Everything below concerns GLP-1. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-04-29. Numbers and descriptions here follow the published literature rather than marketing material.
Native GLP-1 is degraded rapidly by dipeptidyl peptidase-4. Semaglutide resists this cleavage because alanine at position 8 is replaced by alpha-aminoisobutyric acid. A second substitution at position 34 introduces arginine, which further stabilizes the peptide. The most distinctive modification is a spacer and C18 fatty diacid attached at lysine 26, enabling strong albumin affinity. These three changes together produce a half-life measured in days rather than minutes, and the same structural logic underlies other long-acting analogs in this class.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L-cells after food intake. It contains 31 amino acids and differs from native GLP-1 through modifications that slow enzymatic breakdown. The peptide was developed to extend the short circulating half-life of endogenous GLP-1, which is measured in minutes. Researchers introduced the compound in the early 2010s. Two backbone changes and a fatty acid side chain define its structure, distinguishing it from earlier GLP-1 receptor agonists.
The compound binds the GLP-1 receptor on pancreatic beta cells and other tissues, activating a G-protein signaling cascade that raises intracellular cyclic AMP. This action increases glucose-dependent insulin secretion when blood glucose is elevated, while binding also slows gastric emptying and reduces glucagon release. In the central nervous system, receptor activation in the hypothalamus and brainstem contributes to reduced appetite. The fatty acid chain binds albumin, which protects the peptide from renal filtration and enzymatic degradation. This albumin binding is central to its extended circulation time.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide | 31 amino acids |
| Backbone modification | Aib at position 8 | Blocks DPP-4 cleavage |
| Fatty acid chain | C18 diacid | Supports albumin binding |
| Native half-life | 1 to 2 minutes | Endogenous GLP-1 |
| Analog half-life | Approximately one week | Extended by albumin binding |
When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers (μm) in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 μm. With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus's multilobulated shape (as compared to lymphocytes and monocytes, the other types of white cells). The nucleus has a characteristic lobed appearance, the separate lobes connected by chromatin. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the inactivated X chromosome. In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent. The cytoplasm also contains about 200 granules, of which a third are azurophilic. Neutrophils will show increasing segmentation (many segments of the nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal but occurs in some disorders, most notably vitamin B12 deficiency. This is noted in a manual review of the blood smear and is positive when most or all of the neutrophils have 5 or more segments.
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.
extrachromosomal DNA Also extranuclear DNA and cytoplasmic DNA. Any DNA that is not found in chromosomes or in the nucleus of a cell and hence is not genomic DNA. This may include the DNA contained in plasmids or organelles such as mitochondria or chloroplasts, or, in the broadest sense, DNA introduced by viral infection. Extrachromosomal DNA usually shows significant structural differences from nuclear DNA in the same organism.
Sources: en.wikipedia.org
Necrotizing fasciitis is ideally a clinical diagnosis based on symptoms. Due to the need for rapid surgical treatment, the time delay in performing imaging is a major concern. Hence, imaging may not be needed if signs of a necrotizing infection are clear. However, due to the vague symptoms associated with the earlier stages of this disease, imaging is often useful in clarifying or confirming the diagnosis. Both CT and MRI scans are used to diagnose NF, but neither is sensitive enough to rule out necrotizing changes completely.
The General Principles of Software Validation (FDA 2002) defines verification as "Software verification provides objective evidence that the design outputs of a particular phase of the software development life cycle meet all of the specified requirements for that phase." It also defines Validation as "Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through software can be consistently fulfilled". The software validation guideline states: “The software development process should be sufficiently well planned, controlled, and documented to detect and correct unexpected results from software changes." Annex 11 states "The validation documentation and reports should cover the relevant steps of the life cycle." Weichel (2004) recently found that over twenty warning letters issued by the FDA to pharmaceutical companies specifically cited problems in Computer System Validation between 1997 and 2001. Probably the best known industry guidance available is the GAMP Guide, now in its fifth edition and known as GAMP5 published by ISPE (2008). This guidance gives practical advice on how to satisfy regulatory requirements.
The makeup of emergency rations can be adjusted to suit different situations depending on which properties are the most desirable under the specific circumstances. For instance, when comparing trekking to being lost at sea, a high caloric density is more of a priority in the former case and in the latter case the metabolic effects of the macronutrient composition require greater consideration. Emergency rations are used in humanitarian aid. In these contexts, the purpose of the rations is twofold: preventing malnutrition and sustaining physical activity. The energy content required for this depends on several factors, including the level of physical activity and environmental temperature.
== Screening == The United States Preventive Services Task Force (USPSTF) recommended in 2021 screening for type 2 diabetes in adults aged 35 to 70 years old who are overweight (i.e. BMI over 25) or have obesity. For people of Asian descent, screening is recommended if they have a BMI over 23. Screening at an earlier age may be considered in people with a family history of diabetes; some ethnic groups, including Hispanics, African Americans, and Native Americans; a history of gestational diabetes; polycystic ovary syndrome. Screening can be repeated every 3 years. According to the US Preventive Services Task Force in a recommendation statement, screening for diabetes in people without risk factors or symptoms is not recommended. However, the American Diabetes Association (ADA) recommended in 2024 screening in all adults from the age of 35 years. ADA also recommends screening in adults of all ages with a BMI over 25 (or over 23 in Asian Americans) with another risk factor: first-degree relative with diabetes, ethnicity at high risk for diabetes, blood pressure ≥130/80 mmHg or on therapy for hypertension, history of cardiovascular disease, physical inactivity, polycystic ovary syndrome or severe obesity. ADA recommends repeat screening every 3 years at minimum. ADA recommends yearly tests in people with prediabetes. People with previous gestational diabetes or pancreatitis are also recommended screening.
==== Adult ==== Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia. It regulates acute hypothalamic–pituitary–adrenal axis (HPA axis) response under dominance challenge. Androgens including testosterone enhance muscle growth. Testosterone also regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans. Adult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. Some of these effects may decline as testosterone levels might decrease in the later decades of adult life. The brain is also affected by this sexual differentiation; the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice. In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with congenital disorders of androgen formation or androgen receptor function, to be associated with functional androgen receptors. There are some differences between a male and female brain that may be due to different testosterone levels, one of them being size: the male human brain is, on average, larger.
Sources: en.wikipedia.org
It is a synthetic analog of GLP-1 produced through medicinal chemistry to resist enzymatic degradation. The design goal was longer circulation than the native hormone.
A fatty acid side chain attaches the peptide to serum albumin, which shields it from kidney filtration and protease activity. This interaction is the main reason its circulation time is extended.
No. The native hormone is GLP-1, and semaglutide is an engineered variant with three deliberate structural alterations. It does not appear in unmodified biological sources.
Native GLP-1 is a short-lived peptide cleared within one to two minutes by dipeptidyl peptidase-4 and related enzymes. Semaglutide keeps the receptor-binding backbone but adds substitutions and a lipid chain. These changes block the main cleavage site and allow reversible albumin binding, extending the half-life to roughly 165 hours.