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neural Regeneration Research 2024年第3期19卷 542-547页

作者： maría norte-Muñoz David garc.a-Bernal Diego garc.a-Ayuso Manuel Vidal-Sanz 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 Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical *** stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and *** studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional ***,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous ***,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

The immune system:uncharted pathways between senses and the brain

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neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： noelia Casares mar Cuadrado-Tejedor Ana garc.a-Osta Juan JoséLasarte Immunology and Immunotherapy Program Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Division of Gene Therapy for neurological Disorders Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Pathology Anatomy and Physiology DepartmentSchool of MedicineUniversity of NavarraIDISNAPamplonaSpain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth *** perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CnS)and prompting physiological changes in other biological *** addition to the direct effects of sense-induced mediators in the brain.

关键词： prompt system transmitting

Using fused filament fabrication to improve the tribocorrosion behaviour of 17-4 PH SS in comparison to other metal forming techniques

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Friction 2024年第10期12卷 2325-2343页

作者： Cristina garc.a-CABEZÓn Juan Alfonso nARAnJO Celia garc.a-HERnÁnDEZ Cristina BERGES Gemma HERRAnZ Fernando marTÍn-PEDROSA Materials Engineering E.I.I.Universidad de ValladolidValladolid 47011Spain InEI-Escuela Técnica Superior de Ingeniería Industrial(ETSII) Universidad de Castilla La ManchaCastilla-La Mancha 13071Spain

Fused filament fabrication(FFF)is one of the additive manufacturing processes which has gained more interest because of its simplicity and *** technology is similar to the conventional metal injection moulding(MIM)process,consisting of the feedstock preparation of metal powder and polymer binders,followed by layer-by-layer 3D printing(FFF)or injection(MIM)to create green parts and,finally,debinding and ***,both technologies provide near-dense *** work presents an in-depth study of the processing method’s *** porosity,microstructure,hardness,corrosion,and tribocorrosion behaviour are compared for 17-4 PH SS samples processed from powder by additive manufacturing using FFF and MIM,as well as conventional powder metallurgy(PM)*** samples exhibited the highest macro and microhardness,while corrosion behaviour was similar for both MIM and FFF samples,but superior in comparison to conventional PM ***,the FFF-as fabricated samples displayed a significant improvement in tribocorrosion resistance that could be explained by the higher proportion of delta ferrite and retained austenite in their microstructure.

关键词： 17-4 PH SS fused filament fabrication(FFF) metal injection moulding(MIM) corrosion behaviour powder metallurgy(PM) tribocorrosion behaviour

Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk

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Research 2024年第3期6卷 417-432页

作者： Laura garc.a-Mendívil maría Pérez-Zabalza Antoni Oliver-Gelabert Josémaría Vallejo-Gil Javier Fañanás-Mastral Manuel Vázquez-Sancho Javier AndréBellido-Morales Alexánder Sebastián Vaca-núñez Carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental Medicine and Biology of Cuyo(IMBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

Calibration of the DEM sliding friction and rolling friction parameters of a cohesionless bulk material

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Particuology 2024年第9期92卷 126-139页

作者： Jonatan marín Pérez Tugrul Comlekci Yevgen Gorash Donald MacKenzie University of Strathclyde 75 Montrose StreetG11XJGlasgowUnited Kingdom

The discrete element method(DEM)has become a valuable tool for understanding the mechanical behaviour of granular assemblies,however,the accuracy of the DEM simulations depends on several interaction parameters such as the sliding friction and rolling friction ***,these parameters are estimated using bulk calibration approach(BCA)where the draw down test has been suggested as an effective way to approach these *** test provides up to four bulk criteria,the angle of repose,shear angle,mass flow rate and the mass loss which are used to narrow down the possible ***,there is still more research needed around it to fully understand how this methodology *** experimental and numerical study was carried out using the draw down test to assess the influence of different mass flow rates and particle shapes on DEM parameters for a cohesionless bulk *** is concluded that use of multi-sphere particles and three aperture sizes in the draw down test to calibrate the sliding and rolling friction parameters of a cohesionless bulk material can converge to a small feasible region in which a single combination of the friction coefficients can be *** calibrated sliding and rolling friction coefficients were validated using multi-sphere particles,where the maximum deviation was 5.9%from the experimental values.

关键词： Discrete element method Calibration Draw down Sliding friction Rolling friction Particle shape

Stress tensors and quantification of fracture patterns to analyze connectivity and potential fluid flow in a mesa landform of the northern Andes

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Journal of Mountain Science 2024年第1期21卷 271-291页

作者： garc.a-ARIAS Sergio VELAnDIA Francisco ALVAREZ Angélica SAnABRIA-GÓMEZ JoséD TARAZOnA Yessenia VARGAS maría Camila Escuela de Geología Universidad Industrial de SantanderCra.27 Calle 9BucaramangaColombia Escuela de Física Universidad Industrial de SantanderCra.27 Calle 9BucaramangaColombia

This work applies stress tensors inversions and quantification of fracture patterns along the Mesa de Los Santos, in the Eastern Cordillera of Colombia, to better understand the potential fluid flow. It thus contributes to the conceptual hydrogeological model. The area was subdivided into three blocks, separated by the nW Potreros and the Los Santos faults, having minor inner faults of different orientations. This separation facilitates the analysis of the fractures measured in the field, which in general show high dip angles and a conjugate geometry in the northern block, tension fractures(Mode I) in the central block, and a random distribution in the southwestern block. WinTensor treatment of slickensides yielded a maximum horizontal stress(SHmax) of 111o, which coincides with the WnW-ESE tensor observed from the conjugate and tension joints. We then used Frac Pa Q to generate interpolation maps of fracture intensity and density. The maps show the highest values in the central block and the lowest in the northern block,where the precipitation is higher, causing intensive rock weathering and homogenization of the fracture planes. Although the highest values of connectivity by line are found to the south of the mesa, we suggest the possibility of greater flow from the recharge zone(nE) along bedding planes and open nW-SE fractures.

关键词： Mesa de Los Santos Colombia Win-Tensor FracPaQ Strike-slip faults Fractured aquifers

Metabolomics for the diagnosis of bladder cancer: A systematic review

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Asian Journal of Urology 2024年第2期11卷 221-241页

作者： Herney Andrés garc.a-Perdomo Angélica maría Dávila-Raigoza Fernando Korkes Division of Urology/Urooncology Department of SurgerySchool of MedicineUniversidad del ValleCaliColombia UROGIV Research Group School of MedicineUniversidad del ValleCaliColombia Urologic Oncology Division of UrologyABC Medical SchoolSao PauloBrazil

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa ***: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic ***: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes ***: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, rib

关键词： Metabolite Metabolomics Bladder cancer Metabolomicsprofile

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-martínez mar Cuadrado-Tejedor Ana garc.a-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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 garc.a-garc.a 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)

Habitat and food preferences of European rabbits in core and edge populations along the invasion front PatagoniaMonte,Argentina

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Current Zoology 2024年第3期70卷 310-319页

作者： Sabrina Yasmin Bobadilla maría A.Dacar Fabián M.Jaksic Ricardo A.Ojeda maría Fernanda Cuevas Ecología de Mamíferos de Tierras Secas IADIZACCT-Mendoza CONICETAv.Ruiz Leal s/nParque General San MartínMendoza 5500MendozaArgentina Laboratorio de Filogeografía Taxonomía Integrativa y Ecología(LFTIE)IADIZACCT-Mendoza CONICETAv.Ruiz Leal s/nParque General San MartínMendoza 5500MendozaArgentina Center of Applied Ecology and Sustainability(CAPES) Pontifcia Universidad Católica de ChileAv.Libertador Bernardo O'Higgins 340Santiago 8320000Región MetropolitanaChile

The European rabbit Oryctolagus cuniculus is an exotic herbivorous mammal undergoing an active phase of geographical expansion in the arid ecosystems of *** Adaptive Flexibility Hypothesis states that populations at the range edge(new populations)will exhibit greater fexibility in the use of resources compared with populations located in the range core(older populations).The objective of this work was to compare the rabbit’s use of spatial and trophic resources in relation to the establishment time of their *** sampling was carried out for 2 years(2017 and 2018)in sites with different establishment times for rabbit *** sampling stratifed by type of habitat was applied using 115 fxed strip transects of 1,000 m^(2) laid out across the study *** rabbit signs were recorded in each transect,and environmental and anthropic variables were *** results show that the individuals from the range edge are more selective in the use of habitat than those from the range *** the microhabitat level,we observed a pattern in the particular components of habitat use by rabbits mainly linked to food availability and proximity to *** a trophic perspective,rabbits could show fexible adjustment to novel conditions and environments in the range *** variability in resource use by the European rabbit confrms its ecological fexibility,pivotal for their advance toward new environments in Argentina.

关键词： Arid ecosystems invasive species novel environments range invasion spatial use trophic use