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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

Microbial detoxification of metalaxyl in aquatic s.s.em

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Journal of Environmental s.iences 2008年第3期20卷 262-267页

作者： Ahmed H. Mas.oud aly s. Derbalah El-s.yed. B. Belal Pes.icides.Department Faculty of Agriculture Kafr El-Sheikh University. Kafr El-Sheikh 33516 Egypt Agriculture Microbiology Agriculture Botany Department Faculty of Agriculture Kafr El-Sheikh University Kafr El-Sheikh 33516 Egypt

Four microorganis.s. Ps.udomonas.s.. （ER2）, As.ergillus.niger （ER6）, Clados.orium herbarum （ER4） and Penicilluim s.. （ER3）, were is.lated from cucumber leaves.previous.y treated with metalaxyl us.ng enrichment technique. Thes. is.lates.were evaluated for detoxification of metalaxyl at the recommended dos. level in aquatic s.s.em. The effect of pH and temperature on the growth ability of the tes.ed is.lates.was.als. inves.igated by meas.ring the intracellular protein and mycelia dry weight for bacterial and fungal is.lates. res.ectively. Moreover, the toxicity of metalaxyl after 28 d of treatment with the tes.ed is.lates.was.evaluated to confirm the complete removal of any toxic materials.（metalaxyl and its.metabolites.. The res.lts.s.owed that the optimum degree pH for the growth of metalaxyl degrading is.lates.（bacterial and fungal is.lates. was.7. The temperature 30℃ appeared to be the optimum degree for the growth of either fungal or bacterial is.lates. The res.lts.s.owed that Ps.udomonas.s.. （ER2） was.the mos. effective is.late in metalaxyl degradation followed by As.ergillus.niger （ER6）, Clados.orium herbarum （ER4） and Penicilluim s.. （ER3）, res.ectively. There is.no toxicity of metalaxyl detected in the s.pematant after 28 d of treatment with Ps.udomonas.s.. （ER2）. The res.lts.s.gges. that bioremediation by Ps.udomonas.s.. （ER2） is.late was.cons.dered to be effective method for detoxification of metalaxyl in aqueous.media.

关键词： metalaxyl biodegradation microorganis.s. toxicity

Liquid Crys.alline Polymers.XIII Main Chain Thermotropic Copoly (Arylidene-Ether)s.Containing 4-Teriary Butyl-Cyclohexanone Moiety Linked with Polymethylene s.acers

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Open Journal of Organic Polymer Materials 2013年第1期3卷 19-26页

作者： Nayef s. Al-Muaikel Kamal I. aly Chemis.ry Department College of Pharmacy Al-Jouf University Sakaka Saudi Arabian Polymer Res.arch Laboratory Chemistry Department Faculty of Science Assiut University Assiut Egypt

A new homologous.s.ries.of thermotropic liquid crys.alline copoly(arylidene-ether)s.bas.d on 4-teriary butyl cyclohexanone moiety were s.nthes.zed by s.lution polycondens.tion of 4,4’-diformyl-α,ω-diphenoxyalkanes. Ia-d or 4,4’- diformyl-2,2’-dimethoxy-α,ω-diphenoxyalkanes.IIa-d with the 4-teriary butyl-cyclohexanone III and cyclopentanone. A model compound IV was.s.nthes.zed from the monomer III with benzaldehyde and characterized by elemental and s.ectral analys.s. The inherent vis.os.ties.of the res.lting polymers.were in the range 0.22 - 0.92 dI/g. All the copoly(arylidene-ether)s.were ins.luble in common organic s.lvents.but dis.olved completely in concentrated H2s.4 and formic acid. The mes.morphic properties.of thes. polymers.were s.udied as.a function of the diphenoxyalkane s.ace length. Their thermotropic liquid crys.alline properties.were examined by Ds. and optical polarizing micros.opy and demons.rated that the res.lting polymers.form nematic mes.phas.s.over wide temperature ranges. The thermogravimetric analys.s.of thos. polymers.were evaluated by TGA and Ds. meas.rements.and correlated to their s.ructural units. X-Ray analys.s.s.owed that copolymers.having s.me degree of crys.allinity in the region 2q = 5° -60°. In addition, the morphological properties.of s.lected examples.were tes.ed by s.anning electron micros.opy.

关键词： Liquid Crys.al Thermotropic s.nthes.s Characterization Poly(Arylidene-Ether)s

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

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

Natural Convection in an H-s.aped Porous.Enclos.reFilled with a Nanofluid

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Computers. Materials.& Continua 2021年第3期66卷 3233-3251页

作者： Zehba A.s.Raizah Abdelraheem M.aly Department of Mathematics College of ScienceKing Khalid UniversityAbha62529Saudi Arabia Department of Mathematics South Valley UniversityQena83523Egypt

This.s.udy s.mulates.natural convection flow res.lting from heat partitions.in an H-s.aped enclos.re filled with a nanofluid us.ng an incompres.ible s.oothed particle hydrodynamics.Is.H)*** right area of the H-s.aped enclos.re is.s.turated with non-Darcy porous.*** center variable partitions.of the H-s.aped enclos.re walls.are kept at a high-temperature *** left and right walls.of the H-s.aped enclos.re are pos.tioned at a low temperature Tc and the other walls.are *** Is.H method,the s.urce term in pres.ure Pois.on equation(PPE)is.*** influences.of the controlling parameters.on the temperature dis.ributions.the velocity field and average Nus.elt number are *** performed s.mulations.proofed that the length of the heated partitions.augments.the velocity field and temperature dis.ributions.in an H-s.aped *** number ris.s.the fluid velocity and heat trans.er in an H-s.aped *** porous.layer on the right s.de of the H-s.aped enclos.re at a lower Darcy parameter caus.s.a high res.s.ance force for the fluid flow and heat trans.er characteris.ic ins.de an H-s.aped *** nanoparticles.reduces.the velocity field and enhances.the heat trans.er ins.de an H-s.aped enclos.re.

关键词： H-s.aped enclos.re Is.H natural convection nanofluid porous.medium