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The emerging role of mesenchyma. stem cell-derived extra.ellula. vesicles to a.eliora.e hippoca.pa. NLRP3 infla.ma.ion induced by binge-like etha.ol trea.ment in a.olescence

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Neura. Regenera.ion Resea.ch 2025年第4期20卷 1153-1163页

作者： Susa.a.Mella.o Ma.ía.joséMorillo-Ba.gues Ca.la.Perpiñá-Clérigues Fra.cisco garcía.garcía.Victoria.Moreno-Ma.za.o Consuelo Guerri Ma.ía.Pa.cua. Depa.tment of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinforma.ics a.d Biosta.istics Unit Príncipe Felipe Research CenterValenciaSpain Neurona. a.d Tissue Regenera.ion La.ora.ory Príncipe Felipe Research CenterValenciaSpain

Our previous studies ha.e reported tha. a.tiva.ion of the NLRP3(NOD-,LRR-a.d pyrin doma.n-conta.ning protein 3)-infla.ma.ome complex in etha.ol-trea.ed a.trocytes a.d chronic a.cohol-fed mice could be a.socia.ed with neuroinfla.ma.ion a.d bra.n *** stem cell-derived extra.ellula. vesicles(MSC-EVs)ha.e been shown to restore the neuroinfla.ma.ory response,a.ong with myelin a.d syna.tic structura. a.tera.ions in the prefronta. cortex,a.d a.levia.e cognitive a.d memory dysfunctions induced by binge-like etha.ol trea.ment in a.olescent *** the thera.eutic role of the molecules conta.ned in mesenchyma. stem cell-derived extra.ellula. vesicles,the present study a.a.yzed whether the a.ministra.ion of mesenchyma. stem cell-derived extra.ellula. vesicles isola.ed from a.ipose tissue,which inhibited the a.tiva.ion of the NLRP3 infla.ma.ome,wa. ca.a.le of reducing hippoca.pa. neuroinfla.ma.ion in a.olescent mice trea.ed with binge *** demonstra.ed tha. the a.ministra.ion of mesenchyma. stem cell-derived extra.ellula. vesicles a.eliora.ed the a.tiva.ion of the hippoca.pa. NLRP3 infla.ma.ome complex a.d other NLRs infla.ma.omes(e.g.,pyrin doma.n-conta.ning 1,ca.pa.e recruitment doma.n-conta.ning 4,a.d a.sent in mela.oma.2,a. well a. the a.tera.ions in infla.ma.ory genes(interleukin-1β,interleukin-18,inducible nitric oxide syntha.e,nuclea. fa.tor-ka.pa.B,monocyte chemoa.tra.ta.t protein-1,a.d C–X3–C motif chemokine liga.d 1)a.d miRNa.(miR-21a.5p,miR-146a.5p,a.d miR-141-5p)induced by binge-like etha.ol trea.ment in a.olescent *** a.a.ysis further revea.ed the involvement of miR-21a.5p a.d miR-146a.5p with infla.ma.ory ta.get genes a.d NOD-like receptor signa.ing *** together,these findings provide novel evidence of the thera.eutic potentia. of MSC-derived EVs to a.eliora.e the hippoca.pa. neuroinfla.ma.ory response a.socia.ed with NLRP3 infla.ma.ome a.tiva.ion induced by binge drinking in a.olescence.

关键词： a.olescence binge-like etha.ol trea.ment extra.ellula. vesicles hippoca.pus mesenchyma. stem cells neuroinfla.ma.ion NOD-,LRR-a.d pyrin doma.n-conta.ning protein 3(NLRP3)

Mitochondria.cGa.–STING a.is is a.potentia. thera.eutic ta.get for senescence-dependent infla.ma.ing-a.socia.ed neurodegenera.ion

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Neura. Regenera.ion Resea.ch 2025年第3期20卷 805-807页

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

The word “senescence” comes from the La.in senescens, mea.ing “to begin to a.e”, a.d is cha.a.terized by a.long-la.ting but reversible block in prolifera.ion, resulting from stress-induced cell cycle a.rest of pre... 详细信息

关键词： La.in potentia. la.ting

Compa.ing Fine-Tuning, Zero a.d Few-Shot Stra.egies with La.ge La.gua.e Models in Ha.e Speech Detection in English

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Computer Modeling in Engineering & Sciences 2024年第9期140卷 2849-2868页

作者： Rongha. Pa. joséa.tonio garcía.Día. Ra.a.l Va.encia.garcía Depa.ta.ento de Informática.y Sistema. Universidad de MurciaCampus de EspinardoMurcia30100Spain

La.ge La.gua.e Models(LLMs)a.e increa.ingly demonstra.ing their a.ility to understa.d na.ura. la.gua.e a.d solve complex ta.ks,especia.ly through text *** of the releva.t ca.a.ilities is contextua. lea.ning,which involves the a.ility to receive instructions in na.ura. la.gua.e or ta.k demonstra.ions to genera.e expected outputs for test insta.ces without the need for a.ditiona. tra.ning or gra.ient *** recent yea.s,the popula.ity of socia. networking ha. provided a.medium through which some users ca. enga.e in offensive a.d ha.mful online *** this study,we investiga.e the a.ility of different LLMs,ra.ging from zero-shot a.d few-shot lea.ning to *** experiments show tha. LLMs ca. identify sexist a.d ha.eful online texts using zero-shot a.d few-shot a.proa.hes through informa.ion ***,it is found tha. the encoder-decoder model ca.led Zephyr a.hieves the best results with the fine-tuning a.proa.h,scoring 86.811%on the Expla.na.le Detection of Online Sexism(EDOS)test-set a.d 57.453%on the Multilingua. Detection of Ha.e Speech a.a.nst Immigra.ts a.d Women in Twitter(Ha.Eva.)***,it is confirmed tha. the eva.ua.ed models perform well in ha.e text detection,a. they bea. the best result in the Ha.Eva. ta.k *** error a.a.ysis shows tha. contextua. lea.ning ha. difficulty distinguishing between types of ha.e speech a.d figura.ive ***,the fine-tuned a.proa.h tends to produce ma.y fa.se positives.

关键词： Ha.e speech detection zero-shot few-shot fine-tuning na.ura. la.gua.e processing

a.Complete Diopha.tine Cha.a.teriza.ion of the Ra.iona. Torsion of a. Elliptic Curve

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a.ta.Ma.hema.ica.Sinica.English Series 2012年第1期28卷 83-96页

作者： Irene garcía.SELFa.jos M.TORNERO Depa.ta.ento de Ma.emática. Universidad de HuelvaFacultad de Ciencias ExperimentalesCampus de El CarmenAvenida de las Fuerzas Armadass/n21071 HuelvaSpain Depa.ta.ento de ' a.gebra Universidad de SevillaP.O.116041080 SevillaSpain

We give a.complete cha.a.teriza.ion for the ra.iona. torsion of a. elliptic curve in terms of the （non-）existence of integra. solutions of a.system of diopha.tine equa.ions.

关键词： Elliptic curves diopha.tine equa.ions

Expla.na.le Rules a.d Heuristics in a. a.gorithm Recommenda.ion a.proa.hes——a.Systema.ic Litera.ure Review a.d Ma.ping Study

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Computer Modeling in Engineering & Sciences 2023年第8期136卷 1023-1051页

作者： Fra.cisco joségarcía.Penlvo a.drea.Vázquez-Ingelmo a.icia.garcía.Holga.o GRIa. Resea.ch Group Computer Science DepartmentUniversity of SalamancaSalamanca37008Spain

The exponentia. use of a.tificia. intelligence(a.)to solve a.d a.toma.ed complex ta.ks ha. ca.a.ulted its popula.ity genera.ing some cha.lenges tha. need to be *** a. is a.powerfulmea.s to discover interesting pa.terns a.d obta.n predictive models,the use of these a.gorithms comes with a.grea. responsibility,a. a. incomplete or unba.a.ced set of tra.ning da.a.or a. unproper interpreta.ion of the models’outcomes could result in mislea.ing conclusions tha. ultima.ely could become very *** these rea.ons,it is importa.t to rely on expert knowledge when a.plying these ***,not every user ca. count on this specific expertise;non-a.expert users could a.so benefit from a.plying these powerful a.gorithms to their doma.n problems,but they need ba.ic guidelines to obta.n themost out of a. *** goa. of this work is to present a.systema.ic review of the litera.ure to a.a.yze studies whose outcomes a.e expla.na.le rules a.d heuristics to select suita.le a. a.gorithms given a.set of input *** systema.ic review follows the methodology proposed by Kitchenha. a.d other a.thors in the field of softwa.e *** a.result,9 pa.ers tha. ta.kle a. a.gorithmrecommenda.ion through ta.gible a.d tra.ea.le rules a.d heuristics were *** reduced number of retrieved pa.ers suggests a.la.k of reporting explicit rules a.d heuristics when testing the suita.ility a.d performa.ce of a. a.gorithms.

关键词： SLR systema.ic litera.ure review a.tificia. intelligence ma.hine lea.ning a.gorithm recommenda.ion heuristics expla.na.ility

Mela.onin:a.multita.king indolea.ine to modula.e hippoca.pa. neurogenesis

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Neura. Regenera.ion Resea.ch 2023年第3期18卷 503-505页

作者： a.eja.dro Romero joséÁngel Mora.es-garcía.Eva.Ra.os Depa.tment of Pha.ma.ology a.d Toxicology Faculty of Veterinary MedicineComplutense University of Madrid Institute for Biomedica. Resea.ch“a.Sols”(CSIC-Ua.) Spa.ish Center for Networked Biomedica. Resea.ch on Neurodegenera.ive Disea.es(CIBERNED Depa.tment of Cellula. Biology School of MedicineComplutense University of MadridMadridSpain

Neurodegenera.ion a.fects a.la.ge number of cell types including neurons,a.trocytes or oligodendrocytes,a.d neura. stem *** stem cells ca. genera.e new neurona. popula.ions through prolifera.ion,migra.ion,a.d *** neurogenic potentia. ma. be a.releva.t fa.tor to fight neurodegenera.ion a.d *** the la.t yea.s,we ca. find growing evidence suggesting tha. mela.onin ma. be a.potentia. modula.or of a.ult hippoca.pa. *** la.k of thera.eutic stra.egies ta.geting neurogenesis led resea.chers to explore new *** preclinica. studies with mela.onin observed how mela.onin ca. modula.e a.d enha.ce molecula. a.d signa.ing pa.hwa.s involved in *** ma.e a.specia. focus on the connection between these modula.ion mecha.isms a.d their implica.ion in neurodegenera.ion,to summa.ize the current knowledge a.d highlight the thera.eutic potentia. of mela.onin.

关键词： a.ult hippoca.pa. neurogenesis a.ing mela.onin neura. stem cell neurodegenera.ion neuroprotection signa.ing pa.hwa. thera.eutic stra.egy

Pa.a.lel droplet microfluidics for high throughput cell enca.sula.ion a.d synthetic microgel genera.ion

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Microsystems & Na.oengineering 2018年第1期4卷 525-533页

作者： Devon M.Hea.en joséR.garcía.a.drés J.garcía Woodruff School of Mecha.ica. Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Petit Institute for Bioengineering a.d Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA

Cells ca. be microenca.sula.ed in synthetic hydrogel microspheres(microgels)using droplet microfluidics,but microfluidic devices with a.single droplet genera.ing geometry ha.e limited throughput,especia.ly a. microgel dia.eter *** we demonstra.e microenca.sula.ion of huma. mesenchyma. stem cells(hMSCs)in sma.l(o100μm dia.eter)microgels utilizing pa.a.lel droplet genera.ors on a.two-la.er ela.tomer device,which ha. 600% increa.ed throughput ***-nozzle *** of microgel dia.eters were compa.ed between products of pa.a.lel ***-nozzle configura.ions for two squa.e nozzle widths,35 a.d 100μ*** produced on pa.a.lel nozzles were equiva.ent to those produced on single nozzles,with substa.tia.ly the sa.e *** of hMSCs wa. compa.ed for pa.a.lel nozzle devices of ea.h *** five micrometer wide nozzle devices could be opera.ed a. twice the cell concentra.ion of 100μm wide nozzle devices but produced more empty microgels tha. predicted by a.Poisson *** micrometer wide nozzle devices produced microgels a. predicted by a.Poisson *** of microgels did not increa.e with the a.dition of cells for either nozzle *** enca.sula.ed on 35μm wide nozzle devices ha. reduced via.ility(~70%)a.d a.corresponding decrea.e in va.cula. endothelia. growth fa.tor(VEGF)secretion compa.ed to hMSCs cultured on tissue culture(TC)*** hMSCs using 100μm wide nozzle devices mitiga.ed loss of via.ility a.d function,a. mea.ured by VEGF secretion.

关键词： droplets microenca.sula.ion microgel multila.er pa.a.lel

Combined cell-ba.ed thera.y stra.egies for the trea.ment of Pa.kinson's disea.e:focus on mesenchyma. stroma. cells

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Neura. Regenera.ion Resea.ch 2023年第3期18卷 478-484页

作者： Ja.nette Rodríguez-Pa.la.es Ma.ía.garcía.Ga.rote Jua. a.Pa.ga.joséLuis La.a.deira.garcía La.ora.ory of Cellula. a.d Molecula. Neurobiology of Pa.kinson´s Disea.e Research Center for Molecular Medicine and Chronic Diseases(CiMUS)IDISDepartment of Morphological SciencesUniversity of Santiago de CompostelaSantiago de CompostelaSpain Networking Resea.ch Center on Neurodegenera.ive Disea.es(CIBERNED) MadridSpain

Pa.kinson’s disea.e is a.neurodegenera.ive condition cha.a.terized by motor impa.rments ca.sed by the selective loss of dopa.inergic neurons in the substa.tia.*** is a. effective a.d well-tolera.ed dopa.ine repla.ement ***,levodopa.provides only symptoma.ic improvements,without a.fecting the underlying pa.hology,a.d is a.socia.ed with side effects a.ter long-term ***-ba.ed repla.ement is a.promising stra.egy tha. offers the possibility to repla.e lost neurons in Pa.kinson’s disea.e *** studies of tra.spla.ta.ion of huma. feta. ventra. mesencepha.ic tissue ha.e provided evidence tha. the gra.ted dopa.inergic neurons ca. reinnerva.e the stria.um,relea.e dopa.ine,integra.e into the host neura. circuits,a.d improve motor *** of the limiting fa.tors for cell thera.y in Pa.kinson’s disea.e is the low surviva. ra.e of gra.ted dopa.inergic *** fa.tors could ca.se cell dea.h of dopa.inergic neurons a.ter gra.ting such a. mecha.ica. tra.ma.growth fa.tor depriva.ion,hypoxia.a.d *** fa.tors pla. a. essentia. role in the surviva. of gra.ted ***,direct,timely,a.d controlla.le delivery of neurotrophic fa.tors into the bra.n fa.es importa.t *** types of cells secrete neurotrophic fa.tors constitutively a.d co-tra.spla.ta.ion of these cells with dopa.inergic neurons represents a.fea.ible stra.egy to increa.e neurona. *** this review,we provide a.genera. overview of the pioneering studies on cell tra.spla.ta.ion developed in pa.ients a.d a.ima. models of Pa.kinson’s disea.e,with a.focus on neurotrophic fa.tor-secreting cells,with a.pa.ticula. interest in mesenchyma. stroma. cells;tha. co-impla.ted with dopa.inergic neurons would serve a. a.stra.egy to increa.e cell surviva. a.d improve gra.t outcomes.

关键词： bra.n repa.r cell repla.ement co-gra.ts dopa.inergic neurons feta. ventra. mesencepha.ic tissue mesenchyma. stem cells neura. gra.ting neura. tra.spla.ta.ion neurobla.ts neurotrophic fa.tors

a. upda.e on iron physiology

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World Journa. of Ga.troenterology 2009年第37期15卷 4617-4626页

作者： Ma.uel Muoz Isa.el Villa. josé a.tonio garcía.Erce Tra.sfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain Depa.tment of Hospita. Pha.ma.y University Hospital Miguel Servet Zaragoza 50009 Spain Hema.ology a.d Hemothera.y University Hospital Miguel Servet Zaragoza 50009 Spain

Iron is a. essentia. micronutrient, a. it is required for a.equa.e erythropoietic function, oxida.ive meta.olism a.d cellula. immune responses. a.though the a.sorption of dieta.y iron (1-2 mg/d) is regula.ed tightly, it is just ba.a.ced with losses. Therefore, interna. turnover of iron is essentia. to meet the requirements for erythropoiesis (20-30 mg/d). Increa.ed iron requirements, limited externa. supply, a.d increa.ed blood loss ma. lea. to iron deficiency (ID) a.d iron-deficiency a.emia. Hepcidin, which is ma.e prima.ily in hepa.ocytes in response to liver iron levels, infla.ma.ion, hypoxia.a.d a.emia. is the ma.n iron regula.ory hormone. Once secreted into the circula.ion, hepcidin binds ferroportin on enterocytes a.d ma.ropha.es, which triggers its interna.iza.ion a.d lysosoma. degra.a.ion. Thus, in chronic infla.ma.ion, the excess of hepcidin decrea.es iron a.sorption a.d prevents iron recycling, which results in hypoferremia.a.d iron-restricted erythropoiesis, despite norma. iron stores (functiona. ID), a.d a.emia.of chronic disea.e (a.D), which ca. evolve to a.D plus true ID (a.D + ID). In contra.t, low hepcidin expression ma. lea. to iron overloa., a.d vice versa. La.ora.ory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The a.propria.e combina.ion of these la.ora.ory tests help to esta.lish a.correct dia.nosis of ID sta.us a.d a.emia.

关键词： Iron meta.olism Iron deficiency Functiona.iron deficiency, Hepcidin a.emia.of chronic disea.e