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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)

Using mixed integer programming and airborne laser scanning to generate forest management units

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Journal of Forestry Research 2022年第1期33卷 217-226页

作者： Adrián pascual Sándor FTóth Forest Research Centre School of AgricultureUniversity of LisbonTapada da Ajuda1349-017 LisboaPortugal School of Forest Sciences University of Eastern FinlandP.O.Box 11180101 JoensuuFinland School of Environmental and Forest Sciences University of WashingtonSeattleWAUSA

Airborne laser scanning(ALS)has been widely applied to estimate tree and forest attributes,but it can also drive the segmentation of forest *** algorithms are the dominant technique in segmentation but spatial optimization using exact methods remains *** study presents a novel approach to segmentation based on mixed integer programming to create forest management units(FMUs).This investigation focuses on using raster information derived from ALS *** mainstream clustering algorithms were compared to the new MIP formula that simultaneously accounts for area and adjacency restrictions,FMUs size and homogeneity in terms of vegetation *** optimal problem solution was found when using less than 150 cells,showing the problem formulation is *** results for MIP were better than for the clustering algorithms;FMUs were more compact based on the intravariation of canopy height and the variability in size was *** MIP model allows the user to strictly control the size of FMUs,which is not possible in heuristic optimization and in the clustering algorithms *** definition of forest management units based on remote sensing data is an important operation and our study pioneers the use of MIP ALS-based optimal segmentation.

关键词： Segmentation Precision forestry Optimization Mathematical programming Airborne laser scanning

Using GEDI lidar data and airborne laser scanning to assess height growth dynamics in fast-growing species:a showcase in Spain

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Forest Ecosystems 2021年第1期8卷 182-198页

作者： Juan Guerra-Hernández Adrián pascual 3edata Centro de iniciativas empresariaisFundación CEL.O Palomar s/n27004 LugoSpain Forest Research Centre School of AgricultureUniversity of LisbonTapada da Ajuda1349-017 LisbonPortugal Center for Global Discovery and Conservation Science Arizona State UniversityHiloHA 96720USA

Background:The nASA’s Global Ecosystem Dynamics Investigation(GEDI)satellite mission aims at scanning forest ecosystems on a multi-temporal short-rotation *** GEDI data can validate and update statistics from nationwide airborne laser scanning(ALS).We present a case in the northwest of Spain using GEDI statistics and nationwide ALS surveys to estimate forest dynamics in three fast-growing forest ecosystems comprising 211,346 *** objectives were:i)to analyze the potential of GEDI to detect disturbances,ii)to investigate uncertainty source regarding non-positive height increments from the 2015–2017 ALS data to the 2019 GEDI laser shots and iii)to estimate height growth using polygons from the Forest Map of Spain(FMS).A set of 258 national Forest Inventory plots were used to validate the observed height ***:The spatio-temporal assessment from ALS surveying to GEDI scanning allowed the large-scale detection of *** mean annual height growths were 0.79(SD=0.63),0.60(SD=0.42)and 0.94(SD=0.75)m for Pinus pinaster,Pinus radiata and Eucalyptus spp.,*** median annual values from the ALS-GEDI positive increments were close to nFI-based growth values computed for Pinus pinaster and Pinus radiata,*** effect of edge border,spatial co-registration of GEDI shots and the influence of forest cover in the observed dynamics were important factors to considering when processing ALS data and GEDI ***:The use of GEDI laser data provides valuable insights for forest industry operations especially when accounting for fast ***,errors derived from positioning,ground finder and canopy structure can introduce uncertainty to understand the detected growth patterns as documented in this *** analysis of forest growth using ALS and GEDI would benefit from the generalization of common rules and data processing schemes as the GEDI mission is increasingly being utilized in the forest remote sensing community.

关键词： Forest inventory Productivity Multi-temporal LiDAR Full-waveform(FW) Satellite mapping

Combining spatial and economic criteria in tree-level harvest planning

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Forest Ecosystems 2020年第2期7卷 234-246页

作者： Petteri Packalen Timo Pukkala Adrián pascual School of Forest Sciences University of Eastern FinlandPO Box 11180101 JoensuuFinland Forest Research Center School of AgricultureUniversity of LisbonTapada da Ajuda1349-017 LisboaPortugal

Background:Modern remote sensing methods enable the prediction of tree-level forest resource ***,the benefits of using tree-level data in forest or harvest planning is not clear given a relative paucity of *** particular,there is a need for tree-level methods that simultaneously account for the spatial distribution of trees and other *** this study,we developed a spatial tree selection method that considers tree-level(relative value increment),neighborhood related(proximity of cut trees)and global objectives(total harvest).Methods:We partitioned the whole surface area of the stand to trees,with the assumption that a large tree occupies a larger area than a small *** was implemented using a power *** also utilized spatially explicit tree-level growth models that accounted for competition by neighboring *** was conducted with a variant of cellular *** proposed method was tested in stone pine(Pinus pinea L.)stands in Spain where we implemented basic individual tree detection with airborne laser scanning ***:We showed how to mimic four different spatial distributions of cut trees using alternative weightings of objective *** non-spatial selection did not aim at a particular spatial layout,the Single-tree selection dispersed the trees to be cut,and the Tree group and Clearcut selections clustered harvested trees at different ***:The proposed method can be used to control the spatial layout of trees while extracting trees that are the most economically mature.

关键词： Spatial optimization Tree selection Cellular automata Remote sensing Airborne laser scanning

Exosomes as mediators of neuron-glia communication in neuroinflammation

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neural Regeneration Research 2020年第5期15卷 796-801页

作者： María pascual Francesc Ibánez Consuelo Guerri Department of Molecular and Cellular Pathology of Alcohol Príncipe Felipe Research CenterValenciaSpain Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain

In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological *** nanovesicles (30–150 nm) contain proteins,RnAs and lipids,and their internalization by bystander cells could alter their normal *** review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous *** emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative *** the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and ***,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation.

关键词： biomarkers exosomes glial cells neuroinflammation neuron-glia commuication neurons neuropathology therapy

Re-folded structure of syn-orogenic granitoids(Padrón dome, nW Iberia):Assessing rheological evolution of cooling continental crust in a collisional setting

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Geoscience Frontiers 2019年第2期10卷 651-669页

作者： Rubén Díez Fernández Francisco J.Rubio pascual Luis Miguel Martín Parra Departamento de Geodinámica Estratigrafía y PaleontologíaFacultad de Ciencias GeológicasUniversidad Complutense de Madrid Instituto Geológico y Minero de Espana

This contribution discusses about the rheological, kinematic and dynamic frameworks necessary to produce recumbent and upright folds from syn-orogenic granitic massifs that were formed during an early stage of magma genesis related to the onset of a migmatitic dome. Syn-kinematic granitoids occurring within the high-grade infrastructure of the Padron migmatitic dome(nW Iberia) are deformed into largescale recumbent folds(D_2) that are later affected by upright folds(D_3). Petrostructural analysis of a selected area of this dome reveals that after a period of crustal thickening(D_1), nnW-directed extensional flow gave way to recumbent folds and penetrative axial plane foliation(S_2). Superimposed subhorizontal compression resulted in upright folds(D_3). A closer view into the dynamics of the dome allows exploring the factors that may condition the nucleation of folds with contrasting geometries during progressive deformation of molten continental crust. The formation of folds affecting syn-kinematic granitoids suggests a cooling metamorphic path in migmatitic domes. Active and passive folding mechanisms require a crystallizing(cooling) magma to nucleate folds. A more competent metamorphic host inhibits fold nucleation from much less competent magmas. As it crystallizes, magma becomes more rigid(competent),and approaches viscosity values of its host. Passive folding is favored when no significant competence contrast exists between magma and host, so this folding mechanism is more likely shortly after magma genesis and emplacement. In such conditions, and under dominant subhorizontal flow accompanied by flattening(D_2),passive folding would produce isoclinal recumbent geometries. Further magma cooling introduces a shift into the rheological behavior of partially molten crust. Thereon, crystallizing magma bodies would represent significant competence contrasts relative to their host. At this point, buckling is a more likely folding mechanism, and more regular, buckle fo

关键词： Recumbent folds Migmatitic domes Partial melting Crustal-derived granitoids Orogenic collapse Variscan orogen

new advances in hepatocellular carcinoma

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World Journal of Hepatology 2016年第9期8卷 421-438页

作者： Sonia pascual Iván Herrera Javier Irurzun Liver Unit Gastroenterology Department Interventional Radiological Unit Hospital General Universitario de Alicante03010 AlicanteSpain

AIM: To determine if gene-specific DnA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DnA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DnAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DnA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DnA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DnA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WnK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. COnCLUSIOn: These findings support the measurement of methylation markers in WBC DnA as biomarke

关键词： DnA methylation Epigenetics Hepatitis B virus Hepatocellular carcinoma White blood cell DnA

In vivo optical quality of posterior-chamber phakic implantable collamer lenses with a central port

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Eye and Vision 2021年第5期8卷 295-302页

作者： Robert Montés-Micó Francisco Pastor-pascual Enrique Artiaga-Elordi Ramón Ruiz-Mesa Pedro Tañá-Rivero Optics and Optometry&Vision Sciences Department University of Valenciac/o Dr Moliner 5046100 ValenciaSpain Oftalvist Clinic ValenciaSpain

Background:The aim of this review is to summarize the optical quality results in patients following the implantation of the V4c implantable collamer lens with a central port(ICL,STAAR Surgical Inc.).Main text:A literature search in several databases was carried out to identify those publications,both prospective,retrospective and/or comparative with other refractive surgery procedures,reporting optical outcomes of patients who were implanted with the V4c ICL model.A total of 17 clinical studies published between 2012 and 2021 were included in this review.A detailed analysis of the available data was performed including number of eyes,follow-up and preoperative spherical ***,the review focused on several optical parameters including higher-order aberrations(HOAs),modulation transfer function(MTF)cut-off frequency and Strehl *** review encompassed a total of 817 eyes measured using different optical devices based on Hartmann-Shack,retinal image quality measurement and ray-tracing technologies at different ***:The outcomes found in this review lead us to conclude that the ICL V4c model provides good optical quality,by means of different metrics,when implanted.

关键词： Implantable collamer lens Phakic Optical quality Higher order aberrations Modulation transfer function

Optimizing Electroless Plating of ni-Mo-P Coatings Toward Functional Ceramics

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Acta Metallurgica Sinica(English Letters) 2020年第3期33卷 437-445页

作者： n.Ma.Rosas-Laverde A.Pruna J.Cembrero M.pascual J.Orozco-Messana Department of Materials and Mechanical Engineering Universitat Politecnica de ValenciaValenciaSpain Department of Materials Escuela Politecnica NacionalQuitoEcuador Center for Surface Science and nanotechnology Polytechnic University of BucharestBucharestRomania Instituto de Tecnologia de Materiales Universitat Politecnica de ValenciaValenciaSpain

ni-Mo-P coatings are obtained at the surface of ceramic substrate by electroless deposition using palladium as a surface *** influence of catalyst activation conditions on coatings’ properties was assessed by structural,morphological,electrical,mechanical measurements and adhesion strength by using X-ray diffraction,field emission scanning electron microscopy,atomic force microscopy,Hall effect and nanoindentation techniques,*** results indicated the formation of dense,continuous and uniform coatings consisting mainly of *** coatings obtained at 300℃for 12 h exhibited the best electrical properties,namely resistivity of 9.32 μΩ cm,smaller roughness(Ra 0.090 μm) and average mechanical *** adhesion tests showed a firm adherence of the ni-Mo-P coatings to the ceramic *** results of this study could offer an approach for obtaining conducting ceramic substrates in order to be employed in photovoltaic *** performance of demonstrative heterojunction solar cell obtained with such metallized ceramic is indicative of the high potential of the ni-Mo-P electroless coatings for functional ceramics.

关键词： Electroless plating ni-Mo-P Ceramic Solar cell