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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis 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

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 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 Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates.with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Vitreous haemorrhage as the first presentation of undiagnosed waldenstrom macroglobulinemia

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1639-1641页

作者： Christina s Lim Huzaifa malick somnath Banerjee Department of Ophthalmology University Hospitals of Leicester NHS TrustInfirmary SquareLeicester LE15WWUnited Kingdom

Dear Editor, waldenstrom macroglobulinemia(wM) is a rare type of non-Hodgkin’s lymphoma, commonly associated with hyperviscosity syndrome. Unlike non-Hodgkin’s lymphoma, its ocular manifestations are less.well described in the literature. Here we present the first case of undiagnosed wM presenting with dense vitreous haemorrhage. The study was conducted in accordance with the principles of the Declaration of Helsinki. The informed consent was obtained from the subject.

关键词： globulin lymphoma waldenstr

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed wMatthijs Blankesteijn sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-school for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-school for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(csVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term csVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CsVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek w.wheeler Giorgio A.Ascoli Center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study Bioengineering Department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

Combined aqueous misdirection and persistent choroidal effusions following implantation of a Preserflo Micro shunt

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International Journal of Ophthalmology(English edition) 2023年第4期16卷 652-655页

作者： Huzaifa malick Craig wilde Richard E stead University Hospitals of Leicester Leicester Royal InfirmaryInfirmary SquareLeicesterLE15WW***United Kingdom Queens Medical Centre Derby RoadNottingham NG72UHUnited Kingdom

AIM:To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo Micro shunt(PMs)device to treat advanced closed angle ***:A 67-year-old caucasian female with advanced primar y angle-closure glaucoma on four medications.with an intraocular pressure(IOP)of 26 mm Hg was listed for a PMs insertion with mitomycin C(MMC).REsULTs:Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet(YAG)peripheral *** was uneventful but on the first postoperative day,she developed aqueous misdirection complicated by subsequent development of persistent uveal *** treatment strategies including atropine drops,YAG hyaloidotomy and choroidal effusion drainage proved ineffective.A combination of oral steroids and pars plana vitrectomy(PPV)along with an irido-zonulohyloidectomy(IZH)proved ***:To the best of the author’s knowledge,this is the first published case of aqueous misdirection complicated with the presence of significant,unresolving choroidal effusions,highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes.

关键词： combined aqueous misdirections persistent choroidal effusions

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles.were included in the analysis from which 178 separate transplant studies.were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

Dynamic modeling of a three-dimensional braided composite thin plate considering braiding directions

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 123-138页

作者： Chentong GAO Huiyu sUN Jianping GU w.M.HUANG College of Aerospace Engineering Nanjing University of Aeronautics and Astronautics school of Mechanical and Aerospace Engineering Nanyang Technological University Jiangsu Key Laboratory of Advanced structural Materials and Application Technology School of Materials Science and EngineeringNanjing Institute of Technology

Currently, there are a limited number of dynamic models available for braided composite plates.with large overall motions, despite the incorporation of three-dimensional(3D) braided composites into rotating blade components. In this paper, a dynamic model of 3D 4-directional braided composite thin plates considering braiding directions is established. Based on Kirchhoff's plate assumptions, the displacement variables of the plate are expressed. By incorporating the braiding directions into the constitutive equation of the braided composites, the dynamic model of the plate considering braiding directions is obtained. The effects of the speeds, braiding directions, and braided angles on the responses of the plate with fixed-axis rotation and translational motion, respectively, are investigated. This paper presents a dynamic theory for calculating the deformation of 3D braided composite structures undergoing both translational and rotational motions. It also provides a simulation method for investigating the dynamic behavior of non-isotropic material plates in various applications.

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