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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz Computational biology and systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Human herpesvirus 4 and adaptive immunity in Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2077-2078页

作者： Jian-Sheng Kang Pei-Pei Liu clinical systems biology laboratories The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina

In a recent paper published in Nature,Gate et *** adaptive immune changes in Alzheimer’s disease(AD),discovered CD8+T effector memory CD45RA+(TEMRA)cells with proinflammatory and cytotoxic functions in AD patients,and identified two TEMRA cell-recognized antigens of human herpesvirus 4(HHV-4),also known as Epstein–Barr virus(EBV).1 The findings suggested that adaptive immunity might have a role in AD progression.

关键词： immunity CD45RA Alzheimer

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

The effect of selective serotonin reuptake inhibitors on cognitive function in patients with Alzheimer’s disease and vascular dementia: focusing on fluoxetine with long follow-up periods

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Signal Transduction and Targeted Therapy 2019年第1期4卷 386-388页

作者： Yi Xie Pei-Pei Liu Ya-Jun Lian Hong-Bo Liu Jian-Sheng Kang clinical systems biology laboratories The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina

Dear Editors,Alzheimer’s disease(AD)and vascular dementia(VaD)are two of the most common forms of dementia,resulting in increased disability and mortality,impaired quality of life,and serious burdens on society and ***,the presently available drugs can only alleviate symptoms for a short time without delaying the progression of the cognitive *** 2003,no new drugs have been approved by the US Food and Drug Administration for the treatment of *** 2019,phase III clinical trials of crenezumab and aducanumab,two anti-amyloid beta monoclonal antibodies,were *** scant progress in clinical trials urges efforts towards an alternative therapeutic strategy for dementia.

关键词： drugs Alzheimer impaired

Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells

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World Journal of Gastroenterology 2005年第8期11卷 1122-1130页

作者： Elisabetta Ceni Tommaso Mello Mirko Tarocchi David W Crabb Anna Caldini Pietro Invernizzi Calogero Surrenti Stefano Milani Andrea Galli Gastroenterology Unit Farmacogenomic Foundation FioiGen Departments of Medicine and of Biochemistry and Molecular biology clinical Chemistry laboratories Department of Medicine Ospedale San Paolo

AIM: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of same epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferator-activated receptor γ (PPARγ), the mechanism by which TZD exert their anticancer effect is presently unclear. In this study, we analyzed the mechanism by which TZD inhibit growth of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma. METHODS: The effects of TZD in pancreatic cancer cells were assessed in anchorage-independent growth assay. Expression of PPARy was measured by reverse-transcription polymerase chain reaction and confirmed by Western blot analysis. PPARy activity was evaluated by transient reporter gene assay. Flow cytometry and DMA fragmentation,assay were used to determine the effect of TZD on cell cycle progression and apoptosis respectively. The effect of TZD on ductal differentiation markers was performed by Western blot. RESULTS: Exposure to TZD inhibited colony formation in a PPARγ-dependent manner. Growth inhibition was linked to G1 phase cell cycle arrest through induction of the ductal differentiation program without any increase of the apoptotic rate. CONCLUSION: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth by a PPAR-dependent induction of pacreatic ductal differentiation.

关键词： Thiazolidinediones Pancreatic cancer PPARγ Cancer growth Differentiation

Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis

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Neuroscience Bulletin 2024年第10期40卷 1529-1544页

作者： Run-Zhou Yang Dian-Dian Wang Sen-Miao Li Pei-Pei Liu Jian-Sheng Kang clinical systems biology laboratories The First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Mitochondrial membrane potential(MMP)plays a crucial role in the function of cells and organelles,involving various cellular physiological processes,including energy production,formation of reactive oxygen species(ROS),unfolded protein stress,and cell ***,there is a lack of genetically encoded fluorescence indicators(GEVIs)for *** our screening of various GEVIs for their potential monitoring MMP,the Accelerated Sensor of Action Potentials(ASAP)demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell ***,mitochondrial ASAPs also displayed sensitivity to ROS in ***,two ASAP mutants resistant to ROS were generated.A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker ***,four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4(MPI-1-4).In vivo,fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

关键词： M2 cortex Mitochondria Genetically encoded voltage indicators Membrane potential ROS sensitivity Fiber photometry Isoflurane-induced narcosis

Digital Identification of Ecosystem Structure in the FIrtIna Valley of the Kakar Mountains in the Rize City of Turkey

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Journal of Mountain Science 2014年第2期11卷 421-428页

作者： Cagasan KARACAOGLU Selim Sualp CAGLAR Department of biology Faculty of Science Biology Department Ecology Section EBAL Laboratories Hacettepe University

Identifying the structure of protected mountain ecosystems is an important task for understanding conservation sustainability. The study area, the Firtina Valley, located in the Rize City on the Eastern Blacksea Coast, is one of the biological hotspots and a National Park of Turkey. In order to identify the structure of mountain ecosystems, we generated a GIS database for the main environmental parameters of the study area, including elevation,slope and aspect layers for topographic structure, 10year mean values of Normalized Difference Vegetation Index(NDVI), data for vegetation structure, annual mean temperature and precipitation layers for climatic structure, main soil groups for soil structure and stream flow accumulation, stream flow length and stream order layers for hydrological *** identify the complex relations among environmental factors in the study area a data reduction method is applied with Principal Component Analysis(PCA). PCA is performed using data of 16 layers from Geographical Information systems(GIS). PCA analysis reduced 16 dimensions into 5 dimensions containing 75% of the variation in all data. It is also revealed that the topographic structure, mainly altitude, dominates the ecosystems of the Firtina Valley, but it should be considered that the interactions of environmental factors in an ecosystem dynamics are very complex. The ecosystem structure is determined by the environmental factors direct or indirect effects on energy regulation of an ecosystem. Therefore the relationship between topographic elements and other abiotic-biotic elements in the Firtina Valley are important for environmental assessment and sustainability of a protected area, and these effects are explained in this study.

关键词： PCA GIS Firtina Valley Ecosystem structure Protected areas

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Single-model uncertainty quantification in neural network potentials does not consistently outperform model ensembles

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npj Computational Materials 2023年第1期9卷 49-59页

作者： Aik Rui Tan Shingo Urata Samuel Goldman Johannes C.B.Dietschreit Rafael Gómez-Bombarelli Department of Materials Science and Engineering Massachusetts Institute of TechnologyCambridgeMAUSA Innovative Technology laboratories AGC IncTokyoJapan Computational and systems biology Massachusetts Institute of TechnologyCambridgeMAUSA

Neural networks(NNs)often assign high confidence to their predictions,even for points far out of distribution,making uncertainty quantification(UQ)a *** they are employed to model interatomic potentials in materials systems,this problem leads to unphysical structures that disrupt simulations,or to biased statistics and dynamics that do not reflect the true *** UQ techniques can find new informative data and drive active learning loops for robust ***,a variety of UQ techniques,including newly developed ones,exist for atomistic simulations and there are no clear guidelines for which are most effective or suitable for a given *** this work,we examine multiple UQ schemes for improving the robustness of NN interatomic potentials(NNIPs)through active *** particular,we compare incumbent ensemble-based methods against strategies that use single,deterministic NNs:mean-variance estimation(MVE),deep evidential regression,and Gaussian mixture models(GMM).We explore three datasets ranging from in-domain interpolative learning to more extrapolative out-of-domain generalization challenges:rMD17,ammonia inversion,and bulk silica *** is measured across multiple metrics relating model error to *** experiments show that none of the methods consistently outperformed each other across the various *** remained better at generalization and for NNIP robustness;MVE only proved effective for in-domain interpolation,while GMM was better out-of-domain;and evidential regression,despite its promise,was not the preferable alternative in any of the *** broadly,cost-effective,single deterministic models cannot yet consistently match or outperform ensembling for uncertainty quantification in NNIPs.

关键词： ensemble evident neural

Current understanding of multi-species biofilms

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International Journal of Oral Science 2011年第2期3卷 74-81页

作者： Liang Yang Yang Liu Hong Wu Niels Hoiby Soren Molin Zhi-jun Song Department of systems biology Technical University of Denmark Lyngby DK-2800 Denmark Department of clinical Microbiology Rigshospitalet Copenhagen N DK-2100 Denmark

Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contamina- tions of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species hiofilm formation will facilitate the development of methods for combating bacterial hiofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review.

关键词： biofilms extracellular polymeric substances structure development interactions

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