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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

Impact of radiative cooling on the energy performance of courtyards in Mediterranean climate

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Building Simulation 2024年第9期17卷 1491-1513页

作者： Carlos-Antonio domínguez-Torres Antonio domínguez-Delgado Escuela Técnica Superior de Arquitectura Universidad de SevillaAv.de Reina Mercedes241012 SevillaSpain Department of Applied Mathematics 1 Escuela Técnica Superior de ArquitecturaUniversidad de SevillaAv.de Reina Mercedes241012 SevillaSpain

Radiative cooling has proven to be a useful tool to address the problems of lack of comfort and excessive energy consumption in situations of high temperatures,overheating and heat ***,incorporating courtyards in warm climate zones has been found to be highly beneficial in addressing similar ***,there is interest in analyzing the combined effects of both:radiative cooling and *** paper presents an analysis of the impact of the application of radiative cooling on a courtyard using a comprehensive simulation approach that includes a CFD model for the thermodynamic airflow in the adjacent roofs and inside the courtyard,equations for the transient heat conduction through roofs,walls and courtyard slabs,and a hybrid raytracing-radiosity model for the evaluation of the solar radiation reaching the building surfaces and its reflections,both of specular and diffuse origin,and for the calculation of the thermal radiation exchange,especially with the *** results show that in the hot season,the courtyard with radiative cooling always provides lower temperatures than the initial courtyard does,with a temperature range of 18.33℃to 33.78℃,compared to a range of 19.32℃to 38.00℃in the initial courtyard,and producing a greater difference with outdoor temperatures that can reach 12℃versus 8℃for the reference *** addition,it was found that the courtyard with radiative cooling is able to significantly reduce the observed nighttime overheating by providing lower temperatures than the outdoor temperatures in the 50%of the nights *** was also found that the thermal loads to achieve indoor thermal comfort in the spaces adjacent to the courtyard were reduced by 63.46%to 69.85%.

关键词： radiative cooling passive cooling CFD three-dimensional modeling energy saving thermal comfort

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

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)

A fuzzy cognitive map-based algorithm for predicting water consumption in Spanish healthcare centres

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Building Simulation 2023年第11期16卷 2193-2205页

作者： Gonzalo Sánchez-Barroso Jaime González-domínguez Joao Paulo Almeida-Fernandes Justo garcía-Sanz-Calcedo Engineering Projects Area University of ExtremaduraAv.Elvas06006BadajozSpain Department of Paisagem Ambiente e OrdenamentoUniversity of EvoraR.Romão Ramalho7000-650ÉvoraPortugal

The management of water consumption in healthcare centres can have positive impacts on both the environmental performance and profitability of health *** tools assist in the decision-making process of managing the operation and maintenance of healthcare *** research aimed to integrate the empirical knowledge of experts in Healthcare Engineering and the historical data from 66 healthcare centres in a Fuzzy Cognitive *** outputs of the predictive model included water consumption,water cost,and CO_(2) emissions in healthcare facilities,along with eleven variables to discover the causes and consequences of water consumption in healthcare centres.A healthcare centre with about 12350 users,located in a city that experiences an average of 1100 heating degree days,whose facilities be moderately energy-efficient contributing over 50%with renewable energies is expected to consume 8.4 dam^(3) of water with 32.1 k€of cost,and contribute realising 30.8 ton CO_(2)eq *** use of Fuzzy Cognitive Maps for prediction can provide a high level of effectiveness in identifying the factors that contribute to water consumption and in designing key performance indicators to manage the environmental performance of healthcare *** tool is extremely effective in enhancing the performance of the management division of health systems.

关键词： water consumption Fuzzy Cognitive Maps healthcare centres Healthcare Engineering water management

The detrimental effects of lipopolysaccharideinduced neuroinflammation on adult hippocampal neurogenesis depend on the duration of the pro-inflammatory response

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Neural Regeneration Research 2019年第5期14卷 817-825页

作者： Martha Pérez-domínguez Evangelina ávila-Mu?oz Eduardo domínguez-Rivas Angélica Zepeda Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones Biomédicas.Universidad Nacional Autónoma de MéxicoCDMX

Adult hippocampal neurogenesis is a finely tuned process regulated by extrinsic factors. Neuroinflammation is a hallmark of several pathological conditions underlying dysregulation of neurogenesis. In animal models, lipopolysaccharide(LPS)-induced neuroinflammation leads to a neurogenic decrease mainly associated to the early inflammatory response. However, it is not well understood how the neuroinflammatory response progresses over time and if neurogenesis continues to be diminished during the late neuroinflammatory response. Moreover, it is unknown if repeated intermittent administration of LPS along time induces a greater reduction in neurogenesis. We administered one single intraperitoneal injection of LPS or saline or four repeated injections(one per week) of LPS or saline to young-adult mice. A cohort of new cells was labeled with three 5-bromo-2-deoxyuridine injections(one per day) 4 days after the last LPS injection. We evaluated systemic and neuroinflammation-associated parameters and compared the effects of the late neuroinflammatory response on neurogenesis induced by each protocol. Our results show that 1) a single LPS injection leads to a late pro-inflammatory response characterized by microglial activation, moderate astrocytic reaction and increased interleukin-6 levels. This response correlates in time with decreased neurogenesis and 2) a repeated intermittent injection of LPS does not elicit a late pro-inflammatory response although activated microglia persists. The latter profile is not accompanied by a continued longterm hippocampal neurogenic decrease. Hereby, we provide evidence that the neuroinflammatory response is a dynamic process that progresses in a milieu-dependent manner and does not necessarily lead to a neurogenic decrease, highlighting the complex interaction between the immune system and neurogenesis.

关键词： dentate gyrus subgranular zone inflammation microglia astrocytes IL-6 cytokines cell proliferation neural progenitor cells immature neurons long-term short-term adult hippocampal neurogenesis

Behavior of ductile steel X-braced RC frames in seismic zones

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Earthquake Engineering and Engineering Vibration 2019年第4期18卷 845-869页

作者： Eber Alberto Godínez-domínguez Arturo Tena-Colunga Facultad de Ingeniería Universidad Autónoma de Chiapas Tuxtla Gutiérrez 29050 Mexico Departamento de Materiales Universidad Autónoma Metropolitana México City 02200 Mexico

A satisfactory ductile performance of moment-resisting reinforced concrete concentric braced frame structures (RC-MRCBFs) is not warranted by only following the provisions proposed in Mexico’s Federal District Code (MFDC-04). The nonlinear behavior of low to medium rise ductile RC-MRCBFs using steel X-bracing susceptible to buckling is evaluated in this study. The height of the studied structures ranges from 4 to 20 stories and they were located for design in the lakebed zone of Mexico City. The design of RC-MRCBFs was carried out considering variable contribution of the two main lines of defense of the dual system (RC columns and steel braces). In order to observe the principal elements responsible for dissipating the earthquake input energy, yielding mappings for diff erent load-steps were obtained using both nonlinear static and dynamic analyses. Some design parameters currently proposed in MFDC-04 as global ductility capacities, overstrength reduction factors and story drifts corresponding to diff erent limit states were assessed as a function of both the considered shear strength and slenderness ratios for the studied RC-MRCBFs using pushover analyses. Additionally, envelopes of response maxima of dynamic parameters were obtained from the story and global hysteresis curves. Finally, a brief discussion regarding residual drifts, residual drift ratios, mappings of residual deformations in steel braces and residual rotations in RC beams and columns is presented. From the analysis of the obtained results, it is concluded that when a suitable design criterion is considered, good structural behavior of RC-MRCBFs with steel-X bracing can be obtained. It is also observed that the shear strength balance has an impact in the height-wise distribution of residual drifts, and an important “shake-down” eff ect is obtained for all cases. There is a need to improve design parameters currently proposed in MFDC to promote an adequate seismic performance of RC-MRCBFs.

关键词： RC braced-frames seismic design nonlinear dynamic analyses steel-X bracing overstrength collapse mechanism story drifts residual drifts

Taking advantage of the potential of mesenchymal stromal cells in liver regeneration:Cells and extracellular vesicles as therapeutic strategies

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World Journal of Gastroenterology 2018年第23期24卷 2427-2440页

作者： Esteban Juan Fiore Luciana María domínguez Juan Bayo Mariana Gabriela garcía Guillermo Daniel Mazzolini Laboratory of Gene Therapy Instituto de Investigaciones en Medicina TraslacionalCONICET-Universidad Austral

Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases.

关键词： Mesenchymal stem cells Extracellular vesicles Cirrhosis Liver Acute damage Regeneration

Steroid-responsive pancreatitides

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World Journal of Clinical Cases 2020年第16期8卷 3411-3430页

作者： mario Pelaez-Luna Andrea Soriano-Rios Ana C Lira-Treviño Luis Uscanga-domínguez Department of Gastroenterology National Institute of Medical Sciences and Nutrition"Salvador Zubiran"Mexico City 14000Mexico

Autoimmune pancreatitis has received considerable attention,especially due to the marked effect of corticosteroid therapy on its clinical ***,especially regarding type 1 autoimmune pancreatitis,has significantly increased over the last decades,and despite significant differences in pathophysiology and outcomes,both type 1 and 2 autoimmune pancreatitis are still considered different types of the same *** have proposed a different nomenclature reflecting these *** the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis,these are not the only pancreatic conditions that show a response to steroid *** pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid *** review presents current concepts on these disorders,aiming to increase awareness,analyze similarities and differences,and propose a new nomenclature that reflects their specific particularities,clustering them under the term"steroid-responsive pancreatitides".

关键词： Autoimmune pancreatitis Lymphoplasmacytic sclerosing pancreatitis Idiopathic duct centric chronic pancreatitis Vasculitis Immune checkpoint inhibitors Corticosteroids