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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

Typical diseases of a long-span concrete-filled steel tubular arch bridge and their effects on vehicle-induced dynamic response

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Frontiers of structural and Civil Engineering 2020年第4期14卷 867-887页

作者： Jianling HOU Weibing XU Yanjiang CHEN kaida ZHANG Hang sUN Yan LI College of Architecture and Civil Engineering Bejing University of TechnologyBejing 100124China school of Transportation science and Engineering Harbin Institute of TechnologyHarbin 150090China

A long-span concrete-filled steel tubular(CFsT)arch bridge suffers severe vehicle-induced dynamic responses during its service ***,few quantitative studies have been reported on the typical diseases suffered by such bridges and their effects on vehicle-induced dynamic ***,a series of field tests and theoretical analyses were conducted to study the effects of typical diseases on the vehicle-induced dynamic response of a typical CFsT arch *** results show that a support void results in a height difference between both sides of the expansion joint,thus increasing the effect of vehicle impact on the main girder and *** impact factor of the displacement response of the main girder exceeds the design *** variation of the suspender force is significant,and the diseases are found to have a greater effect on a shorter *** theoretical analysis results also show that the support void causes an obvious longitudinal displacement of the main girder that is almost as large as the vertical *** support void can also cause significant changes in the vehicle-induced acceleration response,particularly when the supports and steel box girder continue to collide with each other under the vehicle load.

关键词： long-span arch bridge expansion joint disease vehicle-bridge coupling vibration dynamic response

An unexpected iron(Ⅱ)-promoted reaction of N-arylprop-2-yn-1-imines with water:Facile assembly of multi-substituted pyrroles

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Chinese Chemical Letters 2021年第1期32卷 37-39页

作者： kaida Zhou Jiapian Huang Jie Wu Guanyinsheng Qiu school of Pharmaceutical and Materials Engineering&Institute for Advanced studies Taizhou UniversityTaizhou 318000China state Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China College of Biological Chemical Science and EngineeringJiaxing UniversityJiaxing 314001China

Generation of multi-substituted pyrroles is accomplished through an unexpected iron(Ⅱ)-promoted reaction of N-arylprop-2-yn-1-imines with wate *** transformation proceeds smoothly with excellent chemoselectivityand regioselectivity.A stoichiometric amount of Fe(OTf)_(2) is necessary for the succes s ful conversion.A Lewis acid-promoted tandem reaction pathway is proposed.

关键词： Tandem reaction Iron(Ⅱ)triflate Prop-2-yn-1-imine Pyrrole Water

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

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

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World Journal of Clinical Cases 2018年第8期6卷 161-166页

作者： Flyn kaida-Yip Kaivalya Deshpande Trishla saran Dinesh Vyas College of Medicine California Northstate University Kaivalya Deshpande Department Of SurgeryMichigan State University Trishla saran Department of Medicine the University of Texas of the Permian Basin Dinesh Vyas Department of SurgeryTexas Tech University

Biosimilars are a growing drug class designed to be used interchangeably with *** are cr-eated in living cells and are typically large,complex pr-oteins that may have a variety of *** the field of gastroenterology alone,biologics are used to treat inflammatory bowel diseases,cancers,and endocrine *** biologics have proven to be effective in treating or managing many diseases,patient acce-ss is often limited by high *** development of biosimilars is an attempt to reduce treatment *** must be nearly identical to their reference biologics in terms of efficacy,side effect risk profile,and *** the manufacturing process still involves production within living cells,biosimilars undergo fewer clinical trials than do their reference *** ultimately reduces the cost of production and the cost of the biosimilar drug compared to its reference ***,seven biosimilars have been approved by the United states Food and Drug Administration(FDA)for use in Crohn’s disease,ulcerative colitis,and colorectal *** are other biologics involved in treating gastroenterologic diseases for which there are no FDA approved *** biosimilars have the po-tential to reduce healthcare costs in chronic disease management,they face challenges in establishing a sig-nificant market *** comfort in prescribing reference biologics instead of biosimilars and patient reluctance to switch from a biologic to a biosimilar are two common contributing factors to biosimilars’slow in-crease in *** time will be needed for biosimilars to establish a larger and more consistent market share compared to their reference *** da-ta confirming the safety and efficacy of biosimilars,increased number of available biosimilars,and further cost reduction of biosimilars will all be necessary to im-prove physician confidence in biosimilars and patient comfort with biosimilars.

关键词： Biosimilars Inflammatory bowel disease Biologics Inflammation Drug class

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber