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Multiple sclerosis drug repurposing for neuroregeneration

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Neural Regeneration Research 2024年第3期19卷 507-508页

作者： Peter Göttle Michael dietrich Patrick Küry Department of Neurology Medical FacultyHeinrich-Heine UniversityDüsseldorfGermany

Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all ***-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).

关键词： drugs impaired irreversible

现代教育学和社会教育学的起源和实用性的十大论点

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华东师范大学学报（教育科学版） 2024年第9期42卷 33-41页

作者： [德]底特里希•本纳柏林洪堡大学德国柏林10099

本文强调的观点是,现代教育和教化的基础阶段包括两部分:一是在学校教授的、面向全民的新式基础教育,二是借助社会教育行业得到传授和加强的新式社会基础教育。社会基础教育的组织结构根植于分化的现代社会子系统之上,涵盖了德国各种形... 详细信息

本文强调的观点是,现代教育和教化的基础阶段包括两部分:一是在学校教授的、面向全民的新式基础教育,二是借助社会教育行业得到传授和加强的新式社会基础教育。社会基础教育的组织结构根植于分化的现代社会子系统之上,涵盖了德国各种形式的社会工作,包括家庭社会工作、学校社会工作、就业社会工作,以及社区工作、社会热点和罪犯再社会化方面的社会工作。中国的教育和教化体系已经牢固确立了,普通基础教育和社会基础教育具有同等重要的意义。期望这十大论点的译介,能够有助于对中国特色的基础教育和社会教育展开相应的讨论。

关键词：普通基础教育社会基础教育现代教育和教化过程的自身逻辑社会教育学和社会工作纪律规训性的、拓展经验和交往的、咨询性的教育实践现代社会性分享与参与

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Striatum-specific mechanisms regulate neuronal cell cycle re-entry:the choice between life and death

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Neural Regeneration Research 2023年第3期18卷 523-524页

作者： Paula dietrich Ioannis Dragatsis Department of Physiology The University of TennesseeHealth Science CenterMemphisTNUSA

Mitochondria dysfunction occurs in the aging brain as well as in several neurodegenerative disorders and predisposes neuronal cells to enhanced sensitivity to *** particular,defects in any of the mitochondria respiratory chain complexes lead to impaired adenosine triphosphate production resulting in diseases that often affect the central nervous *** instance,innate deficits in succinate dehydrogenase(SDH)mitochondria respiratory chain complex II activity caused by genetic mutations in SDH subunits lead to early-onset neurodegeneration(Jain-Ghai et al.,2013),while several adult-onset genetic neurodegenerative disorders are associated with variable levels of complex II deficiency in the central nervous system(Túnez et al.,2010).Also,chemically induced complex II deficiency leads to neurodegeneration.

关键词： SDH impaired cycle

Education[Bildung]-Literality-Competence:On Competing Tasks of Public Schools and the Need for New Links Between Teaching and Educational Research

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ECNU Review of Education 2023年第1期6卷 15-32页

作者： dietrich Benner Department of General Education Humboldt University of BerlinUnter den Linden 610099 BerlinGermany

Instead of replacing traditional input control with output measurements,it is important to link teaching and educational research in such a way that competence measurements not only measure the levels of demands achieved by learners but also the quality and effectiveness of ***/Value:The train of thought overcomes the juxtaposition of philosophy of education and empirical research and shows how the two can cooperate theoretically and empirically.

关键词： Basic education competence didactically oriented teaching research input control literacy output control

Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier?

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World Journal of Gastroenterology 2023年第2期29卷 367-377页

作者： Christoph G dietrich Andreas Geier Uta Merle Gastro-Praxis Wiesbaden Leberzentrum WiesbadenWiesbaden 65189Germany Division of Hepatology Department of Medicine IIUniversity Hospital WuerzburgWuerzburg 97080Germany Department of Gastroenterology and Hepatology University Hospital HeidelbergHeidelberg 69120Germany

The pandemics of coronavirus disease 2019(COVID-19)and non-alcoholic fatty liver disease(NAFLD)*** liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD,while preexisting liver damage from NAFLD may influence the course of ***,the prognostic relevance of this interaction,though,is *** is a risk factor for the presence of NAFLD as well as a severe course of *** studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness *** molecular similarities of cytokine pathways in both diseases,including postacute sequelae of COVID-19,suggest common pathways for chronic low-activity *** review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.

关键词： COVID-19 Postacute sequelae of COVID-19 Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Inflammation Fatty liver

Immediate and Long-Term Results of Transcatheter Closure of Patent Ductus Arteriosus—Comparison of Two Decades before and after Change in Antibiotic Infective Endocarditis Prophylaxis Guidelines

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Congenital Heart Disease 2022年第2期17卷 215-230页

作者： Annina dietrich Daniel Quandt Oliver Kretschmar Walter Knirsch Pediatric Cardiology Pediatric Heart CenterDepartment of Surgery and Children’s Research CenterUniversity Children’s Hospital ZurichZurichSwitzerland University of Zurich ZurichSwitzerland

Objectives:To determine immediate and long-term follow-up of transcatheter closure of patent ductus arteriosus(PDA)in ***:National antibiotic prophylaxis(AP)guideline for infective endocarditis changed after 2009,the effect on practice of PDA closure is ***:Observational single center study analyzing follow-up of PDA closure comparing two time periods before(2002–2009)and after(2010–2019)changes in AP ***:332 patients(68.1%female),median(interquartile range)age 3.0 years(1.5–5.7)and body weight 14.0 kg(10.0–19.3),were *** morphology was conical type A(50.3%),window type B(1.2%),tubular type C(40.1%),complex type D(2.1%),elongated type E(0.9%)and other(5.4%).Minimal PDA diameter and length were 1.9 mm(1.3–2.5)and 8.0 mm(6.2–10.2).PDA was closed using coils(56.3%),Amplatzer Duct Occluders(41.9%)and others(1.8%).Complete closure rate was 61.1%at catheter intervention,72.3%on day 1,87.7%after 6 months and 98.4%at last follow-up on *** complication rate(severity level 3)was 4.2%and major complication rate(severity level 4)0.3%,with no catastrophic complications(severity level 5).Annual PDA closure rate declined in the second time period(22.6/year vs.15.5/year,p=0.018),PDA size increased(1.6 mm vs.2.0 mm,p=0.002)and proportion of coils decreased(72.4%vs.37.1%,p98%)and only a small number of complications leading to reintervention or *** in AP guidelines changed indication for and practice of PDA closure.

关键词： Patent arterial duct device closure congenital heart disease infective endocarditis

Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells

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Journal of Molecular Cell Biology 2023年第8期15卷 40-53页

作者： PawełGłodowicz Konrad Kuczynski Romain Val Andrédietrich Katarzyna Rolle Department of Molecular Neurooncology Institute of Bioorganic ChemistryPolish Academy of Sciencesul.Z.Noskowskiego 12/1461-704 PoznanPoland Institute of Plant Molecular Biology French National Center for Scientific Research(CNRS)and University of Strasbourg12 rue du Général Zimmer67084 StrasbourgFrance

Mutations in the small genome present in mitochondria often result in severe *** genetic strategies have been explored,aiming to rescue such mutations.A number of these strategies were based on the capacity of human mitochondria to import RNAs from the cytosol and designed to repress the replication of the mutated genomes or to provide the organelles with wild-type versions of mutant ***,the mutant RNAs present in mitochondria turned out to be an obstacle to therapy and little attention has been devoted so far to their ***,we present the development of a strategy to knockdown mitochondrial RNAs in human cells using the transfer RNA-like structure of Brome mosaic virus or Tobacco mosaic virus as a shuttle to drive trans-cleaving ribozymes into the organelles in human cell *** obtained a specific knockdown of the targeted mitochondrial ATP6 mRNA,followed by a deep drop in ATP6 protein and a functional impairment of the oxidative phosphorylation *** strategy provides a powerful approach to eliminate mutant organellar transcripts and to analyse the control and communication of the human organellar genetic system.

关键词： human cells mitochondria ribozyme RNA trafficking transcriptome manipulation tRNA-like structure

Origin of non-uniform plasticity in a high-strength Al-Mn-Sc based alloy produced by laser powder bed fusion

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Journal of Materials Science & Technology 2022年第8期103卷 121-133页

作者： Dina Bayoumy Kwangsik Kwak Torben Boll Stefan dietrich Daniel Schliephake Jie Huang Junlan Yi Kazuki Takashima Xinhua Wu Yuman Zhu Aijun Huang Monash Centre for Additive Manufacturing 15-17 Normanby RdNotting HillVIC 3168Australia Department of Materials Science and Engineering Monash UniversityClaytonVIC 3800Australia Department of Materials Science and Engineering Kumamoto University2-39-1 KurokamiChuo-kuKumamoto 860-8555Japan Karlsruhe Nano Micro Facility(KNMF) Karlsruhe Institute of Technology(KIT)Hermann-von-Helmholtz-Platz 176344Eggenstein-LeopoldshafenGermany Institute for Applied Materials(IAM-WK) Karlsruhe Institute of Technology(KIT)Engelbert-Arnold-Straße 476131 KarlsruheGermany Aeronautical Manufacturing Technology Institute Shanghai Aircraft Manufacturing Co.Ltd.Shanghai 201324China

The Al-Mn-Sc-based alloys specific for additive manufacturing(AM)have been recently developed and can reach ultrahigh strength and adequate ***,these alloys commonly exhibit nonuniform plasticity during tensile deformation,which is a critical issue hindering their wider *** this work,the origin of this non-uniform plasticity of the alloys produced by laser powder bed fusion(LPBF)has been systematically investigated for the first *** results show that the loss of uniform plasticity in the alloy originates from microstructural regions containing equiaxed fine-grains(FGs)(~650nm in size)at the bottom of the melt *** micro-tensile tests,the strength of these FG regions can reach a peak of~630 *** this,an apparent yield drop occurs,followed by rapid strain *** FG behavior is associated with intermetallic particles along grain boundaries and a lack of uniform mobile dislocations during *** columnar coarse-grain(CG)regions in the remaining melt pools show uniform plasticity and moderate work ***,the quantitative calculations indicate that the solid solution strengthening in these two regions is ***,secondary Al_(3)Sc precipitates contribute to~260 MPa strength in the FG,compared to 310 MPa in the CG due to their different number *** addition,grain boundary strengthening can reach 230 MPa in the FG region;nearly double the CG region value.

关键词： Aluminium alloy Laser powder bed fusion Crystal plasticity Microstructures Strengthening