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Mesenchymal stem cell-and extracellular vesicle-based therapies for Alzheimer's disease:progress,advantages,and challenges

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Neural Regeneration Research 2023年第8期18卷 1645-1651页

作者： Renata Guedes de Jesus Gonçalves Juliana Ferreira Vasques Almir Jordão da Silva-Junior Fernanda Gubert Rosalia Mendez-otero Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa Rio de JaneiroBrazil Plataformas Inovadoras em Terapias Avançadas Departamento de Ciência e Tecnologia-Ministério da Saúde(DECIT-MS)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Brazil Programa redes de Pesquisa em Saúde no estado do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa redes de Pesquisa em Nanotecnologia no estado do Rio de Janeiro Rio de JaneiroBrazil

Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.

关键词： Alzheimer's disease amyloid-β cell therapy cell transplantation exosomes extracellular vesicles mesenchymal stem cell micro vesicles neuroinflammation tau protein

Gangliosides in nervous system development,regeneration,and pathologies

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Neural Regeneration Research 2023年第1期18卷 81-86页

作者： Juliana F.Vasques Renata Guedes de Jesus Gonçalves Almir Jordão da Silva-Junior Robertta Silva Martins Fernanda Gubert Rosalia Mendez-otero Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa redes de Pesquisa em Saúde no estado do Rio de Janeiro Rio de JaneiroBrazil Programa Rede NanoSaúde do estado do Rio de Janeiro Rio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa Rio de JaneiroBrazil

Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal *** to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different *** of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous *** GD3 and its o-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous *** in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological *** in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’*** this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.

关键词： 9acGD3 gangliosides GD1a GD1b GD3 glycolipids GM1 GM2 GM3 GM4 GT1b

An Algorithm for optimal Firewall Placement in IeC61850 Substations

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Journal of Power and energy engineering 2015年第4期3卷 16-22页

作者： Hermes eslava Luis Alejandro Rojas Danny Pineda Universidad Distrital Bogotá Colombia openlink Sistemas de redes de Datos S.A.S Bogotá Colombia

Recently, most electric power substations have adopted production control systems, such as SCADA systems, which communicate with field devices and remotely control processes from a computer screen. However, these systems together with protection measures and additional control actions (using protocol IeC61850) seem not to be enough to free substations of security attacks (e.g. virus, intruders, forgery or unauthorized data manipulation). This paper analyzes the main features of an electric power substation together with the aspects that might be significantly affected by cyber-attacks. The paper also presents the implementation of a specific security system (i.e. firewall-wise system) intended to protect a target distribution network.

关键词： Firewall Security Substations electric Power IeC61850

Mitochondrial DNA as a Risk Factor for False Positives in Case-Control Association Studies

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Journal of Genetics and Genomics 2015年第4期42卷 169-172页

作者： Antonio Salas Joanna L.elson Unidade de Xenética Instituto de Medicina Legaland Departamento de Anatomía Patolóxica e Ciencias ForensesFacultad de MedicinaUniversidad de Santiago de CompostelaGalicia 15782Spain Mitochondrial Research Group Institute of Genetic MedicineCentre for LifeNewcastle University Centre for Human Metabolomics North-West University

During the last decade, hundreds of studies have been pub- lished examining whether significant associations exist be- tween mitochondrial DNA （mtDNA） variants and/or haplogroups （clades） and particular diseases （generally com- mon/complex diseases）（Fig. 1）. However, several authors have gathered evidence indicating a high incidence of false positive findings in mtDNA case-control association studies. Raule et al. （2007） and Herrnstadt and Howell （2004） showed various problems affecting mtDNA case-control association studies. Salas et al.

关键词： DNA Mitochondrial DNA as a Risk Factor for False Positives in Case-Control Association Studies

Comprehensive Analysis of Pan-African Mitochondrial DNA Variation Provides New Insights into Continental Variation and demography

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Journal of Genetics and Genomics 2016年第3期43卷 133-143页

作者： Maria Cerezo Leonor Gusmao Viktor Cerny Nabeel Uddin denise Syndercombe-Court Alberto Gdmez-Carballa Tanja Gobel Peter M. Schneider Antonio Salas Unidade de Xenetica Departamento de Anatomia Patoloxica e Ciencias Forenses Instituto de Medicina Legal Facultade de Medicina Universidade de Santiago de Compostela Galicia 15782 Spain The Wellcome Trust Sanger Institute Hinxton CBIO 1SA UK DNA Diagnostic Laboratory Institute of Biology State University of Rio de Janeiro Rio de Janeiro 20550-900 Brazil IPATIMUP Institute of Molecular Pathology and Immunology of the University of Porto Porto 4200-465 Portugal Archaeogenetics Laboratory Institute of Archaeology of the Academy of Sciences of the Czech Republic Prague 118-01 Czech Republic Faculty of Life Sciences and Medicine King's College London London SE1 9NH UK Barts and The London School of Medicine and dentistry Blizard Institute London E1 2AT UK Institute of Legal Medicine Medical Faculty University of Cologne Cologne D-50823 Germany

Africa is the cradle of all human beings, and although it has been the focus of a number of genetic studies, there are many questions that remain unresolved. We have performed one of the largest and most comprehensive meta-analyses of mitochondrial DNA （mtDNA） lineages carried out in the African continent to date. We generated high-throughput mtDNA single nucleotide polymorphism （SNP） data （230 SNPs） from 2024 Africans, where more than 500 of them were additionally genotyped for the control region. These data were analyzed together with over 12,700 control region profiles collected from the literature, representing more than 300 population samples from Africa. Insights into the African homeland of humans are discussed. Phylogeographic patterns for the African continent are shown at a high phylogeographic resolution as well as at the population and regional levels. The deepest branch of the mtDNA tree, haplogroup L0, shows the highest sub-haplogroup diversity in Southeast and east Africa, suggesting this region as the homeland for modem humans. Several demographic estimates point to the coast as a facilitator of human migration in Africa, but the data indicate complex patterns, perhaps mirroring the effect of recent continental-scaled demographic events in re-shaping African mtDNA variability.

关键词： mtDNA Haplotype Haplogroup SNP MALDI-ToF

Carbon dioxide fixation into cyclic carbonates at room temperature catalyzed by heteroscorpionate aluminum complexes

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Green Chemical engineering 2022年第3期3卷 280-287页

作者： Felipe de la Cruz-Martinez Jose A.Castro-osma Agustin Lara-Sanchez Universidad de Castilla-La Mancha Departamento de Quimica InorganicaOrganica y Bioquimica-Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Facultad de Ciencias y Tecnologias QuimicasCiudad Real13071Spain Instituto de Investigaciones Quimicas(IIQ) Departamento de Quimica Inorganica and Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Consejo Superior de Investigaciones Cientificas(CSIC)and University of SevillaSevilla41092Spain Universidad de Castilla-La Mancha Departamento de Quimica InorganicaOrganica y Bioquimica-Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Facultad de FarmaciaAlbacete02071Spain

Novel mono-and bimetallic scorpionate aluminum compounds have been designed and characterized by spec-troscopic *** organometallics complexes,in combination with tetrabutylammonium bromide as cocatalyst,displayed good catalytic activity for the cycloaddition of styrene oxide and Co_(2) under ambient *** the compounds tested,monometallic complex 3 featuring diethylamino groups showed the highest catalytic *** catalytic system catalyzed the formation of cyclic carbonate products from their corresponding epoxides at room temperature and 1 bar of Co_(2) pressure in the absence of a solvent in good yields and excellent selectivities.

关键词： Co_(2) epoxides Cyclic carbonates Aluminum complexes

evaluating the influence of air pollution on solar radiation observations over the coastal region of Alicante(Southeastern Spain)

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Journal of environmental Sciences 2023年第4期126卷 633-643页

作者： Igor Gómez Sergio Molina Juan JoséGaliana-Merino department of Applied Physics Faculty of SciencesUniversity of AlicanteSection 99E-03080 AlicanteSpain Multidisciplinary Institute for environmental Studies(MIeS)“Ramón Margalef” University of AlicanteSection 99E-03690 AlicanteSpain department of Physics Systems Engineering and Signal TheoryUniversity of AlicanteSection 99E-03080 AlicanteSpain University Institute of Physics Applied to Sciences and Technologies University of AlicanteSection 99E-03080 AlicanteSpain

The present study evaluates ground-based downward surface shortwave radiation (Rs) over the coastal region of Alicante (Southeastern Spain).Hourly measurements collected over the eleven-year period 2010-2020 are *** weather stations located over the region capital,Alicante,have been selected as representative of urban and suburban *** additional weather stations far from the city have been selected representing rural *** is significantly reduced over the urban station during the morning hours within the winter season compared to the observations recorded over the suburban and rural stations,with a global mean difference of-81 and-120 W/m^(2)at 10 LT,***,no significant differences are obtained during the midday sun,with a global mean difference of-20 W/m^(2)between the urban and rural *** the aim of explaining these differences,the current paper investigates the relationship between Rsand different air pollutants:Nox,So_(2),and fine particulate matter (PM_(2.5)and PM_(10)) as well as the wind field measured at the urban and suburban *** results found in this work point towards a close relationship between Rsand Noxconcentrations annual cycles,which are also influenced by the prevailing wind circulations observed over the study area.A global mean Noxconcentration of 107μg/m^(3)is observed over the urban station at 10 LT during the winter *** contrast,these high concentrations are significantly reduced over the suburban station,with global mean value of 40μg/m^(3)at 10 LT,for this period of the year.

关键词： Solar radiation Air pollution Weather-concentration relationship Coastal cities Atmospheric conditions Wind field

eULeR SCHeMe FoR FRACTIoNAL deLAY SToCHASTIC DIFFeReNTIAL eQUATIoNS BY RoUGH PATHS TeCHNIQUeS

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Acta Mathematica Scientia 2019年第3期39卷 747-763页

作者： Johanna GARZoN Samy TINdeL Soledad ToRReS departamento de Matematicas Universidad Nacional de ColombiaBogota D.C.Colombia department of Mathematics Purdue University150 N.University StreetW.LafayetteIN 47907USA Facultad de Ingenierza CIMF AV Universidad de ValparaisoCasilla 123-V4059 ValparaisoChile

In this note, we study a discrete time approximation for the solution of a class of delayed stochastic differential equations driven by a fractional Brownian motion with Hurst parameter H ∈(1/2,1). In order to prove convergence, we use rough paths techniques. Theoretical bounds are established and numerical simulations are displayed.

关键词： Fractional Brownian motion stochastic differential equations rough paths,discrete time approximation

Animal models applied to acute-on-chronic liver failure:Are new models required to understand the human condition?

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World Journal of Clinical Cases 2022年第9期10卷 2687-2699页

作者： Jaciara Fernanda Gomes Gama Liana Monteiro da Fonseca Cardoso Jussara Machado Lagrota-Candido LuizAnastacio Alves Laboratory of Cellular Communication Oswaldo Cruz InstituteOswaldo Cruz FoundationRio de Janeiro 21045900Rio de JaneiroBrazil Laboratory of Immunopathology Department of ImmunobiologyFluminense Federal UniversityNiteroi 24210-200Rio de JaneiroBrazil

The liver is a multifaceted organ;its location and detoxifying function expose this organ to countless ***-on-chronic failure liver(ACLF)is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver *** infection environment,ascites,increased liver enzymes and prothrombin time,encephalopathy and fast-evolving multiorgan failure,leading to death,usually accompany *** pathophysiology remains poorly *** this context,animal models become a very useful tool in this regard,as understanding;the disease may be helpful in developing novel therapeutic methodologies for ***,although animal models display several similarities to the human condition,they do not represent all ACLF manifestations,resulting in significant *** initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-Ga IN,potentiating liver damage supports the methodologies applied to induce experimental *** entire methodology has been described mostly for ***,a quick Pub Med database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure *** findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.

关键词： Liver disease Acute-on-chronic liver failure Cirrhosis Acute decompensate event Translational study Animal models