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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-Pastor Mónica García Eva Ayet Anna Cabot javier burgueño Xavier Monroy Bertrand Aubel Xavier Codony Luz Romero Rosalía Pascual Maria Teresa Serafini Gregorio Encina Carmen Almansa Daniel Zamanillo Manuel Merlos JoséMiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1R)and mu-opioid(MoR)***-73502 is an antagonist at the *** behaved as a partial MoR agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on MoR at both signalling *** its partial MoR agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1R and MoR to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1R antagonist and partial MoR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor Mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

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Transformation of leather waste into microwave-activated and N-doped carbon for Li-S batteries

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新型炭材料(中英文) 2025年

作者： Carolina Pano-Azucena Roberto Rosas-Rangel Miguel olvera-Sosa David Salvador González-González Rene Rangel-Mendez Luis Felipe Chazaro-Ruiz Miguel Avalos-Borja javier Antonio Arcibar-orozco CIATEC.Center for Applied Innovation in Competitive Technologies Tecnologico de Monterrey School of Engineering and Sciences Instituto Potosino de Investigación Científica y Tecnológica Universidad Autónoma de Coahuila Facultad de SistemasCiudad Universitaria

The use of carbon from waste biomass has the potential to buffer the drawbacks of Li-S batteries and improve their overall performance. Chrome-Tanned-LeatherShavings(CTLS) are undesirable wastes, highly available for transformation into porous carbon. Microwave activation is an efficient state-of-the-art procedure to obtain unique porous structures and nitrogen incorporation can improve the performance of porous carbons. This study proposes the transformation of CTLS into a microwave activated porous carbon, and then was modified to introduce nitrogen. A microporous activated carbon with a specific surface area of 556 m2g-1 with honeycomb-like structure was obtained. Both urea thermal decomposition and ethanolamine impregnation improves the nitrogen and amine presence of surface groups. However,the results indicated that only urea treatment was effective in improving the initial capacity of the cell(1363 mAhg-1), which is probably linked with the sorption of long-chain polysulfides. This investigation confirms that it is possible to obtain carbon materials from CTLS, for use as sulfur-host cathodes in Li-S batteries, and improve their performance with urea thermal decomposition. Furthermore, a Radial basis function neural network was fitted to provide statistical support to the experimental results. The trained model corroborated the importance of nitrogen content of the carbons in the discharge capacity of the cells.

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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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Post-transcriptional regulation of seed dormancy and germination: Current understanding and future directions

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Plant Communications 2021年第4期2卷 1-22页

作者： Rocío Soledad Tognacca javier Francisco Botto Consejo Nacional de Investigaciones Científicas y Técnicas Universidad de Buenos AiresInstituto de FisiologíaBiología Molecular y Neurociencias(IFIBYNE)Facultad de Ciencias Exactas y NaturalesCP1428 Buenos AiresArgentina Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Investigaciones Fisiològicas y Ecològicas Vinculadas a la Agricultura(IFEVA)Facultad de AgronomíaCP1417 Buenos AiresArgentina

Seed dormancy is a developmental checkpoint that prevents mature seeds from germinating under conditions that are otherwise favorable for *** and light are themost relevant environmental factors that regulate seed dormancy and *** environmental cues can trigger molecular and physiological responses including hormone signaling,particularly that of abscisic acid and *** balance between the content and sensitivity of these hormones is the key to the regulation of seed *** and light tightly regulate the transcription of thousands of genes,as well as other aspects of gene expression such asmRNAsplicing,translation,and *** remodeling determines specific transcriptional outputs,and alternative splicing leads to different outcomes and produces transcripts that encode proteins with altered or lost *** regulation of chromatin remodeling and alternative splicing may be highly relevant to seed ***,microRNAs are also critical for the control of gene expression in *** review aims to discuss recent updates on post-transcriptional regulation during seed maturation,dormancy,germination,and post-germination *** propose future prospects for understanding howdifferent post-transcriptional processes in crop seeds can contribute to the design of genotypes with better performance and higher productivity.

关键词： alternative splicing chromatin remodeling dormancy germination microRNA(miRNA) seeds

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The ALPPS procedure-As Limited Procedures as Possible, leads to improved Survival

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Hepatobiliary Surgery and Nutrition 2022年第4期11卷 636-639页

作者： Ruben Ciria javier Briceño Unit of Hepatobiliary Surgery and Liver Transplantation University Hospital Reina SofíaCórdobaSpain

The history of procedures for liver regeneration in the context of extended resections changed with the incorporation of Associating Liver Partition to Portal Vein Ligation in Two-Staged Hepatectomy(ALPPS)(1).The main well-known advantages of the ALPPS procedure are a fast and feasible increase in liver volume within a short period of time which leads to a second-stage procedure in 2-3 weeks.

关键词： ALPPS Survival liver

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The Rhyacian El Cortijo suture zone: Aeromagnetic signature and insights for the geodynamic evolution of the southwestern Rio de la Plata craton, Argentina

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Geoscience Frontiers 2014年第1期5卷 43-52页

作者： Carlos J.Chernicoff Eduardo o.Zappettini javier Peroni Council for Scientifc and Technical Research (CoNICET) Argentina Argentine Geological-Mining Survey (SEGEMAR) Argentina

The amalgamation of the southern Rio de la Plata craton involves two possibly coeval Rhyacian sutures associated with the Transamazonian orogeny, rather than a single one as previously envisaged, i.e. the El Cortijo suture zone and the Salado suture. We circumscribe the Tandilia terrane to the region between these two sutures. The E1 Cortijo suture zone runs along a roughly WNW oriented magnetic low aligned along the southern boundary of the Tandilia terrane, i.e. boundary between the Tandilia and Balcarce terranes. This extensive magnetic low, ca. 300 km long, and ca. 90 km wide, would be caused by demagnetization associated with shearing. At a more local scale, the trend of the El Cortijo suture zone often turns toward the E-W. At this scale, WNW trending tholeiitic dykes of Statherian age are seen to cut the Rhyacian E1 Cortijo suture zone. Spatially associated with the El Corti]o suture zone, there are small magnetic highs interpreted to be related to unexposed basic bodies of ophiolitic nature related to those forming part of the El Cortijo Formation. We envisage the pre-Neoproterozoic evolution of the Tandilia belt to have been initiated by the extension of Neoarchean （ - 2650 Ma） crust occurred during Siderian times （2500-2300 Ma）, causing the separation between the Balcarce, Tandilia and Buenos Aires terranes, and the development of narrow oceans at both north and south sides of the Tandilia terrane, accompanied by -2300-2200 Ma sedi- mentation over transitional -continental to oceanic- crust, and arc magmatism developed in the Tan- dilia terrane. The island arc represented by the El Cortijo Formation was also developed at this time. At late Rhyacian times, it occurred in both the closure of the narrow oceans developed previously, the entrapment of the El Cortijo island arc, as well as anatectic magmatism in the Balcarce terrane.

关键词： El Cortijo suture zone Rhyacian Rio de la Plata craton Aeromagnetics

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New perspectives in occult hepatitis C virus infection

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World Journal of Gastroenterology 2012年第23期18卷 2887-2894页

作者： Vicente Carreño javier Bartolomé Inmaculada Castillo Juan Antonio Quiroga Foundation for the Study of Viral Hepatitis C/Guzmán el Bueno 7228015 MadridSpain

occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.

关键词： occult hepatitis C virus Hepatitis C virusRNA Liver Peripheral blood mononuclear cells T-cellresponse

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Nanoparticles embedded into glass matrices:glass nanocomposites

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Frontiers of Materials Science 2022年第3期16卷 1-81页

作者： javier FoNSECA Department of Chemical Engineering Northeastern UniversityBoston 02115USA

Research on glass nanocomposites(GNCs)has been very active in the past *** have attracted—and still do—great interest in the fields of optoelectronics,photonics,sensing,electrochemistry,catalysis,biomedicine,and *** this review,the potential applications of GNCs in these fields are briefly described to show the reader the possibilities of these *** most important synthesis methods of GNCs(melt-quenching,sol-gel,ion implantation,ion-exchange,staining process,spark plasma sintering,radio frequency sputtering,spray pyrolysis,and chemical vapor deposition techniques)are extensively *** major aim of this review is to systematize our knowledge about the synthesis of GNCs and to explore the mechanisms of formation and growth of NPs within glass *** size-controlled preparation of NPs within glass matrices,which remains a challenge,is essential for advanced ***,a thorough understanding of GNC synthesis techniques is expected to facilitate the preparation of innovative GNCs.

关键词： glass nanocomposites melt-quenching sol-gel ion implantation ion-exchange

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