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Multimodal Omics Approaches to Aging and Age‑Related Diseases

Phenomics 2024年第1期4卷 56-71页

作者： Qianzhao Ji Xiaoyu Jiang Minxian Wang Zijuan Xin Weiqi Zhang jing Qu guang‑Hui Liu State Key Laboratory of Membrane Biology Instituteof ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and ReproductiveBiology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academyof Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academyof SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China School of Future Technology University of ChineseAcademy of SciencesBeijing 100190China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for GeriatricDisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Centerfor Aging and CancerXuanwu HospitalCapital MedicalUniversityBeijing 100053China

Aging is associated with a progressive decline in physiological capacities and an increased risk of aging-associated *** increasing body of experimental evidence shows that aging is a complex biological process coordinately regulated by multiple factors at diferent molecular ***,it is difcult to delineate the overall systematic aging changes based on single-layer ***,multimodal omics approaches,in which data are acquired and analyzed using complementary omics technologies,such as genomics,transcriptomics,and epigenomics,are needed for gaining insights into the precise molecular regulatory mechanisms that trigger *** recent years,multimodal omics sequencing technologies that can reveal complex regulatory networks and specifc phenotypic changes have been developed and widely applied to decode aging and age-related *** review summarizes the classifcation and progress of multimodal omics approaches,as well as the rapidly growing number of articles reporting on their application in the feld of aging research,and outlines new developments in the clinical treatment of age-related diseases based on omics technologies.

关键词： Multimodal omics approaches Aging Genome Epigenome

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Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

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Zoological Research 2024年第2期45卷 355-366页

作者： jing-Yi Jia guang-Hui Chen Ting-Ting Shu Qi-Yong Lou Xia Jin Jiang-Yan He Wu-Han Xiao Gang Zhai Zhan Yin College of Fisheries Huazhong Agriculture UniversityWuhanHubei 430070China State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyChinese Academy of SciencesWuhanHubei 430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes Chinese Sturgeon Research InstituteChina Three Gorges CorporationYichangHubei 443100China Hubei Hongshan Laboratory Huazhong Agriculture UniversityWuhanHubei 430070China Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100049China

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in ***,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in *** this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)*** assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-*** androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis *** Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd ***,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally ***,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

关键词： Cyp17a1 Testosterone Androgen receptor De novo lipogenesis Fatty acid synthesis

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Spatial transcriptomics:recent developments and insights in respiratory research

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Military Medical Research 2024年第3期11卷 430-448页

作者： Wen-Jia Wang Liu-Xi Chu Li-Yong He Ming-jing Zhang Kai-Tong Dang Chen Gao Qin-Yu Ge Zhou-guang Wang Xiang-Wei Zhao State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035ZhejiangChina Orthopaedic Bioengineering Research Group Division of Surgery and Interventional ScienceUniversity College LondonLondon HA74LPUK

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this *** bulk RNA sequencing and single-cell RNA sequencing(scRNA-seq)have provided insights into cell types and heterogeneity in the respiratory system,the relevant specific spatial localization and cellular interactions have not been clearly *** transcriptomics(ST)has filled this gap and has been widely used in respiratory *** review focuses on the latest iterative technology of ST in recent years,summarizing how ST can be applied to the physiological and pathological processes of the respiratory system,with emphasis on the ***,the current challenges and potential development directions are proposed,including high-throughput full-length transcriptome,integration of multi-omics,temporal and spatial omics,bioinformatics analysis,*** viewpoints are expected to advance the study of systematic mechanisms,including respiratory studies.

关键词： Spatial transcriptomics Lung Tumor Spatial multi-omics

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Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

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Asian Journal of Andrology 2024年第2期26卷 175-182页

作者： Jian-Fang Che Hui-Xia Wu Si-Cong Zeng Yue-Ren Wu jing Dai De-Hua Cheng Fei Gong guang-Xiu Lu Ge Lin Can Dai School of Medicine Hunan Normal UniversityChangsha 410013China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410008China Clinical Research Center for Reproduction and Genetics in Hunan Province Changsha 410078China National Engineering and Research Center of Human Stem Cell Changsha 410205China

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete *** in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain ***,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)*** staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) *** with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live ***,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January *** found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total *** optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing *** study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

关键词： conventional IVF gene variants PLCζ polyspermy

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Evaluation of microRNA expression profiles in human sperm frozen using permeable cryoprotectant-free droplet vitrification and conventional methods

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Asian Journal of Andrology 2024年第4期26卷 366-376页

作者： Li-Xin Zhang jing Mao Yan-Dong Zhou guang-Yao Mao Run-Fa Guo Hong-Shan Ge Xia Chen Department of Histology and Embryology Medical SchoolNantong UniversityNantong 226001China Department of Reproductive Medicine The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou School of Clinical MedicineNanjing Medical UniversityTaizhou 225300China.

For sperm cryopreservation,the conventional method,which requires glycerol,has been used for a long *** addition,the permeable cryoprotectant-free vitrification method has been continuously *** the differences of cryopreservation effects between the two methods have being studied,differences in microRNA(miRNA)profiles between them remain *** this study,we investigated the differences in miRNA expression profiles among conventional freezing sperm,droplet vitrification freezing sperm and fresh human *** also analyzed the differences between these methods in terms of differentially expressed miRNAs(DEmiRs)related to early embryonic development and paternal *** results showed no significant differences between the cryopreservation methods in terms of sperm motility ratio,plasma membrane integrity,DNA integrity,mitochondrial membrane potential,acrosome integrity,and ultrastructural ***,sperm miRNA-sequencing showed differences between the two methods in terms of the numbers of DEmiRs(28 and 19 with vitrification using a nonpermeable cryoprotectant and the conventional method,respectively)in postthaw and fresh sperm *** related to early embryonic development and paternal epigenetics mainly included common DEmiRs between the *** results showed that the differences between conventional freezing and droplet vitrification were minimal in terms of miRNA expression related to embryonic development and *** in sperm miRNA expression due to freezing are not always detrimental to embryonic *** study compared differences in miRNA expression profiles before and after cryopreservation between cryopreservation by conventional and vitrification *** offers a new perspective to evaluate various methods of sperm cryopreservation.

关键词： cryopreservation cryoprotectant-free vitrification early embryonic development paternal epigenetic inheritance sperm miRNAs sucrose

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Evaluation of the injection and plugging ability of a novel epoxy resin in cement cracks

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Petroleum Science 2024年第2期21卷 1211-1220页

作者： guang-Yao Leng Wei Yan Hai-Mu Ye Er-Dong Yao Ji-Bin Duan Zheng-Xian Xu Ke-Pei Li jing-Ru Zhang Zhong Li State Key Laboratory of Petroleum Resource&Prospecting China University of Petroleum(Beijing)Beijing102249China CNPC Liaohe Oilfield Gas Storage Co.LTD Panjin124000LiaoningChina CNOOC Research Institute Co. Ltd.Beijing100028China

Sustained casing pressure(SCP)is a crucial issue in the oil and gas production *** resins,exhibiting exceptional compressive strength,ductility,and shear bonding strength,have the potential to form reliable *** injectivity and sealing capacity of the epoxy resin is crucial parameters for the success of shallow remediation *** study aimed to develop and assess a novel solid-free resin sealant as an alternative to Portland cement for mitigating fluid *** investigation evaluated the viscosity,compressive strength,and brittleness index of the epoxy resin sealant,as well as its tangential and normal shear strengths in conjunction with casing *** flow characteristics and sealing abilities of conventional cement and epoxy resin were comparatively analyzed in *** results showed that the application of a viscosity reducer facilitated control over the curing time of the epoxy resin,ranging from 1.5 to 6 h,and reduced the initial viscosity from 865.53 to 118.71 m Pa,*** mechanical properties of the epoxy resin initially increased with a rise in curing agent content before experiencing a minor *** epoxy resin containing 30%curing agent exhibited optimal mechanical *** a 14-day curing period,the epoxy resin's compressive strength reached81.37 MPa,2.12 times higher than that of cement,whereas the elastic modulus of cement was 2.99 times greater than that of the epoxy *** brittleness index of epoxy resin is only 3.42,demonstrating high flexibility and *** tangential and normal shear strengths of the epoxy resin exceeded those of cement by 3.17 and 2.82 times,*** a 0.5 mm-wide crack,the injection pressure of the epoxy resin remained below 0.075 MPa,indicating superior injection and flow ***,the injection pressure of cement surged dramatically to 2.61 MPa within 5 *** breakthrough pressure of0.5 PV epoxy resin reached 7.53 MPa,decreasing the crack's perme

关键词： Sustained casing pressure Epoxy resin sealant Curing agent Viscosity reducer Mechanical properties Crack sealing

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Degeneration Directory:a multi-omics web resource for degenerative diseases

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Protein & Cell 2024年第5期15卷 385-392页

作者： Haoteng Yan Changfa Lu Chenyang Lan Si Wang Weiqi Zhang Zan He jinghao Hu Jiaqi Ai guang-Hui Liu Shuai Ma Yuanchun Zhou jing Qu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Computer Network Information Center Chinese Academy of SciencesBeijing 100190China The Fifth People’s Hospital of Chongqing Chongqing 400062China Aging Biomarker Consortium Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Background of *** degeneration refers to the gradual decline in organ function and structure deterioration that occurs during aging,which represents the greatest risk factor for various degenerative diseases,including cardiovascular diseases,neurodegenerative diseases,and osteoarthritis,etc.(Aging Biomarker et al.,2023;Becker et al.,2018;Cai et al.,2022).

关键词： Directory web Becker

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MCSTransWnet:A new deep learning process for postoperative corneal topography prediction based on raw multimodal data from the Pentacam HR system

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Medicine in Novel Technology and Devices 2024年第1期21卷 53-63页

作者： Nan Cheng Zhe Zhang jing Pan Xiao-Na Li Wei-Yi Chen guang-Hua Zhang Wei-Hua Yang College of Biomedical Engineering Taiyuan University of TechnologyTaiyuan 030600ShanxiChina Shenzhen Eye Hospital Jinan UniversityShenzhen Eye InstituteShenzhen 518040GuangdongChina Department of Intelligence and Automation Taiyuan UniversityTaiyuan 030032ShanxiChina Graphics and Imaging Laboratory University of GironaGirona 17004Spain

This work provides a new multimodal fusion generative adversarial net(GAN)model,Multiple Conditions Transform W-net(MCSTransWnet),which primarily uses femtosecond laser arcuate keratotomy surgical parameters and preoperative corneal topography to predict postoperative corneal topography in astigmatism-corrected *** MCSTransWnet model comprises a generator and a discriminator,and the generator is composed of two *** first sub-generator extracts features using the U-net model,vision transform(ViT)and a multi-parameter conditional module branch.The second sub-generator uses a U-net network for further image *** discriminator uses the pixel discriminator in ***,most GAN models are convolutional neural networks;however,due to their feature extraction locality,it is difficult to comprehend the relationships among global ***,we added a vision Transform network as the model branch to extract the global *** is normally difficult to train the transformer,and image noise and geometric information loss are ***,we adopted the standard U-net fusion scheme and transform network as the generator,so that global features,local features,and rich image details could be obtained *** experimental results clearly demonstrate that MCSTransWnet successfully predicts postoperative corneal topographies(structural similarity=0.765,peak signal-to-noise ratio=16.012,and Fréchet inception distance=9.264).Using this technique to obtain the rough shape of the postoperative corneal topography in advance gives clinicians more references and guides changes to surgical planning and improves the success rate of surgery.

关键词： Deep learning Generative adversarial networks Corneal topography Transformer W-net U-net Medical imaging Multimodal fusion

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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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Protein & Cell 2024年第6期15卷 441-459页

作者： Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang jing Qu guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Sports Medicine Department Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Division of Life Sciences and Medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230001China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint ***,the mechanism underlying human synovial aging remains poorly ***,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged *** delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged ***,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue *** particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged *** human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged *** data indicate an important role of FOXO1 in the regulation of human synovial ***,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关键词： FOXO1 degeneration inflammation

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Gene cloning,protein expression,and enzymatic characterization of a double-stranded RNA degrading enzyme in Apolygus lucorum

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Insect Science 2024年第1期31卷 119-133页

作者： Jie-Yu Zhang jing Zhao Keyan Zhu-Salzman Qin-Qin Ji Yi-Ping Jiang Liu-Bin Xiao De-Jin Xu guang-Chun Xu Lin-Quan Ge Yong-An Tan College of Plant Protection Yangzhou UniversityYangzhouJiangsu ProvinceChina Institute of Plant Protection Jiangsu Academy of Agricultural SciencesNanjingJiangsu ProvinceChina Department of Entomology Texas A&M UniversityCollege StationTXUSA Taizhou Customs of the People's Republic of China TaizhouJiangsu ProvinceChina

RNA interference(RNAi)is a powerful tool that post-transcriptionally silences target genes in eukaryotic ***,silencing efficacy varies greatly among different insect ***,we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA *** disappearance of double-stranded RNA(dsRNA)could be a potential factor that restricts RNAi ***,we found that dsRNA can be degraded in midgut fluids,and a dsRNase of ***(AldsRNase)was identified and *** alignment indicated that its 6 key amino acid residues and the Mg2+-binding site were similar to those of other insects’*** signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali *** showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle,with peaks at the 4th instar ecdysis in the whole *** purified AldsRNase protein obtained by heterologously expressed can rapidly degrade *** comparing the substrate specificity of AldsRNase,3 specific substrates(dsRNA,small interfering RNA,and dsDNA)were all degraded,and the most efficient degradation is ***,immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut *** cloning and functional study of AldsRNase,the enzyme activity and substrate specificity of the recombinant protein,as well as the subcellular localization of nuclease,the reason for the disappearance of dsRNA was explained,which was useful in improving RNAi efficiency in *** and related species.

关键词： Apolygus lucorum cloning dsRNase enzymatic activity protein expression

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