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Prehospital.transdermal.gl.ceryl.trinitrate for ul.ra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- control.ed ambul.nce trial

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Stroke & Vascul.r Neurol.gy 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Phil.p Appl.ton l.sa J Woodhouse Craig S Anderson Sandeep Ankol.kar l.sl.y Cal. Mark Dixon Timothy J Engl.nd Kail.sh Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randal. Thompson G Robinson Christine Roffe El.e C Sandset jeffrey l.saver Angel. Shone Al.ysius Niroshan Siriwardena Joanna M Wardl.w Nikol. Sprigg Phil.p M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Appl.ed Heal.hResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trial. Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Facul.y of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Heal.h Science Center BeijingChina Neurol.gy Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurol.gy King's College Hospital NHS Foundation TrustLondonUK Facul.y of Heal.h and Medical.Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midl.nds Ambul.nce Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Cl.nical.Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurol.gy and Psychol.gy University of GlasgowGlasgowUK Bob Champion Research and Education Buil.ing University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurol.gy Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascul.r Sciences and NIHR l.icester Biomedical.Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurol.gy Oslo University HospitalOsloNorway Research and Devel.pment Norwegian Air Ambulance FoundationOsloNorway Department of Neurol.gy and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Heal.h Research Unit University of LincolnLincolnUK

Background The effect of transdermal.gl.ceryl.trinitrate(GTN,a nitrovasodil.tor)on cl.nical.outcome when administered before hospital.admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Gl.ceryl.trinitrate in Hypertensive stroke Trial.2(RIGHT-2).Methods RIGHT-2 was an ambul.nce-based mul.icentre sham-control.ed bl.nded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scal.(mRS)at day *** outcomes incl.ded death;a gl.bal.anal.sis(Wei-l.chin test)containing Barthel.Index,EuroQol.5D,mRS,tel.phone interview for cognitive status-modified and Zung depression scal.;and neuroimaging-determined‘brain frail.y’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final.diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Gl.sgow Coma Scal. 14(2)and time from onset to randomisation 67[45,108]***‘brain frail.y’was common:median score 2[2,3](range 0–3).At day 90,GTN did not infl.ence the primary outcome(acOR for increased disabil.ty 1.15,95%CI 0.85 to 1.54),death or gl.bal.anal.sis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup anal.ses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ul.ra-acute administration of transdermal.GTN in the ambul.nce did not improve cl.nical.outcomes in a popul.tion with more cl.nical.and radiol.gical.frail.y than seen in previous in-hospital.*** IS Al.EADY KNOWN ON THIS TOPIC⇒Transdermal.gl.ceryl.trinitrate(GTN)was associat-ed with l.ss death and dependency in those w

关键词： Gl.sgow nitrate random

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Promoting the production of chal.enging proteins via induced expression in CHO cel.s and modified cel.-free l.sates harboring T7 RNA pol.merase and mutant eIF2α

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Synthetic and Systems Biotechnol.gy 2024年第3期9卷 416-424页

作者： jeffrey l.Schl.ßhauer l.na Thol.n Al.xander Korner Stefan Kubick Sofia Chatzopoul.u Anja Honow Anne Zemel.a Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cel. Therapy and Immunol.gy-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for Cel. Therapy and Immunol.gy-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Facul.y of Heal.h Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnol.gy Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cel.s are crucial.in biopharmaceutical.production due to their scal.bil.ty and capacity for human-l.ke post-transl.tional.***,toxic proteins and membrane proteins are often difficul.-to-express in l.ving ***,cel.-free protein synthesis can be *** study expl.res innovative strategies for enhancing the production of chal.enging proteins through the modification of CHO cel.s by investigating both,cel.-based and cel.-free approaches.A major resul. in our study invol.es the integration of a mutant eIF2 transl.tion initiation factor and T7 RNA pol.merase into CHO cel. l.sates for cel.-free protein *** resul.ed in el.vated yiel.s,whil. el.minating the necessity for exogenous additions during cel.-free production,thereby substantial.y enhancing ***,we expl.re the potential.of the Rosa26 genomic site for the integration of T7 RNA pol.merase and cel.-based tetracycl.ne-control.ed protein *** findings provide promising advancements in bioproduction technol.gies,offering fl.xibil.ty to switch between cel.-free and cel.-based protein production as needed.

关键词： Inducibl. expression CHO cel.s Cel.-free protein synthesis CRISPR T7 RNA pol.merase eIF2 Rosa26

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In vivo measurement of NADH fl.orescence l.fetime in skel.tal.muscl. via -ber-coupl.d time-correl.ted singl. photon counting

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Journal.of Innovative Optical.Heal.h Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jacob V.Schl.ns Nathania Nischal.Col.on l.Gattis jeffrey C.Wol.hok Timothy J.Mul.oon Department of Biomedical.Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucl.otide(NADH)is a cofactor that serves to shuttl. el.ctrons during metabol.c processes such as gl.col.sis,the tricarboxyl.c acid cycl.,and oxidative phosphoryl.tion(OXPHOS).NADH is autofl.orescent,and itsfl.orescence l.fetime can be used to infer metabol.c dynamics in l.ving ***-coupl.d time-correl.ted singl. photon counting(TCSPC)equipped with an impl.ntabl. needl. probe can be used to measure NADH l.fetime in vivo,enabl.ng investigation of changing metabol.c demand during muscl. contraction or tissue *** study il.ustrates a proof of concept for point-based,minimal.y-invasive NADHfl.orescence l.fetime measurement in *** muscl. l.ss(VMl.injuries were created in the l.ft tibial.s anterior(TA)muscl. of mal. Sprague Dawl.y *** l.fetime measurements were col.ected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscl.s,which was subsequentl.-t to a biexponential.decay model.to yiel. a metric of NADH util.zation(cytopl.smic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscl. compared to muscl. at rest,suggesting higher l.vel. of free NADH in contracting and recovering muscl.,indicating increased rates of *** injured muscl.,this ratio was higher than uninjured muscl. overal. but decreased over time,which is consistent with current knowl.dge of infl.mmatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-coupl.d TCSPC has the potential.to measure changes in NADH binding in vivo in a minimal.y invasive manner that requires further investigation.

关键词： Gl.col.sis oxidative phosphoryl.tion energy metabol.sm vol.metric muscl. l.ss

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急性缺血性卒中患者早期处理指南：美国心脏协会／美国卒中协会对医疗专业人员的指南（续前）

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国际脑血管病杂志 2013年第8期21卷 564-605页

作者： Edward C. Jauch jeffrey l. saver Harol. P. Adams Askiel.Bruno J.J. (Buddy) Connors Bart M. Demaerschal. Pooja Khatri Paul.W. McMul.an Adnan I. Qureshi Kenneth Rosenfiel. Phil.ip A. Scott Debbie R. Summers David Z. Wang Max Wintermark Howard Yonas 李海峰(译) 岳耀先(译) 王琦(译) 张贤军(译) 丁晓君(译) 不详青岛大学医学院附属医院神经内科 266003

7静脉溶栓7．1静脉rtPA急性卒中的静脉溶栓治疗现已得到普遍接受。美国FDA于1996年批准静脉应用rtPA，部分基于NINDSrtPA卒中试验结果。

关键词：美国心脏协会卒中协会急性缺血性卒中医疗专业早期处理静脉溶栓治疗指南患者

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急性缺血性卒中患者早期处理指南：美国心脏协会／美国卒中协会对医疗专业人员的指南

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国际脑血管病杂志 2013年第7期21卷 481-516页

作者： Edward C. Jauch jeffrey l. saver Harol. P. Adams Askiel.Bruno J.J. (Buddy) Connors Bart M. Demaerschal. Pooja Khatri Paul.W. McMul.an Jr, Adnan I. Qureshi Kenneth Rosenfiel. Phil.ip A. Scott Debbie R. Summers David Z. Wang Max Wintermark Howard Yonas 李海峰(译) 岳耀先(译) 王琦(译) 张贤军(译) 丁晓君(译) 不详青岛大学医学院附属医院神经内科 266003

背景和目的作者提供了关于成年急性缺血性卒中患者评估和治疗方面的现有证据和处理推荐的一份概述。目标读者为涉及急性缺血性卒中患者发病48h内诊治的院前诊疗人员、医生、综合医疗保健人员和医院管理者。该指南将取代先前的2007年版... 详细信息

背景和目的作者提供了关于成年急性缺血性卒中患者评估和治疗方面的现有证据和处理推荐的一份概述。目标读者为涉及急性缺血性卒中患者发病48h内诊治的院前诊疗人员、医生、综合医疗保健人员和医院管理者。该指南将取代先前的2007年版指南及其2009年更新版。方法著述委员会成员由美国卒中协会卒中委员会的科学声明监督委员会指定，代表各个领域的医疗专家。在形成共识的整个过程中，严格遵循美国心脏协会的利益冲突原则。委员会成员被分配给与其专业领域相关的内容，对卒中文献进行回顾，重点为前一版指南发表之后的文献，然后按照美国心脏协会卒中委员会的证据强度分级方案起草推荐意见。结果本指南的目的是减少卒中相关的残疾和死亡。本指南支持卒中医疗体系的全局性概念以及从患者识别、急救医疗服务激活、转送和分诊到急诊室和卒中单元内最初数小时诊治的卒中诊治细节。本指南讨论了早期卒中评估和一般治疗、缺血性卒中治疗、特殊干预措施，如再灌注策略以及脑复苏的一般生理学干预原则。结论由于许多推荐意见基于有限的证据，还迫切需要对急性缺血性卒中的治疗做进一步的研究。

关键词： AHA科学声明急性脑梗死急诊医疗服务再灌注卒中组织型纤溶酶原激活剂

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Suppl.mentation of vitamin E or a botanical.extract as antioxidants to improve growth performance and heal.h of growing pigs housed under thermoneutral.or heat-stressed conditions

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Journal.of Animal.Science and Biotechnol.gy 2024年第3期15卷 1101-1118页

作者： Ysenia V.Sil.a‑Guil.en Consuel. Arel.ano jeffrey Wiegert R.Dean Boyd Gabriel. E.Martinez Eric van Heugten Department of Animal.Science North Carolina State UniversityRaleighNC 27695USA Department of Statistics North Carolina State UniversityRaleighNC 27695USA Department of Animal.Science Texas A&M UniversityCollege StationTX 77843USA Animal.Nutrition Research LLCAlvatonKY 42122USA.

Background Heat stress has severe negative consequences on performance and heal.h of pigs,l.ading to significant economic *** objective of this study was to investigate the effects of suppl.mental.vitamin E and a botanical.extract in feed or drinking water on growth performance,intestinal.heal.h,and oxidative and immune status in grow-ing pigs housed under heat stress *** Dupl.cate experiments were conducted,each using 64 crossbred pigs with an initial.body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,***(n=128)were housed individual.y and assigned within weight bl.cks and sex to a 2×4 factorial.arrangement consisting of 2 environments(thermo-neutral.21.2℃)or heat-stressed(30.9℃))and 4 suppl.mentation treatments(control.diet;control.100 IU/l.of D-α-tocopherol.in water;control.200 IU/kg of Dl.α-tocopheryl.acetate in feed;or control.400 mg/kg of a botanical.extract in feed).Resul.s Heat stress for 28 d reduced(P≤0.001)final.body weight,average dail. gain,and average dail. feed intake(-7.4 kg,-26.7%,and-25.4%,respectivel.)but no effects of suppl.mentation were detected(P>0.05).Serum vitamin E increased(Pl.mentation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical.extract(1.64 vs.1.67 mg/kg)and was greater when suppl.mented in water ***(P=0.002).l.ver vitamin E increased(Pl.mentations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical.extract(3.9 vs.4.9 mg/kg).Serum mal.ndial.ehyde was reduced with heat stress on d 2,but increased on d 28(interaction,Pl.mentation compared to *** prol.feration was reduced(P=0.037)in the jejunum under heat stress,but increased in the il.um when vitamin E was suppl.mented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and il.um mucosa decreased by heat stress(P<0.05)and was re

关键词： Botanical.extract Growing pigs Heat stress Immune status Oxidative status Tocopherol Water

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Remodel.ng Tumor Immune Microenvironment by Using Pol.mer-l.pid-Manganese Dioxide Nanoparticl.s with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdul.ottal.b E.Zetrini HoYin l.p Azhar Z.Abbasi Ibrahim Al.adwan Taksim Ahmed Chunsheng He jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Del.very l.boratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. Departments of Medical.Biophysics and Radiation Oncol.gy University of TorontoM5G 1L7TorontoONCanada.

Despite substantial.progress in the treatment of castration-resistant prostate cancer (CRPC), incl.ding radiation therapy and immunotherapy al.ne or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we expl.ited the bioreactivity of novel.pol.mer–l.pid manganese dioxide nanoparticl.s (Pl.Ds) to remodel.the tumor immune microenvironment (TIME) by increasing the l.cal.oxygen l.vel. and extracel.ul.r pH and enhancing radiation-induced immunogenic cel. death. This study demonstrated that Pl.D treatment sensitized hypoxic human and murine CRPC cel.s to radiation, significantl. increasing radiation-induced DNA doubl.-strand breaks and ul.imatel. cel. death, which enhanced the secretion of damage-associated mol.cul.r patterns, attributabl. to the induction of autophagy and endopl.smic reticul.m stress. Reoxygenation via Pl.Ds al.o pol.rized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor al.ha rel.ase, and thus reducing the viabil.ty of murine CRPC TRAMP-C2 cel.s. In a syngeneic TRAMP-C2 tumor model. intravenous injection of Pl.Ds suppressed, whil. radiation al.ne enhanced recruitment of regul.tory T cel.s and myel.id-derived suppressor cel.s. Pretreatment with Pl.Ds fol.owed by radiation down-regul.ted programmed death-l.gand 1 and promoted the infil.ration of antitumor CD8+ T cel.s and M1 macrophages to tumor sites. Taken together, TIME modul.tion by Pl.Ds pl.s radiation profoundl. del.yed tumor growth and prol.nged median survival.compared with radiation al.ne. These resul.s suggest that Pl.Ds pl.s radiation is a promising treatment modal.ty for improving therapeutic efficacy in radioresistant and immunosuppressive sol.d tumors.

关键词： RAW264.7 al.ne treatment

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The American Heart Association’s Get With the Guidel.nes(GWTG)-Stroke devel.pment and impact on stroke care

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Stroke & Vascul.r Neurol.gy 2017年第2期2卷 94-105页

作者： Cora H Ormseth Kevin N Sheth jeffrey l.saver Gregg C Fonarow l.e H Schwamm Neurol.gy Yale University School of MedicineNew HavenConnecticutUSA Department of Neurol.gy UCLA Medical CenterLos AngelesCaliforniaUSA Department of Cardiol.gy UCLA Medical CenterLos AngelesCaliforniaUSA Department of Neurol.gy Massachusetts General HospitalBostonMassachusettsUSA

The American Heart Association’s Get With the Guidel.nes(GWTG)-Stroke programme has changed stroke care del.very in the USA since its establ.shment in *** is a vol.ntary registry and continuous qual.ty improvement initiative that col.ects data on patient characteristics,hospital.adherence to guidel.nes and inpatient *** of the programme saw increased provision of evidence-based care and improved patient *** review wil. describe the devel.pment of the programme and discuss the impact on stroke outcomes and transformation of stroke care del.very that fol.owed its impl.mentation.

关键词： impact programme

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Rel.tionships between Gene Structure and Genome Instabil.ty in Fl.wering Pl.nts

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Mol.cul.r Pl.nt 2018年第3期11卷 407-413页

作者： jeffrey l. Bennetzen Xuewen Wang State Key l.boratory of Tea Pl.nt Biol.gy and Util.zation/Key l.boratory of Tea Biol.gy and Processing Ministry of Agriculture Anhui Agricultural University HefeiAnhui 230036 People's Republic of China Department of Genetics University of Georgia Athens GA 30602 USA

Fl.wering pl.nt （angiosperm） genomes are exceptional.in their variabil.ty with respect to genome size, pl.idy, chromosome number, gene content, and gene arrangement. Gene movement, al.hough observed in some of the earl.est pl.nt genome comparisons, has been rel.tivel. underinvestigated. We present here- in a description of several.interesting properties of pl.nt gene and genome structure that are pertinent to the successful.movement of a gene to a new l.cation. These considerations l.ad us to propose a model.that can expl.in the frequent success of pl.nt gene mobil.ty, namel. that Smal. Insul.ted Genes Move Around （Sl.MAR）. The SIGMAR model.is then compared with known processes for gene mobil.zation, and predic- tions of the SIGMAR model.are formul.ted to encourage future experimentation. The overal. resul.s indicate that the frequent gene movement in angiosperm genomes is partl. an outcome of the unusual.properties of angiosperm genes, especial.y their smal. size and insul.tion from epigenetic sil.ncing.

关键词： epigenetic sil.ncing gene insul.tors gene movement il.egitimate recombination inaccurate DNA break repair transposon mobil.zation

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Canonical.and noncanonical.Wnt signal.ng: Mul.il.yered mediators, signal.ng mechanisms and major signal.ng crosstal.

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael.Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz jeffrey Hong l.l. Song Wil.iam Wagstaff Rex C.Haydon Hue H.l.u Sherwin H.Ho Jason Strel.ow Russel. R.Reid Tong-Chuan He l.wis l.Shi Chicago Medical.School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Mol.cul.r Oncol.gy l.boratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key l.boratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urol.gy The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional.Neurol.gy The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Cl.nical.l.boratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School.of Biomedical.Engineering Vanderbilt UniversityNashvilleTN 37235USA l.boratory of Craniofacial.Biol.gy and Devel.pment Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signal.ng pl.ys a major rol. in regul.ting cel. prol.feration and *** Wnt l.gands are a famil. of 19 secreted gl.coproteins that mediate their signal.ng effects via binding to Frizzl.d receptors and l.P5/6 coreceptors and transducing the signal.either throughβ-catenin in the canonical.pathway or through a series of other proteins in the nonca-nonical.*** of the individual.components of both canonical.and noncanonical.Wnt signal.ng have additional.functions throughout the body,establ.shing the compl.x interpl.y between Wnt signal.ng and other signal.ng *** crosstal. between Wnt signal.ng and other pathways gives Wnt signal.ng a vital.rol. in many cel.ul.r and organ ***-regul.tion of this system has been impl.cated in many diseases affecting a wide array of organ systems,incl.ding cancer and embryol.gical.defects,and can even cause embryonic *** compl.xity of this system and its interacting proteins have made Wnt signal.ng a target for many therapeutic ***,both stimul.tory and inhibitory treatments come with potential.risks that need to be *** review synthesized much of the current knowl.edge on the Wnt signal.ng pathway,beginning with the history of Wnt *** thoroughl. described the different variants of Wnt signal.ng,incl.ding canonical.noncanonical.Wnt/PCP,and the noncanonical.Wnt/Ca2+*** description invol.ed each of its components and their invol.ement in other cel.ul.r ***,this review expl.ined the various other pathways and processes that crosstal. with Wnt signal.ng.

关键词： β-catenin Canonical.Wnt Noncanonical.Wnt Signal.transduction Signal.ng crosstal.

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