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Popula.ion differentia.ion a. a.regiona. sca.e in spa.efoot toa.s： contributions of dista.ce a.d divergent selective environments

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Current Zoology 2016年第2期62卷 193-206页

作者： a.ber M. RICE michael a. mcquillan Heidi a. SEEa.S Joa.na.a. Wa.REN Depa.tment of Biologica. Sciences Lehigh University BethLehem PA 18015 USA

The ca.ses of popula.ion differentia.ion ca. provide insight into the origins of ea.ly ba.riers to gene flow. Two key drivers of popula.ion differentia.ion a.e geogra.hic dista.ce a.d loca. a.a.ta.ion to divergent selective environments. When reproductive isola.ion a.ises beca.se some popula.ions of a.species a.e under selection to a.oid hybridiza.ion while others a.e not, popula.ion differentia.ion a.d even specia.ion ca. result. Spa.efoot toa. popula.ions Spea.multiplica.a.tha. a.e sympa.ric with a.congener ha.e undergone reinforcement. This reinforcement ha. resulted not only in increa.ed reproductive isola.ion from the congener, but a.so in the evolution of reproductive isola.ion from nea.by a.d dista.t conspecific a.lopa.ric popula.ions. We used multiple a.proa.hes to eva.ua.e the contributions of geogra.hic dista.ce a.d divergent selective environments to popula.ion structure a.ross this regiona. sca.e in S. multiplica.a. ba.ed on genotypes from six nuclea. microsa.ellite ma.kers. We compa.ed groups of popula.ions va.ying in both geogra.hic loca.ion a.d in the presence of a.congener. Hiera.chica. F-sta.istics a.d results from cluster a.a.yses a.d discrimina.t a.a.yses of principa. components a.l indica.e tha. geogra.hic dista.ce is the stronger contributor to genetic differentia.ion a.ong S. multiplica.a.popula.ions a. a.regiona. sca.e. However, we found evidence tha. a.a.ta.ion to divergent selective environments a.so contributes to popula.ion structure. Our findings highlight how va.ia.ion in the ba.a.ce of evolutiona.y forces a.ting a.ross a.species＇ ra.ge ca. lea. to va.ia.ion in the rela.ive contributions of geogra.hic dista.ce a.d loca. a.a.ta.ion to popula.ion differentia.ion a.ross different spa.ia. sca.es.

关键词： ca.ca.e reinforcement cha.a.ter displa.ement reproductive isola.ion spa.ia. sca.e Spea.multipfica.a specia.ion

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Like a.G6-na.:tra.scriptiona. control of G-protein coupled receptors during oligodendroglia. development

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Neura. Regenera.ion Resea.ch 2025年第7期20卷 2001-2002页

作者： Tim a.erle michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multila.ered control of myelina.ion:Quick,sa.ta.ory conduction of a.tion potentia.s a.ong nerve fibers requires the electrica. insula.ion of a.ons by myelina.ing *** the centra. nervous system,this role is ta.en up by *** a.e ma.ked by the expression of the linea.e determina.ts Sox10 a.d Olig2 a.d a.ise from oligodendrocyte precursor cells(OPCs)during embryona. *** the ma.ority of OPCs differentia.e into ma.ure oligodendrocytes when nea.by a.ona. segments require myelina.ion,a.sma.l subpopula.ion of OPCs persist a. a.progenitor ***,the timing of myelina.ion a.d ma.ntena.ce of the OPC pool both need to be precisely *** tra.scription fa.tors either positively or nega.ively a.fect oligodendrocyte differentia.ion a.d ma.ntena.ce of the OPC pool a. components of a.complex gene regula.ory network(reviewed in Sock a.d Wegner,2021).Network a.tivity is a.ditiona.ly influenced by extra.ellula. signa.ing molecules tha. bind to receptors on the oligodendroglia. cell surfa.e a.d a.tiva.e intra.ellula. signa.ing *** the receptors a.e linked to the network is poorly understood so fa.,but pivota. to understa.ding the overa.l regula.ion of centra. nervous system(CNS)myelina.ion in response to environmenta. *** insights were recently ga.ned for Gpr37(Schmidt et a..,2024),a.G-protein coupled receptor(GPCR)with known releva.ce in differentia.ing oligodendrocytes(Ya.g et a.,2016).

关键词： ga.ned insula.ion conduction

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Emerging structures a.d dyna.ic mecha.isms ofγ-secreta.e for a.zheimer’s disea.e

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Neura. Regenera.ion Resea.ch 2025年第1期20卷 174-180页

作者： Yinglong Mia. michael S.Wolfe Computa.iona. Medicine Progra. a.d Depa.tment of Pha.ma.ology University of North Carolina–Chapel HillChapel HillNCUSA Depa.tment of Medicina. Chemistry University of KansasLawrenceKSUSA

γ-Secreta.e,ca.led“the protea.ome of the membra.e,”is a.membra.e-embedded protea.e complex tha. clea.es 150+peptide substra.es with centra. roles in biology a.d medicine,including a.yloid precursor protein a.d the Notch fa.ily of cell-surfa.e *** inγ-secreta.e a.d a.yloid precursor protein lea. to ea.ly-onset fa.ilia. a.zheimer’s disea.e.γ-Secreta.e ha. thus served a. a.critica. drug ta.get for trea.ing fa.ilia. a.zheimer’s disea.e a.d the more common la.e-onset a.zheimer’s disea.e a. ***,critica. ga.s rema.n in understa.ding the mecha.isms of processive proteolysis of substra.es,the effects of fa.ilia. a.zheimer’s disea.e muta.ions,a.d a.losteric modula.ion of substra.e clea.a.e byγ-*** this review,we focus on recent studies of structura. dyna.ic mecha.isms ofγ-*** mecha.isms,including the“Fit-Sta.-Trim,”“Sliding-Unwinding,”a.d“Tilting-Unwinding,”ha.e been proposed for substra.e proteolysis of a.yloid precursor protein byγ-secreta.e ba.ed on a.l-a.om molecula. dyna.ics *** a. incorrect registry of the Notch1 substra.e wa. identified in the cryo-electron microscopy structure of Notch1-boundγ-secreta.e,molecula. dyna.ics simula.ions on a.resolved model of Notch1-boundγ-secreta.e tha. wa. reconstructed using the a.yloid precursor protein-boundγ-secreta.e a. a.templa.e successfully ca.turedγ-secreta.e a.tiva.ion for proper clea.a.es of both wildtype a.d muta.t Notch,being consistent with biochemica. experimenta. *** a.proa.h could be potentia.ly a.plied to decipher the processing mecha.isms of va.ious substra.es byγ-*** a.dition,controversy over the effects of fa.ilia. a.zheimer’s disea.e muta.ions,pa.ticula.ly the issue of whether they sta.ilize or desta.ilizeγ-secreta.e-substra.e complexes,is ***,a. outlook is provided for future studies ofγ-secreta.e,including pa.hwa.s of substra.e binding a.d product relea.e,effects of modula.ors on fa.ilia. a.zheimer’s disea.e muta.ions

关键词： a.zheimer’s disea.e a.yloid precursor protein cryo-EM structures drug design intra.embra.e proteolysis molecula. dyna.ics Notch

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NECa. fa.ily of neurona. ca.cium-binding proteins in hea.th a.d disea.e

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Neura. Regenera.ion Resea.ch 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Scha.er Sudena.Wa.g michael J.Schmeisser a.el Methner Institute for Molecula. Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Depa.tment of a.esthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of a.a.omy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-termina. EF-ha.d ca.cium-binding proteins 1–3(NECa.1–3) constitute a.fa.ily of predomina.tly neurona. proteins cha.a.terized by the presence of a. lea.t one EF-ha.d ca.cium-binding doma.n a.d a.functiona.ly less well cha.a.terized C-termina. a.tibiotic biosynthesis monooxygena.e doma.n. a.l three fa.ily members were initia.ly discovered due to their intera.tions with other proteins. NECa.1 a.socia.es with syna.tota.min-1, a.critica. neurona. protein involved in membra.e tra.ficking a.d syna.tic vesicle exocytosis. NECa.2 intera.ts with predomina.tly stria.a. G-protein-coupled receptors, while NECa.3 pa.tners with a.yloid-β a. precursor protein-binding fa.ily a.members 2 a.d 3, key regula.ors of a.yloid-β production. This demonstra.es the ca.a.ity of the fa.ily for intera.tions with va.ious cla.ses of proteins. NECa. proteins exhibit distinct subcellula. loca.iza.ions: NECa.1 is found in the nucleus a.d cytosol, NECa.2 resides in endosomes a.d the pla.ma.membra.e, a.d NECa.3 is present in the endopla.mic reticulum a.d Golgi a.pa.a.us. The a.tibiotic biosynthesis monooxygena.e doma.n, a. evolutiona.ily a.cient component, is a.in to a.ypica. heme oxygena.es in proka.yotes but is not wellcha.a.terized in vertebra.es. Proka.yotic a.tibiotic biosynthesis monooxygena.e doma.ns typica.ly form dimers, suggesting tha. ca.cium-media.ed conforma.iona. cha.ges in NECa. proteins ma. induce a.tibiotic biosynthesis monooxygena.e doma.n dimeriza.ion, potentia.ly a.tiva.ing some enzyma.ic properties. However, the substra.e for this enzyma.ic a.tivity rema.ns uncerta.n. a.terna.ively, ca.cium-media.ed conforma.iona. cha.ges might influence protein intera.tions or the subcellula. loca.iza.ion of NECa. proteins by controlling the a.a.la.ility of protein–protein intera.tion doma.ns situa.ed between the EF ha.ds a.d the a.tibiotic biosynthesis monooxygena.e doma.n. This review summa.izes wha. is known a.out genomic orga.iza.ion, tissue expression, intra.ellula. loca.iza.ion, intera.

关键词： ca.cium EF ha.d mitochondria nervous system signa. tra.sduction

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Methods a.plied in a.stra.ia. industry to eva.ua.e coa. mine slope sta.ility

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Interna.iona. Journa. of Mining Science a.d Technology 2020年第2期30卷 151-155页

作者： a.ison mcquillan Ismet Ca.bula. Joung Oh School of Minera.s a.d Energy Resources Engineering UNSW SydneyAustralia

Stra.a.fa.lure is a.principa. ha.a.d in open cut coa. mining a. it ha. the potentia. to ca.se multiple *** to the exca.a.ion of a.y slope,a.geotechnica. a.sessment should review the likely slope performa.ce,including the risk of slope *** to ma.a.e this risk to a. a.cepta.le level should a.compa.y the geotechnica. a.a.ysis.a.survey of 43 pra.tising geotechnica. engineers indica.ed tha. kinema.ic a.d 2D limit equilibrium a.a.yses were the methods most commonly a.plied to a.a.yse exca.a.ed slope *** these methods a.e well esta.lished a.d widely a.plied in the broa. rock engineering disciplines(***,ha.d rock),a.recent review of over 60 slope fa.lures suggests these methods ha.e limited suita.ility for modelling the complex fa.lure mecha.isms observed in exca.a.ed coa. mine *** techniques do not a.equa.ely ca.ture the rock ma.s component of exca.a.ed slope fa.lure a.d do not provide a.geospa.ia. loca.ion of potentia. fa.lure,while 2D limit equilibrium techniques do not a.equa.ely ca.ture the 3D mecha.isms of exca.a.ed slope *** which do consider the 3D mecha.isms of slope fa.lure a.e summa.ized for industry considera.ion a.d a.plica.ion.

关键词： Slope sta.ility 2D 3D Open cut coa. mine Limit equilibrium

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Ra.id a.d robust slope fa.lure a.pra.sa. using a.ria. photogra.metry a.d 3D slope sta.ility models

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Interna.iona. Journa. of Mining Science a.d Technology 2020年第5期30卷 651-658页

作者： Neil Ba. michael Kosta.inovski michael Tucker Glen Byng Rully Ra.hma.ulla. a.turo Ma.dona.o Ma.kus Pötsch a.drea. Ga.ch a.ison mcquillan Tha.er Ya.oub BHP PerthWA 6000Australia 3GSM GmbH 8010 GrazStyriaAustria Rocscience Inc. Toronto M5T 1V1Canada

Slope fa.lures a.e a. inevita.le a.pect of economic pit slope designs in the mining *** open pit guidelines a.d industry sta.da.ds a.cept up to 30%of benches in open pits to colla.se provided tha. they a.e controlled a.d tha. no personnel a.e a. *** ground control mea.ures including rea. time monitoring systems a. Ta.P(trigger-a.tion-response-pla.)protocols a.e widely utilized to prevent personnel from being exposed to slope fa.lure *** a.d computing ca.a.ility a.e ra.idly *** photogra.metry techniques using Ua.(unma.ned a.ria. vehicle)ena.le geotechnica. engineers a.d engineering geologists to work fa.ter a.d more sa.ely by removing themselves from potentia. line-of-fire nea. unsta.le *** sta.ility modelling softwa.e using limit equilibrium(LE)a.d finite element(FE)methods in three dimensions(3D)is a.so becoming more a.cessible,user-friendly a.d fa.ter to *** key components ena.le geotechnica. engineers to underta.e site investiga.ions,develop geotechnica. models a.d a.sess slope sta.ility fa.ter a.d in more deta.l with less exposure to fa.l of ground ha.a.ds in the *** pa.er describes the ra.id a.d robust process utilized a. BHP Limited for a.pra.sing a.slope fa.lure a. a. iron ore mine site in the Pilba.a.region of Western a.stra.ia.using a.combina.ion of Ua. photogra.metry a.d 3D slope sta.ility models in less tha. a.shift(*** tha. 12 h).

关键词： Slope sta.ility 3D limit equilibrium a.a.ysis a.ria. ima.ery Photogra.metry Open pit mining

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Sma.l extra.ellula. vesicles derived from cerebra. endothelia. cells with eleva.ed microRNa.27a.promote ischemic stroke recovery

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Neura. Regenera.ion Resea.ch 2025年第1期20卷 224-233页

作者： Yi Zha.g Zhongwu Liu michael Chopp michael Millma. Ya.feng Li Pa.qua.e Ceppa.ulo a.y Kemper Cha. Li Li Zha.g Zheng Ga.g Zha.g Depa.tment of Neurology Henry Ford HospitalDetroitMIUSA Depa.tment of Physics Oakland UniversityRochesterMIUSA Depa.tment of Pa.hology Henry Ford HospitalDetroitMIUSA Division of Pha.ma.ology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

a.ona. remodeling is a.critica. a.pect of ischemic bra.n repa.r processes a.d contributes to sponta.eous functiona. *** previous in vitro study demonstra.ed tha. exosomes/sma.l extra.ellula. vesicles(sEVs)isola.ed from cerebra. endothelia. cells(CEC-sEVs)of ischemic bra.n promote a.ona. growth of embryonic cortica. neurons a.d tha. microRNa.27a.miR-27a.is a. eleva.ed miRNa.in ischemic *** the present study,we investiga.ed whether norma. CEC-sEVs engineered to enrich their levels of miR-27a.27a.sEVs)further enha.ce a.ona. growth a.d improve neurologica. outcomes a.ter ischemic stroke when compa.ed with trea.ment with non-engineered CEC-sEVs.27a.sEVs were isola.ed from the conditioned medium of hea.thy mouse CECs tra.sfected with a.lentivira. miR-27a.expression *** EVs isola.ed from CECs tra.sfected with a.scra.ble vector(Scra.sEVs)were used a. a.*** ma.e mice were subjected to perma.ent middle cerebra. a.tery occlusion a.d then were ra.domly trea.ed with 27a.sEVs or *** a.ra. of beha.ior a.sa.s wa. used to mea.ure neurologica. *** with trea.ment of ischemic stroke with Scra.sEVs,trea.ment with 27a.sEVs significa.tly a.gmented a.ons a.d spines in the peri-infa.ct zone a.d in the corticospina. tra.t of the spina. grey ma.ter of the denerva.ed side,a.d significa.tly improved neurologica. *** vitro studies demonstra.ed tha. CEC-sEVs ca.rying reduced miR-27a.a.olished 27a.sEV-a.gmented a.ona. *** a.a.ysis revea.ed tha. 27a.sEVs systemica.ly a.ministered preferentia.ly loca.ized to the pre-syna.tic a.tive zone,while qua.tita.ive reverse tra.scription-polymera.e cha.n rea.tion a.d Western Blot a.a.ysis showed eleva.ed miR-27a.a.d reduced a.ona. inhibitory proteins Sema.horin 6a.a.d Ra. Homolog Fa.ily Member a.in the peri-infa.ct *** of the Cla.hrin-dependent endocytosis pa.hwa. substa.tia.ly reduced neurona. interna.iza.ion of *** da.a.provide evidence tha. 27a.sEVs ha.e

关键词： a.ona. remodeling cerebra. endothelia. cells exosomes miR-27a mitochondria Sema.horin 6A sma.l extra.ellula. vesicles stroke

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a.ute a.d chronic excitotoxicity in ischemic stroke a.d la.e-onset a.zheimer's disea.e

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Neura. Regenera.ion Resea.ch 2025年第7期20卷 1981-1988页

作者： Sha. Ping Yu Emily Choi michael QJia.g Ling Wei Depa.tment of a.esthesiology Emory University School of MedicineAtlantaGAUSA Center for Visua. a.d Neurocognitive Reha.ilita.ion Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke a.d a.zheimer's disea.e a.e common neurologica. disorders a.d often occur in the sa.e *** comorbidity of the two neurologica. disorders represents a.gra.e hea.th threa. to older *** review presents a.brief ba.kground of the development of novel concepts a.d their clinica. *** a.tivity of gluta.a.ergic N-methyl-D-a.pa.ta.e receptors a.d N-methyl-D-a.pa.ta.e receptor-media.ed Ca.(2+)influx is critica. for neurona. *** ischemic insult induces prompt a.d excessive gluta.a.e relea.e a.d dra.tic increa.es of intra.ellula. Ca.(2+)ma.nly via.N-methyl-D-a.pa.ta.e receptors,pa.ticula.ly of those a. the extra.yna.tic *** Ca.(2+)-evoked neurona. cell dea.h in the ischemic core is domina.ed by necrosis within a.few hours a.d da.s known a. a.ute ***,mild but susta.ned Ca.(2+)increa.es under neurodegenera.ive conditions such a. in the dista.t penumbra.of the ischemic bra.n a.d ea.ly sta.es of a.zheimer's disea.e a.e not immedia.ely toxic,but gra.ua.ly set off deteriora.ing Ca.(2+)-dependent signa.s a.d neurona. cell loss mostly beca.se of a.tiva.ion of progra.med cell dea.h *** on the Ca.(2+)hypothesis of a.zheimer's disea.e a.d recent a.va.ces,this Ca.(2+)-a.tiva.ed“silent”degenera.ive excitotoxicity evolves from yea.s to deca.es a.d is recognized a. a.unique slow a.d chronic *** N-methyl-D-a.pa.ta.e receptor subunit GluN3a.prima.ily a. the extra.yna.tic site,serves a. a.ga.ekeeper for the N-methyl-D-a.pa.ta.e receptor a.tivity a.d is neuroprotective a.a.nst both a.ute a.d chronic *** stroke a.d a.zheimer's disea.e,therefore,sha.e a. N-methyl-D-a.pa.ta.e receptor-a.d Ca.(2+)-media.ed mecha.ism,a.though with much different time *** is thus proposed tha. ea.ly interventions to control Ca.(2+)homeosta.is a. the preclinica. sta.e a.e pivota. for individua.s who a.e susceptible to spora.ic la.e-onset a.zheimer's disea.e a.d a.zheimer's disea.e-rela.ed

关键词： Ca.(2+)hypothesis cognitive deficits hypera.tivity la.e-onset a.zheimer's disea.e neurodegenera.ion N-methyl-D-a.pa.ta.e receptors N-methyl-D-a.pa.ta.e receptor subunits pa.hogenesis preventive trea.ment

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New risk a.sessment methodology for coa. mine exca.a.ed slopes

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Interna.iona. Journa. of Mining Science a.d Technology 2018年第4期28卷 581-590页

作者： a.ison mcquillan Ismet Ca.bula. Da. Pa.ne Joung Oh School of Minera.s a.d Energy Resources Engineering UNSW SydneySydney 2052Australia BHP Billiton Coa. Level 11480 Queen StBrisbaneQueensland 4000Australia

This pa.er presents a.new risk a.sessment methodology for coa. mine exca.a.ed slopes. This new empirica.-sta.istica. *** a.sessment m. ethodology （SSa.! is intended for use by geotechnica. engineers a. both the design review a.d opera.iona. sta.es of a.mine＇s life to ca.egonse the risk of a. exca.a.ed coa. mine slope. a.likelihood of fa.lure is determined using a.new slope sta.ility cla.sifica.ion system for exca.a.ed coa. mine slopes developed using a.da.a.a.e of 119 inta.t a.d fa.led ca.e studies sourced from open cut coa. mines in a.stra.ia. Consequence of fa.lure is ba.ed on slope height a.d sta.d-off dista.ce a. the toe of the exca.a.ed slope. Results a.e presented in a.new risk ma.rix, with slope risk being divided into low, medium a.d high ca.egories. The SSa. is put forwa.d a. a.new risk a.sess- ment methodology to a.sess the potentia. for, a.d consequence of, exca.a.ed coa. mine slope fa.lure. Unlike existing cla.sifica.ion systems, a.sumptions a.out the likely fa.lure mode or mecha.ism a.e not required. Instea., the SSa. a.plies a. a.proa.h which compa.es the conditions present within the exca. va.ed slope fa.e, with the known pa.t performa.ce of slopes with simila. geotechnica. a.d geometrica. conditions, to estima.e the slope＇s propensity for fa.lure. The SSa. is novel in tha. it considers the depo- sitiona. history of stra.a.in a. exca.a.ed slope a.d how this sequence a.fects slope sta.ility. It is further novel in tha. it does not require explicit mea.urements of inta.t rock, rock ma.s a.d/or defect strength to ra.idly ca.cula.e a.slope＇s likelihood of fa.lure a.d overa.l risk. Ra.ings ca. be determined entirely from visua. observa.ions of the exca.a.ed slope fa.e. The new SSa. is designed to be used in conjunction with existing slope sta.ility a.sessment tools.

关键词： Risk a.sessment Slope sta.ility Open cut coa. mine Exca.a.ed slope Likelihood of fa.lure

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a.spotlight on dosa.e a.d subject selection for effective neuroprotection: exploring the centra. role of mitochondria

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Neura. Regenera.ion Resea.ch 2025年第4期20卷 1081-1082页

作者： John Mitrofa.is Jona.ha. Stone michael R.Ha.blin Pierre Ma.istretti a.im-Louis Bena.id Glen Jeffery Fonds Clina.ec UniversitéGrenoble AlpesGrenobleFrance School of Medica. Science University of SydneySydneyAustralia Fa.ulty of Hea.th Sciences University of JohannesburgJohannesburgSouth Africa King a.dulla. University of Science a.d Technology ThuwalSaudi Arabia Institute of Ophtha.mology University College LondonLondonUK

Neurons a.e notoriously vulnera.le cell *** the slightest cha.ge in their interna. a.d/or externa. environments will ca.se much distress a.d dysfunction,lea.ing often to their dea.h.a.ra.ge of pa.hologica. conditions,including stroke,hea. tra.ma.a.d neurodegenera.ive disea.e,ca. genera.e stress in neurons,a.fecting their surviva. a.d proper *** most neura. pa.hologies,mitochondria.become dysfunctiona. a.d this pla.s a.pivota. role in the process of cell *** cha.lenge over the la.t few deca.es ha. been to develop effective interventions tha. improve neurona. homeosta.is under pa.hologica. *** interventions,often referred to a. disea.e-modifying or neuroprotective,ha.e,however,proved frustra.ingly elusive,a. both preclinica. a.d,in pa.ticula.,clinica. *** this perspective,we highlight two fa.tors tha. we feel a.e key to the development of effective neuroprotective *** a.e:firstly,the choice of dose of intervention a.d method of a.plica.ion,a.d secondly,the selection of subjects,whether they be pa.ients or the a.ima. model.

关键词： protective dosa.e distress

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