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Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential

World Journal of Hepatology 2024年第9期16卷 1211-1228页

作者： Margarita Montoya-Buelna Inocencia G Ramirez-lopez Cesar A San Juan-Garcia Jose J Garcia-Regalado Mariana S Millan-Sanchez Ulises de la Cruz-Mosso Jesse Haramati ana l pereira-suarez Jose Macias-Barragan laboratorio de Inmunología Departamento de FisiologíaUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico Departamento de Ciencias de la Salud Centro Universitario de los VallesUniversidad de GuadalajaraAmeca 46600JaliscoMexico Doctorado en Ciencias Biomédicas Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico laboratorio de Inmunología Departamento de FisiologíaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico Red de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes Departamento de NeurocienciasCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico laboratorio de Inmunobiología Departamento de Biología Celular y MolecularCentro Universitario de Ciencias Biológicas y AgropecuariasUniversidad de GuadalajaraZapopan 45200JaliscoMexico Instituto de Investigación en Ciencias Biomédicas Departamento de Microbiología y PatologíaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340JaliscoMexico

Extracellular vesicles(EVs)are small particles released by many cell types in different tissues,including the liver,and transfer specific cargo molecules from originating cells to receptor *** process generally culminates in activation of distant cells and inflammation and progression of certain *** global chronic liver disease(ClD)epidemic is estimated at 1.5 billion patients *** and liver cancer are the most common risk factors for ***,hepatitis C and B virus infection and obesity are also highly associated with ***,the etiology of many ClD pathophysiological,cellular,and molecular events are *** in hepatic lipid metabolism can lead to lipotoxicity events that induce EV ***,we aimed to present an overview of EV features,from definition to types and biogenesis,with particular focus on the molecules related to steatosis-related liver disease,diagnosis,and therapy.

关键词： Extracellular vesicles Exosomes Chronic liver disease Hepatocellular carcinoma Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis

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Performance of evolutionary optimized machine learning for modeling total organic carbon in core samples of shale gas fields

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Petroleum 2024年第1期10卷 150-164页

作者： leonardo Goliatt C.M.Saporetti l.C.Oliveira E.pereira Department of Computational and Applied Mechanics Federal University of Juiz de Fora Department of Computational Modeling Polytechnic Institute Rio de Janeiro State University Petrobras Department of Stratigraphy and Paleontology Rio de Janeiro State University

Rock samples' TOC content is the best indicator of the organic matter in source rocks. The origin rock samples' analysis is used to calculate it manually by specialists. This method requires time and resources because it relies on samples from many well intervals in source rocks. Therefore, research has been done to aid this effort. Machine learning algorithms can estimate total organic carbon instead of well logs and stratigraphic studies. In light of these efforts, the current work present a study on automating the total organic carbon estimation using machine learning approaches improved by an evolutionary methodology to give the model flexibility and precision. Genetic algorithms, differential evolution, particle swarm optimization, grey wolf optimization, artificial bee colony, and evolution strategies were used to improve machine learning models to predict TOC. The six metaheuristics were integrated into four machine learning methods: extreme learning machine, elastic net linear model, linear support vector regression, and multivariate adaptive regression splines. Core samples from the YuDong-Nan shale gas field, located in the Sichuan basin, were used to evaluate the hybrid strategy. The findings show that combining machine learning models with an evolutionary algorithms in a hybrid fashion produce flexible models that accurately predict TOC. The results show that, independent of the metaheuristic used to guide the model selection, optimized extreme learning machines attained the best performance scores according to six metrics. Such hybrid models can be used in exploratory geological research,particularly for unconventional oil and gas resources.

关键词： Total organic carbon Hybrid models Automated machine learning Evolutionary algorithms Geology

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Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel Jiménez-Herrera ana Contreras Juan D.Navarro-lópez lydia Jiménez-Díaz Neurophysiology&Behavior lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the... 详细信息

关键词： Alzheimer predominant estimates

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Carbon Monoxide as C1 Building Block in Fine Chemical Synthesis

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Chinese Journal of Chemistry 2024年第2期42卷 199-221页

作者： Rui M.B.Carrilho Mario J.F.Calvete Gabor Mikle laszlo Kollar Mariette M.pereira University of Coimbra Coimbra Chemistry CentreDepartment of ChemistryRua Larga3004-535 CoimbraPortugal Department of General and Inorganic Chemistry and ElKH-PTE Research Groupfor Selective Chemical Syntheses University of PecsIfjusag utja 6H-7624 PecsHungary

Carbon monoxide(CO)has become one of the most relevant and versatile renewable C1 building blocks for chemical synthesis,especially in the fine chemicals industry,due to the development of efficient and selective catalysts for its *** this review,we present a comprehensive critical analysis of the last 10 years literature on the use of CO as a renewable feedstock for fine chemicals *** review is organized by type of catalytic reaction,namely alkene and alkyne carbonylation,hydroformylation,carbonylation of aryl halides,carbonylative cross-coupling and C-H *** examples of the synthesis of relevant building blocks and/or known pharmaceuticals are *** is placed on examples of utilizing CO as the C1 building block in one or more catalytic *** catalyst used and the reaction conditions are consistently presented throughout all of the examples.

关键词： Carbon monoxide Fine chemicals Carbonylation Hydroformylation C-H functionalization

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Knowledge Is Invented: Addressing Invention and the Art of Saying in the Psychoanalytic Field

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Philosophy Study 2024年第3期14卷 97-105页

作者： ana lúcia Mandelli de Marsillac Universidade Federal de Santa Catarina FlorianópolisBrasil

In the Freudian-lacanian field,there is an important distinction between knowledge and *** truth,of an unconscious nature,is something that inhabits us,directs us,but that escapes ***,in turn,is something to be invented,from the hole of the Real,the Unconscious truth,and the subjective *** relationships between playing,creating,and fantasizing;the dimension of the uncanny,fiction,and imagination in subjectivity;the invention of knowledge of oneself,derived from the pains and flavors of being who one is,are creative dimensions that inhabit the subject,permeate the analytical act,and transversalize *** the practice,we listen to and witness processes of analysis that awaken an invention/reinvention of oneself,in the process of remembering,repeating,and elaborating,but also in what the transference relationship *** of oneself,does not guarantee a life without mishaps,sadness,and illusions,but allows the invention and recognition of knowledge and a *** concept of Sinthome(2007),coined by Jacques lacan,comes in the wake of the processes of self-invention and is a knowing-doing with the symptom,with the paradoxes of joyful suffering,producing,as a result,an art of ***,in this communication,I will articulate elements of theory,practice,and psychoanalytic experience that allow us to expand knowledge of the themes of invention and imagination articulated with the concept of sinthome,their relationships with subjectivity,and the direction of psychoanalytic treatment.

关键词： psychoanalysis invention imagination knowledge sinthome

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández ana Esther Moreno-Martínez Mar Cuadrado-Tejedor ana García-Osta Rafael luján Synaptic Structure laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana M.lópez-Estévez Y.Zhang María Medel Iker Arriaga lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain AlBA Synchrotron light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-lópez Iva Tic David Valle-García Marta Ribalta-Vilella luis labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

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棒与星系整体恒星形成性质关系的统计研究

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天文学进展 2024年第1期42卷 115-127页

作者：穆子豪沈世银 Rafael S.de Souza ana l.Chies-Santos 中国科学院上海天文台星系宇宙学重点实验室上海200030 中国科学院大学北京100049 星系和宇宙学半解析研究重点实验室上海200034 赫特福德大学天体物理研究中心英国哈特菲尔德学院巷AL109AB 南里奥格兰德州联邦大学科学研究所巴西阿雷格里港9500

盘状星系中的棒结构特征与星系自身所处环境及整体恒星形成特征之间存在复杂的相互关系。利用细致的星系形态特征测量计划Galaxy Zoo DECalS中的数据构建了一组目前最大的具有同样恒星质量分布的强棒、弱棒和无棒星系样本。通过引入星... 详细信息

盘状星系中的棒结构特征与星系自身所处环境及整体恒星形成特征之间存在复杂的相互关系。利用细致的星系形态特征测量计划Galaxy Zoo DECalS中的数据构建了一组目前最大的具有同样恒星质量分布的强棒、弱棒和无棒星系样本。通过引入星系所处暗晕质量及相空间特征来控制星系所处的环境效应之后,进一步对比研究强棒、弱棒和无棒星系的恒星形成特征。研究表明,有棒星系中的恒星形成熄灭的比例系统地高于无棒星系,且强棒的效应更为明显。但是,对于仍处于恒星形成主序上的星系来说,强棒、弱棒和无棒星系的恒星形成特征并没有显著差别。以上结果表明,星系中的棒特征在其存在的时标中可能使部分星系迅速地从恒星形成转入熄灭状态。

关键词：棒旋星系恒星形成环境

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Towards efficient strain engineering of 2D materials:A four-points bending approach for compressive strain

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Nano Research 2024年第6期17卷 5317-5325页

作者： Hao li Félix Carrascoso ana Borrás Gloria P.Moreno Francisco J.Aparicio Ángel Barranco Andrés Castellanos Gómez Campus de Cantoblanco Instituto de Ciencia de Materiales de MadridC.Sor Juana Inés de la Cruz328049 MadridSpain Nanotechnology on Surfaces and Plasma lab Instituto de Ciencia de Materiales de Sevilla(CSIC-Universidad de Sevilla).C/Americo Vespucio 49E-41092 SevilleSpain Departamento de Física Aplicada I Escuela Politécnica SuperiorUniversidad de Sevillac/Virgen deÁfrica 7E-41011 SevilleSpain

Strain engineering,as a powerful strategy to tune the optical and electrical properties of two-dimensional(2D)materials by deforming their crystal lattice,has attracted significant interest in recent years.2D materials can sustain ultra-high strains,even up to 10%,due to the lack of dangling bonds on their surface,making them ideal brittle *** remarkable mechanical resilience,together with a strong strain-tunable band structure,endows 2D materials with a broad optical and electrical response upon ***,strain engineering based on 2D materials is restricted by their nanoscale and strain quantification *** this study,we have modified a homebuilt three-points bending apparatus to transform it into a four-points bending apparatus that allows for the application of both compressive and tensile strains on 2D *** approach allows for the efficient and reproducible construction of a strain system and minimizes the buckling effect caused by the van der Waals interaction by adamantane encapsulation *** results demonstrate the feasibility of introducing compressive strain on 2D materials and the potential for tuning their optical and physical properties through this approach.

关键词： uniaxial compressive strain polymer encapsulation differential reflectance spectroscopy exciton tunability

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