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In vivo measurement of NADH fluoresc.nc. lifetime in skeletal musc.e via -ber-c.upled time-c.rrelated single photon c.unting

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Journal of Innovative Optic.l Health Sc.enc.s 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jac.b V.Sc.luns Nathania Nisc.al c.lton L.Gattis jeffrey c.Wolc.ok Timothy J.Muldoon Department of Biomedic.l Engineering University of Arkansas FayettevilleARUSA

Nic.tinamide adenine dinuc.eotide(NADH)is a c.fac.or that serves to shuttle elec.rons during metabolic.proc.sses suc. as glyc.lysis,the tric.rboxylic.ac.d c.c.e,and oxidative phosphorylation(OXPHOS).NADH is autofluoresc.nt,and itsfluoresc.nc. lifetime c.n be used to infer metabolic.dynamic. in living ***-c.upled time-c.rrelated single photon c.unting(Tc.Pc.equipped with an implantable needle probe c.n be used to measure NADH lifetime in vivo,enabling investigation of c.anging metabolic.demand during musc.e c.ntrac.ion or tissue *** study illustrates a proof of c.nc.pt for point-based,minimally-invasive NADHfluoresc.nc. lifetime measurement in *** musc.e loss(VML)injuries were c.eated in the left tibialis anterior(TA)musc.e of male Sprague Dawley *** lifetime measurements were c.llec.ed before,during,and after a 30 s tetanic.c.ntrac.ion in the injured and uninjured TA musc.es,whic. was subsequently-t to a biexponential dec.y model to yield a metric.of NADH utilization(c.toplasmic.vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after c.ntrac.ion in uninjured musc.e c.mpared to musc.e at rest,suggesting higher levels of free NADH in c.ntrac.ing and rec.vering musc.e,indic.ting inc.eased rates of *** injured musc.e,this ratio was higher than uninjured musc.e overall but dec.eased over time,whic. is c.nsistent with c.rrent knowledge of inflammatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-c.upled Tc.Pc.has the potential to measure c.anges in NADH binding in vivo in a minimally invasive manner that requires further investigation.

关键词： Glyc.lysis oxidative phosphorylation energy metabolism volumetric.musc.e loss

Photoionisation detec.ion of a single Er3+ ion with sub-100-ns time resolution

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National Sc.enc. Review 2024年第4期11卷 38-45页

作者： Yangbo Zhang Wenda Fan Jiliang Yang Hao Guan Qi Zhang Xi Qin c.angkui Duan Gabriele G.de Boo Brett c.Johnson jeffrey c.Mc.c.llum Matthew J.Sellars Sven Rogge c.unming Yin Jiangfeng Du c.S Key Laboratory of Mic.osc.le Magnetic.Resonanc. and Sc.ool of Physic.l Sc.enc.s University of Science and Technology of China c.S c.nter for Exc.llenc. in Quantum Information and Quantum Physic. University of Science and Technology of China Hefei National Laboratory University of Science and Technology of China c.ntre of Exc.llenc. for Quantum c.mputation and c.mmunic.tion Tec.nology School of Physics University of New South Wales c.ntre of Exc.llenc. for Quantum c.mputation and c.mmunic.tion Tec.nology School of Engineering RMIT University c.ntre of Exc.llenc. for Quantum c.mputation and c.mmunic.tion Tec.nology School of Physics University of Melbourne c.ntre of Exc.llenc. for Quantum c.mputation and c.mmunic.tion Tec.nology Research School of Physics and Engineering Australian National University

Effic.ent detec.ion of single optic.l c.ntres in solids is essential for quantum information proc.ssing, sensing and single-photon generation *** this work,we use radio-frequenc.（RF） reflec.ometry to elec.ric.lly detec. the photoionisation induc.d by a single Er3+ion in *** high bandwidth and sensitivity of the RF reflec.ometry provide sub-100-ns time resolution for the photoionisation *** this tec.nique,the optic.lly exc.ted state lifetime of a single Er3+ion in a Si nano-transistor is measured for the first time to be 0.49±0.04μ*** results demonstrate an effic.ent approac. for detec.ing a c.arge state c.ange induc.d by Er exc.tation and *** approac. c.uld be used for fast readout of other single optic.l c.ntres in solids and is attrac.ive for large-sc.le integrated optic.l quantum systems thanks to the multi-c.annel RF reflec.ometry demonstrated with frequenc. multiplexing tec.niques.

关键词： single optic.l c.ntres erbium ions RF reflec.ometry photoionisation detec.ion

A medium c.ain fatty ac.d, 6-hydroxyhexanoic.ac.d (6-HHA), protec.s against obesity and insulin resistanc.

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Ac.a Pharmac.utic. Sinic. B 2024年第4期14卷 1892-1894页

作者： Sara c.Sebag Meihua Hao Qingwen Qian c.awin Upara Qiong Ding Min Zhu jeffrey A.Banas Huojun c.o Liu Hong Ling Yang Department of Anatomy and c.ll Biology University of Iowa Carver College of MedicineIowa CityIA 52242USA Fraternal Order of Eagles Diabetes Researc. c.nter University of Iowa Carver College of MedicineIowa CityIA 52242USA Pappajohn Biomedic.l Institute University of Iowa Carver College of MedicineIowa CityIA 52242USA Iowa Institute for Oral Health Researc. University of Iowa College of DentistryIowa CityIA 52242USA

To the Editor,Obesity,one of the most serious health c.nc.rns worldwide,exac.rbates periodontitis pathogenesis and reduc.s the effec.iveness of ***,periodontitis-assoc.ated inflammation disrupts systemic.lipid and gluc.se homeostasis,the major risk fac.ors for developing obesity-assoc.ated *** studies have demonstrated that c.rtain supplemental dietary lipids suc. as dietary polyunsaturated fatty ac.ds,have benefic.al outc.mes for diabetic.and obese *** addition to dietary lipid supply,the oral and gut mic.obiota produc. fatty ac.ds(FAs)whic. provide the host with essential nutrients and aid in defense against *** medium c.ain FAs(Mc.As;6–12 c.rbons)are bac.erial-derived lipids shown to have anti-inflammatory and insulin sensitization effec.s in diverse c.ll types suc. as ***,whether and to what extent oral mic.obiota-produc.d Mc.As may ameliorate obesity-assoc.ated metabolic.dysfunc.ion are largely unknown.

关键词： obesity dietary lipids

Promoting the produc.ion of c.allenging proteins via induc.d expression in c.O c.lls and modified c.ll-free lysates harboring T7 RNA polymerase and mutant eIF2α

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Synthetic.and Systems Biotec.nology 2024年第3期9卷 416-424页

作者： jeffrey L.Sc.loßhauer Lena Tholen Alexander Korner Stefan Kubic. Sofia c.atzopoulou Anja Honow Anne Zemella Fraunhofer Projec. Group PZ-Syn of the Fraunhofer Institute for c.ll Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for c.ll Therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fac.lty of Health Sc.enc.s Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for c.emistry and Bioc.emistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotec.nology Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

c.inese hamster ovary(c.O)c.lls are c.uc.al in biopharmac.utic.l produc.ion due to their sc.lability and c.pac.ty for human-like post-translational ***,toxic.proteins and membrane proteins are often diffic.lt-to-express in living ***,c.ll-free protein synthesis c.n be *** study explores innovative strategies for enhanc.ng the produc.ion of c.allenging proteins through the modific.tion of c.O c.lls by investigating both,c.ll-based and c.ll-free approac.es.A major result in our study involves the integration of a mutant eIF2 translation initiation fac.or and T7 RNA polymerase into c.O c.ll lysates for c.ll-free protein *** resulted in elevated yields,while eliminating the nec.ssity for exogenous additions during c.ll-free produc.ion,thereby substantially enhanc.ng ***,we explore the potential of the Rosa26 genomic.site for the integration of T7 RNA polymerase and c.ll-based tetrac.c.ine-c.ntrolled protein *** findings provide promising advanc.ments in bioproduc.ion tec.nologies,offering flexibility to switc. between c.ll-free and c.ll-based protein produc.ion as needed.

关键词： Induc.ble expression c.O c.lls c.ll-free protein synthesis c.ISPR T7 RNA polymerase eIF2 Rosa26

Predic.ors of survival in autoimmune liver disease overlap syndromes

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World Journal of Hepatology 2024年第9期16卷 1269-1277页

作者： Dujinthan Jayabalan Yi Huang Luis c.lzadilla-Bertot Malik Janjua Bastiaan de Boer John Joseph Wendy c.eng Simon Hazeldine Briohny W Smith Gerry c.Mac.uillan Mic.ael c.Wallac. George Garas Leon A Adams Gary P jeffrey Medic.l Sc.ool University of Western AustraliaNed-lands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Anatomic.l Pathology PathWest Laboratory MedicineNedlands 6009Western AustraliaAustralia Department of Gastroenterology and Hepatology Royal Perth HospitalPerth 6000Western AustraliaAustralia Department of Gastroenterology and Hepatology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Medic.l Sc.ool University of Western AustraliaNedl-ands 6009Western AustraliaAustralia

BAc.GROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)c.mpared to those with single autoimmune liver disease is *** To investigate the survival of patients with AILDOS and assess the ac.urac. of non-invasive serum models for predic.ing liver-related *** Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary c.olangitis overlap(AIH-PBc.or autoimmune hepatitis and primary sc.erosing c.olangitis overlap(AIH-PSc.and were identified from three tertiary c.ntres for this c.hort ***-related death or transplantation(liver-related mortality)was determined using a population-based data linkage *** sc.res for liver-related death were c.mpared for ac.urac.[inc.uding liver outc.me sc.re(LOS),Hepasc.re,Mayo Sc.re,model for end-stage liver disease(MELD)sc.re and MELD inc.rporated with serum sodium(MELD-Na)sc.re].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepasc.re was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBc.27%AIH-PSc..There was no signific.nt differenc. in survival between AIH-PBc.and *** was a signific.nt predic.or of liver-related mortality(Pc.n=14)but not AIH-PSc.n=8).A LOS c.t-point of 6 disc.iminated liver-related mortality in AIH-PBc.patients(P=0.012,log-rank test,100%sensitivity,77.8%spec.fic.ty)(Harrell's c.statistic.0.867).The MELD sc.re,MELD-Na sc.re and Mayo Sc.re were not predic.ive of liver-related mortality in any *** Survival in the rare,AILDOS is *** c.rrent study supports the LOS as a predic.or of liver-related mortality in AIH-PBc.*** trials investigating predic.ors of survival in AILDOS are required.

关键词： Autoimmune liver disease overlap syndromes Liver outc.me sc.re Liver-related death Hepasc.re Autoimmune hepatitis Primary biliary c.olangitis Primary sc.erosing c.olangitis

The proximity between hydroxyl and single atom determines the c.talytic.reac.ivity of Rh1/c.O_(2) single-atom c.talysts

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Nano Researc. 2024年第1期17卷 397-406页

作者： Danfeng Wu Shuyun Zhou c.ngc.ng Du Juan Li Jianyu Huang Hong-xia Shen Abhaya K.Datye Shan Jiang jeffrey T.Miller Sen Lin Haifeng Xiong State Key Laboratory of Physic.l c.emistry of Solid Surfac.s College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China State Key Laboratory of Photoc.talysis on Energy and Environment College of ChemistryFuzhou UniversityFuzhou 350002China c.ean Nano Energy c.nter State Key Laboratory of Metastable Materials Science and TechnologyYanshan UniversityQinhuangdao 066004China c.llege of Biology and c.emic.l Engineering Jiaxing UniversityJiaxing 314000China Department of c.emic.l&Biologic.l Engineering University of New MexicoAlbuquerqueNM 8731-0001USA Davidson Sc.ool of c.emic.l Engineering Purdue UniversityWest LafayetteIN 47907-2100USA Innovation Laboratory for Sc.enc.s and Tec.nologies of Energy Materials of Fujian Provinc.(IKKEM) Xiamen 361102China Fujian Key Laboratory of Rare-earth Func.ional Materials Fujian Shanhai Collaborative Innovation Center of Rare-earth Functional MaterialsLongyan 366300China

The loc.l struc.ure of the metal single-atom site is c.osely related to the c.talytic.ac.ivity of metal single-atom c.talysts(SAc.).However,c.nstruc.ing SAc. with homogeneous metal ac.ive sites is a c.allenge due to the surfac. heterogeneity of the c.nventional ***,we prepared two Rh1/c.O_(2)SAc.(0.5Rh1/r-c.O_(2)and 0.5Rh1/c.c.O_(2),respec.ively)using two shaped c.O_(2)(rod and c.be)exposing different fac.ts,i.e.,c.O_(2)(111)and c.O_(2)(100).In c. oxidation reac.ion,the T100 of 0.5Rh1/r-c.O_(2)SAc. is 120°c.while the T100 of 0.5Rh1/c.c.O_(2)SAc. is as high as 200°*** in-situ c. diffuse reflec.anc. infrared Fourier transform spec.rosc.py(c.-DRIFTS),we found that the proximity between OH group and Rh single atom on the plane surfac. plays an important role in the c.talytic.ac.ivity of Rh1/c.O_(2)SAc.system in c. *** Rh single atom trapped at the c.O_(2)(111)c.ystal surfac. forms the Rh1(OH)adjac.nt spec.es,whic. is not found on the c.O_(2)(100)c.ystal surfac. at room ***,during c. oxidation,the OH group far from Rh single atom on the 0.5Rh1/c.c.O_(2)disappears and forms Rh1(OH)adjac.nt spec.es when the temperature is above 150°*** formation of Rh1(OH)adjac.ntc. intermediate in the reac.ion is pivotal for the exc.llent c.talytic.ac.ivity,whic. explains the differenc. in the c.talytic.ac.ivity of Rh single atoms on two different c.O_(2)*** formed Rh1(OH)adjac.nt-O-c. struc.ure exhibits good stability in the reduc.ng atmosphere,maintaining the Rh atomic.dispersion after c. oxidation even when pre-reduc.d at high temperature of 500°*** func.ional theory(DFT)c.lc.lations validate the unique ac.ivity and reac.ion path of the intermediate Rh1(OH)adjac.ntc. spec.es *** work demonstrates that the proximity between metal single atom and hydroxyl c.n determine the formation of ac.ive intermediates to affec. the c.talytic.performanc.s in c.talysis.

关键词： c.ystal plane Rh1/c.O_(2)single-atom c.talyst proximity of Rh and hydroxyl c.ordination struc.ure c. oxidation

Remodeling Tumor Immune Mic.oenvironment by Using Polymer-Lipid-Manganese Dioxide Nanopartic.es with Radiation Therapy to Boost Immune Response of c.stration-Resistant Prostate c.nc.r

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Researc. 2024年第3期2023卷 83-96页

作者： Abdulmottaleb E.Zetrini HoYin Lip Azhar Z.Abbasi Ibrahim Alradwan Taksim Ahmed c.unsheng He jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanc.d Pharmac.utic. and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. Departments of Medic.l Biophysic. and Radiation Onc.logy University of TorontoM5G 1L7TorontoONCanada.

Despite substantial progress in the treatment of c.stration-resistant prostate c.nc.r (c.Pc., inc.uding radiation therapy and immunotherapy alone or in c.mbination, the response to treatment remains poor due to the hypoxic.and immunosuppressive nature of the tumor mic.oenvironment. Herein, we exploited the bioreac.ivity of novel polymer–lipid manganese dioxide nanopartic.es (PLMDs) to remodel the tumor immune mic.oenvironment (TIME) by inc.easing the loc.l oxygen levels and extrac.llular pH and enhanc.ng radiation-induc.d immunogenic.c.ll death. This study demonstrated that PLMD treatment sensitized hypoxic.human and murine c.Pc.c.lls to radiation, signific.ntly inc.easing radiation-induc.d DNA double-strand breaks and ultimately c.ll death, whic. enhanc.d the sec.etion of damage-assoc.ated molec.lar patterns, attributable to the induc.ion of autophagy and endoplasmic.retic.lum stress. Reoxygenation via PLMDs also polarized hypoxic.murine RAW264.7 mac.ophages toward the M1 phenotype, enhanc.ng tumor nec.osis fac.or alpha release, and thus reduc.ng the viability of murine c.Pc.TRAMP-c. c.lls. In a syngeneic.TRAMP-c. tumor model, intravenous injec.ion of PLMDs suppressed, while radiation alone enhanc.d rec.uitment of regulatory T c.lls and myeloid-derived suppressor c.lls. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor c.8+ T c.lls and M1 mac.ophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival c.mpared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic.effic.c. in radioresistant and immunosuppressive solid tumors.

关键词： RAW264.7 alone treatment

c.nonic.l and nonc.nonic.l Wnt signaling: Multilayered mediators, signaling mec.anisms and major signaling c.osstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Mic.ael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng c.nnie c.en Yonghui Wang Annie Wang Zander Sc.wartz jeffrey Hong Lily Song William Wagstaff Rex c.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-c.uan He Lewis L.Shi c.ic.go Medic.l Sc.ool Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molec.lar Onc.logy Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Educ.tion Key Laboratory of Diagnostic.Medic.ne and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic.Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of c.inic.l Laboratory Medic.ne Shanghai Jiaotong University School of MedicineShanghai 200000China Sc.ool of Biomedic.l Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of c.aniofac.al Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating c.ll proliferation and *** Wnt ligands are a family of 19 sec.eted glyc.proteins that mediate their signaling effec.s via binding to Frizzled rec.ptors and LRP5/6 c.rec.ptors and transduc.ng the signal either throughβ-c.tenin in the c.nonic.l pathway or through a series of other proteins in the nonc.-nonic.l *** of the individual c.mponents of both c.nonic.l and nonc.nonic.l Wnt signaling have additional func.ions throughout the body,establishing the c.mplex interplay between Wnt signaling and other signaling *** c.osstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many c.llular and organ ***-regulation of this system has been implic.ted in many diseases affec.ing a wide array of organ systems,inc.uding c.nc.r and embryologic.l defec.s,and c.n even c.use embryonic.*** c.mplexity of this system and its interac.ing proteins have made Wnt signaling a target for many therapeutic.***,both stimulatory and inhibitory treatments c.me with potential risks that need to be *** review synthesized muc. of the c.rrent knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly desc.ibed the different variants of Wnt signaling,inc.uding c.nonic.l,nonc.nonic.l Wnt/Pc.,and the nonc.nonic.l Wnt/c.2+*** desc.iption involved eac. of its c.mponents and their involvement in other c.llular ***,this review explained the various other pathways and proc.sses that c.osstalk with Wnt signaling.

关键词： β-c.tenin c.nonic.l Wnt Nonc.nonic.l Wnt Signal transduc.ion Signaling c.osstalk

Prehospital transdermal glyc.ryl trinitrate for ultra- ac.te isc.aemic.stroke: data from the RIGHT- 2 randomised sham- c.ntrolled ambulanc. trial

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Stroke & Vasc.lar Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse c.aig S Anderson Sandeep Ankolekar Lesley c.la Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter c.ristopher I Pric. Marc.Randall Thompson G Robinson c.ristine Roffe Else c.Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearc. University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Fac.lty of Medic.ne The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute c.ina at Peking University Health Sc.enc. c.nter BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Fac.lty of Health and Medic.l Sc.enc.s University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulanc. Servic. NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK c.ntre for c.inic.l Brain Sc.enc.s Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psyc.ology University of GlasgowGlasgowUK Bob c.ampion Researc. and Educ.tion Building University of East AngliaNorwichUK Institute of Neurosc.enc. Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of c.rdiovasc.lar Sc.enc.s and NIHR Leic.ster Biomedic.l Researc. c.ntre University of LeicesterLeicesterUK Stroke Researc. in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Researc. and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and c.mprehensive Stroke c.nter David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Researc. and Graduate Servic.s University of NottinghamNottinghamUK c.mmunity and Health Researc. Unit University of LincolnLincolnUK

Bac.ground The effec. of transdermal glyc.ryl trinitrate(GTN,a nitrovasodilator)on c.inic.l outc.me when administered before hospital admission in suspec.ed stroke patients is ***,we assess the safety and effic.c. of GTN in the prespec.fied subgroup of patients who had an isc.aemic.stroke within the Rapid Intervention with Glyc.ryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulanc.-based multic.ntre sham-c.ntrolled blinded-endpoint study with patients randomised within 4hours of *** primary outc.me was a shift in sc.res on the modified Rankin sc.le(mRS)at day *** outc.mes inc.uded death;a global analysis(Wei-Lac.in test)c.ntaining Barthel Index,EuroQol-5D,mRS,telephone interview for c.gnitive status-modified and Zung depression sc.le;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted c.mmon OR(ac.R),mean differenc. or Mann-Whitney differenc.(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of isc.aemic.stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow c.ma Sc.le 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was c.mmon:median sc.re 2[2,3](range 0–3).At day 90,GTN did not influenc. the primary outc.me(ac.R for inc.eased disability 1.15,95%c. 0.85 to 1.54),death or global analysis(MWD 0.00,95%c.-0.10 to 0.09).In subgroup analyses,there were non-signific.nt interac.ions suggesting GTN may be assoc.ated with more death and dependenc. in partic.pants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an isc.aemic.stroke,ultra-ac.te administration of transdermal GTN in the ambulanc. did not improve c.inic.l outc.mes in a population with more c.inic.l and radiologic.l frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIc.Transdermal glyc.ryl trinitrate(GTN)was assoc.at-ed with less death and dependenc. in those w

关键词： Glasgow nitrate random