, kidneys, spleen and brain. If the material mostly migrates away, any benefit will be temporary, and there are safety concerns that it could lead to the formation of foreign body granulomas and the development of sarcoma.
In 2025, Rui Qiu and colleagues named and described a second species of Sinosauropteryx: S. lingyuanensis. The assigned holotype is IVPP V 12415, which comprises a near complete skeleton of a potential juvenile which also preserves traces of feather integument. The specimen was collected around 2010 from the Lower Cretaceous Yixian Formation of Dawangzhangzi (Lingyuan, Western Liaoning, China), and though it is of juvenile nature it represents the largest reported Sinosauropteryx individual. The species name, lingyuanensis, refers to Lingyuan which is the city where the holotype specimen was discovered.
Sources: en.wikipedia.org
==== α2-Adrenergic receptor ==== Antagonism of the α2-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2 heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1A receptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs. Mirtazapine's antagonism of α2-adrenoreceptors is potentially functionally selective for presynaptic α2 receptors. Mirtazapine, at 25 μg/kg IV, in freely moving rats, enhanced the endogenous release of serotonin, specifically due to blockade of α2 heteroreceptors on serotonin neuron terminals, but required a dose of 500 μg/kg IV to block local norepinephrine mediated and postsynaptic α2 mediated inhibition of CA3 dorsal hippocampus pyramidal neurons in those rats. This is an approximate 20-fold functional selectivity for inhibiting presynaptic α2 over postsynaptic α2 (especially postsynaptic α2 in the rat hippocampus).
The music of Brazil was formed mainly from the fusion of European, Native Indigenous, and African elements. Until the nineteenth century, Portugal was the gateway to most of the influences that built Brazilian music, although many of these elements were not of Portuguese origin, but generally European. The first was José Maurício Nunes Garcia, author of sacred pieces with an influence of Viennese classicism. The major contribution of the African element was the rhythmic diversity and some dances and instruments. Popular music since the late eighteenth century, samba was considered the most typical and on the UNESCO cultural heritage list. Samba-reggae, Axé, Maracatu, Frevo and Afoxê are four music traditions that have been popularized by their appearance in the annual Brazilian Carnivals. Capoeira is usually played with its own music referred to as capoeira music, which is usually considered to be a call-and-response type of folk music. Forró is a type of folk music prominent during the Festa Junina in northeastern Brazil. Jack A. Draper III, a professor of Portuguese at the University of Missouri, argues that Forró was used as a way to subdue feelings of nostalgia for a rural lifestyle. Choro is a popular musical instrumental style. Its origins are in 19th-century Rio de Janeiro. The style often has a fast and happy rhythm, characterized by subtle modulations and full of syncopation and counterpoint. lambada and Carimbó achieved success in Latin music, originating from Pará.
The endocrine glands belong to the body's control system. The hormones which they produce help to regulate the functions of cells and tissues throughout the body. Endocrine organs are activated to release their hormones by humoral, neural, or hormonal stimuli. Negative feedback is important in regulating hormone levels in the blood. The nervous system, acting through hypothalamic controls, can in certain cases override or modulate hormonal effects.
=== Basal chordates === Published information on Pikaia gracilens (a well-known Cambrian fossil) explains evolution of swimming ability in chordates related to myomere shape and function. Specifically, myomeres in this species possessed minimal overlap between successive ones and myosepta dividing them were gently curved. In a biomechanical evaluation, it is presumed that Pikaia were not capable of rapid swimming like in living chordates. Several theories for this idea include lacking fast-twitch muscle fibers, ancestral muscle fiber types more like modern slow-twitch fibers, and less tension on myosepta due to less overlap between successive myomeres. In amphioxus, myomeres run longitudinally along the length of the body in a "V"-shape. As sequential contraction for swimming occurs, force from the myomeres is transmitted via connective tissues to the notochord.
In England, Wenger has used his extensive knowledge of the European transfer market and rulings – particularly in his native France – to recruit players. His first purchase as Arsenal manager was Anelka from Paris Saint-Germain for £500,000, a deal which upset the French club as they received little remuneration. The player's subsequent sale to Real Madrid just two years later for £23.5 million highlighted Wenger's shrewdness in the transfer market. He remained in contact with Guillou's Abidjan-based academy, where he discovered future Arsenal players Touré and Emmanuel Eboué, and successfully persuaded Fàbregas and Héctor Bellerín, amongst other La Masia graduates, to leave Barcelona and join him. Wenger's recruitment of young players came under criticism from Bayern Munich chairman Karl-Heinz Rummenigge, who protested it was tantamount to child trafficking. Wenger refuted the analogy and said, "Look at Santa Cruz at Blackburn. Ask him what age he came to Bayern Munich. Then you have an answer for Rummenigge." When Arsenal moved to the Emirates Stadium, Wenger prioritised investing in youth instead of purchasing experienced players. He described it as a way of creating an "identity" with Arsenal: "I felt it would be an interesting experiment to see players grow together with these qualities, and with a love for the club. It was an idealistic vision of the world of football." The departure of Dein, coupled with the saturation of the transfer market, meant Wenger struggled to recruit players as efficiently as before.
Sources: en.wikipedia.org
=== Enzymatic nixtamalization === An alternative process for use in industrial settings has been developed known as enzymatic nixtamalization, which uses protease enzymes to accelerate the changes that occur in traditional nixtamalization, a technique borrowed from modern corn wet-milling. In this process, corn or corn meal is first partially hydrated in hot water, so that enzymes can penetrate the grain, then soaked briefly (for approximately 30 minutes) at 50–60 °C (122–140 °F) in an alkaline solution containing protease enzymes. A secondary enzymatic digestion may follow to further dissolve the pericarp. The resulting nixtamal is ground with little or no washing or hulling. By pre-soaking the maize, minimizing the alkali used to adjust the pH of the alkaline solution, reducing the cooking temperature, accelerating processing, and reusing excess processing liquids, enzymatic nixtamalization can reduce the use of energy and water, lower nejayote (alkaline wastewater) production, decrease maize lost in processing, and shorten the production time (to approximately four hours) compared to traditional nixtamalization with only a minor loss in quality.
=== Selected articles === Adler, V., Yin, Z., Fuchs, S. Y., Benezra, M., Rosario, L., Tew, K. D., ... & Ronai, Z. E. (1999). Regulation of JNK signaling by GSTp. The EMBO journal, 18(5), 1321–1334. Townsend, D. M., Tew, K. D., & Tapiero, H. (2003). The importance of glutathione in human disease. Biomedicine & pharmacotherapy, 57(3-4), 145–155. Townsend, D. M., & Tew, K. D. (2003). The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 22(47), 7369–7375. Tapiero, H., & Tew, K. D. (2003). Trace elements in human physiology and pathology: zinc and metallothioneins. Biomedicine & Pharmacotherapy, 57(9), 399–411. Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020). Oxidative stress in cancer. Cancer cell, 38(2), 167–197. Tew, K.D. Alkylating Agents. In: Principles & Practice of Oncology. Eds. DeVita, Hellman & Rosenberg. pp246–256, 2018. Tew, K.D. Protein S-Glutathionylation & Glutathione S-transferase P. In: Glutathione. Editor: Leopold Flohé. CRC Press. Chapter 12, 201–214, 2018.
Because of its behavior as a prodrug and its pharmacokinetic differences, lisdexamfetamine has a longer duration of therapeutic effect than immediate-release dextroamphetamine and shows reduced misuse potential. CYP2D6, dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase), and glycine N-acyltransferase (GLYAT) are the enzymes known to metabolize amphetamine or its metabolites in humans. Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, N-hydroxyamphetamine, benzoic acid, hippuric acid, norephedrine, and phenylacetone. Among these metabolites, the active sympathomimetics are 4-hydroxyamphetamine, 4-hydroxynorephedrine, norephedrine, and N-hydroxyamphetamine. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination. The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following:
By the early 1980s, genes for these interferons had been cloned, adding further definitive proof that interferons were responsible for interfering with viral replication. Gene cloning also confirmed that IFN-α was encoded by a family of many related genes. The type II IFN (IFN-γ) gene was also isolated around this time. Interferon was first synthesized manually at Rockefeller University in the lab of Dr. Bruce Merrifield, using solid phase peptide synthesis, one amino acid at a time. He later won the Nobel Prize in chemistry. Interferon was scarce and expensive until 1980, when the interferon gene was inserted into bacteria using recombinant DNA technology, allowing mass cultivation and purification from bacterial cultures or derived from yeasts. Interferon can also be produced by recombinant mammalian cells. Before the early 1970s, large scale production of human interferon had been pioneered by Kari Cantell. He produced large amounts of human alpha interferon from large quantities of human white blood cells collected by the Finnish Blood Bank. Large amounts of human beta interferon were made by superinducing the beta interferon gene in human fibroblast cells. Cantell's and Tan's methods of making large amounts of natural interferon were critical for chemical characterisation, clinical trials and the preparation of small amounts of interferon messenger RNA to clone the human alpha and beta interferon genes. The superinduced human beta interferon messenger RNA was prepared by Tan's lab for Cetus.
Sources: en.wikipedia.org
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。
胰岛素释放需要细胞内环腺苷酸与钙信号升高，同时依赖葡萄糖代谢产生的协同信号。血糖水平较低时协同信号不足，分泌增强有限。这一机制在降糖效果与低血糖风险之间提供了缓冲。
白蛋白结合是主要原因，它减少肾小球滤过并保护分子免受蛋白酶降解。序列修饰带来的酶解抵抗同样不可忽略，二者共同作用。脂肪链的疏水性还会影响组织分布，但其对总半衰期的贡献程度仍在研究之中。
Long-term storage is usually at minus 20 to minus 80 degrees Celsius in a sealed, desiccated container. Working aliquots can be held briefly at 2 to 8 degrees Celsius.