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Advance and Application of Single‑cell Transcriptomics in Auditory Research

Neuroscience Bulletin 2024年第7期40卷 963-980页

作者： Xiangyu Ma Jiamin Guo Mengyao Tian Yaoyang Fu Pei jiang Yuan Zhang renjie Chai State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High‑Tech Key Laboratory for Bio‑Medical ResearchSoutheast UniversityNanjing 210096China Department of Psychiatry Affiliated Hangzhou First People’s HospitalZhejiang University school of MedicineHangzhou 310030China Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsu Provincial Key Medical Discipline(Laboratory)NanjingChina Research Institute of Otolaryngology Nanjing 210008China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Co‑Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 101408China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

Hearing loss and deafness,as a worldwide disability disease,have been troubling human ***,the auditory organ of the inner ear is highly heterogeneous and has a very limited number of cells,which are largely uncharacterized in ***,with the development and utilization of single-cell RNA sequencing(scRNA-seq),researchers have been able to unveil the complex and sophisticated biological mechanisms of various types of cells in the auditory organ at the single-cell level and address the challenges of cellular heterogeneity that are not resolved through by conventional bulk RNA sequencing(bulk RNAseq).Herein,we reviewed the application of scRNA-seq technology in auditory research,with the aim of providing a reference for the development of auditory organs,the pathogenesis of hearing loss,and regenerative *** about spatial transcriptomic scRNA-seq,single-cell based genome,and Live-seq technology will also be discussed.

关键词： Single-cell RNA sequencing Inner ear Cochlear Auditory sensory epithelium Spiral ganglion neuron

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eScience 2023年第5期3卷 49-68页

作者： Zhengqing Ye Ying jiang Li Li Feng Wu renjie Chen Beijing Key Laboratory of Environmental Science and Engineering School of Material Science&EngineeringBeijing Institute of TechnologyBeijing100081China State Key Laboratory of Reliability and Intelligence of Electrical Equipment School of Material Science and EngineeringHebei University of TechnologyTianjin300401China Advanced Technology Research Institute Beijing Institute of TechnologyJinan250300China Collaborative Innovation Center of Electric Vehicles in Beijing Beijing100081China

The electrocatalytic sulfur reduction reaction(SRR)and sulfur evolution reaction(SER),two fundamental multistep conversion processes in lithium–sulfur batteries(LSBs),are root-cause solutions to overcome sluggish redox kinetics and the polysulfide shuttling ***–organic framework(MOF)electrocatalysts have emerged as good platforms for catalyzing SRR and SER,but their catalytic performance is challenged by poor electrical conductivity and limited chemical *** MOFs and their hybrids may be beneficial for stabilizing and improving the desired catalytic properties to achieve high-performance *** review provides a detailed overview of engineering principles for improving the activity,selectivity,and stability of MOFrelated electrocatalysts via composition modulation and nanostructure design as well as hybrid *** presents and discusses the various advances achieved by using in situ characterization techniques,simulations,and theoretical calculations to reveal the dynamic evolution of MOF-related electrocatalysts,enabling an in-depth understanding of the catalysis mechanism at the molecular/atomic ***,prospects and possible research directions for MOF-related sulfur electrocatalysts are proposed.

关键词： MOF-related electrocatalysts Sulfur reduction/evolution Composition modulation Structure design Mechanism research Lithium-sulfur batteries

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Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice

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Journal of Molecular Cell Biology 2021年第3期13卷 210-224页

作者： Meiqin Zhang Sichen Du Huayuan Ou renjie Cui Nan jiang Yifeng Lin Runsheng Ge Duan Ma Jin Zhang Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical Sciences&Institutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China Children’s Hospital Fudan UniversityShanghai 201102China

Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem ***4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse *** lacking Zfhx4 died shortly after birth from an apparent inability to initiate *** also found that the electrical rhythm of brainstem‒spinal cord preparations was significantly depressed in Zfhx4-null mice compared to wild-type *** staining revealed that Zfhx4 was coexpressed with Phox2b and Math1 in the brainstem and that Zfhx4 ablation greatly decreased the expression of these proteins,especially in the retrotrapezoid *** ChIP‒seq and mRNA expression microarray analysis identified Phox2b as the direct downstream target gene of Zfhx4,and this finding was validated by ChIP‒*** studies have reported that both Phox2b and Math1 play key roles in the development of the respiratory center,and Phox2b and Math1 knockout mice are neonatal lethal due to severe central *** top of this,our study revealed that Zfhx4 is a critical regulator of Phox2b expression and essential for perinatal breathing.

关键词： parafacial respiratory group Phox2b respiratory center Zfhx4

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固井水泥浆环空顶替效率研究

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非常规油气 2022年第2期9卷 119-124页

作者：余海豪徐兆刚杨浩房孟李海洋吴佳鹏张驰江仁杰中国地质大学(北京) 北京100083 山东招金地质勘查有限公司山东招远265400

为了在固井施工中,保障水泥浆胶结质量和提高水泥环密封效果,针对采用环空水泥浆顶替钻井液固井时,可能出现的钻井液滞留、顶替效率和顶替界面稳定性的问题,利用CFD流体仿真软件Fluent,针对竖直井建立了长度为100 m,外径为215.9 mm,内径... 详细信息

为了在固井施工中,保障水泥浆胶结质量和提高水泥环密封效果,针对采用环空水泥浆顶替钻井液固井时,可能出现的钻井液滞留、顶替效率和顶替界面稳定性的问题,利用CFD流体仿真软件Fluent,针对竖直井建立了长度为100 m,外径为215.9 mm,内径为139.7 mm的环空顶替物理模型,开展偏心度、顶替速度、密度差对环空顶替界面稳定性及顶替效率的影响研究。仿真结果表明,顶替速度是影响顶替界面稳定性及顶替效率的一个因素,当低速度顶替时,顶替界面比较稳定,顶替效率较高;偏心度也会影响顶替界面稳定性及顶替效率,随着偏心度的增加,顶替界面越来越不稳定,界面出现倾斜,顶替效率也随之降低;密度差主要影响顶替界面的形态,在正密度差下,密度差越大,顶替界面越稳定,顶替效率也越高。降低套管偏心度、增大水泥浆的密度及进行低速下的层流顶替可提高界面稳定性,提升顶替效率。以上成果认识,对提升固井效率和固井质量具有一定指导意义。

关键词：固井水泥浆顶替效率偏心度顶替速度密度差

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m^(6)A demethylase ALKBH5 is required for antibacterial innate defense by intrinsic motivation of neutrophil migration

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2608-2622页

作者： Yang Liu renjie Song Lu Zhao Zhike Lu Yini Li Xinyi Zhan Fengjiao Lu jiang Yang Yamei Niu Xuetao Cao Department of Immunology Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical Sciences100005 BeijingChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai University300071 TianjinChina School of Life Sciences Westlake University310024 HangzhouChina Department of Pathology Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical Sciences100005 BeijingChina.

Neutrophil migration into the site of infection is necessary for antibacterial innate defense,whereas impaired neutrophil migration may result in excessive inflammation and even *** neutrophil migration directed by extracellular signals such as chemokines has been extensively studied,yet the intrinsic mechanism for determining neutrophil ability to migrate needs further investigation.N6-methyladenosine(m^(6)A)RNA modification is important in immunity and inflammation,and our preliminary data indicate downregulation of RNA m^(6)A demethylase alkB homolog 5(ALKBH5)in neutrophils during bacterial *** m^(6)A modification and ALKBH5 might intrinsically modulate neutrophil innate response remain *** we report that ALKBH5 is required for antibacterial innate defense by enhancing intrinsic ability of neutrophil *** found that deficiency of ALKBH5 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture(CLP),and Alkbh5-deficient CLP mice exhibited higher bacterial burden and massive proinflammatory cytokine production in the peritoneal cavity and blood because of less neutrophil ***5-deficient neutrophils had lower CXCR2 expression,thus exhibiting impaired migration toward chemokine ***,ALKBH5-mediated m^(6)A demethylation empowered neutrophils with high migration capability through altering the RNA decay,consequently regulating protein expression of its targets,neutrophil migration-related molecules,including increased expression of neutrophil migration-promoting CXCR2 and NLRP12,but decreased expression of neutrophil migration-suppressive PTGER4,TNC,and *** findings reveal a previously unknown role of ALKBH5 in imprinting migrationpromoting transcriptome signatures in neutrophils and intrinsically promoting neutrophil migration for antibacterial defense,highlighting the potential application of targeting neutrophil m^(6)A modification in controlling bacterial infec

关键词： neutrophil impaired immunity

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AKR1B1 promotes pancreatic cancer metastasis by regulating lysosome-guided exosome secretion

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Nano Research 2022年第6期15卷 5279-5294页

作者： Jie Ji Dandan Jin Minxue Xu Yujie Jiao Yue Wu Tong Wu renjie Lin Wenjie Zheng Zhaoxiu Liu Feng jiang Yihui Fan Mingbing Xiao Department of Gastroenterology Affiliated Hospital and Medical School of Nantong UniversityNantong 226001China Third People’s Hospital Affiliated to Nantong University Nantong 226001China Department of Gastroenterology Second People’s Hospital of ChangshuChangshu 215500China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Department of Pathogenic Biology School of MedicineNantong UniversityNantong 226001China

Pancreatic cancer is one of the most lethal neoplasms with high metastatic potential and is resistant to almost all current *** is an aldo-keto reductase family 1 member B1(AKR1B1)inhibitor for the treatment of diabetic neuropathy,but its potential application in cancer treatment and the underlying mechanism are largely ***,we found that AKR1B1 is upregulated in pancreatic cancer and is positively associated with *** AKR1B1 promoted exosome secretion,accelerating cell migration in pancreatic cancer *** analysis indicated that AKR1B1 negatively regulated lysosomal function and multivesicular body(MVB)degradation in ***,AKR1B1 had a minimal role in the generation of *** factor EB(TFEB)and MVB-expressed RAB7A were two molecular targets that are negatively regulated by *** results uncovered a critical role for AKR1B1 in the regulation of lysosomal function and exosome *** targeting of AKR1B1 by clinically used medicines,such as Epalrestat,might represent an efficient way to inhibit pancreatic growth and metastasis.

关键词： aldo-keto reductase family 1 member B1(AKR1B1) pancreatic cancer exosome secretion lysosome Epalrestat

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The biogenesis and secretion of exosomes and multivesicular bodies(MVBs):Intercellular shuttles and implications in human diseases

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Genes & Diseases 2023年第5期10卷 1894-1907页

作者： Minxue Xu Jie Ji Dandan Jin Yue Wu Tong Wu renjie Lin Shengze Zhu Feng jiang Yifei Ji Baijun Bao Mei Li Weisong Xu Mingbing Xiao Department of Gastroenterology and Research Center of Clinical Medicine Affiliated Hospital and Medical School of Nantong UniversityNantongJiangsu 226001China Third People's Hospital Affiliated to Nantong University NantongJiangsu 226001China Medical School of Nantong University Oral Medcine192 NantongJiangsu 226001China Department of Medical Oncology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China Department of Gastroenterology Affiliated Nantong Rehabilitation Hospital of Nantong UniversityNantongJiangsu 226001China

Exosomes carry and transmit signaling molecules used for intercellular *** generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory *** molecules,mainly RAB GTPases,cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor(SNARE),are specifically regulated in response to pathological conditions such as altered cellular microenvironment,stimulation by pathogenic factors,or gene *** interferes with the smooth functioning of endocytosis,translocation,degradation,docking and fusion processes,leading to changes in the secretion of *** numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient *** transmitting characteristic functional proteins and genetic information produced under disease conditions,exosomes can change the physiological state of the recipient cells and their *** microenvironment,in turn,affects the occurrence and development of ***,this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies(MVBs).The overall aim is to find ways to eliminate disease-derived exosomes at their source,thereby providing an important new basis for the clinical treatment of disease.

关键词： Cellular microenvironment Cytoskeleton Exosome secretion RAB GTPase SNARE

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The overexpression of Rps14 in Lgr5+progenitor cells promotes hair cell regeneration in the postnatal mouse cochlea

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Engineered Regeneration 2023年第3期4卷 328-336页

作者： Jingru Ai Pei jiang Jingyuan Huang Hairong Xiao Yanqin Lin Mingchen Dai Yintao Wang Yuan Zhang Mengyao Tian renjie Chai Shasha Zhang State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsu Provincial Key Medical Discipline(Laboratory)NanjingChina Research Institute of Otolaryngology NanjingChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijingChina Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

Sensory hair cells(HCs)in the cochlea cannot regenerate spontaneously in adult mammals after being damaged by external or genetic ***,several genes and signaling pathways are reported to induce cochlear HC regeneration at the early neonatal ***14 encodes a ribosomal protein that is involved in the regulation of cell differentiation and proliferation in ***,its roles in the cochlea have not been reported in ***,we specifically overexpressed Rps14 in Lgr5+progenitor cells in the newborn mouse cochlea and found that Rps14 conditional overexpression(cOE)mice had significantly increased the ectopic HCs,including inner and outer *** further explored the source of these ectopic HCs and found no EdU+supporting cells observed in the Rps14 cOE *** lineage tracing results,on the other hand,revealed that Rps14 cOE mice had significantly more tdTomato+HCs in their cochleae than control *** results indicated that regenerated HCs by cOE of Rps14 are most likely derived from inducing the direct trans-differentiation of Lgr5+progenitor cells into ***,real-time qPCR results suggested that the transcription factor genes Atoh1 and Gfi1,which are important in regulating HC differentiation,were upregulated in the cochlear basilar membrane of Rps14 cOE *** summary,this study provides in vivo evidence that,in the postnatal mouse cochlea,Rps14 is a potential gene that can promote the spontaneous trans-differentiation of Lgr5+progenitor cells into *** gene may one day be exploited as a therapeutic target for treating hearing loss.

关键词： Rps14 Lgr5+progenitor cells Ectopic hair cells Regeneration Proliferation Trans-differentiation

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现浇混凝土空心楼板横向受剪试验研究

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建筑结构学报 2015年第5期36卷 110-115页

作者：尚仁杰蒋方新中冶建筑研究总院有限公司北京100088

对混凝土空心楼板横向受剪时隔离体平衡和受剪破坏机理分析可知,肋宽和翼缘厚度是影响其受剪承载力的主要因素。进行了A、B两类18个现浇混凝土空心楼板试件的受剪试验,A类试件保持板厚和空心管直径不变,肋宽分别为50、75、100 mm,研究... 详细信息

对混凝土空心楼板横向受剪时隔离体平衡和受剪破坏机理分析可知,肋宽和翼缘厚度是影响其受剪承载力的主要因素。进行了A、B两类18个现浇混凝土空心楼板试件的受剪试验,A类试件保持板厚和空心管直径不变,肋宽分别为50、75、100 mm,研究肋宽对受剪承载力影响;B类试件保持板厚不变和较大肋宽,上、下翼缘厚度分别为40、60、80 mm,研究翼缘厚度对受剪承载力影响。试验研究表明,在肋宽较小时,剪切破坏发生在肋上,裂缝先在孔内壁主拉应力较大处出现,随之近似水平开展并与相邻圆孔贯通,受剪承载力随肋宽的增大而增大;当肋宽较大时,空心板剪切破坏发生在上、下翼缘处,裂缝先在孔内壁靠近上、下翼缘位置出现,逐渐延伸到板的表面,受剪承载力与上、下翼缘厚度存在明显正比关系,承载力随翼缘加厚而线性增大。综合试验和理论分析结果给出了混凝土空心楼板横孔方向受剪承载力计算的双控计算式。

关键词：现浇混凝土空心楼板正交各向同性板横向静力试验受剪承载力

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Disruption of the autism-related gene Pak1 causes stereocilia disorganization,hair cell loss,and deafness in mice

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Journal of Genetics and Genomics 2021年第4期48卷 324-332页

作者： Cheng Cheng Yilin Hou Zhonghong Zhang Yanfei Wang Ling Lu Liyan Zhang Pei jiang Song Gao Qiaojun Fang Chengwen Zhu Junyan Gao Xufeng Liu Wei Xie Zhengping Jia Zhigang Xu Xia Gao renjie Chai Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsu Provincial Key Medical Discipline(Laboratory)NanjingJiangsu 210008China Research Institute of Otolaryngology NanjingJiangsu 210008China State Key Laboratory of Bioelectronics School of Life Sciences and TechnologyJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjingJiangsu 210096China Department of Military Psychology Fourth Military Medical UniversityXi'anShanxi 710032China Department of Ophthalmology Zhongda Hospital Southeast UniversityNanjingJiangsu 210009China Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology Shandong University School of Life SciencesQingdaoShandong 266237China jiangsu Rehabilitation Research Center for Hearing and Speech Impairment NanjingJiangsu 210004China Neurosciences&Mental Health The Hospital for Sick ChildrenTorontoOntario M5G 1X8Canada Department of Physiology Faculty of MedicineUniversity of TorontoTorontoOntario M5S 2E8Canada Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226019China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100864China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

Several clinical studies have reported that hearing loss is correlated with autism in ***,little is known about the underlying mechanism between hearing loss and autism.p21-activated kinases(PAKs)are a family of serine/threonine kinases that can be activated by multiple signaling molecules,particularly the Rho family of small *** studies have shown that Pak1 mutations are associated with *** the present study,we take advantage of Pak1 knockout(Pak1a/a)mice to investigate the role of PAK1 in hearing *** find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell(HC)apoptosis and severe hearing *** investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of b II-spectrin,which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1à/à***,our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing *** the first candidate gene linking autism and hearing loss,Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.

关键词： PAK1 Hearing loss Synapse Hair bundle ERM

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