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Design and redesign journey of a drug for transthyretin amyloidosis

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Neural Regeneration Research 2025年第4期20卷 1096-1097页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the *** hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

关键词： amyloid aggregation senile

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

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)

OsDMI3,a Ca^(2+)/calmodulin kinase,integrates and amplifies H_(2)O_(2) and Ca^(2+) signaling in ABA-mediated responses

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Molecular Plant 2023年第6期16卷 968-970页

作者： Miguel-Angel torres Diego jose Berlanga Centro de Biotecnologia y Genomica de Plantas Universidad Politecnica de Madrid(UPM)-Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPM28223 Pozuelo de AlarconMadridSpain Departamento de Biotecnologia-Biologia Vegetal Escuela Técnica Superior de Ingenieria AgronomicaAlimentaria y de BiosistemasUPM28040 MadridSpain

Abscisic acid(ABA)is an important hormone that regulates both plant development and stress responses(Chen et al.,2020).In the absence of ABA,group A PROTEIN PHOSPHATASE 2Cs(PP2Cs)interact with and inhibit SUCROSE-NON-FERMENTING 1-RELATED KINASES 2(SnRK2s).When ABA is present,ABA receptor PYRABACTIN RESISTANCE 1 and PYRABACTIN RESISTANCE 1-LIKE PROTEINS bind to and inhibit PP2Cs,allowing phosphorylation and activation of SnRK2s that,in turn,phosphorylate downstream targets,such as transcription factors,ion channels,and transporters(Figure 1).

关键词： SnRK2 Figure

Methionine adenosyltransferases in liver cancer

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World Journal of Gastroenterology 2019年第31期25卷 4300-4319页

作者： Ben Murray Lucia Barbier-torres Wei Fan joséM Mato Shelly C Lu Division of Digestive and Liver diseases Department of MedicineCedars-Sinai Medical CenterLos AngelesCA 90048United States CIC bioGUNE Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(Ciberehd)TechnologyPark of BizkaiaDerio 48160BizkaiaSpain

Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the *** systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα***1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe *** of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver *** increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular *** we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their *** will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.

关键词： Methionine adenosyltransferases S-adenosylmethionine Liver cancer Hepatocellular carcinoma Cholangiocarcinoma Biomarkers Therapeutic targets

Optimal Design of Hybrid Microgrid in Isolated Communities of Ecuador

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 488-499页

作者： Luis A.Pesantes Ruben Hidalgo-León Johnny Rengifo Miguel torres Jorge Aragundi joséCordova-Garcia Luis F.Ugarte Facultad de Ingeniería en Electricidad y Computación of Escuela Superior Politécnica del Litoral(ESPOL)University GuayaquilEcuador Department of Electrical Engineering at Universidad Técnica Federico Santa María SantiagoChile IEEE

In rural territories, the communities use energy sources based on fossil fuels to supply themselves with electricity, which may address two main problems: greenhouse gas emissions and high fuel prices. Hence, there is an opportunity to include renewable resources in the energy mix. This paper develops an optimization model to determine the optimal sizing, the total annual investment cost in renewable generation, and other operating costs of the components of a hybrid microgrid. By running a k-means clustering algorithm on a meteorological dataset of the community under study, the hourly representative values become input parameters in the proposed optimization model. The method for the optimal design of hybrid microgrid is analyzed in six operating scenarios considering:(1) 24-hour continuous power supply;(2) load shedding percentage;(3) diesel power generator(genset) curtailment;(4) the worst meteorological conditions;(5) the use of renewable energy sources including battery energy storage systems(BESSs);and(6) the use of genset. A mathematical programming language(AMPL) tool is used to find solutions of the proposed optimization model. Results show that the total costs of microgrid in the scenarios that cover 100% of the load demand(without considering the scenario with 100% renewables) increase by over 16% compared with the scenario with genset operation limitation. For the designs with power supply restrictions, the total cost of microgrid in the scenario with load shedding is reduced by over 27% compared with that without load shedding.

关键词： Battery energy storage system(BESS) isolated community microgrid renewable energy optimization

Touristic urbanization and greening of coastal dune fields:A long-term assessment of a temperate sandy barrier of Argentina

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Journal of Geographical Sciences 2025年第1期 206-230页

作者： GARZO Pedro Andrés DADON josé Roberto ISLA Federico Ignacio Instituto de Investigaciones Marinas y Costeras (IIMyC-CONICET/UNMDP) Instituto de Geología de Costas y del Cuaternario Dr.Enrique J.Schnack (IGCC-CIC/UNMDP) Universidad de Buenos Aires Facultad de Arquitectura Dise?o y Urbanismo Centro de Investigaciones Gestión de Espacios Costeros (GEC-FADU/UBA) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

Dune barrier systems represent highly sought-after coastal landscapes for tourism and urban development around the world. However, a century ago, they were considered hazardous environments due to their great dynamic nature. As a result, stabilization practices were considered necessary. The systematic introduction of fast-growing exotic trees helped stabilize the sand, making it easier for tourism urbanization to take place, but also leading to erosion processes. This paper aims to assess long-term changes in vegetation cover over a large temperate barrier in Argentina. This complex region includes urban resorts, afforestation zones, and protected areas. A GIS-based geospatial analysis was conducted using a large satellite database(> 350 images), and the future evolution of the vegetation was modeled. The results revealed two primary spatiotemporal patterns associated with a gradual expansion of vegetation cover, accompanied by a concurrent reduction in sandy areas. In 1986, the dune area comprised 75% more surface than vegetation, whereas in 2021, it represented 60% less than vegetation. Furthermore, the 2050 scenario suggests a potential 40% reduction of dunes in certain areas. It is necessary to enhance management actions aimed at maintaining dune mobility and ensuring local and regional sediment balance. Long-term management strategies must focus on restoring native plant communities and controlling invasive species, and avoiding new dune fixation initiatives based on the introduction of exotic species.

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Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

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Neural Regeneration Research 2019年第11期14卷 1897-1898页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autonoma de BarcelonaBellaterraSpainDepartament de Bioquimica i Biologia MolecularUniversitat Autonoma de BarcelonaBellaterraSpain

Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery (Ciechanover and Kwon, 2015). When misfolded protein conformers cannot be degraded, they tend to self-assemble to form aggregates, a characteristic of many neurodegenerative diseases.

关键词： inhibitingα-synuclein aggregation native states protein quality control machinery

Liver cirrhosis and sarcopenia:a dreadful combination

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Hepatobiliary Surgery and Nutrition 2022年第5期11卷 729-731页

作者： Mohammad Shafi Kuchay joséIgnacio Martínez-Montoro Camilo Julio Llamoza-torres joséCarlos Fernández-García Bruno Ramos-Molina Division of Endocrinology and Diabetes Medanta The Medicity HospitalGurugramHaryanaIndia Department of Endocrinology and Nutrition Virgen de la Victoria University HospitalInstituto de Investigación Biomédica de Málaga(IBIMA)Faculty of MedicineUniversity of MálagaMálagaSpain Department of Gastroenterology Unit of HepatologyHospital Clínico Universitario Virgen de la ArrixacaMurciaSpain Department of Endocrinology and Nutrition Regional University Hospital of MálagaInstituto de Investigación Biomédica de Málaga(IBIMA)Faculty of MedicineUniversity of MálagaMálagaSpain Obesity and Metabolism Research Laboratory Biomedical Research Institute of Murcia(IMIB)MurciaSpain

Patients with liver cirrhosis,irrespective of etiology,have increased risk of liver-related and all-cause mortality(1).Also,the severity of cirrhosis determines health *** instance,patients with compensated cirrhosis have a nearly five-fold increased risk of death,while those with decompensated cirrhosis have approximately a 10-fold increased risk compared with the general population(1).Furthermore,the median survival time of patients with compensated cirrhosis is 12 years,while it is only 1.8 years in those with decompensated cirrhosis(2).Moreover,the presence of intercurrent conditions,such as sarcopenia(loss of skeletal muscle mass and function)may also compromise the prognosis of patients with cirrhosis(3).

关键词： cirrhosis mortality prognosis