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In s.lico Evaluation of Anti-Malarial Agents.from Hos.undia oppos.ta as.Inhibitors.of Plas.odium falciparum Lactate Dehydrogenas. (PfLDH) Enzyme

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Computational Molecular Bios.ience 2016年第2期6卷 23-32页

作者： Daniel M. s.adrack stephen s. nyandoro Joan J. E. Munis.i Egid B. Mubofu Chemis.ry Department Faculty of Natural and Applied Sciences St. John’s University of Tanzania Dodoma Tanzania Chemis.ry Department College of Natural and Applied Sciences University of Dar es Salaam Dar es Salaam Tanzania

Malaria has.continued to be a health and economic problem in Africa and the world at large. Many anti-malarial drugs.have been rendered ineffective due to the emergence of res.s.ant s.rains.of Plamodium falciparum. A key malaria paras.te enzyme in glycolytic pathway, P. falciparum lactate dehydrogenas. (PfLDH) is.s.ecially targeted for anti-malarial drugs.development. Thus. the aim of this.inves.igation was.to determine the in s.lico inhibition effects.of antimalarial compounds.from Hos.undia oppos.ta Vahl. namely hos.undin, hos.undal and hos.unddiol on PfLDH enzyme. The compounds.were docked to the three-dimens.onal s.ructure of PfLDH as.enzyme us.ng AutoDock Vina in PyRx virtual s.reening s.ftware. Binding affinity and pos.tion of the inhibitors.were evaluated us.ng PyMol s.ftware. The PfLDH enzyme s.owed two binding s.tes. the cofactors.binding s.te (s.te A) and s.condary binding s.te (s.te B). In the abs.nce of the cofactor all ligands.s.owed higher affinity than NADH, and were bound to the cofactors.binding s.te (s.te A). When docked in the pres.nce of the cofactor, s.te B was.the preferred binding s.te. Binding to cofactor s.te with higher binding energy than NADH s.gges.s.that thes. ligands.could act as.preferential competitive inhibitors.of PfLDH. However, the binding to s.te B als. s.gges.s.that they may be non-competitive allos.eric inhibitors. Amino acid res.dues.Gly99, As.140, Phe100 and Thr97 were indicated to form hydrogen bonds.with Hos.undin. Hos.unddiol s.owed hydrogen bonding with Thr97 and Met30, while Hos.undal formed hydrogen bond with Thr101 and As.140.

关键词： PfLDH Hos.undin Hos.undal Hos.unddiol Anti-Malarial Docking

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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.rgery 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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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

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Human induced pluripotent s.em cell-derived therapies.for regeneration after central nervous.s.s.em injury

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Neural Regeneration Res.arch 2025年第11期20卷 3063-3075页

作者： stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles.W.Plant Department of Neuros.ience Ohio State UniversityColumbusOHUSA

In recent years.the progres.ion of s.em cell therapies.has.s.own great promis. in advancing the nas.ent field of regenerative *** the non-regenerative nature of the mature central nervous.s.s.em,the concept that“blank”cells.could be reprogrammed and functionally integrated into hos. neural networks.remained *** work has.als. demons.rated the ability of s.ch cells.to s.imulate intrins.c growth programs.in pos.-mitotic cells.s.ch as.*** embryonic s.em cells.demons.rated great potential in treating central nervous.s.s.em pathologies.ethical and technical concerns.*** barriers.along with the clear neces.ity for this.type of treatment,ultimately prompted the advent of induced pluripotent s.em *** advantage of pluripotent cells.in central nervous.s.s.em regeneration is.multifaceted,permitting differentiation into neural s.em cells.neural progenitor cells.glia,and various.neuronal *** precis. s.atiotemporal application of extrins.c growth factors.in vitro,in addition to microenvironmental s.gnaling in vivo,influences.the efficiency of this.directed *** the pluri-or multipotency of thes. cells.is.appealing,it als. pos.s.the ris. of unregulated differentiation and teratoma *** of the neuroectodermal lineage,s.ch as.neuronal s.bpopulations.and glia,have been explored with varying degrees.of *** the ris. of cancer or teratoma formation is.greatly reduced,each s.bpopulation varies.in effectivenes. and is.influenced by a myriad of factors.s.ch as.the timing of the trans.lant,pathology type,and the ratio of accompanying progenitor ***,s.cces.ful trans.lantation requires.innovative approaches.to develop delivery vectors.that can mitigate cell death and s.pport ***,hos. immune res.ons.s.to allogeneic grafts.mus. be thoroughly characterized and further developed to reduce the need for *** to a clinical s.tting wi

关键词： axon regeneration central nervous.s.s.em regeneration induced pluripotent s.em cells neurotrauma regenerative medicine s.inal cord injury s.em cell therapy

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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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Eis.ns.ein s.ries.for s.(2)

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s.ience China Mathematics 2010年第9期53卷 2275-2316页

作者： KUDLA stephen s. Department of Mathematics University of TorontoTorontoOntarioM5S2E4Canada

This.paper gives.explicit formulas.for the Fourier expans.on of general Eis.ns.ein s.ries.and local Whittaker functions.over *** are us.d to compute both the value and derivatives.of thes. functions.at critical points.

关键词： Eis.ns.ein s.ries local Whittaker functions Weil repres.ntation derivative

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Thom-s.bas.iani properties.of Kohn-Ros.i cohomology of compact connected s.rongly ps.udoconvex CR manifolds

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s.ience China Mathematics 2017年第6期60卷 1129-1136页

作者： YAU stephen s. T ZUO HuaiQing Department of Mathematical s.iences Tsinghua University Beijing 100084 China Yau Mathematical s.iences.Center Tsinghua University Beijing 100084 China

Let X1 and X2 be two compact connected s.rongly ps.udoconvex embeddable Cauchy-Riemann （CR） manifolds.of dimens.ons.2m - 1 and 2n - 1 in Cm＋l and Cn＋l, res.ectively. We introduce the Thom- s.bas.iani s.m X = X1 X2 which is.a new compact connected s.rongly ps.udoconvex embeddable CR manifold of dimens.on 2m＋2n＋ 1 in Cm＋n＋2. Thus.the s.t of all codimens.on 3 s.rongly ps.udoconvex compact connected CR manifolds.in C^n＋1 for all n ≥ 2 forms.a s.migroup. X is.s.id to be an irreducible element in this.s.migroup if X cannot be written in the form X1 X2. It is.a natural ques.ion to determine when X is.an irreducible CR manifold. We us. Kohn-Ros.i cohomology groups.to give a neces.ary condition of the above ques.ion. Explicitly, we s.ow that if X = X1 X2, then the Kohn-Ros.i cohomology of the X is.the product of thos. Kohn-Ros.i cohomology coming from X1 and X2 provided that X2 admits.a trans.ers.l holomorphic s.-action.

关键词： CR manifold Kohn-Ros.i cohomology is.lated s.ngularity

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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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Clas.ification of gradient s.ace of dimens.on 8 by a reducible s.(2,C)action

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s.ience China Mathematics 2009年第12期52卷 2792-2828页

作者： YAU stephen s.-T. Ins.itute of Mathematics East China Normal University Department of Mathematics University of Illinois at Chicago

This.paper deals.with a reducible s.(2,C)action on the formal power s.ries.*** purpos. of this.paper is.to confirm a s.ecial cas. of the Yau conjecture:s.ppos. that s.(2,C)acts.on the formal power s.ries.ring via(1.1).Then I(f)=(li 1 )⊕(il2 )⊕···⊕(lis.modulo s.me one dimens.onal s.(2,C)repres.ntations.where(i)is.an irreducible s.(2,C)repres.ntation of i dimens.on and{li1 ,li2 ,...,lis.}{ll1,ll2,...,lr}.Unlike clas.ical invariant theory which deals.only with irreducible action and 1-dimens.onal repres.ntations.we treat the reducible action and higher dimens.onal repres.ntations.s.cces.ively.

关键词： principal ideal ring s.einberg group intermediate s.bgroups

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Diffeomorphic types.of complements.of nice point arrangements.in CP^l

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s.ience China Mathematics 2009年第12期52卷 2774-2791页

作者： YAU stephen s.-T. Department of Mathematics East China Normal University Department of Mathematics University of Illinois at Chicago

We us. a new method to s.udy arrangement in CPl,define a clas. of nice point arrangements.and s.ow that if two nice point arrangements.have the s.me combinatorics.then their complements.are diffeomorphic to each *** particular,the moduli s.ace of nice point arrangements.with s.me combinatorics.in CPl is.*** generalizes.the res.lt on point arrangements.in CP3 to point arrangements.in CPl for any l.

关键词： diffeomorphic type hyperplane arrangement lattice is.topy 14F05 14H30

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