Everything below concerns GLP-1 analog. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-10-17. Numbers and descriptions here follow the published literature rather than marketing material.
Clinical studies of semaglutide generally measure glycated hemoglobin, fasting plasma glucose, body weight, and composite cardiovascular endpoints. The SUSTAIN program enrolled adults with type 2 diabetes, while the STEP program focused on obesity without diabetes. Administration follows a stepwise escalation schedule designed to limit gastrointestinal effects during the first weeks. Reported outcomes include mean percentage weight change, the proportion of participants reaching defined weight-loss thresholds, and rates of nausea, vomiting, and diarrhea. Long-term data on durability after treatment stops are still limited and remain a topic of ongoing research.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, developed by Novo Nordisk and first approved in 2017 for type 2 diabetes. It belongs to the incretin mimetic class, a group of agents that reproduce the glucose-dependent actions of endogenous GLP-1. The molecule was engineered to resist degradation by dipeptidyl peptidase-4 and to bind serum albumin, extending its half-life from minutes to roughly one week. Approval for chronic weight management followed in 2021, based on large cardiovascular and obesity outcome trials.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | Peptide backbone with a C18 fatty diacid side chain |
| Molecular weight | Approximately 4113 Da | Consistent with a 31-residue peptide plus linker |
| Appearance | White to off-white powder | Lyophilized solid; hygroscopic if left open |
| Solubility class | Sparingly soluble to soluble in water | Varies with pH and ionic strength |
| Typical analytical method | Reversed-phase HPLC with UV detection | Often paired with mass spectrometry for identity |
Encouraged by South Africa's apparent failure to detect the initial incursion, larger insurgent groups made their own infiltration attempts in February and March 1966. The second unit, "Group 2", was led by Leonard Philemon Shuuya, also known by the nom de guerre "Castro" or "Leonard Nangolo". Group 2 apparently become lost in Angola before it was able to cross the border, and the guerrillas dispersed after an incident in which they killed two shopkeepers and a vagrant. Three were arrested by the Portuguese colonial authorities in Angola, who were working off tips received from local civilians. Another eight, including Shuuya, had been captured between March and May by the South African police, apparently in Kavangoland. Shuuya later resurfaced at Kongwa, claiming to have escaped his captors after his arrest. He helped plan two further incursions: a third SWALA group entered Ovamboland that July, while a fourth was scheduled to follow in September.
== 20th Century == 1901: Florence Bascom became the first female geologist to present a paper before the Geological Survey of Washington. 1903: Marie Curie became the first woman to win the Nobel Prize, awarded in Physics, and went on to also win the Nobel Prize in Chemistry. She performed pioneering research in radioactivity, and discovered two elements (polonium and radium). 1912: Henrietta Swan Leavitt studied the bright-dim cycle periods of Cepheid stars, then found a way to calculate the distance from such stars to Earth. 1924: Florence Bascom became the first woman elected to the Council of the Geological Society of America. 1925: Florence Sabin became the first woman elected to the National Academy of Sciences. 1928: Alice Evans became the first woman elected president of the Society of American Bacteriologists. 1936: Edith Patch became the first female president of the Entomological Society of America.
== Description == The death cap has a large and imposing epigeous (aboveground) fruiting body (basidiocarp), usually with a pileus (cap) from 5 to 15 cm across (2 to 5.8 inches) across, initially rounded and hemispherical, but flattening with age. The color of the cap can be pale-green, yellowish-green, olive-green, bronze, or (in one form) white; it is often paler toward the margins, which can have darker streaks; it is also often paler after rain. The cap surface is sticky when wet and easily peeled—a troublesome feature, as that is allegedly a feature of edible fungi. The remains of the partial veil are seen as a skirtlike, floppy annulus usually about 1 to 1.5 cm (3⁄8 to 5⁄8 in) below the cap. The crowded white lamellae (gills) are free. The stipe is white with a scattering of grayish-olive scales and is 8 to 15 cm (3+1⁄8 to 5+7⁄8 in) long and 1 to 2 cm (3⁄8 to 3⁄4 in) thick, with a swollen, ragged, sac-like white volva (base). As the volva, which may be hidden by leaf litter, is a distinctive and diagnostic feature, it is important to remove some debris to check for it. Spores: 7-12 x 6-9 μm. Smooth, ellipsoid, amyloid. The smell has been described as initially faint and honey-sweet, but strengthening over time to become overpowering, sickly-sweet and objectionable. Young specimens first emerge from the ground resembling a white egg covered by a universal veil, which then breaks, leaving the volva as a remnant. The spore print is white, a common feature of Amanita.
As a result of this change tropical cyclones are 50% less likely to make landfall on Queensland, while the risk of a tropical cyclone is elevated for island nations like Niue, French Polynesia, Tonga, Tuvalu, and the Cook Islands.
Sources: en.wikipedia.org
The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs. The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.
The most commonly used dye in agarose gel gel electrophoresis of DNA and RNA, dating as far back as the 1970s, is ethidium bromide (2,7-diamino-10-ethyl-9-phenylphenanthridiniumbromide). Ethidium Bromide (EtBr) is an orange-colored fluorescent intercalating dye. The dye inserts itself between the double helical structure of nucleic acids, allowing for visualization of the molecules under UV light. EtBr has absorbance maxima at 300-360 nm and fluorescent emission maxima at 500-590 nm, with the detection limit of 0.5-5.0 ng/band. The dye, however, has reduced sensitivity in the detection of single-stranded nucleic acid samples. EtBr should be handled with care, as it is a potent mutagen. A more sensitive alternative for nucleic acid staining in gel electrophoresis is SYBR™ Green I. The dye is 25 times more sensitive than EtBr in the staining of dsDNA, and is especially useful in staining assays containing single-stranded nucleic acids. SYBR Green is, however, more expensive when compared to EtBr.
=== Synthesis in nuclear explosions === The analysis of the debris at the 10-megaton Ivy Mike nuclear test was a part of long-term project, one of the goals of which was studying the efficiency of production of transuranium elements in high-power nuclear explosions. The motivation for these experiments was as follows: synthesis of such elements from uranium requires multiple neutron capture. The probability of such events increases with the neutron flux, and nuclear explosions are the most powerful neutron sources, providing densities on the order 1023 neutrons/cm2 within a microsecond, i.e. about 1029 neutrons/(cm2·s). For comparison, the flux of the HFIR reactor is 5×1015 neutrons/(cm2·s). A dedicated laboratory was set up right at Enewetak Atoll for preliminary analysis of debris, as some isotopes could have decayed by the time the debris samples reached the U.S. The laboratory was receiving samples for analysis, as soon as possible, from airplanes equipped with paper filters which flew over the atoll after the tests. Whereas it was hoped to discover new chemical elements heavier than fermium, those were not found after a series of megaton explosions conducted between 1954 and 1956 at the atoll.
The International Cryosphere Climate Initiative (ICCI) publishes its annual State of the Cryosphere Report. It warns of rapid, irreversible sea-level rise from Earth's ice sheets, which could potentially reach 12–20 metres in the coming centuries. 17 November – The global average temperature temporarily exceeds 2 °C above the pre-industrial average for the first time in recorded history. 20 November – A study of censorship in science finds it to be often driven by scientists themselves, motivated by prosocial concerns or reputation protection. 22 November – An autonomous excavator is demonstrated. Using sensors, the machine can generate 3D maps of a construction site, localising individual blocks and stones in order to build a wall. 23 November Astrophysicists report the detection of "Amaterasu", the second highest-energy cosmic ray ever known, second only to the Oh-My-God particle of 1991. Amaterasu originated from the Local Void and its energy exceeded 240 exa-electron volts (EeV). Researchers report the deep learning-based discovery of nearly 200 functionally diverse natural machineries for CRISPR gene editing. 26 November – Astronomers report evidence, for the first time, of an overmassive black hole galaxy (O.B.G.), the result of "heavy black hole seed formation from direct collapse", an alternative way of producing a black hole other than the collapse of a dead star. This discovery was found in studies of UHZ1, a very early galaxy containing a quasar, by the Chandra X-ray Observatory and James Webb Space Telescope.
=== Biodegradation === Because of the volume of surfactants released into the environment, for example laundry detergents in waters, their biodegradation is of great interest. Attracting much attention is the non-biodegradability and extreme persistence of fluorosurfactant, e.g. perfluorooctanoic acid (PFOA). Strategies to enhance degradation include ozone treatment and biodegradation. Two major surfactants, linear alkylbenzene sulfonates (LAS) and the alkyl phenol ethoxylates (APE) break down under aerobic conditions found in sewage treatment plants and in soil to nonylphenol, which is thought to be an endocrine disruptor. Interest in biodegradable surfactants has led to much interest in "biosurfactants" such as those derived from amino acids. Biobased surfactants can offer improved biodegradation. However, whether surfactants damage the cells of fish or cause foam mountains on bodies of water depends primarily on their chemical structure and not on whether the carbon originally used came from fossil sources, carbon dioxide or biomass.
Sources: en.wikipedia.org
=== Pharmacokinetics === Ketamine can be absorbed by many different routes due to its water and lipid solubility. Intravenous ketamine bioavailability is 100% by definition, intramuscular injection bioavailability is slightly lower at 93%, and epidural bioavailability is 77%. Subcutaneous bioavailability has never been measured but is presumed to be high. Among the less invasive routes, the intranasal route has the highest bioavailability (45–50%) and oral – the lowest (16–20%). Sublingual and rectal bioavailabilities are intermediate at approximately 25–50%. After absorption ketamine is rapidly distributed into the brain and other tissues. The plasma protein binding of ketamine is variable at 23–47%.
Whirlpool Corporation is an American multinational manufacturer and marketer of home appliances headquartered in Benton Charter Township, Michigan, United States. In 2023, the Fortune 500 company had an annual revenue of approximately $19 billion in sales, around 59,000 employees, and more than 55 manufacturing and technology research centers globally. The company's flagship brand, Whirlpool, is marketed alongside a range of other brands, including Maytag, KitchenAid, JennAir, Amana, Gladiator GarageWorks, Inglis, Estate, Brastemp, Bauknecht, InSinkErator, and Consul. In its domestic U.S. market, Whirlpool has eleven manufacturing facilities which employs about 15,000 workers.
== Interactions == The main IGFBP-3 ligands in the circulation are IGF-1 and IGF-2, and the acid-labile subunit (ALS). The serum proteins transferrin, fibronectin, and plasminogen are also known to bind IGFBP-3. In the cell and tissue environment many other interactions have been described (see Table). Two unrelated cell-surface proteins have been designated as IGFBP-3 receptors: low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor or type V TGFβ receptor and the transmembrane protein TMEM219. Both are believed to mediate antiproliferative effects. Functional interactions with the EGF receptor and the type I/type II TGFβ receptor system have also been reported, and other cell-surface proteins such as proteoglycans also bind IGFBP-3. IGFBP-3 can enter cells by both clathrin-mediated and caveolin-mediated endocytosis. possibly involving the transferrin receptor. IGFBP-3 enters the cell nucleus by a mechanism that is incompletely understood, but involves its binding to importin-β. Within the nucleus, it can modulate nuclear hormone receptor activity by direct binding to retinoid X receptor, retinoic acid receptor, vitamin D receptor, PPARγ, and nur77, IGFBP-3 also interacts with DNA-dependent protein kinase within the nucleus to promote the repair of DNA damage. IGFBP3 has been shown to interact with:
==== Other nuclear receptors ==== DHEA does not bind to or activate the progesterone, glucocorticoid, or mineralocorticoid receptors. Other nuclear receptor targets of DHEA besides the androgen and estrogen receptors include the PPARα, PXR, and CAR. However, whereas DHEA is a ligand of the PPARα and PXR in rodents, it is not in humans. In addition to direct interactions, DHEA is thought to regulate a handful of other proteins via indirect, genomic mechanisms, including the enzymes CYP2C11 and 11β-HSD1 – the latter of which is essential for the biosynthesis of the glucocorticoids such as cortisol and has been suggested to be involved in the antiglucocorticoid effects of DHEA – and the carrier protein IGFBP1.
Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13 receptor signalling (IL-4R, IL-13R), used for allergic diseases such as atopic dermatitis (eczema), asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis, prurigo nodularis and chronic obstructive pulmonary disease. The most common side effects reported by the US Food and Drug Administration (FDA) include injection site reactions, upper respiratory tract infections, joint pain, and herpes viral infections. The most common side effects reported by the European Medicines Agency (EMA) include injection-site reactions (such as redness, swelling including due to fluid build-up, itching and pain), conjunctivitis (redness and discomfort in the eye) including conjunctivitis due to allergy, joint pain, cold sores, and increased blood levels of a type of white blood cell called eosinophils. It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme. It received approval from the US Food and Drug Administration (FDA) for moderate-to-severe atopic dermatitis in 2017, and for asthma in 2018. The FDA considers it to be a first-in-class medication. Dupilumab is the first treatment for eosinophilic esophagitis approved by the U.S. Food and Drug Administration (FDA). Eosinophilic esophagitis is a chronic inflammatory disorder in which eosinophils, a type of white blood cell, are found in the tissue of the esophagus. Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway.
Sources: en.wikipedia.org
It is given either as a once-weekly subcutaneous injection or as an oral tablet taken once daily. The two forms use different absorption strategies, so they are not interchangeable on a milligram-for-milligram basis.
Structural modifications, including a fatty acid side chain and non-natural amino acid substitutions, slow enzymatic breakdown and promote albumin binding. These changes support once-weekly dosing rather than twice-daily administration.
The pathways involving insulin, glucagon, gastric emptying, and appetite signaling are well described. How much each pathway contributes to weight reduction in a given person is not fully established.
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.