The short version of 脂肪酸侧链 fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-01-18 and is reviewed periodically as new material appears.
Both receptors are class B G protein-coupled receptors that signal largely through Gs-mediated cyclic AMP production. Activation within pancreatic islets increases glucose-dependent insulin secretion and suppresses glucagon release when glucose is elevated. Outside the pancreas, signaling in the central nervous system and gut appears to influence appetite and gastric emptying. The relative contribution of each receptor to observed clinical effects remains under investigation, and the two pathways are not simply additive in practice.
Reported outcomes in large trials include dose-dependent weight reduction and improvements in glycemic markers over periods ranging from several months to more than a year. Whether the compound alters long-term cardiovascular or renal outcomes is being examined in dedicated outcome studies, so those questions remain open. Labeling describes gastrointestinal effects such as nausea and diarrhea, which tend to appear during dose escalation. Discontinuation rates and the durability of effects after treatment stops vary across study populations and are still debated.
In clinical research, tirzepatide has been studied in randomized controlled trials for glycemic control and body weight reduction. These trials typically measure changes in hemoglobin A1c and body weight over periods of several months. The drug is administered by subcutaneous injection, and its pharmacokinetic profile supports once-weekly dosing. Post-marketing surveillance continues to evaluate long-term outcomes and rare adverse events.
Tirzepatide is a synthetic peptide that acts as a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The molecule contains 39 amino acids and features a C20 fatty diacid moiety attached via a linker, which promotes albumin binding and extends its circulating half-life. Its sequence incorporates non-natural amino acids and modifications that reduce susceptibility to degradation by dipeptidyl peptidase-4. This dual receptor activity distinguishes it from selective GLP-1 receptor agonists.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic 39-residue peptide | GIP-derived backbone with non-natural residues |
| Molar mass | Approximately 4.8 kDa | Peptide chain plus linker and lipid modifications |
| Appearance | White to off-white powder | Typical of lyophilized research material |
| Solubility | Soluble in water and aqueous buffer | Practically insoluble in nonpolar solvents |
| Storage temperature | Typically −20 °C for dry powder | Solutions usually held at 2–8 °C short term |
Receptor activation by tirzepatide raises intracellular cyclic AMP through Gs-coupled signalling at both targets. At the GLP-1 receptor the downstream effect includes glucose-dependent insulin release, suppressed glucagon secretion, delayed gastric emptying, and reduced appetite signalling in the hypothalamus. GIP receptor engagement adds insulinotropic activity and appears to influence lipid handling in adipose tissue. Because both receptors are stimulated at the same time, the pharmacological profile differs from that of selective GLP-1 receptor agonists, and the relative contribution of each arm remains an area of active investigation.
Clinical development proceeded through large phase 3 programmes in type 2 diabetes and in obesity or overweight with at least one weight-related comorbidity. Regulatory approvals followed in several jurisdictions for both indications. Weekly subcutaneous dosing reflects an elimination half-life of roughly five days. Open questions include the durability of metabolic effects after treatment stops, long-term cardiovascular and hepatic outcomes beyond completed trials, and whether the dual mechanism confers benefits independent of total receptor occupancy. Published literature continues to expand on these points. Substantial uncertainty remains about interindividual variability in response.
当前公开资料把 tirzepatide 归为肠促胰素类受体双重激动剂。它并非激素天然变体，而是经过序列改造的工程化肽。其分子量、等电点与疏水性等基础参数已在药典和化学数据库中收录，可作为分析检测和质量研究的参照。
Tirzepatide 是一种由 39 个氨基酸组成的合成肽，分子结构上以 GIP 序列为骨架并引入脂肪酸侧链修饰，使其能够同时与葡萄糖依赖性促胰岛素多肽（GIP）受体和胰高血糖素样肽-1（GLP-1）受体结合。这种双重激动特性使它在同类肽类药物中区别于选择性 GLP-1 受体激动剂。该分子最早由一家制药公司在 2010 年代报道，随后进入糖尿病与体重管理领域的临床研究。
Pharmacologically, tirzepatide activates two distinct G protein-coupled receptors: the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Binding at each target triggers cyclic AMP accumulation and downstream signaling in pancreatic beta cells, adipose tissue and the central nervous system. Because the two pathways overlap only partially, the combined effect on insulin secretion, glucagon suppression and appetite signaling differs from that of selective single-receptor compounds. Affinity is not equal across the two targets, and the clinical meaning of that imbalance remains an area of active study.
Clinical research programs have evaluated tirzepatide in adults with type 2 diabetes and in adults with obesity or excess weight. Trials generally reported reductions in glycated hemoglobin and body weight across treatment periods of several months. Since these studies enrolled defined populations under controlled conditions, the findings describe group averages rather than individual outcomes. Open questions include the durability of effects after treatment stops, variation among subgroups, and the long-term consequences of sustained dual receptor stimulation. Published trial summaries should be consulted for exact measurements rather than secondary accounts.
== Synthetic/native nanodisc == Another way to mimic the native lipid membrane are synthetic polymers. Styrene-maleic acid co-polymers (SMAs) called SMALPs or Lipodisq and Diisobutylene-maleic acid (DIBMA) are such synthetic polymers (DIBMALPs). They can solubilize membrane proteins directly from cells or raw extract. They also have been used to study the lipid composition of several organisms. It was discovered that all synthetic polymers which contained a styrene and maleic acid group can solubilize proteins. These SMA nanoparticles have also been tested as possible drug delivery vehicle and for the study of folding, post-translational modifications and lipid interactions of membrane proteins by native mass spectrometry. They are now routinely used to solve membrane protein structures for cryo-EM, such as the aerolysin pore-forming toxins (2.1Å resolution), where some lipid density was modelled and key interactions relevant for the understanding of pore formation mechanism, its correct positioning and anchoring in the membrane were elucidated.
Malaysian cleric and politician Fathul Bari Mat Jahya also condemned Mahathir's remarks. Mahathir responded that his comments were taken out of context and he was not "promoting massacre of the French". Facebook and Twitter later removed his posts.
==== Bedrocan ==== Bedrocan is a medicinal cannabis variety cultivated from a Dutch medical marijuana Cannabis sativa L. strain, having a standardized content of THC (22%) and CBD (1%). It is currently cultivated by Bedrocan Nederland, Bedrocan Canada and Bedrocan Danmark. It was introduced in 2003 and, as of 2007, was only available with a prescription.
Although Jaffe's name is synonymous with clinical creatinine testing, his paper only described the principle behind what would later become the enduring method. It was Otto Folin (1867–1934), a Harvard biochemist, who adapted Jaffe's research—abandoning the standard Neubauer reaction of the time—and published several papers using the Jaffe reaction to analyze creatinine levels in both blood and urine. Folin began using the picric acid procedure in 1901 and included it in his 1916 Lab Manual of Biological Chemistry. During his career, Folin modified and improved several quantitative colorimetric procedures, the first of which was for creatinine. He took advantage of technology available at the time, using a Duboscq colorimeter for measurement precision, and is credited for introducing colorimetry into modern biochemical analysis. Folin's research did not focus on creatinine as a renal function indicator. Since the precursors of creatinine are synthesized in the liver, at this point in history, creatinine was considered indicative of liver function. It was not until 1926 that Poul Kristian Brandt Rehberg suggested creatinine was a significant marker for renal function.
While the Treaties and Regulations will have direct effect (if clear, unconditional and immediate), Directives do not generally give citizens (as opposed to the member state) standing to sue other citizens. In theory, this is because TFEU article 288 says Directives are addressed to the member states and usually "leave to the national authorities the choice of form and methods" to implement. In part this reflects that directives often create minimum standards, leaving member states to apply higher standards. For example, the Working Time Directive requires that every worker has at least 4 weeks paid holidays each year, but most member states require more than 28 days in national law. However, on the current position adopted by the Court of Justice, citizens have standing to make claims based on national laws that implement Directives, but not from Directives themselves. Directives do not have so called "horizontal" direct effect (i.e. between non-state parties). This view was instantly controversial, and in the early 1990s three Advocate Generals persuasively argued that Directives should create rights and duties for all citizens. The Court of Justice refused, but there are five large exceptions. First, if a Directive's deadline for implementation is not met, the member state cannot enforce conflicting laws, and a citizen may rely on the Directive in such an action (so called "vertical" direct effect).
Sources: en.wikipedia.org
Adenine and guanine are the two nitrogenous bases classified as purines. In purine synthesis, phosphoribosyl pyrophosphate (PRPP) is converted into inosine monophosphate (IMP). The production of IMP from PRPP requires glutamine, glycine, aspartate, and six molecules of adenosine triphosphate (ATP), among other components. IMP serves as a precursor for both adenosine monophosphate (AMP) and guanosine monophosphate (GMP). AMP is synthesized from IMP using guanosine triphosphate (GTP) and aspartate, with aspartate being converted into fumarate. In contrast, the synthesis of GMP requires an intermediate step: IMP is first oxidized by NAD⁺ to form xanthosine monophosphate (XMP), which is subsequently converted into GMP via the hydrolysis of one ATP molecule and the conversion of glutamine to glutamate. Both AMP and GMP can be phosphorylated by kinases to form adenosine triphosphate (ATP) and guanosine triphosphate (GTP), respectively. ATP stimulates the production of GTP, while GTP stimulates the production of ATP. This cross-regulation maintains a balanced ratio of ATP and GTP, preventing an excess of either nucleotide, which could increase the risk of DNA replication errors and purine misincorporation. Lesch–Nyhan syndrome is caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), an enzyme that catalyzes the salvage of guanine to GMP. This X-linked congenital disorder leads to the overproduction of uric acid and is associated with neurological symptoms, including intellectual disability, spasticity, and compulsive self-mutilation.
===== "Cave of the Hippocampi" (Cave 118, 300–350 CE) ===== The Cave of the Hippocampi (Cave 118) was visited and photographed by the Third German Expedition of 1906–1907, and by the French expedition of Paul Pelliot in 1907. Large portions of the murals were removed and sent to Germany, especially by von Le Coq in 1914, who removed the lunettes and the sides of the vault. The cave consists of a rectangular room (3.6 x 4.8 meters; 12 x 15 feet), the entrance being on the long side, and the ceiling of which forms a transverse barrel vault. In front of the cave, which is accessible through a door, there used to be an equally wide open space, perhaps adorned with paintings, with remains of a pyramid roof. The two rooms are separated by a 1-meter (3 foot) thick wall. The model for this kind of vaulted cave can be found in Bactria at Kara Tepe, dating from the 2nd-3rd century CE. In the middle of the back wall of the main cella stands a large painting (3.42 metres; 135 inches wide and 2.16 metres; 85 inches high), with an unidentified scene of a King with attendants, possibly "The skill and music in the heavenly palace" (天宫伎乐). The attitudes and postures of the figures remind the reliefs of 3rd–4th century CE Nagarjunakonda. A king is seated at the center, with numerous attendants surrounding him, especially a near-naked woman seated to his left. They wear heavy round earrings with a central rosette design. The modeling of the faces reminds of the statuary of Hadda in Gandhara.
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently it is classified as a non-polar, aliphatic α-amino acid. Under biological conditions, alanine exists in its zwitterionic form with its amine group protonated (as −NH+3) and its carboxyl group deprotonated (as −CO−2). Alanine is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG). The L-isomer of alanine (left-handed) is the one that is incorporated into proteins. L-alanine is second only to L-leucine in rate of occurrence, accounting for 7.8% of the primary structure in a sample of 1,150 proteins. The right-handed form, D-alanine, occurs in peptides in some bacterial cell walls (in peptidoglycan) and in some peptide antibiotics, and occurs in the tissues of many crustaceans and molluscs as an osmolyte. Alanine is not an essential amino acid in humans because it can be synthesized metabolically and does not need to be present in the diet. However hypoalaninemia (alanine deficiency) is possible under certain conditions such as ketotic hypoglycemia.
The ambassador from the Netherlands explained his negative vote as being due to the reference in the preamble to the resolution "to potential harmful effects of the use of depleted uranium munitions on human health and the environment [which] cannot, in our view, be supported by conclusive scientific studies conducted by relevant international organizations." None of the other permanent members of the United Nations Security Council supported the resolution as China was absent for the vote, Russia abstained and the United States voted against the resolution. In September 2008, and in response to the 2007 General Assembly resolution, the UN Secretary General published the views of 15 states alongside those of the International Atomic Energy Agency (IAEA) and World Health Organization (WHO). The IAEA and WHO evidence differed little from previous statements on the issue. The report was largely split between states concerned about depleted uranium's use, such as Finland, Cuba, Japan, Serbia, Argentina, and predominantly NATO members, who do not consider the use of depleted uranium munitions problematic. In December 2008, 141 states supported a resolution requesting that three UN agencies: United Nations Environment Programme (UNEP), WHO and IAEA update their research on the impact of uranium munitions by late 2010—to coincide with the General Assembly's 65th Session, four voted against, 34 abstained and 13 were absent. As before Britain and France voted against the resolution.
Sources: en.wikipedia.org
== Works cited == Hudson, Rex A.; Hanratty, Dennis Michael, eds. (1991). Bolivia: a country study. Washington, D.C.: Federal Research Division, Library of Congress. This article incorporates text from this source, which is in the public domain.{{cite encyclopedia}}: CS1 maint: postscript (link)
In 2015 fire and heat resulted in 67 million injuries. This resulted in about 2.9 million hospitalizations and 238,000 dying. This is down from 300,000 deaths in 1990. This makes it the fourth leading cause of injuries after motor vehicle collisions, falls, and violence. About 90% of burns occur in the developing world. This has been attributed partly to overcrowding and an unsafe cooking situation. Overall, nearly 60% of fatal burns occur in Southeast Asia with a rate of 11.6 per 100,000. The number of fatal burns has decreased from 280,000 in 1990 to 176,000 in 2015. In the developed world, adult males have twice the mortality as females from burns. This is most probably due to their higher risk occupations and greater risk-taking activities. In many countries in the developing world, however, females have twice the risk of males. This is often related to accidents in the kitchen or domestic violence. In children, deaths from burns occur at more than ten times the rate in the developing than the developed world. Overall, in children it is one of the top fifteen leading causes of death. From the 1980s to 2004, many countries have seen both a decrease in the rates of fatal burns and in burns generally.
=== Novels and other fiction === Atomsk by Paul Linebarger, published in 1949, is the first espionage novel of the Cold War. Alas, Babylon by Pat Frank Arc Light by Eric L. Harry Cat's Cradle by Kurt Vonnegut The Dispossessed by Ursula Le Guin is a science fiction novel exploring the differences in culture and philosophy between several alien societies, including that of an anarcho-syndicalist planet where most of the novel is set. Red Alert by Peter George Resurrection Day by Brendan DuBois Twilight 2000, role-playing game. Warday by Whitley Strieber and James Kunetka Tom Clancy novels: Red Storm Rising a 1986 novel by Tom Clancy, about a conventional NATO/Warsaw Pact war. Other Tom Clancy novels which are part of the Jack Ryan universe, most especially The Hunt for Red October and The Cardinal of the Kremlin, though all of his books from this era are featured against a background of east–west conflict. Later Red Rabbit narrates a "What-If" scenario of the Soviets being behind the 1981 assassination attempt on the Pope. 1984 by George Orwell Frederick Forsyth's spy novels sold in the hundreds of thousands. The Fourth Protocol, whose title refers to a series of conventions that, if broken, will lead to nuclear war and that are now, of course, all broken except for the fourth and last thread, was made into a major film starring British actor Michael Caine. The Manchurian Candidate, by Richard Condon, took a different approach and portrayed a Communist conspiracy against the US acting not through leftists or pacifists but through a thinly veiled allusion to Joseph McCarthy.
On January 8, 2026, the House of Representatives voted 397 - 28 for a three-bill package, known as a "minibus", which House and Senate negotiators had put forward earlier that week. There was a partial shutdown from January 31 till February 3, 2026. On February 3, the House passed and President Trump signed the Senate version to fund the United States government through September, which the exception of the Department of Homeland Security (DHS) only being funded through February 13. This is the result of disagreement between Democrats and Republicans over how to move forward from the situation in Minneapolis, Minnesota. In the end, 21 House Democrats had voted for the funding bill and 21 House Republicans had voted against it.
The National Institutes of Health Clinical Center, the world's largest clinical research hospital, is designed to foster smooth transitions between laboratory work, patient studies, and bedside cures, facilitating the translation of laboratory findings to new approaches for the prevention and cure of human diseases.
Sources: en.wikipedia.org
It acts as an agonist at both the GIP and GLP-1 receptors, two related class B G protein-coupled receptors. This dual activity distinguishes it from single-receptor GLP-1 agonists. The clinical consequences of engaging both receptors are still being characterized.
It is given by subcutaneous injection, generally on a weekly schedule. Dosing usually begins low and increases in steps to limit gastrointestinal side effects. Formulated product is supplied as a ready-to-use pen or vial in most markets.
No. Receptor engagement is documented, but how central appetite circuits, gut signals, and insulinotropic effects combine is incompletely resolved. Investigators continue to separate GIP-driven from GLP-1-driven contributions in animal and human models.
It activates both GIP and GLP-1 receptors. This dual action differentiates it from selective GLP-1 agonists.