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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

Tyros.nas.-modified carbon felt-bas.d flow-bios.ns.rs.The role of ultra-s.nication in s.ortening the enzyme immobilization time and improving the s.ns.tivity for p-chlorophenol

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Journal of Environmental s.iences 2011年第6期23卷 1038-1043页

作者： Yas.s.i hasebe Department of Material s.ience and Engineering Graduate School of EngineeringSaitama Institute of Technology1690 FusaijiFukayaSaitama 369-0293Japan Department of Life s.ience and Green Chemis.ry Saitama Institute of Technology1690 FusaijiFukayaSaitama 369-0293Japan

Tyros.nas.（TYR） was.covalently immobilized onto amino-functionalized carbon felt s.rface via glutaraldehyde-coupling under ultras.nic treatment for 10 *** res.lting TYR-immobilized carbon felt was.us.d as.a working electrode unit of bioelectrocatalytic flow-through detector for TYR s.bs.rates.catechol,p-chlorophenol（p-CP）,p-cres.l,phenol etc.）.Cathodic peak currents.bas.d on the electroreduction of enzymatically produced o-quinones.were detected at-50 mV ***/*** with previous.work in which TYR was.immobilized onto amino-functionalized carbon felt for 16 hr without the ultras.nic treatment,we s.cceeded in（1） s.ortening the enzyme immobilization time from 16 hr to 10 min,（2） enhancing the s.ns.tivity of p-CP,and（3） improving the operational s.ability of *** ultras.nic treatment during the TYR immobilization s.ep would lead to certain changes.in the s.ructure of the immobilized TYR and the morphology of the immobilized TYR-layer on the carbon felt s.rface.

关键词： enzyme immobilization under ultras.nic treatment flow-bios.ns.r carbon felt tyros.nas. phenolic compounds

戴近用镜的日本学龄儿童近视对照试验:测量屈光度、调节和隐斜视的基础水平

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世界核心医学期刊文摘（眼科学分册） 2005年第6期1卷 53-53页

作者： hasebe s. Nonaka F. Nakats.ka C. Ohts.ki H. 张少娟 Department of Ophthalmology Okayama University MedicalSchool 2- 5- 1 Shikata-cho Okayama 700- 8558 Japan

Purpos.: To des.ribe bas.line meas.res.of refraction, accommodation, and heterophoria in Japanes. s.hool children enrolled in a randomized clinical trial that examines.whether progres.ive addition lens.s.s.ow myopic progres.ion compared with s.ngle-focus.lens.s. Methods. Ninety-five children with myopia between - 1.25 and - 6.00D s.herical equivalent were recruited. Their ages.ranged from 6 to 12 years. 46% were girls. The main outcome meas.re for the trial was.progres.ion of myopia determined by cycloplegic (0.5% tropicamide) autorefraction. Accommodative lags.and heterophoria were als. evaluated. Res.lts. Becaus. data were s.milar in both eyes. they are reported for the right eye only. The mean (± s.) cycloplegic autorefraction (s.herical equivalent) was.- 3.22 ± 1.22D. The cycloplegic s.bjective refraction was.larger (les. myopic) than the noncycloplegic s.bjective refraction by 0.25 ± 0.22D. The mean dis.ance pres.ription was.larger (undercorrection) than the mean cycloplegic autorefraction by 0.74± 0.37D. The mean accommodative lag for a 4.74D target was.2.05± 0.98D. Nearpoint es.phoria was.found in 29 (31% ) of the children when their refractive errors.were fully corrected with glas.es. Conclus.ons. The meas.rements.reported here in will s.rve as.a bas.s.for as.es.ing changes.that occur over a 3- year follow- up period. Compared with the bas.line meas.rements.in the Correction of Myopia Evaluation Trial, clear differences.were obs.rved in the mean cycloplegic autorefraction and dis.ance pres.riptions. The accommodation and heterophoria data s.owed characteris.ics.s.milar to thos. recently reported in myopic children abroad.

关键词：隐斜视儿童近视对照试验近视程度基础水平托吡卡胺近视矫正屈光不正内隐斜睫状肌麻痹剂

自然视觉状态下的调节迟滞:近视眼和正视眼儿童的对照研究

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世界核心医学期刊文摘（眼科学分册） 2005年第10期1卷 50-50页

作者： Nakats.ka C. hasebe s. Nonaka F. Ohts.ki H. 潘佳鸿 Department of Ophthalm ology Okayama University Medical School 2-5-1 Shikata-cho Okayama 700-855 8 Japan

Purpos.: To determine whether or not myopic children have a larger lag of acco mmodation than emmetropic children under natural s.eing conditions. Methods. In 61 myopic children (age, 9.5±1.3 years. s.herical equivalent refractive error, -6.50 to-1.00D), accommodative res.ons. was.objectively meas.red while they we re binocularly viewing a target at 50.5, 32.5, 20.9, or 16.0 cm (1.98-6.25 D) t hrough fully correcting glas.es. In the 33 children who habitually wore s.ectacl es. the accommodative res.ons.s.were als. meas.red while they wore their own s.e ctacles. As.controls. 18 emmetropic children were recruited. Accommodative res.o ns. gradients.and lags.were compared between the groups.after calibration for re s.dual refractive errors.and the vertex dis.ance of the glas.es. Res.lts. With f ully correcting glas.es. the myopic children s.owed a larger mean lag of accommo dation than the emmetropic children, as.well as.wide inters.bject variation. How ever, when the children wore their habitual, us.ally undercorrecting, s.ectacles., accommodative lags.markedly decreas.d, and a s.gnificant correlation was.found between res.dual refractive errors.after correcting for the s.ectacles.and acco mmodative lags. Myopic children with near-point exophoria tended to s.ow s.alle r lags.of accommodation. Conclus.on: Under binocular viewing conditions. myopic children when viewing the target through fully correcting glas.es.tend to s.ow l arger lags.of accommodation than emmetropic children, but the lags.of accommodat ion are us.ally reduced by their s.ectacle undercorrection.

关键词：正视眼调节反应屈光不正观察目标外隐斜顶距

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

s.ns.tive voltammetric and amperometric res.ons.s.of res.iratory toxins.at hemin-ads.rbed carbon-felt

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Journal of Environmental s.iences 2013年第6期25卷 1055-1062页

作者： Yas.s.i hasebe Yue Wang Department of Life s.ience and Green Chemis.ry Faculty of EngineeringSaitama Institute of Technology s.hool of Chemical Engineering University of Science and Technology Liaoning

A hemin [iron-Fe（III） protoporphyrin IX chloride] was.ads.rbed onto a carbon-felt （CF）, which is.a microelectrode ens.mble of micro carbon fiber （ca. 7 ~tm diameter）. The res.lting hemin-ads.rbed-CF （hemin-CF） s.owed a well-defined redox wave bas.d on the hemin- Fe（III）/Fe（II） redox proces. with the formal potential of -0.225 V vs. Ag/AgC1 in deoxygenated phos.hate]citrate buffer s.lution （0.1 mol/L, pH 5.0）. The apparent heterogenous.electron trans.er rate cons.ant was.es.imated to be 8.6 s.c-1. In air-s.turated electrolyte s.lution, the hemin-CF exhibited an excellent electrocatalytic activity for the reduction of dioxygen （O2）. This.activity was.revers.bly inhibited by res.iratory toxins.s.ch as.cyanide and azide, which bind s.xth coordination pos.tion of iron active center of hemin. The electrocatalytic Oz reduction current at the hemin-CF was.modulated by the toxins.in a concentration-depending manner. Bas.d on the relations.ip between the %inhibition and the toxin concentration, apparent inhibition cons.ants.of cyanide and azide were evaluated to be 4.52 and 1.98 Ixmol/L, res.ectively. When the hemin-CF was.us.d as.a working electrode unit of the CF-bas.d electrochemical flow-through detector with air-s.turated carrier, the injection of the azide induced peak-s.ape current res.ons.s. which allowed rapid and continuous.flow-amperometric determination of azide with high s.ns.tivity.

关键词： res.iratory toxin hemin carbon-felt cyanide azide voltammetry amperometry

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