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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 *** 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)

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Single-cell technologies: current and near future

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Science China Life Sciences 2025年第01期 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Key Laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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Anticarcinogenic and antioxidant activity of diindolylmethane derivatives

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Acta Pharmacologica Sinica 2004年第5期25卷 124-129页

作者： Sakina Hayat BENABADJI Department of medicinal Chemistry Medical center of Fudan University

AIM: To investigate the synthesis methods and the bioactivity of diindolylmethane (DIM) derivatives. METHODS:1) A 3D-Quantitative Structure-Active Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) studyof 14 DIM derivatives was investigated to predict their anticarcinogenic activity. 2) Based on CoMFA model, aseries of new derivatives of DIM were designed and synthesized. 3) Their free radical scavenging and antioxidantpotentials were tested using in-vitro DPPH radical scavenging and b-carotene antioxidant models. 4) Theanticarcinogenic activities of some compounds were tested by using microculture tetrazolium assay (MTT) andsulforhodamine B (SRB) proteochromosomic assays. RESULTS: 1) The CoMFA model derived from DIM ana-logues proved a good predictive ability with q2 value of 0.827. 2) New designed compounds 3c and 4c exhibited3-fold more potent radical scavenging activity than reference substance Vitamin E in DPPH model expressed by IC50values. 3) The primary antitumor screening essay showed that some DIM derivatives designed exhibited theinhibitory activities to some tumor cell growth at relatively high concentration, and DIM was the most effectiveamong them. CONCLUSION: DIMs 3D-QSAR model is reliable. According to it, eleven DIM derivatives weresynthesized, and two derivatives of them possess potent radical scavenging activities and some showed the inhibi-tory activities in primary anticancer assay in vitro.

关键词： indole-3-carbinol diindolylmethane CoMFA analysis antioxidants free radical scavengers 1,1-DPPH carotenoids antitumor drug screening assay

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Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei Jianqiang Yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China medicinal Chemistry and bioinformatics center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China medicinal Chemistry and bioinformatics center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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Streamlined and on-demand preparation of mRNA products on a universal integrated platform

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Microsystems & Nanoengineering 2023年第4期9卷 119-128页

作者： Hongjuan Wei Zhen Rong Liyan Liu Ye Sang Jing Yang Shengqi Wang bioinformatics center of AMMS Beijing 100850P.R.China

Vaccines are used to protect human beings from various *** vaccines simplify the development process and reduce the production cost of conventional vaccines,making it possible to respond rapidly to acute and severe diseases,such as coronavirus disease *** this study,a universal integrated platform for the streamlined and ondemand preparation of mRNA products directly from DNA templates was *** DNA templates were amplified in vitro by a polymerase chain reaction module and transcribed into mRNA sequences,which were magnetically purified and encapsulated in lipid *** an initial example,enhanced green fluorescent protein(eGFP)was used to test the *** expression capacity and efficiency of the products were evaluated by transfecting them into HEK-293T *** batch production rate was estimated to be 200–300μg of eGFP mRNA in 8 ***,an mRNA vaccine encoding the receptor-binding domain(RBD)of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike protein was produced by this *** proposed integrated platform shows advantages for the universal and on-demand preparation of mRNA products,offering the potential to facilitate broad access to mRNA technology and enable the development of mRNA products,including the rapid supply of new mRNA-based vaccines in pandemic situations and personalized mRNA-based therapies for oncology and chronic infectious diseases,such as viral hepatitis and acquired immune deficiency syndrome.

关键词： preparation template offering

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Management of acute cough by Zataria multiflora Boiss as an alternative treatment

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Journal of Integrative Medicine 2018年第1期16卷 20-25页

作者： Mohaddese Mahboubi Department of Microbiology Medicinal Plants Research Center of Barij

Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bron- chioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional med- icine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled informa- tion about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone （n = 1 ）, in combination with Althaea officinalis （n = 2） or Foeniculum vulgate essential oil （n = 1 ）, in the form of syrup （n = 3）, oral drop （n = 1 ） and soft capsule （n = 1 ）, for the treatment of acute cough in comparison with placebo or synthetic drugs （bromhexine, dextromethorphan and clobutinol）. All clinical studies confirmed the efficacy ofZ multiflora in the amelioration of acute cough in pediatric （n = 1） and adult patients （n = 4） without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in com- bination with ivy leaf extract or primrose root extract on patients with cough.

关键词： Zataria multiflora Foeniculum vulgate Althaea officinalis Cough Medicine. Iranian traditiona

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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha Department of medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Institute of Laboratory Animal center Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina Department of Hyperbaric Oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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VASC: Dimension Reduction and Visualization of Single-cell RNA-seq Data by Deep Variational Autoencoder

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Genomics, Proteomics & bioinformatics 2018年第5期16卷 320-331页

作者： Dongfang Wang Jin Gu MOE Key Laboratory of bioinformatics BNRIST Bioinformatics Division & Center for Synthetic and Systems BiologyDepartment of Automation Tsinghua University

Single-cell RNA sequencing(scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities at the single cell level. It is an important step for studying cell subpopulations and lineages, with an effective low-dimensional representation and visualization of the original scRNA-Seq data. At the single cell level, the transcriptional fluctuations are much larger than the average of a cell population, and the low amount of RNA transcripts will increase the rate of technical dropout events. Therefore, scRNA-seq data are much noisier than traditional bulk RNA-seq data. In this study, we proposed the deep variational autoencoder for scRNA-seq data(VASC), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. VASC can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on over 20 datasets, VASC shows superior performances in most cases and exhibits broader dataset compatibility compared to four state-of-the-art dimension reduction and visualization methods. In addition, VASC provides better representations for very rare cell populations in the 2D visualization. As a case study, VASC successfully re-establishes the cell dynamics in pre-implantation embryos and identifies several candidate marker genes associated with early embryo development. Moreover, VASC also performs well on a 10× Genomics dataset with more cells and higher dropout rate.

关键词： Single cell RNA sequencing Deep variational autoencoder Dimension reduction Visualization Dropout

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Structured Learning in Biological Domain

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Journal of Systems Science and Systems Engineering 2020年第4期29卷 440-453页

作者： Canh Hao Nguyen bioinformatics center Instute for Chemical ResearchKyoto UniversityUjiKyotoJapan

Biological domain has been blessed with more and more data from biotechnologies as well as data integration *** the renaissance of machine learning and artificial intelligence,there is so much promise of data-driven biological knowledge ***,it is not straight forward due to the complexity of the domain knowledge hidden in the *** any level,be it atoms,molecules,cells or organisms,there are rich interdependencies among biological *** learning approaches in this domain usually involves analyzing interdependency structures encoded in graphs and related *** this report,we review our work in developing new Machine Learning methods for these applications with improved performances in comparison with state-of-the-art *** show how the networks among biological components can be used to predict properties.

关键词： Structured learning sparse modeling systems biology deep learning

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