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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 maría Fernanda González Ana maría 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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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(Sma)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of Sma was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of Sma-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of Sma,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe Sma phenotypes and vice ***,the etiology of Sma is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Development and assessment of algorithms for DEM-LES simulations of fluidized bed

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Particuology 2023年第12期83卷 241-257页

作者： Fatima ez-Zahra El Hamra Radouan Boukharfane UM6P College of Computing Mohammed Ⅵ Polytechnic University(UM6P)BenguerirMorocco

The use of high-fidelity Discrete Element Method(DEM)coupled with Computational Fluid Dynamics(CFD)for particle-scale simulations demands extensive simulation times and restricts application to small particulate ***-CFD simulations require good performance and satisfactory scalability on high-performance computing platforms.A reliable parallel computing strategy must be developed to calculate the collision forces,since collisions can occur between particles that are not on the same processor,or even across processors whose domains are *** present paper describes a parallelization technique and a numerical verification study based on a number of tests that allow for the assessment of the numerical performance of DEM used in conjunction with Large-Eddy Simulation(LES)to model dense flows in fluidized *** fluid phase is computed through solving the volume-averaged four-way coupling Navier-Stokes equations,in which the Smagorinsky sub-grid scale tensor model is ***,the performance of Sub-Grid Scale(SGS)turbulence models applied to Fluidized Bed Reactor(FBR)configurations has been assessed and *** developed numerical solver represents an interesting combination of techniques that work well for the present purpose of studying particle formation in fluidized beds.

关键词： DEM-LES Fluidized bed Computational efficiency Numerical accuracy

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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

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Numerical modeling of cracking pattern's influence on the dynamic response of thickened tailings disposals: a periodic approach

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Earthquake Engineering and Engineering Vibration 2018年第1期17卷 179-190页

作者： Gabriel Ferrer Esteban Sáez Christian Ledezma School of Engineering Pontificia Universidad Católica de Chile National Research Center for Integrated Natural Disaster management

Copper production is an essential component of the Chilean economy. During the extraction process of copper, large quantities of waste materials（tailings） are produced, which are typically stored in large tailing ponds. Thickened Tailings Disposal（TTD） is an alternative to conventional tailings ponds. In TTD, a considerable amount of water is extracted from the tailings before their deposition. Once a thickened tailings layer is deposited, it loses water and it shrinks, forming a relatively regular structure of tailings blocks with vertical cracks in between, which are then filled up with ＂fresh＂ tailings once the new upper layer is deposited. The dynamic response of a representative column of this complex structure made out of tailings blocks with softer material in between was analyzed using a periodic half-space finite element model. The tailings＇ behavior was modeled using an elasto-plastic multi-yielding constitutive model, and Chilean earthquake records were used for the seismic analyses. Special attention was given to the liquefaction potential evaluation of TTD.

关键词： Thickened tailings Liquefaction Periodic modeling

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Distribution of DNA damage in the human sperm nucleus:implications of the architecture of the sperm head

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Asian Journal of Andrology 2020年第4期22卷 401-408页

作者： Silvia González-Rojo Cristina Fernández-Díez marta Lombó maría Paz Herráez Department of Molecular Biology Faculty of BiologyUniversidad de LeónCampus de Vegazana s/n LeónLeón 24071Spain

The sperm nucleus is prone to sustain DNA damage before and after *** of the damage is not homogeneous,and the factors determining differential sensitivity among nuclear regions have not yet been *** sperm chromatin contains three structural domains,two of which are considered the most susceptible to DNA damage:the histone bound domain,harboring developmental related genes,and the domain associated with nuclear matrix *** a quantitative polymerase chain reaction(qPCR)approach,we analyzed the number of lesions in genes homeobox A3(HOXA3),homeobox B5(HOXB 5),sex-determining region Y(SRY)-box 2(SOX2),β-GLOBIN,rDNA 18S,and rDNA 28S in human sperm after ultraviolet irradiation(400μW cm−2,10 min),H2O2treatment(250 mmol l−1,20 min),and cryopreservation,which showed differential susceptibility to genetic *** vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription *** of 8-hydroxy-2'-deoxyguanosine(8-OHdG)showed that the highest level of oxidation was observed after *** distribution of oxidative lesions also differed depending on the genotoxic agent.8-OHdG did not colocalize either with histone 3(H3)or with type IIα+βtopoisomerase(TOPO IIα+β)after H2O2treatment but matched perfectly with peroxiredoxin 6(PRDX6),which is involved in *** study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas,whereas chromatin packaging has a very limited *** histone-enriched genes analyzed cannot be used as biomarkers of oxidative DNA damage.

关键词： biomarkers DNA damage human sperm oxidative stress sperm chromatin sperm quality

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Correlation between mechano-electronic features and scattering rates using deformation potential theory

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Communications in Theoretical Physics 2024年第2期76卷 166-181页

作者： Meryem Ziati Sanaa Lahlali Hamid ez-Zahraouy Laboratory of Condensed matter and Interdisciplinary Sciences `Unitéde recherche labellisée CNRST'Faculty of SciencesMohammed V UniversityRabatMorocco Mohammed VI Polytechnic University(UM6P) BenGuerir 43150Morocco

This research paper provides valuable insight into the electronic,mechanical and transport properties of the Sr_(2)RuO_(2)F_(2)*** study shows that the Sr_(2)RuO_(4)compound exhibits a metallic ground state and that the energy gap widens with oxygen substitution with *** concept of absolute deformation potential and its correlation with band energies and strains is explained using deformation potential *** paper also examines the mechanical features of Sr_(2)RuO_(2)F_(2)using the Voigt-Reuss-Hill approximation method and analyzes its elastic constants,bulk modulus and shear modulus,indicating flexibility and suitability for optoelectronic *** role of acoustic phonons in scattering rates and carrier mobility in Sr_(2)RuO_(2)F_(2)and its potential for phonon-mediated superconductivity is *** intrinsic resistivity of electrons and holes under strain and its potential impact on superconductivity and electrical resistivity are also *** insight provided by this study contributes to the current understanding of Sr_(2)RuO_(2)F_(2),and its potential applications.

关键词： density functional theory deformation potential theory scattering rates carrier mobility intrinsic resistivity

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Energy level engineering of charge selective contact and halide perovskite by modulating band offset:Mechanistic insights

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Journal of Energy Chemistry 2021年第3期30卷 822-829页

作者： Yassine Raoui Hamid ez-Zahraouy Samrana Kazim Shahzada Ahmad BCmaterials Basque Center for MaterialsApplications and NanostructuresBld.Martina CasianoUPV/EHU Science ParkBarrio Sarriena s/n48940 LeioaSpain IKERBASQUE Basque Foundation for ScienceBilbao 48013Spain Laboratory of Condensed matter and Interdisciplinary Sciences Faculty of SciencesMohammed V UniversityRabatMorocco

Mixed cation and anion based perovskites solar cells exhibited enhanced stability under outdoor conditions,however,it yielded limited power conversion efficiency when TiO_(2) and Spiro-OMeTAD were employed as electron and hole transport layer(ETL/HTL)*** inevitable interfacial recombination of charge carriers at ETL/perovskite and perovskite/HTL interface diminished the efficiency in planar(n-i-p)perovskite solar *** employing computational approach for uni-dimensional device simulator,the effect of band offset on charge recombination at both interfaces was *** noted that it acquired cliff structure when the conduction band minimum of the ETL was lower than that of the perovskite,and thus maximized interfacial ***,if the conduction band minimum of ETL is higher than perovskite,a spike structure is formed,which improve the performance of solar *** optimum value of conduction band offset allows to reach performance of 25.21%,with an open circuit voltage(VOC)of 1231 mV,a current density JSC of 24.57 ma/cm^(2) and a fill factor of 83.28%.Additionally,we found that beyond the optimum offset value,large spike structure could decrease the *** an optimized energy level of Spiro-OMeTAD and the thickness of mixed-perovskite layer performance of 26.56% can be *** results demonstrate a detailed understanding about the energy level tuning between the charge selective layers and perovskite and how the improvement in PV performance can be achieved by adjusting the energy level offset.

关键词： Device modelling Electron affinity Conduction band offset Valence band offset Charge recombination Perovskite solar cell

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Atrial fibrillation in the elderly

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Journal of Geriatric Cardiology 2019年第1期16卷 49-53页

作者： Pablo Díez-Villanueva Fernando Alfonso Department of Cardiology Hospital Universitario de la Princesa

Atrial fibrillation(AF)is the most common arrhythmia in elderly population,with age being one of the most important factors involved in its *** disturbances may be present on the surface electrocardiogram before AF onset in some *** this arrhythmia is diagnosed,antithrombotic therapy is mandatory in most cases,as this is the only treatment that has demonstrated to improve *** increases both the risk of thromboembolic and bleeding complications,while benefits from anticoagulant therapy outweigh that from bleeding in most scenarios,also in very elderly ***,elderly patients with AF are often ***-vitamin K antagonist oral anticoagulants have emerged as an alternative to vitamin K antagonists,with significant less adverse events and better profile in terms of efficacy and *** conditions related to age should be carefully evaluated in these patients(including frailty,comorbidity and polypharmacy)to ensure an individualized clinical and therapeutic approach.

关键词： Atrial fibrillation Antithrombotic therapy Frailty Non-vitamin K antagonist oral anticoagulants The elderly

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Combination of hydrotreating and delayed coking technologies for conversion of residue

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Chinese Journal of Chemical Engineering 2023年第11期63卷 209-219页

作者： José A.D.Munoz Gabriel Páez Jorge Ancheyta Instituto Mexicano del Petróleo Eje Central Lázaro Cárdenas Norte 152Col.San Bartolo AtepehuacanMéxico City 07730México

Residue conversion by combining catalytic hydrotreating and delayed coking has been evaluated comparatively with both processes *** operating conditions are defined to achieve the greatest economic benefit for upgrading an atmospheric residue from a heavy crude oil.A literature model was adapted to simulate the hydrotreating reactor,and for delayed coking,correlations reported in the literature were *** results with both approaches were employed to calculate the techno-economic feasibility of the combined process *** combination of hydrotreating and delayed coking presented an increase in light fractions of 29% and a reduction in coke production of 47.8%.Based on the calculated net benefit values,it was demonstrated that the combination of hydrotreating and delayed coking is technically and economically better than using each process alone,with highest benefit of 57.7 USD·m^(-3).

关键词： Economic benefit Heavy oil Hydrotreating Delayed coking

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