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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

Does wetland watershed land use influence amphibian larval development? A relevant effect of agriculture on biota

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Journal of Oceanology and Limnology 2019年第1期37卷 160-168页

作者： GARCíA-MU?OZ Enrique GUERRERO francisco ARECHAGA Garbi?e parra Gema Departamento de Biología Animal Biología Vegetal y Ecología Campus de las Lagunillas Centro de Estudios Avanzados en Ciencias de la Tierra Campus de las Lagunillas Departamento de Ciencias de la Salud Campus de las Lagunillas

Agriculture practices have been widely proposed as the major cause of amphibian population decline. However, the majority of these results have been based on laboratory experiments. The present study was conducted to test the repercussion of wetland sediment provenance on amphibian larval *** bufo larvae were used in two dif ferent treatments in an outdoor experiment, the ?rst one using sediment from one wetland surrounded by intensive agricultural practices, and the second using sediment with no record of agrochemical uses. A negative ef fect was observed in the agricultural treatment, from subcellular to individual level. The results showed that the sediment from agricultural practices watershed generates a reduction in survival. Furthermore, individuals that developed under this treatment showed a lower total length and a delay in the time necessary to complete metamorphosis; these features are connected with recruitment success. In the same way, biochemical analysis showed high values of lipid peroxidation in metamorphs developing in sediments from an agricultural area. Finally, the results obtained highlight the importance of considering the sediments, not only the water, as origin treatment, allowing us to understand the consequences on amphibian populations that inhabit areas af fected by intensive agriculture.

关键词： amphibian decline Bufo bufo survival ecotoxicology agricultural practices

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)

Green ionic metal-organic frameworks as nanocatalysts for CO_(2)fixation

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Nano Research 2025年第1期18卷 260-269页

作者： Nuria Martín Miguel Maireles-Porcar Julián Sánchez Velandia Belén Altava francisco G.Cirujano Eduardo García-Verdugo Departamento de Química Inorgánica y Orgánica Universidad Jaume IAv.Sos Baynats/nCastellóde la PlanaCastellón 12071Spain

Co,Ni,and Zn iso-reticular coordination polymers of 2,5-dihydroxyterphthalic acid(H_(2)dot)can be rapidly obtained under room temperature and aqueous conditions using either sodium or ammonium hydroxide as the bases to deprotonate the *** use of metal bromides and tetrabutylammonium hydroxide(TBAOH)as the base allows the green synthesis of ionic metal-organic frameworks(MOFs),characterized by X-ray diffraction(XRD),Fourier transform infrared(FTIR),scanning electron microscopy(SEM),thermo gravimetric analysis(TGA),H-nuclear magnetic resonance(NMR),elemental analysis,and X-ray photoelectron spectroscopy(XPS),and employed in the pressure,solvent,and additive-free CO_(2)fixation to epoxides by its cycloaddition to epichlorohydrin,exhibiting a cooperative behavior between the MOF and the ionic liquid formed within the framework,achieving TONs of the confined tetrabutylammonium bromide(TBABr)up to 700.

关键词： metal-organic frameworks(MOFs) ionic liquids heterogeneous catalysis CO_(2)conversion

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

The challenge of drug resistance in pancreatic ductal adenocarcinoma:a current overview

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Cancer Biology & Medicine 2019年第4期16卷 688-699页

作者： francisco Quinonero Cristina Mesas Kevin Doello Laura Cabeza Gloria Perazzoli Cristina Jimenez-luna Ana Rosa Rama Consolación Melguizo Jose Prados Institute of Biopathology and Regenerative Medicine(IBIMER) Center of Biomedical Research(CIBM)University of Gran adaz Gran ada 18100Spain Department of An atomy and Embryology Faculty of Medici neUn iversity of Gran adaGranada 18071Spain Instituto Biosanitario de Granada(ibs.GRANADA) Granada 18014Spain Medical Oncology Service Virgen de las Nieves HospitalGranada 1812Spain Department of Oncology Ludwig Institute for Cancer ResearchUniversity of LausanneEpalinges 1066Switzerland Department of Health Scienee University of JaenJa6n 23071Spain

Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer *** delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and ***,these strategies are insufficient to improve its poor *** the advances made in chemotherapy(***-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug ***,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and ***,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(***-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and ***,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage *** the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.

关键词： Pancreatic ductal adenocarcinoma chemotherapy drug resistance cancer stem cells therapeutic strategies

Ayahuasca:Uses,Phytochemical and Biological Activities

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Natural Products and Bioprospecting 2019年第4期9卷 251-265页

作者： Edgar Antonio Estrella‑parra Julio Cesar Almanza‑Pérez francisco Javier Alarcón‑Aguilar Laboratorio de Farmacología.Dpto.Ciencias de la Salud.Div.C.B.S.Universidad Autónoma Metropolitana Unidad Iztapalapa.Av.San Rafael Atlixco No.186Col.Vicentina09340 Mexico CDMXMexico Laboratorio de Fitoquímica Laboratorio de FarmacognosiaLaboratorio de Fisiología VegetalUnidad UBIPROFES-IztacalaUNAMTlalnepantla de Baz54090 Mexico CDMXMexico

Ayahuasca(caapi,yajé),is a psychoactive brew from the Amazon Basin region of South America traditionally considered a“master plant.”It is prepared as a decoction from Banisteriopsis caapi and Psychotria viridis,which it is thought that it stimulates creative thinking and visual *** healers of the Orinoco and Amazon basins have used traditionally ayahuasca as a healing tool for multiple purposes,particularly to treat psychological disorders in the patients,with some beneficial effects experimentally and clinically ***,several syncretic religions,as the“Uniao de Vegetal”(UDV)group in Brazil,have been spread around the *** use of ayahuasca has been popularized by internet and smart-shops,bringing the psychoactive substance to new highs,emerging new“ayahuasqueros.”Ayahuasca has alkaloids asβ-carbolines and dimethyltryptamines,which inhibit the monoamine oxidase and active the 5-HT_(2A)(5-hydroxytryptamine)receptor,respectively,resulting in hallucinations in the *** induces a psychedelic change in the anteroposterior coupling of the electrophysiological brain oscillations in *** ayahuasca beverage is generating pharmacological,commercial and spiritual interest among the scientific community,government people,and different populations *** goal of this article is to report about the uses,chemistry and biological activities of ayahuasca.

关键词： Ayahuasca Banisteriopsis caapi Psychotria viridis-dimethyltryptamine β-carbolines Psychotherapy

End-of-life care in a cardiology department： have we improved？

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Journal of Geriatric Cardiology 2016年第7期13卷 587-592页

作者： Juan Rulz-Garcia Pablo Dlez-Villanueva Ana Ayesta Vanessa Brufia Lourdes M Figueiras-Graillet Laura Gallego-parra francisco Fernandez-Aviles Manuel Martinez-Selles Department of Cardiology Hospital General Universitario Gregorio Maranon Calle Doctor Esquerdo Madrid Spain Department of Cardiology Hospital Universitario de Torrejon Calle Mateo Inurria Torrejon de Ardoz Madrid Spain Universidad francisco de Vitoria Carretera Pozuelo a Majadahonda Pozuelo de Alareon Madrid Spain Department of Cardiology Hospital Universitario de la Princesa Calle de Diego de Leon Madrid Spain Departmet of Cardiology Hospital Universitario del Sureste Ronda del Sur Arganda del Rey Madrid Spain Universidad Complutense de Madrid Av. Seneca Madrid Spain Universidad Europea de Madrid Urbanizacion E1Bosque Calle Tajo Villaviciosa de Odon Madrid Spain

Background End-of-life care is not usually a priority in cardiology departments. We sought to evaluate the changes in end-of-life care after the introduction of a do-not-resuscitate （DNR） order protocol. Methods ＆ Results Retrospective analysis of all deaths in a cardiology department in two periods, before and after the introduction of the protocol. Comparison of demographic characteristics, use of DNR orders, and end-of-life care issues between both periods, according to the presence in the second period of the new DNR sheet （Group A）, a conven- tional DNR order （Group B） or the absence of any DNR order （Group C）. The number of deaths was similar in both periods （n = 198 vs. n = 197）. The rate of patients dying with a DNR order increased significantly （57.1% vs. 68.5%; P = 0.02）. Only 4% of patients in both periods were aware of the decision taken about cardiopulmonary resuscitation. Patients in Group A received the DNR order one day earlier, and 24.5% received it within the first 24 h of admission （vs. 2.6% in the first period; P 〈 0.001）. All patients in Group A with an implantable cardioverter defibrillator （ICD） had shock therapies deactivated （vs. 25.0% in the first period; P = 0.02）. Conclusions The introduction of a DNR order protocol may improve end-of-life care in cardiac patients by increasing the use and shortening the time of registration of DNR orders. It may also contribute to increase ICD deactivation in patients with these orders in place. However, the introduction of the sheet in late stages of the disease failed to improve patient participation.

关键词： Cardiology Cardiopulmonary resuscitation End-of-life Palliative care