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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez mar.a fernanda González Ana mar.a Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDis) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó Joan serrano-marín Rafael Rivas-santisteban Jaume Lillo Molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network Center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain school of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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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： mar.a 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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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： mar.a Norte-Muñoz mar.a Portela-Lomba Paloma sobrado-Calvo Diana simón Johnny Di Pierdomenico Alejandro Gallego-Ortega mar Pérez JoséMCabrera-Maqueda Javier sierra Manuel Vidal-sanz mar.a Teresa Moreno-Flores mar.a 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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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 mar.a JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri mar.a 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)

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A demand side management approach to increase self-consumption in buildings

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Building simulation 2023年第2期16卷 317-335页

作者： Carlos fernández Bandera Gabriela Bastos Porsani mar.a fernández-Vigil Iglesias school of Architecture University of Navarra31009 PamplonaSpain

There is a growing interest in increasing the presence of renewable energy in the electric *** production from grid-connected systems is leading this growth in terms of *** this development,concern about network security has emerged,because excesses of intermittent renewable energy on the grid could exceed voltage ***-consumption,understood as the capacity of the producer to consume his or her own production,can partially solve these *** controllable loads,such as heating and cooling,represent 50%of the total amount of energy consumed by buildings;the proper allocation of these loads could be a driving force for *** this study,a demand side management strategy is proposed based on a building energy model equipped with an inverter heat pump coupled with a photovoltaic *** goal is to maximize the use of local energy from the photovoltaic plant(self-consumption),reducing the export and import of energy to and from the *** goal is achieved by optimizing the set-points in each *** array of optimal set-points over six years is *** results show the capacity of the methodology to match similar values of self-consumption(70%in winter and 50%in summer)obtained by strategies based on chemical *** findings are shown in an energy matching chart at different levels of detail(yearly and monthly).Color bubbles are added to the matching chart to help visualize the unmatched energy of the system *** comparison with actual model predictive control technologies,this study’s strategy offers great simplicity and a large saving in computational time.

关键词： sensor data internal thermal mass energy simulation EnergyPlus inverse model

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Elastic smart Contracts in Blockchains

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IEEE/CAA Journal of Automatica sinica 2021年第12期8卷 1901-1912页

作者： schahram Dustdar Pablo fernández Josémar.a García Antonio Ruiz-Cortés Distributed systems Group Vienna University of TechnologyWien 1040Austria smart Computer systems Research and Engineering Lab Research Institute of Computer EngineeringUniversity of SevillaSevilla 41012Spain

In this paper,we deal with questions related to blockchains in complex Internet of Things(IoT)-based *** ecosystems are typically composed of IoT devices,edge devices,cloud computing software services,as well as people,who are decision makers in scenarios such as smart *** decisions related to analytics can be based on data coming from IoT sensors,software services,and ***,they are typically based on different levels of abstraction and *** poses a number of challenges when multiple blockchains are used together with smart *** work proposes to apply our concept of elasticity to smart contracts and thereby enabling analytics in and between multiple blockchains in the context of *** propose a reference architecture for Elastic smart Contracts and evaluate the approach in a smart city scenario,discussing the benefits in terms of performance and self-adaptability of our solution.

关键词： Blockchain elasticity Internet of Things(IoT) smart cities smart contracts virtual chains

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Tracking the change in spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental sciences 2024年第5期139卷 114-122页

作者： Paula fernández González mar.a José Presno Manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this *** this paper we pursue two ***,we analyze the evolution of GHG emissions in spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining ***,we propose several actions specifically oriented to more tightly controlling the level of *** results showed a remar.able reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita *** detected somewhat different patterns among the various sectors *** the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of *** carbonization effect was revealed as crucial in the commerce *** above findings highlight the importance of the energy efficiency measures taken in recent years in the spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in *** efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition spain GHG emissions

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Determination of soil Aggregate Porosity Using the Modified Water saturation Method

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Pedosphere 2019年第6期29卷 794-800页

作者： David MORET-fernández mar.a Victoria LóPEZ Departamento de suelo y Agua Estación Experimental de Aula Dei Consejo Superior de Investigaciones Científicas (EEAD-CSIC)

The need to find a simple method for measuring soil aggregate porosity (φ) is justified by the growing interest of researchers in this important parameter of soil physical status. The aim of this study was to present a simple method (AM) for estimating the total 0 of a single soil aggregate. In this case, soil aggregate 0 was calculated as the quotient between the pore volume, estimated from the weight of the aggregate saturated with ethanol, and the total volume (V T ) of aggregate, calculated from the particle density and dry aggregate weight. The V T estimated with AM was compared with the corresponding volume measured with the photogrammetry (PHM) technique using soil aggregates of 8–16 mm in diameter and collected from three different tillage systems: conventional tillage (CT), reduced tillage (RT), and no tillage (NT). Next, the AM was used to study the effects of the tillage system on soil aggregate φ. Although a strong relationship ( R 2 = 0.99, P sured with PHM and that estimated with AM was obtained, AM tended to underestimate aggregate V T with an average deviation of 2.85%. This difference may be due to ethanol evaporation during the first 10 s before the ethanol-saturated aggregate was weighed. The use of AM to determine the effects of different tillage systems on aggregate φ showed that this method was sensitive to detect significant differences among the tillage treatments. The results showed that AM could be an accurate, simple, and inexpensive alternative to estimate φ of a single soil aggregate.

关键词： Aggregate stability Bulk density Particle density Photogrammetry technique Tillage system

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Programmed cell death in seeds of angiosperms

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Journal of Integrative Plant Biology 2015年第12期57卷 996-1002页

作者： mar.a Paula López-fernández sara Maldonado Laboratory of Plant Development Department of Biodiversity and Experimental Biology Faculty of Exact and Natural Sciences University of Buenos Aires National Research Council of Argentine (CONICET)

During the diversification of angiosperms, seeds have evolved structuralp chemical, molecular and physiolog- ically developing changes that specially affect the nucellus and endosperm. All through seed evolution, programmed celldeath （PCD） has played a fundamental role. However, examples of PCD during seed development are limited. The present review examines PCD in integuments, nucellus, suspensor and endosperm in those representative examples of seeds studied to date.

关键词： Caspases endosperm KDEL-CysEP metacaspases nucellus nucleases programmed cell death perisperm ricinosomes

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