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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 damage.Mesenchymal 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 mice.Considering 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 drinking.We 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 mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken 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)

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A systematic review of salivary biomarkers in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo Claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly Department of Human Neurosciences Sapienza University of RomeRomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly Department of Experimental morphology and Microscopy-Integrated Research Center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,a

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

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Multimodal Nature of the Single-cell Primate Brain Atlas:morphology,Transcriptome,Electrophysiology,and Connectivity

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Neuroscience Bulletin 2024年第4期40卷 517-532页

作者： Yuhui Shen Mingting Shao Zhao-Zhe Hao Mengyao Huang Nana Xu Sheng Liu State Key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou510060China Guangdong Province Key laboratory of Brain Function and Disease Guangzhou510080China

Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate

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Neuroinflammation and glial activation in the central nervous system: a metabolic perspective

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Neural Regeneration Research 2023年第5期18卷 1025-1026页

作者： Assunta Virtuoso Ciro De Luca Sohaib Ali Korai Michele Papa Giovanni Cirillo Division of Human Anatomy Laboratory of Morphology of Neuronal Networks and Systems BiologyDepartment of Mental and Physical Health and Preventive MedicineUniversity of Campania“Luigi Vanvitelli”NaplesItaly

Decades of research in glial biology have investigated mechanisms of neuro-glial interplay,demonstrating that neurons and glia intimately cooperate for energy metabolism in the central nervous system(CNS)(Magistretti ... 详细信息

关键词： metabolism inflammation system

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Cerebral furin deficiency causes hydrocephalus in mice

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Genes & Diseases 2024年第3期11卷 438-451页

作者： Shiqi Xie Xiaoyong Xie Jing Tang Biao Luo Jian Chen Qixin Wen Jianrong Zhou Guojun Chen Nursing College Chongqing Medical UniversityChongqing 400016China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Major Neurological and Mental DisordersChongqing Key Laboratory of NeurologyChongqing 400016China

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway.We have previously reported that cerebral overexpres-sion of furin promotes cognitive functions in mice.Here,by generating the brain-specific furin conditional knockout(ckO)mice,we investigated the role of furin in brain development.We found that furin deficiency caused early death and growth retardation.Magnetic resonance im-aging showed severe hydrocephalus.In the brain of furin cko mice,impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expres-sion of RAB28,a ciliary vesicle protein.In line with the widespread neuronal loss,ependymal cell layers were damaged.Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice;and astrocyte overgrowth was accompanied by the reduced expression of sox9,indicating a disrupted differ-entiation into ependymal cells.Together,whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis,dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin ckO mice.The structural and mo-lecular alterations provided a clue for further studying the potential mechanisms of furin.

关键词： Astrocyte Ciliogenesis Conditionalknockout Ependymal Furin Hydrocephalus Proteomics

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Screen-printed graphite electrode on polyvinyl chloride and parchment strips integrated with genetic programming for in situ nitrate sensing of aquaponic pond water

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Information Processing in Agriculture 2024年第2期11卷 187-201页

作者： Ronnie ConcepcionⅡ Bernardo Duarte Maria Gemel Palconit Jonah Jahara BaunArgel Bandala Ryan Rhay Vicerra Elmer Dadios Department of Manufacturing Engineering and Management De La Salle UniversityManila 1004 Philippines MARE-Marine and Environmental Sciences Centre.&ARNET-Aquatic Research Infrastructure network Associated laboratory Faculdade de Ciencias da Universidade de LisboaCampo Grande1749-016 LisboaPortugal Departamento de Biologia Vegetal da Faculdade de Ciencias da Universidade de Lisboa Campo Grande 1749-016 LisboaPortugal Department of Electronics and Computer Engineering De La Salle UniversityManila 1004 Philppines

Nitrate is the primary water-soluble macronutrient essential for plant growth that is converted from excess fish feeds,fish effluents,and degrading biomaterials on the aquaponic pond floor,and when aquacultural malpractices occur,large amounts of it retain in the water system causing increase rate in eutrophication and toxifies fish and aquaculture plants.Recent nitrate sensor prototypes still require performing the additional steps of water sample deionization and dilution and were constructed with expensive materials.In response to the challenge of sensor enhancement and aquaponic water quality monitoring,this study developed sensitive,repeatable,and reproducible screen-printed graphite electrodes on polyvinyl chloride and parchment paper substrates with silver as electrode material and 60:40 graphite powder:nail polish formulated conductive ink for electrical traces,integrated with 9-gene genetic expression model as a function of peak anodic current and electrochemical test time for nitrate concentration prediction that is embedded into low-power Arduino ESP32 for in situ nitrate sensing in aquaponic pond water.Five SPE electrical traces were designed on the two types of substrates.Scanning electron microscopy with energy dispersive X-ray confirmed the electrode surface morphology.Electrochemical cyclic voltammetry using 10 to 100 mg/L KNO3 and water from three-depth regions of the actual pond established the electrochemical test time(10.5 s)and electrode potential(0.135 V)protocol necessary to produce peak current that corresponds to the strength of nitrate ions during redox.The findings from in situ testing revealed that the proposed sensors have strong linear predictions(R2=0.968 MSE=1.659 for nSPEv and R2=0.966 MSE=4.697 for nSPEp)in the range of 10 to 100 mg/L and best detection limit of 3.15μg/L,which are comparable to other sensors of more complex construction.The developed three-electrode electrochemical nitrate sensor confirms that it is reliable for both biosensing in controlled solutions and in situ

关键词： Aquaponic water quality Electrochemical technology Genetic programming Graphite electrode Nitrate sensor Precision agriculture Printed electronics Scanning electron microscopy Screen-printed electrode Voltammetry

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Stress relaxation properties of calcium silicate hydrate:a molecular dynamics study

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第2期25卷 97-115页

作者： Zhicheng GENG Shengwen TANG Yang WANG Hubao A Zhen HE Kai WU Lei WANG State Key laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan430072China Key laboratory of Advanced Civil Engineering Materials of Ministry of Education School of Materials Science and EngineeringTongji UniversityShanghai200092China College of Materials Science and Engineering Xi’an University of Architecture and TechnologyXi’an710055China

The time-dependent viscoelastic response of cement-based materials to applied deformation is far from fully understood at the atomic level.Calcium silicate hydrate(C-S-H),the main hydration product of Portland cement,is responsible for the viscoelastic mechanism of cement-based materials.In this study,a molecular model of C-S-H was developed to explain the stress relaxation characteristics of C-S-H at different initial deformation states,Ca/Si ratios,temperatures,and water contents,which cannot be accessed experimentally.The stress relaxation of C-S-H occurs regardless of whether it is subjected to initial shear,tensile,or compressive deformation,and shows a heterogeneous characteristic.Water plays a crucial role in the stress relaxation process.A large Ca/Si ratio and high temperature reduce the cohesion between the calcium-silicate layer and the interlayer region,and the viscosity of the interlayer region,thereby accelerating the stress relaxation of C-S-H.The effect of the hydrogen bond network and the morphology of C-S-H on the evolution of the stress relaxation characteristics of C-S-H at different water contents was elucidated by nonaffine mean squared displacement.Our results shed light on the stress relaxation characteristics of C-S-H from a microscopic perspective,bridging the gap between the microscopic phenomena and the underlying atomic-level mechanisms.

关键词： Calcium silicate hydrate(C-S-H) Stress relaxation Ca/Si ratio Temperature Water content Atomic simulation

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Transcriptome and morphological analyses of double flower formation in Dianthus chinensis

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Horticultural Plant Journal 2024年第1期10卷 181-193页

作者： Xiaoni Zhang Shengnan Lin Quanshu Wu Qijian Wang Chunmei Shi Manzhu Bao Mohammed Bendahmane Xiaopeng Fu Zhiqiang Wu Guangdong laboratory for Lingnan Modern Agriculture Genome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenGuangdong 518120China Key laboratory of Horticultural Plant Biology College of Horticulture and Forestry SciencesHuazhong Agricultural UniversityWuhanHubei 430070China Laboratoire Reproduction et Development des Plantes INRA-CNRS-Lyon1-ENSEcole Normale Superieure de LyonLyon 520074France

The double flower developmental process is regulated via a complex transcriptional regulatory network.To understand this highly dynamic and complex developmental process of Dianthus spp.,we performed a comparative analysis of floral morphology and transcriptome dynamics in simple flowers and double flowers.We found that the primordium of double flowers of‘X’was larger in size compared to that of simple flowers of‘L’in Dianthus chinensis.RNA-seq and Weighted Gene Co-expression network Analysis(WGCNA)during flower development,identified stage-specific gene network modules.Expression analysis by RNA-seq indicated that a group of genes related to floral meristem identity,primordia position and polarity were highly expressed in double flowers genotypes compared to simple flowers genotypes,suggesting their roles in double-petal formation.A total of 21 DEGs related to petal number were identified between simple and double flowers.The experiments of in situ hybridization revealed that DcaAP2L,DcaLFY and DcaUFO genes were expressed in the intra-sepal boundary and petal boundary.We proposed a potential transcriptional regulatory network for simple and double flower development.This study provides novel insights into the molecular mechanism underlying double flower formation in Dianthus spp.

关键词： Dianthus spp. Petal boundary Floral morphology Double flower Co-expression network

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Visualization and characterization of experimental hydraulic fractures interacting with karst fracture-cavity distributions

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第5期16卷 1667-1683页

作者： Hanzhi Yang Xin Chang Chunhe Yang Wuhao Guo Lei Wang Guokai Zhao Yintong Guo State Key laboratory of Coal Mine Disaster Dynamics and Control Chongqing UniversityChongqing400044China State Key laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China

Karst fracture-cavity carbonate reservoirs,in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances,have become significant fields of oil and gas exploration and exploitation.Proppant fracturing is considered as the best method for exploiting carbonate reservoirs;however,previous studies primarily focused on the effects of individual types of geological formations,such as natural fractures or cavities,on fracture propagation.In this study,true-triaxial physical simulation experiments were systematically performed under four types of stress difference conditions after the accurate prefabrication of four types of different fracture-cavity distributions in artificial samples.Subsequently,the interaction mechanism between the hydraulic fractures and fracture-cavity structures was systematically analyzed in combination with the stress distribution,cross-sectional morphology of the main propagation path,and three-dimensional visualization of the overall fracture network.It was found that the propagation of hydraulic fractures near the cavity was inhibited by the stress concentration surrounding the cavity.In contrast,a natural fracture with a smaller approach angle(0°and 30°)around the cavity can alleviate the stress concentration and significantly facilitate the connection with the cavity.In addition,the hydraulic fracture crossed the natural fracture at the 45°approach angle and bypassed the cavity under higher stress difference conditions.A new stimulation effectiveness evaluation index was established based on the stimulated reservoir area(SRA),tortuosity of the hydraulic fractures(T),and connectivity index(CI)of the cavities.These findings provide new insights into the fracturing design of carbonate reservoirs.

关键词： Karst fracture-cavity reservoir Fracturing experiment Fracture propagation Cross-sectional morphology Stimulation effectiveness

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Advances in memristor based artificial neuron fabrication-materials,models,and applications

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International Journal of Extreme Manufacturing 2024年第1期6卷 27-50页

作者： Jingyao Bian Zhiyong Liu Ye Tao Zhongqiang Wang Xiaoning Zhao Ya Lin Haiyang Xu Yichun Liu Key laboratory for UV Light-Emitting Materials and Technology(Northeast Normal University) Ministry of Education5268 Renmin StreetChangchunPeople’s Republic of China

Spiking neural network(SNN),widely known as the third-generation neural network,has been frequently investigated due to its excellent spatiotemporal information processing capability,high biological plausibility,and low energy consumption characteristics.Analogous to the working mechanism of human brain,the SNN system transmits information through the spiking action of neurons.Therefore,artificial neurons are critical building blocks for constructing SNN in hardware.Memristors are drawing growing attention due to low consumption,high speed,and nonlinearity characteristics,which are recently introduced to mimic the functions of biological neurons.Researchers have proposed multifarious memristive materials including organic materials,inorganic materials,or even two-dimensional materials.Taking advantage of the unique electrical behavior of these materials,several neuron models are successfully implemented,such as Hodgkin–Huxley model,leaky integrate-and-fire model and integrate-and-fire model.In this review,the recent reports of artificial neurons based on memristive devices are discussed.In addition,we highlight the models and applications through combining artificial neuronal devices with sensors or other electronic devices.Finally,the future challenges and outlooks of memristor-based artificial neurons are discussed,and the development of hardware implementation of brain-like intelligence system based on SNN is also prospected.

关键词： artificial neuron memristor memristive materials neuron model micro-nano manufacturing spiking neural network

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