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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： joshua S.Fleishman Sunil Kumar Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

Phrenic nerve block: the key to managing acute biliary pain?

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World Journal of Emergency Medicine 2024年第1期15卷 62-63页

作者： Michael Shalaby joshua luftig Department of Emergency Medicine and Critical Care Herbert Wertheim College of Medicine at Florida International UniversityMiami 33199USA Advanced Emergency Ultrasound Mount Sinai Medical CenterMiami Beach 33140USA Department of Emergency Medicine Highland HospitalAlameda Health SystemOakland 94602USA

Over the past two decades,the USA has witnessed a steep rise in the incidence of acute cholecystitis(AC),[1]even among children,[2]with over 200,000 cases annually.[3]Patients with AC often present to the emergency department(ED)experiencing severe distress,with most describing their pain level as“intolerable.”[4]Furthermore,there is usually a considerable delay before surgery,with a median time from diagnosis of AC to surgery of 28.5 h,[5]and a substantial percentage of patients wait as long as 10 d.[6]Prolonged delays before surgery lead to increased opioid use,which is associated with extended hospital stays and higher rates of readmission after cholecystectomy.[7]Furthermore,opioids can lead to vomiting,respiratory depression,delirium,and ultimately addiction.[8]We propose a novel regional anesthesia technique for managing AC:right phrenic nerve *** method could offer improved pain control and a more favorable risk profile in selected patients when compared to current ED practices.

关键词： pain anesthesia diagnosis

In Situ Mineralization of Biomass-Derived Hydrogels Boosts Capacitive Electrochemical Energy Storage in Free-Standing 3D Carbon Aerogels

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Energy & Environmental Materials 2024年第2期7卷 359-371页

作者： Anjali Achazhiyath Edathil Babak Rezaei Kristoffer Almdal Stephan Sylνest keller National Centre for Nano Fabrication and Characterization DTU NanolabTechnical University of Denmark2800LyngbyDenmark DTU Chemistry Technical University of Denmark2800LyngbyDenmark

Here,a novel fabrication method for making free-standing 3D hierarchical porous carbon aerogels from molecularly engineered biomass-derived hydrogels is *** situ formed flower-like CaCO_(3)molecularly embedded within the hydrogel network regulated the pore structure during in situ mineralization assisted one-step activation graphitization(iMAG),while the intrinsic structural integrity of the carbon aerogels was *** homogenously distributed minerals simultaneously acted as a hard template,activating agent,and graphitization *** decomposition of the homogenously distributed CaCO_(3)during iMAG followed by the etching of residual CaO through a mild acid washing endowed a robust carbon aerogel with high porosity and excellent electrochemical *** 0.5 mA cm^(-2),the gravimetric capacitance increased from 0.01 F g^(-1)without mineralization to 322 F g^(-1)with iMAG,which exceeds values reported for any other free-standing or powder-based biomass-derived carbon *** outstanding cycling stability of~104%after 1000 cycles in 1 M HClO4 was *** assembled symmetric supercapacitor device delivered a high specific capacitance of 376 F g^(-1)and a high energy density of 26 W h kg^(-1)at a power density of 4000 W kg^(-1),with excellent cycling performance(98.5%retention after 2000 cycles).In combination with the proposed 3D printed mold-assisted solution casting(3DMASC),iMAG allows for the generation of free-standing carbon aerogel architectures with arbitrary ***,the novel method introduces flexibility in constructing free-standing carbon aerogels from any ionically cross-linkable biopolymer while maintaining the ability to tailor the design,dimensions,and pore size distribution for specific energy storage applications.

关键词： biomass carbon aerogel sustainable energy materials free-standing supercapacitors

The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang Anke Baranowsky Johannes keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis

Untangling the biotic stress in the late Maastrichtian Deccan-benchmark interval of Bidart(France)

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Journal of Palaeogeography 2024年第2期13卷 181-198页

作者： Subham Patra Gerta keller Eric Font Thierry Adatte Jahnavi Punekar Indian Institute of Technology Bombay PowaiMumbai 400076India Princeton University PrincetonNJ 08544USA Departamento de Ciencias da Terra Faculdade de Ciencias e TecnologiaUniversidade de Coimbra3000-272 CoimbraPortugal Institute of Earth Sciences University of Lausanne1015 LausanneSwitzerland

The late Maastrichtian witnessed substantial surges in Deccan volcanism,prompting the hypothesis that these voluminous pulses may have instigated repeated episodes of ocean acidification during this *** Cretaceous-Palaeogene(K/Pg)boundary at Bidart(France)is preceded by a~0.5 m thick interval with geochemical and taphonomic vestiges of an ocean acidification event linked with Deccan *** planktic foraminifera census and morphometric data now confirm biotic stress conditions related to acidification in the Deccan benchmark *** absolute abundance data of larger(>150μm)heavily calcified planktic morphogroups show fluctuating populations throughout zone CF1(spanning the final~225 ky),lowest peaks within the Deccan benchmark,and a demographic collapse(>90%)at the K/Pg *** analyzed species are generally reduced in size,with thinner test walls in this~0.5 m interval,indicating the likelihood of calcification stress as a contributor to the overall biotic *** the K/Pg boundary,maximum biotic stress is recorded in all the tested faunal proxies.A preliminary graphic correlation of zone CF1 at Bidart with the auxiliary GSSP at Elles(Tunisia)constrains the Deccan benchmark interval of high biotic stress to the final~58ky of the late Maastrichtian,culminating in the K/Pg mass *** volcanogenic Hg peaks coincident with faunal and taphonomic evidence of ocean acidification strengthen the Deccan-related ocean acidification hypothesis.

关键词： Deccan volcanism K/Pg mass extinction Biotic stress Calcification stress

Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao joshua Kuruvilla Eng-King Tan Department of Neurology National Neuroscience InstituteSingaporeSingapore Neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

Managing type 2 diabetes:targeting a microbial enzyme as a novel treatment option

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Signal Transduction and Targeted Therapy 2024年第1期9卷 3-5页

作者： Anikó keller-Pintér Tamás Korcsmáros Tibor Vellai Department of Biochemistry Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged6720Hungary Department of Metabolism Digestion and ReproductionImperial College LondonLondonW120NNUK Quadram Institute Bioscience Norwich Research ParkNorwichNR47UQUK Department of Genetics Eötvös Loránd University(ELTE)Budapest1117Hungary Hungarian Research Network HUN-REN-ElTE Genetics Research Group Budapest1117Hungary

In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GlP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.

关键词： homeostasis stimulating clinical

Biocompatible Biphasic Iontronics Enable Neuron-like Ionic Signal Transmission

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Research 2024年第3期2024卷 795-796页

作者： Xiaoyi Wang Aleksandar P.Ivanov joshua B.Edel Department of Chemistry Imperial College LondonMolecular Sciences Research HubLondon W12 OBZUK

Biocompatible connections between external artificial devices and living organisms show promise for future neuroprosthetics and *** study in Science by Zhao and colleagues introduces a cascade-heterogated biphasic gel(HBG)iontronic device,which facilitates electronic-to-multi-ionic signal transduction for abiotic–biotic *** by neuron signaling,the HBG device demonstrated its biocompatibility by regulating neural activity in biological tissue,paving the way for wearable and implantable devices,including brain–computer interfaces.

关键词： asi Signal Neuron

Obstructive sleep apnea:Overlooked comorbidity in patients with diabetes

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World Journal of Diabetes 2024年第7期15卷 1448-1460页

作者： Eric D Tenda joshua Henrina Jin H Cha Muhammad R Triono Ersananda A Putri Dahliana J Aristy Dicky l Tahapary Division of Respirology and Critical Care Department of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia Head of Research Group Artificial Intelligence and Digital Health Indonesian Medical Education and Research InstituteFaculty of Medicine University of IndonesiaDKI JakartaJakarta Pusat 10430Indonesia Division of Endocrinology Metabolism and DiabetesDepartment of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia

In this review article,we explore the interplay between obstructive sleep apnea(OSA)and type 2 diabetes mellitus(T2DM),highlighting a significant yet often overlooked *** delve into the pathophysiological links between OSA and diabetes,specifically how OSA exacerbates insulin resistance and disrupts glucose *** research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related *** the importance of comprehensive management,including weight control and positive airway pressure therapy,the study advocates integrated approaches to improve outcomes for patients with T2DM and *** review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

关键词： Obstructive sleep apnea Type 2 diabetes mellitus Macrovascular Microvascular Weight loss Positive airway pressure