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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado maría joséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri maría Pascual department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOd-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOd-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOd-,LRR-and pyrin domain-containing protein 3(NLRP3)

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differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： maría Norte-Muñoz maría Portela-Lomba Paloma Sobrado-Calvo diana Simón Johnny di Pierdomenico Alejandro Gallego-Ortega mar Pérez joséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz maría Teresa Moreno-Flores marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： joséM.Izquierdo Centro de Biología Molecular Severo Ochoa(CBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

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Combination of hydrotreating and delayed coking technologies for conversion of residue

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Chinese Journal of Chemical Engineering 2023年第11期63卷 209-219页

作者： josé A.d.Munoz Gabriel Páez Jorge Ancheyta Instituto Mexicano del Petróleo Eje Central Lázaro Cárdenas Norte 152Col.San Bartolo AtepehuacanMéxico City 07730México

Residue conversion by combining catalytic hydrotreating and delayed coking has been evaluated comparatively with both processes *** operating conditions are defined to achieve the greatest economic benefit for upgrading an atmospheric residue from a heavy crude oil.A literature model was adapted to simulate the hydrotreating reactor,and for delayed coking,correlations reported in the literature were *** results with both approaches were employed to calculate the techno-economic feasibility of the combined process *** combination of hydrotreating and delayed coking presented an increase in light fractions of 29% and a reduction in coke production of 47.8%.Based on the calculated net benefit values,it was demonstrated that the combination of hydrotreating and delayed coking is technically and economically better than using each process alone,with highest benefit of 57.7 USd·m^(-3).

关键词： Economic benefit Heavy oil Hydrotreating delayed coking

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Integral Representation Formulas Related to the Lamé–Navier System

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Acta Mathematica Sinica,English Series 2020年第12期36卷 1341-1356页

作者： Ricardo ABREU-BLAYA Juan BORY-REYES marcos Antonio-HERRERA-PELáez josé maría SIGARRETA-ALMIRA Facultad de Matemáticas Universidad Autónoma de GuerreroGuerreroMéxico Instituto Politécnico Nacional SEPI-ESIME-ZAC CD-MXMéxico

The paper provides integral representations for solutions to a certain first order partial differential equation natural arising in the factorization of the Lamé–Navier system with the help of Clifford analysis *** representations look like in spirit to the Borel–Pompeiu and Cauchy integral formulas both in three and higher dimensional setting.

关键词： Lamésystem Clifford analysis dirac operator

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ddRAd sequencing-based genotyping for population structure analysis in cultivated tomato provides new insights into the genomic diversity of Mediterranean‘da serbo’type long shelf-life germplasm

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Horticulture Research 2020年第1期7卷 1047-1060页

作者： Salvatore Esposito Teodoro Cardi Gabriele Campanelli Sara Sestili maría jos.díez Salvador Soler Jaime Prohens Pasquale Tripodi CREA Research Centre for Vegetable and Ornamental Crops Pontecagnano(SA)Italy CREA Research Centre for Vegetable and Ornamental Crops Monsampolo del Tronto(AP)TrontoItaly Instituto de Conservación y Mejora de la Agrodiversidad Valenciana Universitat Politècnica de València46022 ValenciaSpain

double digest restriction-site associated sequencing(ddRAd-seq)is a flexible and cost-effective strategy for providing in-depth insights into the genetic architecture of germplasm *** this methodology,we investigated the genomic diversity of a panel of 288 diverse tomato(Solanum lycopersicum L.)accessions enriched in‘da serbo’(called‘de penjar’in Spain)long shelf life(LSL)materials(152 accessions)mostly originating from Italy and *** rest of the materials originate from different countries and include landraces for fresh consumption,elite cultivars,heirlooms,and breeding *** from their LSL trait,‘da serbo’landraces are of remarkable interest for their *** identified 32,799 high-quality SNPs,which were used for model ancestry population structure and non-parametric hierarchical *** genetic subgroups were revealed,clearly separating most‘da serbo’landraces,but also the Spanish germplasm,suggesting a subdivision of the population based on type and geographical *** disequilibrium(Ld)in the collection decayed very rapidly withind SNPs showing contrasted minor frequency allele(MAF)in‘da serbo’materials,resulting in the identification of high frequencies in this germplasm of several mutations in genes related to stress tolerance and fruit maturation such as CTR1 and ***,a mini-core collection of 58 accessions encompassing most of the diversity was selected for further exploitation of key *** findings suggest the presence of a genetic footprint of the‘da serbo’germplasm selected in the Mediterranean ***,we provide novel insights on LSL‘da serbo’germplasm as a promising source of alleles for tolerance to stresses.

关键词： germplasm breeding shelf

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Morphoagronomic characterization and wholegenome resequencing of eight highly diverse wild and weedy *** and *** *** accessions used for the first interspecific tomato MAGIC population

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Horticulture Research 2020年第1期7卷 477-492页

作者： Pietro Gramazio Leandro Pereira-dias Santiago Vilanova Jaime Prohens Salvador Soler Javier Esteras Alfonso Garmendia maría jos.díez Faculty of Life and Environmental Sciences University of Tsukuba1-1-1 Tennodai305-8572 TsukubaJapan Instituto de Conservación y Mejora de la Agrodiversidad Valenciana Universitat Politècnica de ValènciaCamino de Vera 1446022 ValenciaSpain departamento de Ecosistemas Agroforestales Universitat Politècnica de ValènciaCamino de Vera 1446022 ValenciaSpain Instituto Agroforestal Mediterráneo Universitat Politècnica de ValènciaCamino de Vera 1446022 ValenciaSpain

The wild Solanum pimpinellifolium(SP)and the weedy *** ***(SLC)are largely unexploited genetic reservoirs easily accessible to breeders,as they are fully cross-compatible with cultivated tomato(*** ***).We performed a comprehensive morphological and genomic characterization of four wild SP and four weedy SLC accessions,selected to maximize the range of variation of both *** eight accessions are the founders of the first tomato interspecific multi-parent advanced generation inter-cross(MAGIC)*** morphoagronomic characterization was carried out with 39 descriptors to assess plant,inflorescence,fruit and agronomic traits,revealing the broad range of diversity *** of the morphological variation observed in SP was likely associated to the adaptation of the accessions to different environments,while in the case of SLC to both human activity and adaptation to the ***-genome resequencing of the eight accessions revealed over 12 million variants,ranging from 1.2 to 1.9 million variants in SLC and from 3.1 to 4.8 million in SP,being 46.3%of them(4,897,803)private *** genetic principal component analysis also confirmed the high diversity of SP and the complex evolutionary history of *** was also reflected in the analysis of the potential footprint of common ancestors or old introgressions identified within and between the two *** functional characterization of the variants revealed a significative enrichment of GO terms related to changes in cell walls that would have been negatively selected during domestication and *** comprehensive morphoagronomic and genetic characterization of these accessions will be of great relevance for the genetic analysis of the first interspecific MAGIC population of tomato and provides valuable knowledge and tools to the tomato community for genetic and genomic studies and for breeding purposes.

关键词： agronomic breeding MAGIC

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Efficient Handling of Lock Hand-off in dSM Multiprocessors with Buffering Coherence Controllers

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Journal of Computer Science & Technology 2012年第1期27卷 75-91页

作者： Benjamín Sahelices Agustín de dios Pablo Ibáez Víctor Vials-Yúfera josé maría Llabería Computer Science department and HiPEAC European Network of Excellence University of Valladolid Valladolid Spain Computer Science and Systems Engineering department I3A Research Institute and HiPEAC European Network of Excellence University of Zaragoza Zaragoza Spain Computer Architecture department and HiPEAC European Network of Excellence Polytechnic University of Catalua Barcelona Spain

Synchronization in parallel programs is a major performance bottleneck in multiprocessor systems. Shared data is protected by locks and a lot of time is spent on the competition arising at the lock hand-off. In order to be serialized, requests to the same cache line can either be bounced （NACKed） or buffered in the coherence controller. In this paper, we focus mainly on systems whose coherence controllers buffer requests. In a lock hand-off, a burst of requests to the same line arrive at the coherence controller. during lock hand-off only the requests from the winning processor contribute to progress of the computation, since the winning processor is the only one that will advance the work. This key observation leads us to propose a hardware mechanism we call request bypassing, which allows requests from the winning processor to bypass the requests buffered in the coherence controller keeping the lock line. We present an inexpensive implementation of request bypassing that reduces the time spent on all the execution phases of a critical section （acquiring the lock, accessing shared data, and releasing the lock） and which, as a consequence, speeds up the whole parallel computation. This mechanism requires neither compiler or programmer support nor ISA or coherence protocol changes. By simulating a 32-processor system, we show that using request bypassing does not degrade but rather improves performance in three applications with low synchronization rates, while in those having a large amount of synchronization activity （the remaining four）, we see reductions in execution time and in lock stall time ranging from 14% to 39% and from 52% to 7170, respectively. We compare request bypassing with a previously proposed technique called read combining and with a system that bounces requests, observing a significantly lower execution time with the bypassing scheme. Finally, we analyze the sensitivity of our results to some key hardware and software parameters.

关键词： distributed shared memory multiprocessors synchronization buffer coherence controller request bypass

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c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases

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Neural Regeneration Research 2023年第2期18卷 237-243页

作者： daniela A.Gutiérrez América Chandía-Cristi maría joséYáñez Silvana Zanlungo Alejandra R.Alvarez Cell Signaling Laboratory Department of Cellular and Molecular BiologyCenter for Aging and Regeneration(CARE)Millennium Institute on Immunology and ImmunotherapyBiological Sciences FacultyPontificia Universidad Católica de ChileSantiagoChile School of Medical Technology Health Sciences FacultyUniversidad San SebastianSede Los LeonesSantiagoChile department of Gastroenterology Faculty of MedicinePontificia Universidad Católica de ChileSantiagoChile

Our ability to learn and remember depends on the active formation,remodeling,and elimination of ***,the development and growth of synapses as well as their weakening and elimination are essential for neuronal *** structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic *** has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative *** is known about downstream signaling of activated N-methyl-d-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and *** non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the *** review focuses on c-Abl and its synaptic and neuronal ***,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative ***,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative ***,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against *** re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic *** summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how

关键词： actin cytoskeleton activity-dependent plasticity Alzheimer's disease c-Abl dendritic spines learning synapse synaptic plasticity transcription tyrosine kinase

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Heuristics of node selection criteria to assess robustness of world airport network

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Chinese Journal of Aeronautics 2017年第4期30卷 1473-1480页

作者： Manel SORIA Oriol LORdAN josmaría SALLAN department of Physics Aeronautics Engineering Universitat Politecnica de Catalunya-BarcelonaTech Terrassa 08222 Spain department of Management Universitat Politecnica de Catalunya-BarcelonaTech Terrassa 08222 Spain

The world airport network（WAN） is one of the networked infrastructures that shape today＇s economic and social activity, so its resilience against incidents affecting the WAN is an important problem. In this paper, the robustness of air route networks is extended by defining and testing several heuristics to define selection criteria to detect the critical nodes of the *** addition to heuristics based on genetic algorithms and simulated annealing, custom heuristics based on node damage and node betweenness are defined. The most effective heuristic is a multiattack heuristic combining both custom heuristics. Results obtained are of importance not only for advance in the understanding of the structure of complex networks, but also for critical node detection.

关键词： Adaptive strategy Air route networks Complex networks Intentional attacks Network robustness

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