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Small molecule inhibitor DDQ-treated hip.ocamp.l neuronal cells show imp.oved neurite outgrowth and synap.ic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangamp.lli Adi p.adeep.iran p.iyanka Rawat Arubala p.Reddy Erika Orlov p.emachandra Reddy Dep.rtment of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Dep.rtment of p.armacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Sp.ech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of p.blic Health Texas Tech University Health Sciences CenterLubbockTXUSA

The p.ocess of neurite outgrowth and branching is a crucial asp.ct of neuronal develop.ent and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we exp.ored the effects of diethyl(3,4-dihydroxyp.enethylamino)(quinolin-4-yl)methylp.osp.onate(DDQ)on neurite develop.ental features in HT22 neuronal *** this work,we examined the p.otective effects of DDQ on neuronal p.ocesses and synap.ic outgrowth in differentiated HT22cells exp.essing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural p.ocesses can be seen and measured with a fluorescence microscop. by manually tracing and measuring the length of the neurite *** neuronal p.ocesses can be observed and quantified with a fluorescent microscop. by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to disp.ay increased levels of synap.op.ysin,MAp.2,andβ-***,we confirmed and noted reduced levels of both total and p.Tau,as well as elevated levels of microtubule-associated p.otein 2,β-tubulin,synap.op.ysin,vesicular acetylcholine transp.rter,and the mitochondrial biogenesis p.otein-p. roxisome p.olife rator-activated recep.or-gamma coactivator-1α.In mTa u-exp.essed HT22 neurons,we observed DDQ enhanced the neurite characteristics and imp.oved neurite develop.ent through increased synap.ic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite develop.ental chara *** key finding is that,in mTa u-HT22 cells,DDQ p.eserves neuronal structure and may even enhance nerve develop.ent function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyp.enethylamino)(quinolin-4-yl)methylp.osp.onate(DDQ) hip.ocamp.l neuronal cells HT22 neurite outgrowth neuronal develop.ent small molecule

Adding new dimension to non-directed C（sp.）–H functionalizations

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Science China Chemistry 2025年

作者： Konstantin p.Bryliakov Laboratory of Selective Oxidation Catalysis N.D.Zelinsky Institute of Organic Chemistry RAS

Alip.atic C–H group. are among the most abundant yet least reactive functional group. in organic molecules. Nature has evolved metalloenzymes such as those of the cytochrome p.50 sup.rfamily that efficiently activate individual tertiary（3） and secondary （2） C（sp.）–H bonds in comp.ex molecules with the highest level of regio-and stereoselectivity [1], thus encouraging studies aimed at engineering artificial metalloenzymes for synthetic ap.lications [2].

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From single to combinatorial therap.es in sp.nal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-p.rez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hosp.tal Nacional de p.rap.éjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Sp.nal cord injury results in p.ralysis, sensory disturbances, sp.incter dysfunction, and multip.e systemic secondary conditions, most arising from autonomic dysregulation. All this p.oduces p.ofound negative p.ychosocial imp.ications for affected p.op.e, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the sp.nal cord after sp.nal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most p.blished works on structural/functional restoration in acute and chronic sp.nal cord injury stages use a single typ. of treatment: a drug or trop.ic factor, transp.ant of a cell typ., and imp.antation of a biomaterial. Desp.te the significant benefits rep.rted in animal models, when translating these successful therap.utic strategies to humans, the result in clinical trials has been considered of little relevance because the imp.ovement, when p.esent, is usually insufficient. Until now, most studies designed to p.omote neurop.otection or regeneration at different stages after sp.nal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute p.ases of sp.nal cord injury, it is reasonable to sp.culate that more than one therap.utic agent could be required to p.omote structural and functional restoration of the damaged sp.nal cord. Treatments that combine several therap.utic agents, targeting different mechanisms of injury, which, when used as a single therap., have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therap.utic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neurop.otection sp.nal cord injury rep.ir sp.nal cord injury treatments structural restoration of sp.nal cord injury

Sp.stin and alsin p.otein interactome analyses begin to reveal key canonical p.thways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Dep.rtment of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Develop.ng effective and long-term treatment strategies for rare and comp.ex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among p.tients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have imp.ications for a broad sp.ctrum of p.tients. One p.tential solution is to develop.p.rsonalized medicine ap.roaches based on strategies that target the most p.evalent cellular events that are p.rturbed in p.tients. Esp.cially in p.tients with a known genetic mutation, it may be p.ssible to understand how these mutations contribute to p.oblems that lead to neurodegeneration. p.otein–p.otein interaction analyses offer great advantages for revealing how p.oteins interact, which cellular events are p.imarily involved in these interactions, and how they become affected when key genes are mutated in p.tients. This line of investigation also suggests novel druggable targets for p.tients with different mutations. Here, we focus on alsin and sp.stin, two p.oteins that are identified as “causative” for amyotrop.ic lateral sclerosis and hereditary sp.stic p.rap.egia, resp.ctively, when mutated. Our review analyzes the p.otein interactome for alsin and sp.stin, the canonical p.thways that are p.imarily imp.rtant for each p.otein domain, as well as comp.unds that are either Food and Drug Administration–ap.roved or are in active clinical trials concerning the affected cellular p.thways. This line of research begins to p.ve the way for p.rsonalized medicine ap.roaches that are desp.rately needed for rare neurodegenerative diseases that are comp.ex and heterogeneous.

关键词： ALS2 alsin amyotrop.ic lateral sclerosis hereditary sp.stic p.rap.egia neurodegenerative diseases p.rsonalized medicine p.ecision medicine p.otein interactome p.otein-p.otein interactions Sp.ST sp.stin

Imp.cts of p.3K/p.otein kinase B p.thway activation in reactive astrocytes: from detrimental effects to p.otective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón p.rez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant typ. of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morp.ological and functional *** on their p.enotyp.c classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neurop.otective resp.nses,***,this binary classification does not fully cap.ure the diversity of astrocyte resp.nses observed across different diseases and *** analysis has revealed that reactive astrocytes have a comp.ex landscap. of gene exp.ession p.ofiles,which emp.asizes the heterogeneous nature of their *** actively p.rticip.te in regulating central nervous system inflammation by interacting with microglia and other cell typ.s,releasing cytokines,and influencing the immune *** p.osp.oinositide 3-kinase(p.3K)/p.otein kinase B(AKT)signaling p.thway is a central p.ayer in astrocyte reactivity and imp.cts various asp.cts of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the p.o-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling p.thways that regulate astrocyte reactivity,including the p.3K/AKT/mammalian target of rap.mycin(mTOR),αvβ3 integrin/p.3K/AKT/connexin 43,and Notch/p.3K/AKT *** targeting the inactivation of the p.3K/AKT cellular signaling p.thway to control reactive astrocytes and p.event central nervous system damage,evidence suggests that activating this p.thway could also yield beneficial *** dual function of the p.3K/AKT p.thway underscores its comp.exity in astrocyte reactivity and brain function *** review emp.asizes the imp.rtance of emp.oying astrocyte-exclusive models to underst

关键词： inflammation integrins neurop.otective neurotoxic p.osp.atidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

High black carbon and ozone concentrations during p.llution transp.rt in the Himalayas: Five years of continuous observations at NCO-p.global GAW station

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Journal of Environmental Sciences 2013年第8期25卷 1618-1625页

作者： A. Marinoni p. Cristofanelli p. Laj R. Duchi D. p.tero F. Calzolari T. C. Landi E. Vuillermoz M. Maione p. Bonasoni Institute for Atmosp.eric Sciences and Climate National Research Council of Italy Laboratoire de Glaciologie et Géop.ysique de l'Environnement Université Grenoble 1 CNRS EV-K2-CNR Committee Urbino University DiSBeF

To study the influence of p.lluted air-mass transp.rt carrying ozone （O3） and black carbon （BC） in the high Himalayas, since March 2006 the Nep.l Climate Observatory at p.ramid （NCO-p. GAW-WMO global station （Nep.l, 5079 m a.s.l.） is op.rative. During the first 5-year measurements, the O3 and BC concentrations have shown a mean value of 48 ± 12 p.b （± standard deviation） and 208 ± 374 ng/m3, resp.ctively. Both O3 and BC showed well defined seasonal cycles with maxima during p.e-monsoon （O3 ： 61.3 ± 7.7 p.bV; BC： 444 ± 433 ng/m3） and minima during the summer monsoon （O3 ： 40.1 ± 12.4 p.bV; BC： 64 ± 101 ng/m3）. The analysis of the days characterised by the p.esence of a significant BC increase with resp.ct to the typ.cal seasonal cycle identified 156 days affected by ＂acute＂ p.llution events, corresp.nding to 9.1% of the entire data-set. Such events mostly occur in the p.e-monsoon p.riod, when the O3 diurnal variability is strongly related to the transp.rt of p.lluted air-mass rich on BC. On average, these ＂acute＂ p.llution events were characterised by dramatic increases of BC （352%） and O3 （29%） levels comp.red with the remaining days.

关键词： ozone black carbon Himalayas p.llution biomass burning trop.sp.ere

Scattering and diffraction of p.ane p.waves in a 2-D elastic half-sp.ce Ⅱ：shallow arbitrary shap.d canyon

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Earthquake Engineering and Engineering Vibration 2017年第3期16卷 459-485页

作者： Heather p.Brandow Vincent Lee Civil and Environmental Engineering University of Southern California Los Angeles 90089 United States

Scattering and Diffraction of elastic in-p.ane p.and SV-waves by a surface top.grap.y such as an elastic canyon at the surface of a half-sp.ce is a classical p.oblem which has been studied by earthquake engineers and strong-motion seismologists for over forty years. The case of out-of-p.ane SH waves on the same elastic canyon that is semi-circular in shap. on the half-sp.ce surface is the first such p.oblem that was solved by analytic closed form solutions over forty years ago by Trifunac. The corresp.nding case of in-p.ane p.and SV-waves on the same circular canyon is a much more comp.icated p.oblem because, the in-p.ane p.and SV-scattered waves have different wave sp.eds and together they must have zero normal and shear stresses at the half-sp.ce surface. It is not until recently in 2014 that analytic solution for such p.oblem is found by the author in the work of Lee and Liu. This p.p.r uses the technique of Lee and Liu of defining these stress-free scattered waves to solve the p.oblem of the scattered and diffraction of these in-p.ane waves on an almost-circular surface canyon that is arbitrary in shap..

关键词： diffraction elastic p.waves SV-waves weighted-residual method arbitrary-shap.d canyon

Machine learning ap.lications in healthcare clinical p.actice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros p.p.p.dakos Research Unit of Radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Dep.rtment of Radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Dep.rtment of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a typ. of artificial intelligence that assists comp.ters in the acquisition of knowledge through data analysis,thus creating machines that can comp.ete tasks otherwise requiring human *** its various ap.lications,it has p.oven groundbreaking in healthcare as well,both in clinical p.actice and *** this editorial,we succinctly introduce ML ap.lications and p.esent a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multip.e linear regression(MLR)and ML methods to investigate the significant factors that may imp.ct the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results imp.icated age as the most imp.rtant determining factor in both group.,followed by lactic dehydrogenase,uric acid,forced exp.ratory volume in one second,and *** addition,for the NAFLD-group.the 5th and 6th most imp.rtant imp.ct factors were thyroid-stimulating hormone and systolic blood p.essure,as comp.red to p.asma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adop.ion of ML methodologies,showcasing their sup.riority over traditional statistical ap.roaches(herein MLR),thereby highlighting the p.tential of ML to rep.esent an invaluable advanced adjunct tool in clinical p.actice and research.

关键词： Machine Learning Artificial Intelligence Clinical p.actice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

Existence of Solutions to Nonlinear Neumann Boundary Value p.oblems with p.Lap.acian Op.rator and Iterative Construction

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Acta Mathematicae Ap.licatae Sinica 2011年第3期27卷 463-470页

作者： Li Wei Hai-yun Zhou Ravi p. Agarwal School of Mathematics and Statistics Hebei University of Economics and Business Shijiazhuang 050061 China Institute of Ap.lied Mathematics Ordnance Engineering College Shijiazhuang 050003 China Dep.rtment of Mathematical Sciences Florida Institute of Technology Melbourne FL 32901 U.S.A.

By using some results of p.eudo-monotone op.rator, we discuss the existence and uniqueness of the solution of one kind nonlinear Neumann boundary value p.oblems involving the p.Lap.acian op.rator. We also construct an... 详细信息

关键词： maximal monotone op.rator p.eudo-monotone op.rator p.Lap.acian op.rator iterative scheme