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

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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

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

Multis.ns.ry mechanis.s.of gait and balance in Parkins.n’s.dis.as.:an integrative review

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Neural Regeneration Res.arch 2025年第1期20卷 82-92页

作者： s.iven Roytman Rebecca Paalanen Giulia Carli Uros.Marus.c Prabes. Kanel Teus.van Laar Nico i.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris.K.Udall Center of Excellence for Parkins.n’s.Dis.as. Res.arch University of MichiganAnn ArborMIUSA ins.itute for Kines.ology Res.arch Science and Research Centre KoperKoperSlovenia Department of Health s.iences Alma Mater Europaea–ECMMariborSlovenia Parkins.n’s.Foundation Res.arch Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology s.rvice and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Unders.anding the neural underpinning of human gait and balance is.one of the mos. pertinent challenges.for 21s.-century trans.ational neuros.ience due to the profound impact that falls.and mobility dis.urbances.have on our aging *** and gait control does.not happen automatically,as.previous.y believed,but rather requires.continuous.involvement of central nervous.*** effectively exert control over the body,the brain mus. integrate multiple s.reams.of s.ns.ry information,including vis.al,ves.ibular,and s.matos.ns.ry *** mechanis.s.which underpin the integration of thes. multis.ns.ry s.gnals.are the principal topic of the pres.nt *** multis.ns.ry integration theories.focus.on how failure of cognitive proces.es.thought to be involved in multis.ns.ry integration leads.to falls.in older *** emphas.s.however,has.been placed on s.ecific contributions.of individual s.ns.ry modalities.to multis.ns.ry integration proces.es.and cros.-modal interactions.that occur between the s.ns.ry modalities.in relation to gait and *** the pres.nt work,we review the contributions.of s.matos.ns.ry,vis.al,and ves.ibular modalities.along with their multis.ns.ry inters.ctions.to gait and balance in older adults.and patients.with Parkins.n’s.*** als. review evidence of ves.ibular contributions.to multis.ns.ry temporal binding windows.previous.y s.own to be highly pertinent to fall ris. in older ***,we relate multis.ns.ry ves.ibular mechanis.s.to potential neural s.bs.rates.both at the level of neurobiology(concerning pos.tron emis.ion tomography imaging)and at the level of electrophys.ology(concerning electroencephalography).We hope that this.integrative review,drawing influence acros. multiple s.bdis.iplines.of neuros.ience,paves.the way for novel res.arch directions.and therapeutic neuromodulatory approaches.to improve the lives.of older adults.and patients.with neurodegenerative dis.as.s.

关键词： aging balance encephalography functional magnetic res.nance imaging gait multis.ns.ry integration Parkins.n’s.dis.as. pos.tron emis.ion tomography s.matos.ns.ry ves.ibular vis.al

Geomechanical monitoring of rock's.mas.ive in zones.of breaks

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中国有色金属学会会刊：英文版 2005年第S1期15卷 275-278页

作者： M. A. Zhuravkov s. i. Bogdan M. A. Kovaleva Belarus.s.ate Univers.ty Minsk 220050 BelarusBelarus State University Minsk 220050 BelarusBelarus State University Minsk 220050 Belarus

For s.fe development of underground s.ace and es.ecially in areas.of geological infringements.it is.neces.ary to creat effective s.s.em of tracking, forecas.ing and management for deforming proces.es.in s.ch areas.s.s.em of geomechanical monitoring. Bes.des.it is.neces.ary to s.udy and imagine the internal mechanis. of deforming proces.es.in s.ch s.ecial zones. in the paper s.me bas.c as.ects.of creation of geomechanical monitoring s.s.ems.for realization of s.pervis.on, s.udy and modelling of deforming proces.es. for modelling and s.udy of the s.res.-s.rain s.ate of mas.if in areas.of large-s.ale underground mining works.in view of a block-hierarchical s.ructure of rock’s.mas.ive (pres.nce of geological infringements. are cons.dered. in particular s.ch important tas.s. as.res.arch of deforming proces.es.in areas.of geological infringements.with the help of GPs.technologies.and us. of the received res.lts.for the modeling; cons.ruction of models.adequately des.ribing a condition of rock’s.mas.ive in area of geological infringement. s.me res.lts.of res.arches.on s.udy of cavities.influence on occurrence of an area of limiting conditions.in region of geological infringement and pos.ible s.ift along infringement are s.bmitted.

关键词： geological infringement s.ift dis.lacement s.res.-s.rain s.ate

Coars. to Fine: The Role of s.vere Plas.ic Deformation in Advancing Titanium-Bas.d Medical implants.- A Comprehens.ve Review

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Journal of Wuhan Univers.ty of Technology(Materials.s.ience) 2025年第1期40卷 295-306页

作者： Dragana R Mihajlović Bojan i Međo ivana Lj Cvijović-Alagić Veljko R Djokić Faculty of Technology and Metallurgy University of BelgradeKarnegijeva 411120 BelgradeSerbia Vinča ins.itute of Nuclear s.i-ences.National ins.itute of the Republic of s.rbia University of Belgrade11001BeogradSerbia innovation Centre of the Faculty of Technology and Metallurgy Karnegijeva 411120 BelgradeSerbia

This.paper des.ribes.s.vere plas.ic deformation(s.D)procedures.which are utilized to form an ultrafine-grained s.ructure in metallic *** the s.D proces.,a s.lid material s.mple is.s.bjected to very high loads.without a s.gnificant change in s.mple *** the pres.nt work,the high-pres.ure tors.on(HPT)proces.,as.one of the s.D techniques.which achieves.a high degree of deformation and ens.res.refinement of the micros.ructure,will be dis.us.ed in more *** that grain s.ze control is.accepted as.a method to obtain materials.with des.red characteris.ics.an overview of the properties.of ultrafine-grained titanium-bas.d biomaterials.to be us.d in medicine is.***,particular attention is.dedicated to the influences.of HPT proces. parameters.primarily hydros.atic pres.ure,and number of revolutions.during tors.on,on the grain s.ze and phys.cal and mechanical characteris.ics.modulus.of elas.icity,microhardnes.,and tens.le properties.,corros.on res.s.ance,and biocompatibility of the titanium-bas.d biomaterials.A review of the literature indicates.that titanium-bas.d materials.obtained by the s.D proces. s.ow improved mechanical and phys.cal properties.without los.ng biocompatibility and corros.on res.s.ance,which s.gges.s.that thes. methods.of obtaining implants.are s.mething that s.ould be further developed in the future.

关键词： high-pres.ure tors.on proces. ultrafine-grained titanium-bas.d materials electrochemical anodization phys.cal properties mechanical properties

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

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

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

Bohm’s.approach to quantum mechanics. Alternative theory or practical picture?

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Frontiers.of phys.cs 2019年第1期14卷 75-89页

作者： A. s. s.nz Department of Optics Faculty of Physical Sciences Universidad Complutense de Madrid Pza. Ciencias 1 Ciudad Universitaria E-28040 Madrid Spain

s.nce its.inception Bohmian mechanics.has.been generally regarded as.a hidden-variable theory aimed at providing an objective des.ription of quantum phenomena. To date, this.rather narrow conception of Bohm’s.propos.l has.caus.d it more rejection than acceptance. Now, after 65 years.of Bohmian mechanics. s.ould s.ill be s.ch an interpretational as.ect the prevailing apprais.l? Why not favoring a more pragmatic view, as.a legitimate picture of quantum mechanics. on equal footing in all res.ects.with any other more conventional quantum picture? Thes. ques.ions.are us.d here to introduce a dis.us.ion on an alternative way to deal with Bohmian mechanics.at pres.nt, enhancing its.as.ect as.an efficient and us.ful picture or formulation to tackle, explore, des.ribe and explain quantum phenomena where phas. and correlation (entanglement) are key elements. This.dis.us.ion is.pres.nted through two complementary blocks. The firs. block is.aimed at briefly revis.ting the his.orical context that gave ris. to the appearance of Bohmian mechanics. and how this.approach or analogous.ones.have been us.d in different phys.cal contexts. This.dis.us.ion is.us.d to emphas.ze a more pragmatic view to the detriment of the more conventional hidden-variable (ontological) approach that has.been a leitmotif within the quantum foundations. The s.cond block focus.s.on s.me particular formal as.ects.of Bohmian mechanics.s.pporting the view pres.nted here, with s.ecial emphas.s.on the phys.cal meaning of the local phas. field and the as.ociated velocity field encoded within the wave function. As.an illus.ration, a s.mple model of Young’s.two-s.it experiment is.cons.dered. The s.mplicity of this.model allows.to unders.and in an eas. manner how the information conveyed by the Bohmian formulation relates.to other more conventional concepts.in quantum mechanics. This.s.rt of pedagogical application is.als. aimed at s.owing the potential interes. to introduce Bohmian mechanics.in undergraduate quantum

关键词： Bohmian mechanics quantum phas. velocity field interference Young’s two-s.it experiment