If you have been reading about LY3437943 and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2025-10-31. Numbers and descriptions here follow the published literature rather than marketing material.
Development has progressed through early- and mid-stage human studies in adults with obesity and with type 2 diabetes. Published phase 2 data reported reductions in body weight and improvements in glycemic markers over the treatment period. No regulatory agency has approved the compound for any indication, and it remains available only within controlled research settings. Whether benefits observed in trials translate into durable outcomes after treatment stops is not yet established.
Retatrutide is an investigational synthetic peptide that acts as an agonist at three distinct G protein-coupled receptors. It combines activity at the glucagon-like peptide-1 receptor, the glucose-dependent insulinotropic polypeptide receptor, and the glucagon receptor within a single molecule. This multi-receptor profile distinguishes it from earlier incretin-based compounds that engage one or two of these pathways. Researchers designed the molecule to test whether simultaneous activation produces greater metabolic effects than single or dual agonism alone.
Mechanistic proposals link each receptor to a different physiological role. Activation of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors is associated with reduced appetite, slower gastric emptying, and glucose-dependent insulin release. Glucagon receptor signaling, by contrast, is associated with increased energy expenditure and altered lipid handling, though it can also raise blood glucose. The design intent is to balance these contributions so that weight reduction is enhanced without unacceptable glycemic trade-offs. How well that balance holds across individuals is not fully resolved.
Published information places retatrutide in clinical development rather than on the market as an approved therapy. Early-stage and mid-stage trials have examined tolerability and changes in body weight, and larger studies continue to report results over time. Open questions include the durability of effects after treatment stops, the composition of weight lost, and cardiovascular outcomes over long periods. Statements about definitive benefit should therefore be treated as provisional. Regulatory status varies by jurisdiction and changes as applications are reviewed.
Retatrutide is an investigational synthetic peptide designed to activate three distinct receptor systems within a single molecule. Its pharmacological profile combines activity at the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This arrangement places it within a broader class of agents often described as multi-agonists, which contrast with compounds that engage one or two targets. Research interest centers on whether simultaneous signaling produces effects that single-receptor agonists cannot achieve alone. A single molecular entity also simplifies manufacturing and delivery logistics compared with combining separate agents.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide | Not a small molecule |
| Receptor targets | GLP-1, GIP, glucagon | Triple agonist activity |
| Appearance | White to off-white powder | Lyophilized solid |
| Solubility | Soluble in water | Also in aqueous buffers |
| Storage | −20 °C or below | Protect from light and moisture |
Human evidence remains limited to controlled studies. A phase 2 trial in adults with obesity reported large, dose-dependent reductions in body weight over 48 weeks, with gastrointestinal events as the most frequently recorded adverse effect. Phase 3 programs designated TRIUMPH, for obesity, and TRANSCEND, for type 2 diabetes, are intended to confirm efficacy and to characterize safety in larger populations. Related studies are examining conditions such as knee osteoarthritis in people with obesity and metabolic liver disease. Open questions include long-term tolerability, effects on lean mass, and what happens after treatment is stopped.
Retatrutide is an investigational synthetic peptide that acts on three receptor targets at once: glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon. It is developed by Eli Lilly and appears in the literature and in trial registries under the code LY3437943. The molecule belongs to a class of engineered peptides designed to resist rapid breakdown and permit infrequent subcutaneous administration. No regulatory agency has approved it for clinical use, and all available human data come from controlled trials rather than from routine practice.
开发进程从早期单次和多次给药研究推进至大规模后期试验。公开报告显示，参与者在体重和相关代谢指标上出现变化，但完整数据需经同行评审并接受独立复核。试验设计通常包括随机、双盲和对照设置，以区分药物效应与行为干预。监管提交和标签范围尚未确定；长期维持效果与心血管结局仍是开放问题。
与仅靶向单一受体的同类药物相比，瑞他鲁肽增加胰高血糖素受体成分，理论上可提高能量消耗并改变脂肪分布。临床中观察到的体重变化是否主要来自该额外机制，目前尚无定论。胃肠道反应是该类药物常见不良事件，试验中通过剂量递增和监测进行管理。停药后体重反弹、个体差异和长期耐受性仍需更多数据。
Clinical studies have reported notable reductions in body weight among participants. Early trials measured safety and explored several dose levels, and later studies tracked body-weight change over months of treatment. Investigators also monitor effects on glycemic markers, liver fat, and blood lipids. Because the compound is still in development, questions about long-term safety, cardiovascular outcomes, and durability after treatment ends remain open.
The three-receptor design places retatrutide in a distinct category relative to older incretin-based therapies. Single agonists target one receptor, and dual agonists target two. Adding a third target broadens the pharmacological footprint and introduces new trade-offs among efficacy, tolerability, and glucose control. How these trade-offs resolve in large trials is a central focus of current research.
However, 1–5% of patients taking docetaxel may develop severe pneumotoxicity. Patients may develop exertional breathlessness and desaturation which needs to be detected early. Chest X-Ray may show bilateral opacities and High Resolution CT chest may reveal Organizing Pneumonia (OP) pattern or Non-Specific Organizing Pneumonia (NSIP) pattern or a combination. Docetaxel-induced DPLD is a fatal adverse effect, which can be managed by the cessation of the drug and starting on steroids in adequate doses. Observations of severe side effects in the above 40 phase II and phase III studies were also recorded. Many more side effects have been reported for conjunctive and adjuvant treatment with docetaxel as well as rare post-marketing events.
=== 2011–2012: Early career === Hibberd was drafted by the Essendon Football Club with their only selection and fourth overall in the 2011 pre-season draft. He made his AFL debut in the 139-point win against Gold Coast at Etihad Stadium in round six. He was omitted the next week for the match against West Coast, before returning in round eight in the thirty-six point win against Brisbane at the Gabba, where he recorded twenty-two disposals and was praised by then-Essendon coach, James Hird, in particular for his courage around the ball. Playing the next seven matches, he missed the round seventeen match against Adelaide at AAMI Stadium due to a hamstring injury. After playing the first five matches for the 2012 season, he suffered a hamstring injury during the first quarter of the Anzac Day clash against Collingwood in round five, which forced him to miss six weeks of football. He made his return from injury through the Victorian Football League (VFL), playing for Essendon's affiliate team, Bendigo. After playing two matches in the VFL, he returned to the AFL side for the twenty-four point win against Fremantle at Patersons Stadium in round thirteen. He played the next three matches before injuring his quad in the fifty point win against Port Adelaide at AAMI Stadium in round sixteen. He missed three weeks due to the injury and returned to the side for the twenty-four point loss against North Melbourne at Etihad Stadium in round twenty.
Biko is viewed as the "father" of the Black Consciousness Movement and the anti-apartheid movement's first icon. Nelson Mandela called him "the spark that lit a veld fire across South Africa", adding that the Nationalist government "had to kill him to prolong the life of apartheid". Opening an anthology of his work in 2008, Manning Marable and Peniel Joseph wrote that his death had "created a vivid symbol of black resistance" to apartheid that "continues to inspire new black activists" over a decade after the transition to majority rule. Johann de Wet, a professor of communication studies, described him as "one of South Africa's most gifted political strategists and communicators". In 2004 he was elected 13th in SABC 3's Great South Africans public poll. Although Biko's ideas have not received the same attention as Frantz Fanon's, in 2001 Ahluwalia and Zegeye wrote that the men shared "a highly similar pedigree in their interests in the philosophical psychology of consciousness, their desire for a decolonising of the mind, the liberation of Africa and in the politics of nationalism and socialism for the 'wretched of the earth'". Some academics argue that Biko's thought remains relevant; for example, in African Identities in 2015, Isaac Kamola wrote that Biko's critique of white liberalism was relevant to situations like the United Nations' Millennium Development Goals and Invisible Children, Inc.'s KONY 2012 campaign.
==== Live delivery systems ==== Live delivery systems, also known as vectors, are cells modified with ligands or antigens to improve the immunogenicity of recombinant subunits via altering antigen presentation, biodistribution and trafficking. Subunits may either be inserted within the carrier or genetically engineered to be expressed on the surface of the vectors for efficient presentation to the mucosal immune system.
Sources: en.wikipedia.org
=== 1988 === 11 February Running to Time, about the new InterCity 225; the National Express Coaches Rapide service; the project team of the Intercity 225, with project director Mike Rollin, and Mike Newman of GEC; the 225 train had to be delivered on 14 February 1988, with an operational life of thirty years; the InterCity 125 was not intended to have been primarily developed - in a board meeting, the commercial directors were not technologically knowledgeable of trains, and asked about alternatives, to be told by an engineering director that a 125 mph diesel train could be developed in two years, so the HST began at that meeting; the British Rail APT-E prototype, powered by the Leyland 2S/350 gas turbine; in 1974 BR commissioned the APT-P, which had ten years of development, due to the active tilting suspension; the 225 train was possibly to enter service on the UK's only large electrified line, the West Coast Main Line, but the much-straighter and faster East Coast Main Line was being electrified, so BR decided to implement the 225 train on the ECML instead; Crewe railway station, which opened in 1837, and where trains were first built nearby in 1843; Steve Corfield, of Crewe Works; the unsprung mass of a train, and Cardan shafts; Roger Ford of Modern Railways; John Prideaux, director of InterCity; David Carter of DCA in Warwick, who designed the livery; the Modernisation Plan was published in December 1954, which had advocated the electrification of the ECML, and the phasing-out of steam travel; the late-1980s ECML electrification had cost BR £350m - it was not government-funded, with 2,800 miles of copper wire, and 33,000 support masts, overseen by Don Heath; all of the improvements in the UK were on old lines of track, but France and Germany had built entire new electrified lines - the TGV was planned from the mid-1960s; G. Freeman Allen of Jane's World Railways; the 225 train underframe being built at Crewe Works; GEC Traction at Preston, Lancashire, Al Reed, the separately excited (Armature Controlled DC Motor) brushed DC electric motor, and Gerald West; the right-angle gearboxes were built by David Brown Ltd and Voith of Heidenheim an der Brenz in southern Germany; Eric Black of Metro-Cammell in Washwood Heath; the ST41 bogies were made by SIG Combibloc Group of Neuhausen am Rheinfall in Switzerland. Narrated by Robin Ellis, produced by Patrick Uden, directed by Paul Fabricius, made by Uden Associates. 12 February Playing with Fire 17 July The Air Fix!, about aviation safety; a television adaptation of a black comedy theatre production by 35-year-old James Castle, dressed as an airline pilot, largely featuring Turkish Airlines Flight 981, the Ermenonville air disaster, in France on 3 March 1974, to this day the worst airliner crash, without any survivors, with 177 British people killed, when a cargo door ruptured, and the subsequent enquiry led to a cover up by the airline and aviation authority; the DC10 had known design failings in its fuselage, and its cargo door design was known to be faulty by the aircraft manufacturer; the American Airlines Flight 96 crash had happened on 12 June 1972, involving a design failure of the cargo door, but the FAA nonetheless gave the DC-10 a certificate of airworthiness; the DC10 had been rushed into service; James Castle accused the aircraft industry of callous negligence; James Castle had been a British Airways aircraft maintenance technician from 1969 to 1977 at Heathrow Airport; he listed the numbers of children that lost one or both parents in the crash, and the numbers of women who were widowed; the theatre production had been going since December 1986, directed by Caroline Noh Narrated by James Castle, produced by Ben Gooder, made by Uden Associates 24 July Nic's Boat, about Nic Bailey, a 37-year-old architect with Foster and Partners; he designed a 40-ft trimaran, called MTC, for the Carlsberg Single-Handed Trans-Atlantic Race on 5 June 1988; he had helped to design the 1978 Sainsbury Centre for Visual Arts in Norwich and the Renault Centre in Swindon; boat builder Spud Rowsell in Exmouth, with Phil Morrison; the hull cost £46,000, and the rigging cost £46,000; the mast and rigging were fitted at Topsham, Devon; Robin Knox-Johnston; French yacht designer Bruno Fehrenbach; he sailed the Atlantic between the Rhumb Line Route and the Great Circle Route; some yachts made the journey to Newport, Rhode Island in ten days; the yacht mast was constructed by Proctor South West. Produced by Michael Wills, directed by Bob Bee, made by Juniper Productions 31 July The Living Dead 7 August Zen and the Art of TV Manufacture, a Panasonic TV factory in South Wales; in 1933 the company founder Kōnosuke Matsushita established seven guiding commercial principles; the Fidelity TV factory in west London was given one year - 1988 - to turn its fortunes around or be closed; the factory's closure was announced to the workforce on 25 January 1988, with the site closing at the end of July 1988; Amstrad bought the Fidelity name in May 1988. Narrated by Alan Howard, directed by Patrick Uden, produced by Michael Proudfoot, made by Uden Associates 14 August How Good Is Soviet Science?, about the political inhibition of Soviet technology in the 1980s; in many ways the Soviet Union in 1987 was a backward and underdeveloped nation, with food queues; the Soviet system didn't respond to changes in demand - everything was planned years in advance; physicist Alexander Prokhorov, who won the Nobel Prize for Physics in 1964; Russians were proud of mathematicians Pafnuty Chebyshev and Nikolai Lobachevsky; large government centrally planned projects were compatible with the communist system, notably its space programme; by the 1970s, the Russians realised that they were some distance behind other countries, such as in disciplines of computing and genetics; science teaching was emphasised at Soviet schools, and English was well taught as well; after secondary schools, half went into science; theoretical science was where Soviet teaching excelled, such as at the Steklov Institute of Mathematics; Yuri Ovchinnikov wanted to improve Soviet science; in the early 1950s, the Soviet Union tried to ignore the findings of genetics, through the work of Trofim Lysenko, who claimed that genetics was anti-communist, known as Lysenkoism leading to many scientists being imprisoned and executed; in the 1960s, a set of large biological research centres were built at Pushchino; one of the most well-built research institutes was the Shemyakin Institute of Bioorganic Chemistry, for biotechnology; Stalin did not like computer science, and it was largely banned until 1958; the Soviets were always years behind in computer science; the first recognisable transistor Soviet computer was the BESM-6 in the 1960s; later computers were the ES EVM series, copied from the IBM System/360; the Akademgorodok (Academic City) in Novosibirsk; the Institute of Automation and Electrometry researched optical memory on holographic slides to and much work on lasers; collaboration between Soviet research and Soviet industry was long-winded, maybe almost impossible - the centrally planned Soviet industry could not sufficiently adapt for short-term changes, as it had to be monotonously planned years in advance, for mass production; Soviet government research was perhaps excellent nonetheless; not many Soviet scientists could travel to international conferences; dissemination of current worldwide science was limited throughout the Soviet Union, due to widespread government restrictions; Suite No. 2 in B minor, BWV 1067. Narrated by US technology historian Loren Graham, produced by Chris Durlacher, directed by Martin Smith, made by Uden Associates, NDR and WGBH. Shown on Nova on 17 November 1987 and 22 March 1988 21 August Toys for the Boys, about the Williams racing team; Graham Hill and Jim Clark in 1967; Tomorrow's World in 1967, narrated by Derek Cooper; journalist Peter Windsor of Williams; aerodynamicist Frank Dernie, head of research at Williams; Keith Botsford, motor racing editor of the Sunday Times; the German racing manager Alfred Neubauer, in the late 1930s; there were 18 F1 teams, with 7 being British; Mobil Oil paid Williams £2.5m for advertising on the cars of Nigel Mansell and Riccardo Patrese; the Williams FW11; racing driver Howden Ganley; part of a BBC Horizon documentary broadcast on 9 March 1981, featuring the Williams FW07, and likewise narrated by Martin Jarvis and produced by Patrick Uden; engineering director Sir Patrick Head; Bach Mass in B minor; Mike Hawthorn, was killed on a public road, the A3 Guildford bypass, in his Jaguar Mark 1 on 22 January 1959; Canadian Gilles Villeneuve was thrown from his Ferrari, when qualifying for the 1982 Belgian Grand Prix; Swedish Ronnie Peterson, died after an accident on the start line at the 1978 Italian Grand Prix; Italian Elio de Angelis was killed in May 1986 at the Circuit Paul Ricard in south-east France; British Piers Courage burned to death at the 1970 Dutch Grand Prix; Jim Clark hit a tree on 7 April 1968 at the 1968 Deutschland Trophäe in the north-west of Baden-Württemberg; German Jochen Rindt was killed at the 1970 Italian Grand Prix after winning the championship in the same year, which was awarded posthumously; Bach Mass in B minor; Frank Williams had a crash on 8 March 1986 in the south of France, with Peter Windsor, in a Ford Sierra, making him quadraplegic; the Williams wind tunnel; Alan Jones waving the British flag at the 1980 Grand Prix; the 1988 season Williams car had a Judd V8 engine; the closing fanfare of Les préludes by Liszt; the documentary ends with German military march Prussia's Glory. Narrated by Martin Jarvis, produced by Patrick Uden, made by Uden Associates 28 August Cold Spring, Morning Sun, about atomic physicist Joan Hinton and her husband Erwin Engst. Joan's mother was teacher Carmelita Hinton. Joan worked on the top secret Manhattan Project at Los Alamos in 1944 which produced the atomic bombs that were dropped on Hiroshima and Hagasaki in the summer of 1945. After the war, Joan, her brother Bill, and her husband Erwin (Sid) Engst travelled to China to join Mao Ze Dong and the cultural revolution. Over the next five decades, Joan and Sid became pioneers in Chinese agricultural science and technology. Narrated by Liza Goddard, written, produced and directed by Chris Haws, Made by InCA. 18 September Taking the Tunnel, who would be travelling through the Channel Tunnel; the tunnel would open in May 1993; Colin Kirkland, technical director of Eurotunnel; Roger Vickerman of the University of Kent; historian Corelli Barnett, and how France and Germany spent money after the war improving rail infrastructure; journalist Kathy Watson; a working model was built of the two Channel rail terminals; 90% of the tunnel went through chalk; the French end was built much more water-tight than the English end, due to the worse geology; the tunnel was around one mile long at the English end, to meet the French side in 1990; the Single Market would stop duty free sales on the Channel ferries; the former Night Ferry across the Channel, which operated until 30 October 1980; TGV Est would connect Bordeaux, and TGV Nord would connect to Germany, the Netherlands, with a spur to the new tunnel; Richard D. North; tolls on the autoroutes discouraged local traffic, which slowed down British motorways; Daniel Ghouzi of Transmanche; Martin Simmons of Kent County Council; A292 junction of M20; Corelli Barnett believed that the British civil service was best at fudging, whereas the French civil service had been trained differently at the French grandes ecoles; a VTG ship from Dover to Dieppe carried trains; freight journeys over 250 miles were most cost effective by rail, but did lack logistical flexibility at either end; Michael Barclay of Tiphook Rail; a distribution centre in Paddock Wood in Kent, built by the Spanish Transfesa; UIC gauge was the main European gauge for freight; Artura Boix of Transfesa; Richard Hope of Railway Gazette; British trains had a 25 tonne axle weight, more than the European 22 tonnes; early plans for the new Eurostar trains, which would be dual voltage for travelling in England and France; rail writer Geoffrey Freeman Allen; the French trains would leave from the Gard du Nord; customs checks would be at the British end in London, but not in France; British Rail planned a high speed line across Kent to open in 1998 from King's Cross, but it would not open until September 2003, and to London in November 2007; Roger Ford of Modern Railways. Narrated by Geoffrey Palmer, produced by Patrick Uden, directed by Paul Fabricius, made by Uden Associates 25 September Road Test about road transport in the UK; there were two million vehicles in the UK in 1930; a test drive would be conducted from The Point, Milton Keynes at 8.30am to Maidstone, by different routes - Mike McDonald of the University of Southampton and Margaret Bell of the University of Nottingham in a Volvo 850 would go across London, and Peter Bonsall and Howard Kirby of the University of Leeds in a Volkswagen Passat B3, would follow the M25 to the north of London, George Hazel of Napier College and John Wootten in a Ford Granada would follow the M25 south of London, and Martin J. H. Mogridge would take the train on the new Thameslink from Bedford railway station via Blackfriars Railway Bridge; the test would be directed from the Road Traffic Research Centre at Middlesex Polytechnic, with Chris Wright, Peter Hills from Newcastle University, and psychologist Ivan Brown from the Applied Psychology Unit (MRC Cognition and Brain Sciences Unit) in Cambridge; variable-message signs (VMS) on the M6; before joining the M25, the vehicles had an average speed of 50 mph; the early plans in the 1940s for the M25, which the M25 to the south and west of London, now largely follows; when the M25 needed to be built, in the 1960s, many environmental objections had arisen for it to be built; Russ Kane in Capital Radio's Flying Eye; David Marsh at the AA Roadwatch studio in north London; the ramp meter, installed on the M6 by John Wootten; all of London's traffic lights were controlled from a computer centre in Westminster, with software (Split Cycle Offset Optimisation Technique) developed by Dennis Robertson; the Volvo 850 enters London along the Edgware Road and Park Lane to Hyde Park Corner; the prototype Autoguide system invented by Ian Catling; automatic vehicle identification (AVI) and piezoelectric strips developed at the University of Nottingham Department of Civil Engineering, and tested by Peter Davies on the Nottingham ring road, next to the QMC; the Volkswagen Passat arrives first at the Great Danes Hotel, making the 107 miles in two hours seventeen minutes, an average speed of 47 mph; the route south of London - 119 miles, also has a 47 mph average speed; the 96-mile rail journey had an average speed of 35 mph; the programme content would be copied by Top Gear fifteen years later. Narrated by Martin Jarvis, produced by David Sharp, directed by Mike Tomlinson, made by Orlando Productions 9 October Look, No Hands! about technology outpacing human knowledge; Hubert Dreyfus of University of California, Berkeley; Martin Corbett, industrial psychologist at the University of Warwick; work by Mike Cooley, and systems design; mechanical engineer Frederick Winslow Taylor and his meticulous improvements to industrial methods, in his book The Principles of Scientific Management; John Harris, manager of the Rolls-Royce helicopter engine plant at Leavesden, Hertfordshire; perhaps automation in engineering manufacturing processes could perhaps add or enhance, rather than totally replace, which required and produced less directly competent workers. Produced by Debra Hauer, directed by Christopher Rawlence, made by Hauer Rawlence Productions 16 October Spytech, John Pike of the Federation of American Scientists and how the Space Shuttle was built mostly for low Earth orbit reconnaissance satellites; but the Titan 34D was also available for many spy satellite launches; Christopher Andrew of the University of Cambridge; Harry Rositzke of the CIA, and the disastrous Operation Red Sox, from 1949 to 1953; William Colby, Director from 1973 to 1976 of the CIA, and how spying methods that worked in Germany during World War II were simply hopeless in a possibly more bizarre culture of communist eastern Europe in the early 1950s, so Ferret missions by B-29 aircraft over the border were attempted instead, but many were shot down; the Americans decided to go for high-altitude reconnaissance; on 1 May 1960, an aircraft photographing a missile construction factory, pilot was sentenced to 10 years, but released after two years in exchange for Rudolf Abel; H. Keith Melton and notorious improvised technology of the KGB; the Russian defector Stanislav Levchenko; the burst transmission method; camera lenses for spy satellites made by Itek; the Space Shuttle was built to maintain and repair the Key Hole set of spy satellites, such as KH-11 KENNEN, launched by the National Reconnaissance Office (NRO) in 1976, and introduced digital photography, and EOSAT and its Landsat program; Jeffrey T. Richelson, a writer on national security; Major-General George Keegan of the Twenty-Fifth Air Force described how the Soviet Union got to know when spy satellites would be overhead, and would hide anything sensitive; listening satellites sent their data to the NSA at Fort Meade in Maryland, such as data from Magnum, launched by the secret STS-51-C mission in January 1985; Paul Bracken and all-source intelligence fusion; Soviet intelligence in the US was quite widespread, with up to 800 spies operating out of Soviet trade missions, and operated much more widespread than the US had attempted; the new KH-12 satellite, that launched in November 1992, could see through clouds. Narrated by Mike Short, produced by Claudia Milne, made by Twenty Twenty 23 October Bamboo, the importance of bamboo to the Chinese economy; Prof Hsiung Wenyue of the Bamboo Research Centre of Nanjing Forestry University; bamboo structures do not collapse in high winds; over a thousand species of bamboo; bamboo dies out for ten years, then grows again; only 15% of China can be cultivated; bamboo can grow four feet in 24 hours, it is the fastest growing plant; bamboo has a tensile strength twice as much as timber; hospitals in China worked with herbal remedies; bamboo traders had quotas set by the Chinese government; bamboo shoots were mostly exported to Japan; growing bamboo helped soil structure; the Chinese government encouraged the growing of bamboo, as an alternative to timber. Narrated by Jenny Agutter, produced by Michael Blakstad, directed by Patrick Fleming, made by Workhouse Productions, made in cooperation with China Central Television 30 October Heavy Metal, chemist Neil Ward of the University of Surrey, who found abnormal pregnancies; medical doctor Robin Russell-Jones of the Campaign for Lead Free Air; environmental chemist Brian Davies of the University of Bradford; footage from the 1971 BBC A Public Poison, with chemist Derek Bryce-Smith, and Patrick Lawther of St Bartholomew's Hospital; Gloria all'Egitto from Aida by Giuseppe Verdi, with the assembly line of the Rover 800; Robin Brundle; Eric Fountain of Vauxhall Motors; Ojos Criollos by Louis Moreau Gottschalk. Narrated by Catherine Robins, produced by Michael Blakstad, made by Workhouse Productions 13 November Free Flight, about gliding, with Derek Piggott in a Rolladen-Schneider LS4 at Booker Gliding Centre in Buckinghamshire; in the UK there were about 350,000 flights and 2 deaths each year; a Schleicher ASW 24 in a wind tunnel with Loek Boermans at TU Delft Faculty of Aerospace Engineering in the Netherlands; the Schleicher ASH 25 with glider pilot John Jeffries at London Gliding Club west of Dunstable; at Wasserkuppe, a 3,000 ft mountain in the east of Hesse in the centre of Germany is where gliding mostly developed in the 1920s by the Deutsche Forschungsanstalt für Segelflug, due to German powered-aircraft manufacturing being legally restricted; nearby at Poppenhausen, Hesse is Alexander Schleicher GmbH & Co, with designer Gerhard Waibel, where gliders had wings made from carbon fibre, and covered in kevlar for torsional stiffness; the first glider of a contemporary design was the Akaflieg Stuttgart fs24 in 1951. Narrated by Robert Gary 20 November Chaos, Tim Palmer of the ECMWF; mathematician Robert L. Devaney; German mathematician Heinz-Otto Peitgen and fractal geometry; strange attractors in dynamical systems, such as weather systems; David Rand of the University of Warwick, and period-doubling bifurcation, discovered in 1975 by mathematician Mitchell Feigenbaum discovered; fractal landscapes; British mathematician Michael Barnsley, and affine transformations, which are applied to digital image processing; the chaos game; Soviet physicist Lev Landau; physicist Harry Swinney of the University of Texas; economist James B. Ramsey; Ian Stewart of the University of Warwick, and the unpredictable rotation of Hyperion. Written, produced and directed by Chris Haws, the programme was made by Independent Communications Associates (InCA). In 1989, it won the SciTech Award for best scientific documentary. 27 November The Art of Deception, about camouflage, deception, decoys and stealth. The Northrop Grumman B-2 Spirit was first displayed on Tuesday 22 November 1988, just five days before the programme was aired. Featured interviewees include: Richard P. Hallion of Wright-Patterson Air Force Base; Peter Varnish of the Admiralty Research Establishment at Funtington in West Sussex; defence writer Antony Preston; Roy Behrens of the Art Academy of Cincinnati; Lt Col Chris Nash of Surveillance, Target Acquisition, Night Observation and Counter-surveillance (STANOC); Major William Marshak of the AAMRL - now the 711th Human Performance Wing; Captain Brian Perowne, commanding officer of HMS Brazen (F91); aviation writer Bill Sweetman, and Commander Patrick Walker, commanding officer of HMS Trafalgar (S107) a Royal Navy hunter-killer submarine; John Hall of the Admiralty Research Establishment (former Admiralty Experiment Works) at Haslar. Narrated by Nick Chilvers, Written, produced and directed by Chris Haws, made by InCA and WGBH Boston
G protein dependent activation of phospholipase C (PLC) which results in the breakdown of the membrane constituent phospholipid, phosphatidylinositol (4,5)-bisphosphate (PIP2) into inositol (1,4,5)-trisphosphate (IP3) and diacyl glycerol (DAG). IP3 is one of the most effective inducers of Ca2+ increase from cytoplasmic pools and from outside the cell via opening Ca2+ channels. DAG in turn is an inducer of protein kinase C (PKC). Activation of the regulatory small GTPase, RAS. The active RAS can in turn activate RAF, a Ser/Thr kinase. In the next step mitogen-activated protein kinases (MAP kinases) are activated. (Also known as extracellular signal-regulated kinases - ERKs or MAP/ERK kinase (MEK)). As a result of the last step, ERK1 and ERK2 are activated. The phosphorylated forms of ERKs can continue the cascade by triggering activation more interacting kinases which results in altered transcriptional activity in the nucleus. Ligand binding to FPR can also induce the activation of CD38, an ectoenzyme of the surface membrane. As a result of activation NAD+ molecules will enter the cytoplasm. NAD+ is converted into cyclic ADP ribose (cADPR), a second messenger which interacts with ryanodine receptors (RyR) on the surface of the rough endoplasmic reticulum. The overall result of the process is increased cytoplasmic Ca2+ levels via the direct pathway described above and also via indirect pathways such as opening of Ca2+ channels in the cell membrane. The sustained increase of Ca2+ is required for directed migration of the cells.
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It is administered under the tongue, in the cheek, by injection (intravenous or subcutaneous), or as a skin patch or implant. Maximum pain relief generally occurs within an hour and lasts up to 24 hours. In the United States, buprenorphine/naloxone (Suboxone) is usually prescribed to discourage injection misuse. Both formulations are Schedule III controlled substances. Buprenorphine acts as an agonist, partial agonist, or antagonist at different opioid receptors. It relieves opioid withdrawal and reduces the effects of other opioids. Unlike full agonists such as heroin and methadone, it has a ceiling effect for some effects, including respiratory depression, but retains misuse potential. Side effects include respiratory depression, sleepiness, adrenal insufficiency, QT prolongation, low blood pressure, allergic reactions, constipation, and opioid addiction. It may increase seizure risk in susceptible people; opioid withdrawal after discontinuation is generally less severe than with other opioids. Safety during pregnancy is unclear, but use while breastfeeding is probably safe: infants receive approximately 1–2% of the maternal weight-adjusted dose. The compound acts as a partial agonist of the μ-opioid receptor (MOR), exhibiting approximately 48% maximal efficacy in the reported functional assay. Its signaling profile is biased toward G-protein-mediated signaling, with comparatively weak recruitment of β-arrestins.
== Pharmacology == Taxifolin is not mutagenic and less toxic than the related compound quercetin. It acts as a potential chemopreventive agent by regulating genes via an ARE-dependent mechanism. Taxifolin has shown to inhibit the ovarian cancer cell growth in a dose-dependent manner. However, in this same study, taxifolin was the least effective flavonoid in the inhibition of VEGF expression. There is also a strong correlation (with a correlation coefficient of 0.93) between the antiproliferative effects of taxifolin derivatives on murine skin fibroblasts and human breast cancer cells. Taxifolin has shown to have anti-proliferative effects on many types of cancer cells by inhibiting cancer cell lipogenesis. By inhibiting the fatty acid synthase in cancer cells, taxifolin is able to prevent the growth and spread of cancer cells. Taxifolin also stops the effects of overexpression of P-glycoprotein, which prevents the development of chemoresistance. Taxifolin does this via inhibition of rhodamine 123 and doxorubicin. The capacity of taxifolin to stimulate fibril formation and promote stabilization of fibrillar forms of collagen can be used in medicine. Also taxifolin inhibited the cellular melanogenesis as effectively as arbutin, one of the most widely used hypopigmenting agents in cosmetics. Taxifolin also enhances the efficacy of conventional antibiotics such as levofloxacin and ceftazidime in vitro, which have potential for combinatory therapy of patients infected with methicillin-resistant Staphylococcus aureus (MRSA).
Liraglutide, a GLP-1 receptor agonist taken by subcutaneous injection once daily. Naltrexone/bupropion, a combination of naltrexone and bupropion taken by mouth twice daily. Orlistat is a lipase inhibitor taken by mouth three times daily with each main meal containing fat. Orlistat reduces intestinal fat absorption by inhibiting pancreatic lipase. Over the longer term, average weight loss on orlistat is 2.9 kg (6.4 lb). It leads to a reduced incidence of diabetes, and has some effect on cholesterol. However, there is little information on how it affects the longer-term complications or outcomes of obesity. It also inhibits absorption of fat soluble vitamins; vitamins A, D, E and K, so supplementation is needed for those on orlistat. Phentermine/topiramate combination of phentermine and topiramate taken by mouth once daily. Semaglutide, a GLP-1 receptor agonist taken by subcutaneous injection once weekly. Tirzepatide is a gastric inhibitory polypeptide (GIP) analog and a GLP-1 receptor agonist taken by subcutaneous injection once weekly. As of 2023, tirzepatide has shown the greatest weight reduction of medications. Phendimetrazine, diethylpropion, and phentermine are approved by the FDA for short term use, up to 12 weeks at a time.
Sources: en.wikipedia.org
Retatrutide is an investigational synthetic peptide that activates three metabolic receptors: GLP-1, GIP, and glucagon. It is being studied for obesity and type 2 diabetes. It has not been approved for clinical use.
Earlier incretin therapies engage one or two receptors. Retatrutide adds glucagon receptor activity, which may raise energy expenditure. Whether this produces larger clinical benefits is still being tested.
It has completed phase 2 trials and moved into later-stage evaluation. No regulator has granted approval. Access outside research settings is not authorized.
It is described as a single molecule that acts at three receptors: the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This triple activity distinguishes it from agents that target one or two of these pathways.