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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia castillo-gonzález Elena gonzález-Rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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)

Multi-Step clustering of Smart Meters Time Series:Application to Demand Flexibility characterization of SME customers

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computer Modeling in Engineering & Sciences 2025年第1期142卷 869-907页

作者： santiago Bañales Raquel Dormido Natividad Duro Department of computer Sciences and Automatic control Universidad Nacional de Educación a Distancia(UNED)Madrid28040Spain Iberdrola Innovation Middle East Doha210177Qatar

customer segmentation according to load-shape profiles using smart meter data is an increasingly important application to vital the planning and operation of energy systems and to enable citizens’participation in the energy *** study proposes an innovative multi-step clustering procedure to segment customers based on load-shape patterns at the daily and intra-daily time *** meter data is split between daily and hourly normalized time series to assess monthly,weekly,daily,and hourly seasonality patterns *** dimensionality reduction implicit in the splitting allows a direct approach to clustering raw daily energy time series *** intraday clustering procedure sequentially identifies representative hourly day-unit profiles for each customer and the entire *** the first time,a step function approach is applied to reduce time series *** attributes embedded in surveys are employed to build external clustering validation metrics using cramer’s V correlation factors and to identify statistically significant determinants of load-shape in energy *** addition,a time series features engineering approach is used to extract 16 relevant demand flexibility indicators that characterize customers and corresponding clusters along four different axes:available Energy(E),Temporal patterns(T),consistency(c),and Variability(V).The methodology is implemented on a real-world electricity consumption dataset of 325 Small and Medium-sized Enterprise(SME)customers,identifying 4 daily and 6 hourly easy-to-interpret,well-defined *** application of the methodology includes selecting key parameters via grid search and a thorough comparison of clustering distances and methods to ensure the robustness of the *** research can test the scalability of the methodology to larger datasets from various customer segments(households and large commercial)and locations with different weather and socioeconomic conditio

关键词： Electric load clustering load profiling smart meters machine learning data mining demand flexibility demand response

Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： joséM.Izquierdo centro de Biología Molecular Severo Ochoa(cBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

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 María 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 remarkable 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

Enhancement of the cO_(2)adsorption and hydrogenation to cH_(4)capacity of Ru–Na–ca/γ–Al_(2)O_(3)dual function material by controlling the Ru calcination atmosphere

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Journal of Environmental Sciences 2024年第6期140卷 292-305页

作者： Alejandro Bermejo-López Beñat Pereda-Ayo Jon A.Onrubia-calvo joséA.gonzález-Marcos Juan R.gonzález-Velasco Department of chemical Engineering Faculty of Science and TechnologyUniversidad del País Vasco UPV/EHUBarrio Sarrienas/n48940 LeioaBizkaiaSpain

Integrated cO_(2)capture and utilization(IccU)technology requires dual functional materials(DFMs)to carry out the process in a single reaction *** influence of the calcination atmosphere on efficiency of 4%Ru-8%Na_(2)cO_(3)-8%caO/γ-Al_(2)O_(3)DFM is *** adsorbent precursors are first co-impregnated onto alumina and calcined in ***,Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols:static air in muffle or under different mixtures(10%H_(2)/N_(2),50%H_(2)/N_(2)and N_(2))*** are characterized by XRD,N_(2)adsorption-desorption,H_(2)chemisorption,TEM,XPS,H_(2)-TPD,H_(2)-TPR,cO_(2)-TPD and *** catalytic behavior is evaluated,in cycles of cO_(2)adsorption and hydrogenation to cH_(4),and temporal evolution of reactants and products concentrations is *** calcination atmosphere influences the physicochemical properties and,ultimately,activity of *** data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic *** calcined under N_(2)flow(RuNaca-N_(2))shows the highest cH_(4)production(449μmol/g at 370℃),because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases,maximizing the specific surface area,the Ru-basic sites interface and the participation of different basic sites in the cO_(2)methanation ***,the calcination in a N_(2)flow is revealed as the optimal calcination protocol to achieve highly efficient DFM for integrated cO_(2)adsorption and hydrogenation applications.

关键词： cO_(2)methanation Integrated cO_(2)capture and utilization(IccU) Dual functional material(DFM) Ru calcination atmosphere

Hyperthermic intraperitoneal chemotherapy:Rationale and technique

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World Journal of Gastrointestinal Oncology 2010年第2期2卷 68-75页

作者： santiago gonzález-Moreno Luis A gonzález-Bayón Gloria Ortega-Pérez Peritoneal Surface Oncology Program Department of Surgical OncologyCentro Oncológico MD Anderson International Espaa28033 MadridSpain

The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms,either primary or secondary to digestive or gynecologic *** intraperitoneal chemotherapy (HIPEc) delivered in the operating room once the cytoreductive surgical procedure is fi nalized,constitutes the most common form of administration of perioperative intraperitoneal *** may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIc).HIPEc combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs,which results in regional dose intensification,with the direct cytotoxic effect of *** exhibits a selective cell-killing effect in malignant cells by itself,potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered *** chemotherapeutic agents employed in HIPEc need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic *** of HIPEc requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the *** open abdomen (coliseum) or closed abdomen technique may be used,with no signif icant differences in eff icacy proven to *** ic technical training and a solid knowledge of regional chemotherapy management are *** about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are *** HIPEc drug regimens and dosages are currently in use.A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy,so-called "HIPEc plus") has been observed in rece

关键词： Hyperthermia Intracavitary chemotherapy Peritoneal neoplasms Peritoneal carcinomatosis cytoreductive surgery

Mushroom Production as an Alternative for Rural Development in a Forested Mountainous Area

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Journal of Mountain Science 2014年第2期11卷 535-543页

作者： josé *** josé R.gonzález-OLABARRIA Juan MARTíNEZ DE ARAGóN Departament de Producció Vegetal i ciència Forestal Universitat de Lleida-Agrotecnio Center (UdL-Agrotecnio).Av. Rovira Roure 191 E-25198 Lleida Spain centre Tecnològic Forestal de catalunya (cTFc-cEMFOR). ctra. de St. Lloren? de Morunys km 2 E-25280 Solsona Spain

Wild mushrooms are recognized as important non-wood forest products in mountainous ecosystems, but their real potential for generating rural economies has not been fully evaluated due to the difficulties in obtaining reliable productivity data, minimizing their true potential as contributor to rural economies. Mushroom yield models based on large data series from Pinus forest ecosystems in the region of catalonia(Spain), combined with data from the Spanish National Forest Inventory allow us to estimate the potential mushroom productivity by forest ecosystems. The results of 24,500 tons/yr of mushrooms of which 16,300 tons are classified as edible and 7,900 tons are commonly marketed demonstrate the importance of mushroom productions in catalonian pine forests, mostly located in mountainous areas where the development of agricultural activities is limited. Economic mushroom value is estimated at 48 million € for the edible mushroom and 32 million € for those corresponding to marketable yields, confirming the potential of this non-wood forest product. These production results and corresponding economic values provide a basis for the incorporation of wild mushrooms as significant non-wood forest products in the development of forest policies in mountainous areas.

关键词： Non-wood forest products Mushroom models National Forest Inventory Economic value Mushroom potential estimation

Areas of research and clinical approaches to the study of liver abscess

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World Journal of Gastroenterology 2017年第2期23卷 357-365页

作者： Gregorio gonzález-Alcaide Jorge Peris josé Manuel Ramos Department of History of Science and Documentation University of Valencia Deparment of Internal Medicine Hospital Universitario Sant Joan d’Alacant Departament of clinical Medicine Universidad Miguel Hernández de Elche Department of Internal Medicine Hospital General Universitario de Alicante

AIMTo analyze the research activity on liver abscess (LA) and identify the main topic clusters in the *** identified all documents using the medical subject heading “LA” indexed in the MEDLINE database between 2001 and 2015. We performed a descriptive bibliometric analysis, characterizing the evolution of scientific activity, the publication types of the documents, the document categories of clinical interest (case reports, clinical trials, evaluation studies, meta-analysis, observational studies, practice guidelines and validation studies) and the geographic distribution of the research. We also carried out an analysis of networks and research clusters in order to identify the main topic areas of *** search yielded a total of 1278 documents, showing a stable scientific production over the study period and a marked multidisciplinary nature. The research was dominated by case reports (65.9% of the documents analyzed). In terms of geographic distribution, researchers from the United States led in the number of signatures (n = 229), followed by those from Taiwan (n = 185), India (n = 145), Japan (n = 144), South Korea (n = 100), and china (n = 84). With regard to amebic LA, the top-producing countries were India and Mexico (n = 69 each), followed by the United States (n = 29). In the case of pyogenic LA, Taiwan Residents researchers led scientific production (n = 71), followed by the United States (n = 39) and china (n = 29). The most active areas of research in the field are diagnosis via computerized tomography scan, differential diagnosis with regard to liver cancer, treatment with antimicrobial agents, and Klebsiella infections (including bacteremia).cONcLUSIONclinical case reports associated with diagnosis and treatment are the main topic of study, highlighting the importance of this document type in advancing knowledge.

关键词： Liver abscess cluster analysis Amebic abscess Pyogenic abscess Bibliometrics