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PathogenTrack and Yeskit:tools for identifying intracellular pathogens from single-cell RNA-sequencing datasets as illustrated by application to COVID-19

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Frontiers of Medicine 2022年第2期16卷 251-262页

作者： Wei Zhang Xiaoguang Xu ziyu fu Jian Chen Saijuan Chen Yun Tan Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Department of Thoracic Surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China

Pathogenic microbes can induce cellular dysfunction,immune response,and cause infectious disease and other diseases including cancers.However,the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods.Taking advantage of single-cell RNA-sequencing(scRNA-seq)analysis,we can assess the transcriptomic features at the single-cell level.Still,the tools used to interpret pathogens(such as viruses,bacteria,and fungi)at the single-cell level remain to be explored.Here,we introduced PathogenTrack,a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level.In addition,we established an R package named Yeskit to import,integrate,analyze,and interpret pathogen abundance and transcriptomic features in host cells.Robustness of these tools has been tested on various real and simulated scRNA-seq datasets.PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track,and the first tools for identifying bacteria at the single-cell level.Using the raw data of bronchoalveolar lavage fluid samples(BALF)from COVID-19 patients in the SRA database,we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages.SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module.Additionally,we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells,indicating a co-infection of the bacterium in some severe cases of COVID-19.The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.

关键词： scRNA-seq intracellular pathogen microbe COVID-19 SARS-CoV-2

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Integrated analysis of gut microbiome and host immune responses in COVID-19

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Frontiers of Medicine 2022年第2期16卷 263-275页

作者： Xiaoguang Xu Wei Zhang Mingquan Guo Chenlu Xiao ziyu fu Shuting Yu Lu Jiang Shengyue Wang Yun Ling Feng Liu Yun Tan Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School ofMedicineShanghai 200025China Schoolof Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Shanghai Public Health Clinical Center Shanghai 201508China Department of Laboratory Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19 SARS-COV-2 gut microbiome immune response

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Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai

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Frontiers of Medicine 2023年第3期17卷 562-575页

作者： ziyu fu Dongguo Liang Wei Zhang Dongling Shi Yuhua Ma Dong Wei Junxiang Xi Sizhe Yang Xiaoguang Xu Di Tian Zhaoqing Zhu Mingquan Guo Lu Jiang Shuting Yu Shuai Wang Fangyin Jiang Yun Ling Shengyue Wang Saijuan Chen Feng Liu Yun Tan Xiaohong Fan Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University(SJTU)School of MedicineShanghai 200025China National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an 710032China Shanghai Public Health Clinical Center Fudan UniversityShanghai 201508China Department of Nephrology Traditional Chinese Medicine Hospital of KunShanSuzhou 215300China Department of Infectious Diseases Ruijin Hospital Affiliated to Shanghai Jiao Tong University(SJTU)School of MedicineShanghai 200025China

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022.Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020,BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood.In particular,severe/critical cases of COVID19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment.Importantly,the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototypeinactivated vaccines,supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records.furthermore,even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection,vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged≥60 years old.Together,our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

关键词： SARS-CoV-2 COVID-19 host response bronchoalveolar lavage fluid(BALF)

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Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

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Frontiers of Medicine 2020年第6期14卷 746-751页

作者： Yun Tan Feng Liu Xiaoguang Xu Yun Ling Weijin Huang Zhaoqin Zhu Mingquan Guo Yixiao Lin ziyu fu Dongguo Liang Tengfei Zhang Jian Fan Miao Xu Hongzhou Lu Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Public Health Clinical Center Shanghai 201508China National Institutes for Food and Drug Control(NIFDC) Beijing 102629China

The ongoing pandemic of coronavirus disease 19(COVID-19)is caused by a newly discoveredβcoronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination.Here we examined,using ELISA,the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6–7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection.All samples were positive for IgGs against the S-and N-proteins of SARS-CoV-2.Notably,14 samples available at 6–7 months post-infection all showed significant neutralizing activities in a pseudovirus assay,with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2.furthermore,in 10 blood samples from cases at 6–7 months post-infection used for memory T-cell tests,we found that interferonγ-producing CD4+and CD8+cells were increased upon SARS-CoV-2 antigen stimulation.Together,these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population,and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2.

关键词： SARS-CoV-2 neutralizing antibodies T-cell response

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一氧化氮在新型冠状病毒感染中的应用

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内科理论与实践 2024年第1期19卷 82-87页

作者：王亚婷贺春伟付紫玉王慧马德东山东大学齐鲁医院呼吸与危重症医学科山东济南250012

新型冠状病毒感染(coronavirus disease 2019,COVID-19)的发生造成了世界范围的医疗危机和卫生资源紧张。一氧化氮(nitric oxide,NO)在2003年严重急性呼吸综合征(severe acute respiratory syndrome,SARS)期间被证明可以改善氧合,降低肺动脉压力,减少无创通气的需求。SARS冠状病毒(SARS coronavirus,SARS-CoV)与SARS-CoV-2遗传结构和病理特征具有重叠性,并且NO具有抗病毒、舒张血管、抗凝、抗炎作用。本文拟对NO在COVID-19中的应用展开综述,以期为后续COVID-19患者的治疗提供思路。

关键词：一氧化氮新型冠状病毒感染急性呼吸综合征冠状病毒-2 血管舒张抗病毒

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Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

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Neural Regeneration Research 2024年第1期19卷 171-179页

作者： Weilin Tan Jun Ma Jiayuanyuan fu Biying Wu ziyu Zhu Xuekang Huang Mengran Du Chenrui Wu Ehab Balawi Qiang Zhou Jie Zhang Zhengbu Liao Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

关键词： axon guidance bioinformatics analysis competing endogenous RNA erythropoietin Gene Ontology Kyoto Encyclopedia of Genes and Genomes non-coding RNA RNA sequencing transcriptomics traumatic brain injury

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Polydopamine-modified metal-organic frameworks nanoparticles enhance the corrosion resistance and bioactivity of polycaprolactone coating on high-purity magnesium

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Journal of Magnesium and Alloys 2024年第5期12卷 2070-2089页

作者： Qingyun fu Shaojie He Junjie Yang ziyu Su Ping Li Xincheng Yu Weihong Jin Shulan Xu Zhentao Yu Dingsheng Zha Center of Oral Implantology Stomatological Hospital Southern Medical University Panyu Hospital of Chinese Medicine Institute of Advanced Wear&Corrosion Resistant and functional Materials Jinan University First Affiliated Hospital of Jinan University

Biodegradable magnesium（Mg） and its alloys exhibit excellent biocompatibility and mechanical compatibility, demonstrating tremendous potential for applications in orthopedics. However, the rapid degradation rate has limited their clinical application. Polycaprolactone（PCL）is commonly employed as a polymer coating to impede the rapid degradation of Mg. Unfortunately, its long-term anti-corrosion capability and bioactivity are inadequate. To address these issues, polydopamine（PDA）-modified zeolitic imidazolate framework-8（PZIF-8） bioactive nanoparticles are fabricated and incorporated into the PCL coating. The PZIF-8 particles, featuring catechol motifs, can enhance the compactness of the PCL coating, reduce its defects, and possess biomineralization ability, thereby effectively improving its anti-corrosive and bioactive properties. Moreover, the active substances released from the degradation of the PZIF-8 particles such as Zn2+and PDA are beneficial for osteogenesis. The corrosion tests indicate that the corrosion current density of PCL-treated sample decreases by more than one order of magnitude and the amount of H2released decreases from 0.23 ± 0.12 to 0.08 ± 0.08 ml cm-2after doping with the PZIF-8. furthermore,the improved corrosion resistance and released PDA and Zn2+from the coating can promote osteogenic differentiation by up-regulating the expression of alkaline phosphatase activity, related osteogenic genes, and proteins. In addition, in vivo implantation experiments in rabbit femur defects further offer strong evidence that the doping of PZIF-8 nanoparticles accelerates bone reconstruction of the PCL coating. In summary, this work implies a new strategy to fabricate a PCL-based coating on Mg-based implants by introducing the PZIF-8 particles for orthopedic applications.

关键词： Polydopamine ZIF-8 High-purity magnesium Polycaprolactone coating Anticorrosion Bone regeneration

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远海风电DRU-HVDC送出系统构网控制与启动方法综述

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电力系统自动化 2023年第24期47卷 63-79页

作者：俞露杰付子玉朱介北李瑞彭国平赵成勇智能电网教育部重点实验室(天津大学) 天津市300072 哈尔滨工业大学电气工程及自动化学院黑龙江省哈尔滨市150001 广东安朴电力技术有限公司广东省中山市528437 新能源电力系统国家重点实验室(华北电力大学) 北京市102206

随着海上风电开发的不断规模化和远海化,海上风电直流送出技术成为研究热点。针对低成本的二极管整流单元(DRU)型高压直流(HVDC)输电,重点指出了分布式DRU在均压、部分退出运行等方面的主要技术特点,论述了该技术与柔性直流送出、传统... 详细信息

随着海上风电开发的不断规模化和远海化,海上风电直流送出技术成为研究热点。针对低成本的二极管整流单元(DRU)型高压直流(HVDC)输电,重点指出了分布式DRU在均压、部分退出运行等方面的主要技术特点,论述了该技术与柔性直流送出、传统直流输电的差异。由于DRU的不可控性,海上电网的构建须由风电机组通过自身控制实现。因此,对现有研究的风电机组集中式和分散式构网控制进行详细综述,并对全构网型控制采用P-V和Q-f功率控制机理进行风电场-DRU层面以及风电机组层面的梳理解释。针对DRU单向潮流引起的启动问题,综述了辅助中压交流脐带电缆、辅助模块化多电平换流器、海上风电机组配置储能以及辅助低压直流电缆等启动方法,指出利用辅助中压交流脐带电缆是相对成熟的方案,而利用海上风电机组储能和全构网型控制具有较高的灵活性,但现有技术下仍面临风电机组塔筒内部安装空间不足、储能安全隐患等问题。最后,对海上风电经DRU-HVDC送出系统未来值得深入探索的研究方向进行了展望。

关键词：海上风电高压直流输电风电机组构网控制启动方法

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符文彬教授整合思维“一针二灸三巩固”模式治疗喉带状疱疹伴声带麻痹的临床经验

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中国针灸 2024年第2期44卷 195-199页

作者：叶子愚刘露梁雪松符文彬广州中医药大学针灸康复临床医学院广东广州510006 广东省中医院广州510120

介绍符文彬教授采用“一针二灸三巩固”的整合针灸模式治疗喉带状疱疹伴声带麻痹的临床经验。外感热毒化火并流窜喉部为本病核心病机,疏肝泄热为治则贯穿整个治疗过程。一针即毫针针刺,选取百会、印堂、廉泉、四关穴、“引气归元”组穴... 详细信息

介绍符文彬教授采用“一针二灸三巩固”的整合针灸模式治疗喉带状疱疹伴声带麻痹的临床经验。外感热毒化火并流窜喉部为本病核心病机,疏肝泄热为治则贯穿整个治疗过程。一针即毫针针刺,选取百会、印堂、廉泉、四关穴、“引气归元”组穴,双侧风池、完骨、翳风等,并点刺咽后壁以疏肝调神,泄热利咽;二灸即精灸疗法,选取风池、肺俞、四花穴、肾俞、命门等,可温养脾肾,以热引热;三巩固即选取心俞、肝俞、肩井运用刺络拔罐疏肝排淤,并通过皮内针埋针持续刺激巩固疗效。

关键词：喉带状疱疹声带麻痹整合针灸名医经验符文彬

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基于算法归因框架的专利维持时间影响因素探究

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信息资源管理学报 2024年第1期14卷 68-83,97页

作者：付振康柳炳祥鄢春根周子钰宫秀燕南京大学信息管理学院南京210023 景德镇陶瓷大学信息工程学院景德镇333403 景德镇陶瓷大学知识产权信息中心景德镇333403 黑龙江八一农垦大学经济管理学院大庆163316

基于生物学视角构建算法归因框架,探究不同因素对专利维持时间的影响效应及其在不同文献生命周期阶段和不同技术领域的变化态势。以中国2001—2017年授权的专利作为样本,采用融合生存分析的可解释机器学习方法构建了算法归因的实证研究... 详细信息

基于生物学视角构建算法归因框架,探究不同因素对专利维持时间的影响效应及其在不同文献生命周期阶段和不同技术领域的变化态势。以中国2001—2017年授权的专利作为样本,采用融合生存分析的可解释机器学习方法构建了算法归因的实证研究框架,根据生物学视角探究了先天因素、行为因素和环境因素对专利维持行为的影响效应。研究表明,基于算法归因框架可以准确有效地揭示不同因素与专利维持时间之间的效应关系,在三类因素当中,先天因素和行为因素占据主要地位,环境因素对专利维持的影响较弱,在不同文献生命周期阶段和不同技术领域,不同因素对专利维持时间的影响效应也有所不同。研究结论可以为专利维持时间预测和专利价值评估提供有价值的指标和较为创新的方法。

关键词：专利维持时间算法归因生存分析可解释机器学习专利价值

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