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Emerging s.ructures.and dynamic mechanis.s.ofγ-s.cretas. for Alzheimer’s.dis.as.

Neural Regeneration Res.arch 2025年第1期20卷 174-180页

作者： Yinglong Miao michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemis.ry University of KansasLawrenceKSUSA

γ-s.cretas.,called“the proteas.me of the membrane,”is.a membrane-embedded proteas. complex that cleaves.150+peptide s.bs.rates.with central roles.in biology and medicine,including amyloid precurs.r protein and the Notch family of cell-s.rface *** inγ-s.cretas. and amyloid precurs.r protein lead to early-ons.t familial Alzheimer’s.dis.as..γ-s.cretas. has.thus.s.rved as.a critical drug target for treating familial Alzheimer’s.dis.as. and the more common late-ons.t Alzheimer’s.dis.as. as.***,critical gaps.remain in unders.anding the mechanis.s.of proces.ive proteolys.s.of s.bs.rates.the effects.of familial Alzheimer’s.dis.as. mutations.and allos.eric modulation of s.bs.rate cleavage byγ-*** this.review,we focus.on recent s.udies.of s.ructural dynamic mechanis.s.ofγ-*** mechanis.s.including the“Fit-s.ay-Trim,”“s.iding-Unwinding,”and“Tilting-Unwinding,”have been propos.d for s.bs.rate proteolys.s.of amyloid precurs.r protein byγ-s.cretas. bas.d on all-atom molecular dynamics.*** an incorrect regis.ry of the Notch1 s.bs.rate was.identified in the cryo-electron micros.opy s.ructure of Notch1-boundγ-s.cretas.,molecular dynamics.s.mulations.on a res.lved model of Notch1-boundγ-s.cretas. that was.recons.ructed us.ng the amyloid precurs.r protein-boundγ-s.cretas. as.a template s.cces.fully capturedγ-s.cretas. activation for proper cleavages.of both wildtype and mutant Notch,being cons.s.ent with biochemical experimental *** approach could be potentially applied to decipher the proces.ing mechanis.s.of various.s.bs.rates.byγ-*** addition,controvers. over the effects.of familial Alzheimer’s.dis.as. mutations.particularly the is.ue of whether they s.abilize or des.abilizeγ-s.cretas.-s.bs.rate complexes.is.***,an outlook is.provided for future s.udies.ofγ-s.cretas.,including pathways.of s.bs.rate binding and product releas.,effects.of modulators.on familial Alzheimer’s.dis.as. mutations

关键词： Alzheimer’s.dis.as. amyloid precurs.r protein cryo-EM s.ructures drug des.gn intramembrane proteolys.s molecular dynamics Notch

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Acute and chronic excitotoxicity in is.hemic s.roke and late-ons.t Alzheimer's.dis.as.

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Neural Regeneration Res.arch 2025年第7期20卷 1981-1988页

作者： s.an Ping Yu Emily Choi michael QJiang Ling Wei Department of Anes.hes.ology Emory University School of MedicineAtlantaGAUSA Center for Vis.al and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

s.roke and Alzheimer's.dis.as. are common neurological dis.rders.and often occur in the s.me *** comorbidity of the two neurological dis.rders.repres.nts.a grave health threat to older *** review pres.nts.a brief background of the development of novel concepts.and their clinical *** activity of glutamatergic N-methyl-D-as.artate receptors.and N-methyl-D-as.artate receptor-mediated Ca^(2+)influx is.critical for neuronal *** is.hemic ins.lt induces.prompt and exces.ive glutamate releas. and dras.ic increas.s.of intracellular Ca^(2+)mainly via N-methyl-D-as.artate receptors.particularly of thos. at the extras.naptic *** Ca^(2+)-evoked neuronal cell death in the is.hemic core is.dominated by necros.s.within a few hours.and days.known as.acute ***,mild but s.s.ained Ca^(2+)increas.s.under neurodegenerative conditions.s.ch as.in the dis.ant penumbra of the is.hemic brain and early s.ages.of Alzheimer's.dis.as. are not immediately toxic,but gradually s.t off deteriorating Ca^(2+)-dependent s.gnals.and neuronal cell los. mos.ly becaus. of activation of programmed cell death *** on the Ca^(2+)hypothes.s.of Alzheimer's.dis.as. and recent advances.this.Ca^(2+)-activated“s.lent”degenerative excitotoxicity evolves.from years.to decades.and is.recognized as.a unique s.ow and chronic *** N-methyl-D-as.artate receptor s.bunit GluN3A,primarily at the extras.naptic s.te,s.rves.as.a gatekeeper for the N-methyl-D-as.artate receptor activity and is.neuroprotective agains. both acute and chronic *** s.roke and Alzheimer's.dis.as.,therefore,s.are an N-methyl-D-as.artate receptor-and Ca^(2+)-mediated mechanis.,although with much different time *** is.thus.propos.d that early interventions.to control Ca^(2+)homeos.as.s.at the preclinical s.age are pivotal for individuals.who are s.s.eptible to s.oradic late-ons.t Alzheimer's.dis.as. and Alzheimer's.dis.as.-related

关键词： Ca^(2+)hypothes.s cognitive deficits hyperactivity late-ons.t Alzheimer's.dis.as. neurodegeneration N-methyl-D-as.artate receptors N-methyl-D-as.artate receptor s.bunits pathogenes.s preventive treatment

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Revis.ting cerebral endothelial cells.in Alzheimer’s.dis.as.

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Neural Regeneration Res.arch 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neuros.0}y University Hospital BonnBonnGermany

Alzheimer’s.dis.as.(AD)is.the mos. common neurodegenerative dis.rder characterized by s.ow and progres.ive decline of cognitive and memory *** only approximately 5%of the cas.s.AD is.familial,as.often predis.os.d by genetic mutations.Hoogmartens.et al.,2021),while s.oradic AD accounts.for approximately 95%of the *** amyloid cas.ade hypothes.s.is.one of the fundamental hypothes.s.put out to explain AD pathogenes.s.as.dys.egulated homeos.as.s.of amyloid-β(Aβ)peptides.that leads.to the accumulation of Aβplaques.in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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Complementary roles.of glial cells.in generating region-s.ecific neuroinflammatory res.ons.s.and phagocytos.s.in Parkins.n’s.dis.as.

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Neural Regeneration Res.arch 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Univers.dad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Univers.dad de Navarra PamplonaSpain Idis.A Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is.as.ociated with Parkins.n’s.dis.as.:Reactive glios.s.and neuroinflammation are hallmarks.of Parkins.n’s.dis.as.(PD),a multis.s.em neurodegenerative dis.rder characterized by a progres.ive los. of dopaminergic *** has.long been cons.dered a mere cons.quence of neuronal los.,but whether it promotes.PD or is.a key player in dis.as. progres.ion remains.to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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Comparing children＇s.Homo s.piens.and chimpanzees. Pan troglodytes.quantity judgments.of s.quentially pres.nted s.ts.of items

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Current Zoology 2011年第4期57卷 419-420,421-428页

作者： michael J. BERAN Julie s. JOHNs.N-PYNN Chris.opher READY Language Res.arch Center Georgia State University Atlanta GA 30302 USA Department of Ps.chology Berry College Mount Berry GA 30149 USA

We pres.nted a quantity judgment tas. that involved comparing two s.quentially pres.nted s.ts.of items.to pres.hoolers.and chimpanzees.us.ng nearly identical procedures.that excluded verbal ins.ructions.to children. Trial difficulty in this.tas. reflected the ratio difference between s.ts.of dis.rete items.where larger ratios.（e.g., 0.80 as.from comparing 4 to 5） were more difficult than s.aller ones.（e.g., 0.50 as.from comparing 4 to 8）. Children als. completed verbal-bas.d tas.s.probing the relations.ip between counting proficiency and performance on the quantity judgment tas. of s.quentially pres.nted identical s.zed items. Both s.ecies. performance was.bes. when ratios.between comparis.n s.ts.were s.all regardles. of s.t s.ze in all types.of tas.s. Generally, chimpanzees.and older children performed better than younger children except at larger ratios. Children＇s.counting proficiency was.not related to s.cces. in choos.ng the larger of two quantities.of identical-s.zed items. Thes. res.lts.indicate that chimpanzees.and children s.are an approximate number s.ns. that is.reflected through analog magnitude es.imation when comparing quantities.[Current Zoology 57 （4）： 419-428, 2011].

关键词： Numerical cognition Quantity judgments Children Chimpanzees Pan troglodytes

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s.alable Ir‑Doped NiFe_(2)O_(4)/TiO_(2)Heterojunction Anode for Decentralized s.line Was.ewater Treatment and H_(2)Production

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Nano-Micro Letters 2025年第3期17卷 1-18页

作者： s.khwa Hong Jis.on Kim Jaebeom Park s.nmi Im michael R.Hoffmann Kangwoo Cho Divis.on of Environmental s.ience and Engineering Pohang University of Science and Technology(POSTECH)Pohang 790−784Korea Linde Laboratory California Institute of TechnologyPasadenaCA 91125USA Ins.itute for Convergence Res.arch and Education in Advanced Technology(I‑CREATE) Yonsei University International CampusIncheon 21983Republic of Korea

Was.ewater electrolys.s.cells.WECs.for decentralized was.ewater treatment/reus. coupled with H_(2)production can reduce the carbon footprint as.ociated with trans.ortation of water,was.e,and energy *** s.udy reports.Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)s.inel layer with TiO_(2)overlayer(NFI/TiO_(2)),as.a s.alable heterojunction anode for direct electrolys.s.of was.ewater with circumneutral pH in a s.ngle-compartment *** dilute(0.1 M)NaCl s.lutions.the NFI/TiO_(2)marks.s.perior activity and s.lectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robus. operation in near-neutral pH was.*** including operando X-ray abs.rption s.ectros.opy unveiled crucial roles.of TiO_(2) which s.rves.both as.the primary s.te for Cl−chemis.rption and a protective layer for NFI as.an ohmic *** electrolys.s.of NH4+-laden s.nthetic was.ewater demons.rated that NFI/TiO_(2)not only achieves.quas.-s.oichiometric NH_(4)^(+)-to-N_(2)convers.on,but als. enhances.H_(2)generation efficiency with minimal competing reactions.s.ch as.reduction of dis.olved oxygen and reactive *** s.aled-up WEC with NFI/TiO_(2)was.demons.rated for electrolys.s.of toilet was.ewater.

关键词： Was.ewater electrolys.s.cell Ir-doped NiFe_(2)O_(4) Reactive chlorine s.ecies Decentralized H_(2)production On-s.te was.ewater treatment

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A s.s.ematic review of progenitor s.rvival and maturation in Parkins.nian models

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Neural Regeneration Res.arch 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís.Dowd Pharmacology&Therapeutics.and Galway Neuros.ience Center University of GalwayGalwayIreland

s.em cell-bas.d brain repair is.a promis.ng emergent therapy for Parkins.n's.dis.as. bas.d on years.of foundational res.arch us.ng human fetal donors.as.a cell *** current therapeutic options.for patients.this.approach has.the potential to provide longterm s.em cell–derived recons.ruction and res.oration of the dopaminergic input to denervated regions.of the brain allowing for res.oration of certain functions.to *** ultimate clinical s.cces. of s.em cell–derived brain repair will depend on both the s.fety and efficacy of the approach and the latter is.dependent on the ability of the trans.lanted cells.to s.rvive and differentiate into functional dopaminergic neurons.in the Parkins.nian *** the pre-clinical literature s.gges.s.that there is.cons.derable variability in s.rvival and differentiation between s.udies.the aim of this.s.s.ematic review was.to as.es. thes. parameters.in human s.em cell-derived dopaminergic progenitor trans.lant s.udies.in animal models.of Parkins.n's.dis.as..A defined s.s.ematic s.arch of the PubMed databas. was.completed to identify relevant s.udies.publis.ed up to March *** s.reening,76 articles.were included in the analys.s.from which 178 s.parate trans.lant s.udies.were *** thes.,graft s.rvival could be as.es.ed in 52 s.udies.and differentiation in 129 ***,we found that graft s.rvival ranged froms.trans.lanted,with a median of 51%of trans.lanted cells.s.rviving in the brain;while dopaminergic differentiation of the cells.ranged from 0% to 46% of cells.trans.lanted with a median of 3%.This.s.s.ematic review s.gges.s.that there is.cons.derable s.ope for improvement in the differentiation of s.em cell-derived dopaminergic progenitors.to maximize the therapeutic potential of this.approach for patients.

关键词： cell replacement therapy differentiation embryonic s.em cells graft induced pluripotent s.em cells Parkins.n's.dis.as. s.rvival trans.lant

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Propagation of P-and s.waves.in initially s.res.ed gravitating half s.ace

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Applied Mathematics.and Mechanics.Englis. Edition) 2013年第7期34卷 847-860页

作者： s. GUPTA s. K. VIs.WAKARMA Department of Applied Mathematics Indian School of Mines

The pres.nt paper contributes.in s.udying the phas. velocities.of P- and s.waves.in a half s.ace s.bjected to a compres.ive initial s.res. and gravity field. The dens.ty and acceleration due to gravity vary quadratically along the depth. The dis.ers.on equation is.derived in a clos.d form. It is.s.own that the phas. velocities.depend not only on the initial s.res., gravity, and direction of propagation but als. on the inhomogeneity parameter as.ociated with the dens.ty and acceleration due to gravity. Various.particular cas.s.are obtained, and the res.lts.match with the clas.ical res.lts. Numerical inves.igations.on the phas. velocities.of P- and s.waves.agains. the wave number are made for various.s.ts.of values.of the material parameters. and the res.lts.are illus.rated graphically. The graphical us.r interface model is.developed to generalize the effect.

关键词： P-wave s.wave initial s.res. gravity half s.ace graphical us.r interface

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Deciphering the mechanobiology of microglia in traumatic brain injury with advanced micros.s.ems

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Neural Regeneration Res.arch 2025年第8期20卷 2304-2306页

作者： Anthony Procès.s.lvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials.Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced micros.s.ems.in traumatic brain injury res.arch:Traumatic brain injury(TBI)res.lts.from a mechanical ins.lt to the brain,leading to neuronal and axonal damage and s.bs.quently caus.ng a s.condary *** minutes.... 详细信息

关键词： traumatic injury damage

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Neumann＇s.method for boundary problems.of thin elas.ic s.ells

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Applied Mathematics.and Mechanics.Englis. Edition) 2017年第4期38卷 543-556页

作者： Y. s. NEUs.ADT Department of Civil Engineering Samara State Architectural and Building University Samara 443001 Russia

The pos.ibility of us.ng Neumann＇s.method to s.lve the boundary problems.for thin elas.ic s.ells.is.s.udied. The variational s.atement of the s.atic problems.for the s.ells.allows.for a problem examination within the dis.ribution s.ace. The convergence of Neumann＇s.method is.proven for the s.ells.with holes.when the boundary of the domain is.not completely fixed. The numerical implementation of Neumann＇s.method normally requires.s.gnificant time before any reliable res.lts.can be achieved. This.paper s.gges.s.a way to improve the convergence of the proces., and allows.for parallel computing and evaluation during the calculations.

关键词： boundary problem thin elas.ic s.ell theory Neumann's.method variational principle Korn's.inequality dis.ribution embedding theorem Green tens.r

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