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The role of TIA1 and TIAL1 in germinal center B cell function and survival

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Cellular & Molecular Immunology 2023年第9期20卷 1090-1092页

作者： Yongqiang Wang Jisheng Liu fangfang zhou Department of Otolaryngology Head and Neck Surgery The First Affiliated Hospital of Soochow UniversitySuzhou215123China Institutes of Biology and Medical Science Soochow UniversitySuzhou215123China

B cells are essential components of the adaptive immune system and undergo differentiation and maturation during infection or immune stimulation to produce antibodies that can specifically recognize and bind to *** centers(GCs)are microanatomical sites for the clonal expansion and antibody affinity maturation of B *** the dark zone(DZ)of the germinal center,B cells rapidly proliferate,and somatic hypermutation(SHM)of B cell antigen receptors(BCRs)occurs.B cells then migrate to the light zone(LZ).

关键词： stimulation center migrate

NF2/YAP信号通路通过FSP1诱导CD24高表达的三阴性乳腺癌细胞铁死亡

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中华乳腺病杂志（电子版） 2024年第4期18卷 206-211页

作者：蒲卢兰李静佳陈宇周瑜清荣欣欣侯令密周方方川北医学院基础医学与法医学院四川南充637000 川北医学院附属医院甲状腺乳腺外科/乳腺癌生物靶向实验室四川南充637000

目的研究NF2和YAP表达对CD24高表达的三阴性乳腺癌细胞铁死亡的影响,探讨铁死亡的相关分子机制。方法培养CD24^(high)和CD24^(low)MDA-MB-231细胞,通过台盼蓝染色(TBA)实验检测经半胱氨酸饥饿、铁死亡诱导剂Erastin和RSL3处理后细胞的... 详细信息

目的研究NF2和YAP表达对CD24高表达的三阴性乳腺癌细胞铁死亡的影响,探讨铁死亡的相关分子机制。方法培养CD24^(high)和CD24^(low)MDA-MB-231细胞,通过台盼蓝染色(TBA)实验检测经半胱氨酸饥饿、铁死亡诱导剂Erastin和RSL3处理后细胞的死亡情况,TBA法检测丙二醛(MDA)含量,分析细胞铁死亡水平。使用Western blot检测NF2和YAP在CD24^(high)和CD24^(low)MDA-MB-231细胞中的蛋白表达情况,并用慢病毒分别进行敲除和过表达,观察细胞铁死亡水平,并采用实时定量RT-PCR和Western blot检测成纤维细胞特异蛋白1(FSP1)的表达变化。结果经半胱氨酸饥饿、铁死亡诱导剂Erastin和RSL3分别处理后MDA-MB-231细胞死亡率增加,CD24^(low)细胞死亡率高于CD24^(high)细胞(t=14.548,P<0.001;t=8.310,P=0.001;t=8.600,P=0.001)。同时,TBA法结果显示,在含或不含半胱氨酸条件下,CD24^(high)和CD24^(low)MDA-MB-231细胞的MDA含量差异有统计学意义(t=-3.920,P=0.017;t=11.566,P<0.001);与对照组(DMSO)相比,CD24^(high)和CD24^(low)细胞经铁死亡诱导剂Erastin和RSL3处理后MDA水平增加,其中CD24^(low)细胞的MDA含量比CD24^(high)更高(t=10.763,P=0.006;t=24.067,P<0.001)。Western blot实验结果表明,NF2与YAP在CD24^(low)和CD24^(high)细胞的蛋白含量差异有统计学意义(t=-4.331,P=0.012;t=4.219,P=0.013),CD24^(low)细胞中YAP的蛋白表达更高(t=4.219,P=0.013),而CD24^(high)细胞中NF2的蛋白表达更高(t=-4.331,P=0.012)。在CD24^(high)MDA-MB-231细胞中构建NF2敲除或(和)YAP过表达细胞株,并用实时定量RT-PCR和Western blot检测,结果显示铁死亡关键蛋白FSP1在4组间的表达差异有统计学意义(F=30.297,P<0.001)。同时,检测NF2敲除或(和)YAP过表达后CD24^(high)MDA-MB-231细胞的铁死亡情况,结果表明敲除NF2或(和)过表达YAP后加入铁死亡诱导剂Erastin均可在一定程度上促进细胞死亡(F=38.911,P<0.050),其中在NF2敲除联合YAP过表达条件下,CD24^(high)MDA-MB-231细胞死亡率最高,而在Erastin的基础上添加铁死亡抑制剂Fer-1后细胞的死亡率下降,4组间比较差异无统计学意义(F=0.256,P=0.855)。结论在CD24高表达的三阴性乳腺癌细胞中敲除NF2联合过表达YAP会抑制FSP1表达,促进细胞铁死亡。

关键词：乳腺肿瘤铁死亡成纤维细胞特异蛋白1 NF2 YAP

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黑灰产网络资产图谱构建与可视化

计算机辅助设计与图形学学报 2024年第8期36卷 1181-1193页

作者：赵颖付铄雯赵鑫徐雅琦赵勇陈运鹏周芳芳黄鑫李玉伟陈卓中南大学计算机学院长沙410083 奇安信科技集团股份有限公司北京100015

黑灰产团伙的网络化运作严重破坏着网络生态和社会治安.查封黑灰产团伙掌握的核心资产,如重要IP地址和安全证书,是目前打击黑灰产的主要手段之一.为此,提出黑灰产网络资产图谱构建与可视化.首先提出一种黑灰产网络资产图谱构建方法.从... 详细信息

黑灰产团伙的网络化运作严重破坏着网络生态和社会治安.查封黑灰产团伙掌握的核心资产,如重要IP地址和安全证书,是目前打击黑灰产的主要手段之一.为此,提出黑灰产网络资产图谱构建与可视化.首先提出一种黑灰产网络资产图谱构建方法.从多源异构数据中广泛获取黑灰产网络资产信息及关联关系,并整合到点边双异质有向图;然后提出一组黑灰产网络资产图可视化方法,基于资产图拓扑特性改进经典力导引布局算法和社区检测算法,帮助用户观察和理解资产间复杂关联,并快速地识别核心资产及其影响范围;最后公布一个大规模黑灰产网络资产图谱数据集,梳理数据集可支持的黑灰产治理需求,并展望图谱分析面临的技术挑战,旨在推动面向黑灰产治理的大数据分析技术的发展和创新.

关键词：黑灰产网络资产图可视化公开数据集

Protein N-myristoylation:functions and mechanisms in control of innate immunity

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Cellular & Molecular Immunology 2021年第4期18卷 878-888页

作者： Bin Wang Tong Dai Wenhuan Sun Yujun Wei Jiang Ren Long Zhang Mengdi Zhang fangfang zhou Institute of Biology and Medical Science Soochow UniversitySuzhouJiangsu 215123China Anhui Anlong Gene Technology Co. LtdHefei 230041China The Eighth Affiliated Hospital Sun Yat-sen UniversityGuangdong 518033China MOE Key Laboratory of Biosystems Homeostasis&Protection and Innovation Center for Cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhouZhejiang 310058China

Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases(NMTs),which are ubiquitous enzymes in ***,attachment of a myristoyl group is vital for proteins participating in various biological functions,including signal transduction,cellular localization,and *** studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral *** this review,we describe the current understanding of protein N-myristoylation(mainly focusing on myristoyl switches)and summarize its crucial roles in regulating innate immune responses,including TLR4-dependent inflammatory responses and demyristoylation-induced innate immunosuppression during Shigella flexneri ***,we examine the role of myristoylation in viral assembly,intracellular host interactions,and viral spread during human immunodeficiency virus-1(HIV-1)*** insight into the relationship between protein N-myristoylation and innate immunity might enable us to clarify the pathogenesis of certain infectious diseases and better harness protein N-myristoylation for new therapeutics.

关键词： N-myristoylation Innate immunity Myristoyl switches Infection TLR4 Viral assembly

Ferroptosis in cancer and cancer immunotherapy

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Cancer Communications 2022年第2期42卷 88-116页

作者： Lei Zhao Xiaoxue zhou Feng Xie Lei Zhang Haiyan Yan Jun Huang Chong Zhang fangfang zhou Jun Chen Long Zhang Epartment of urology surgery Zhejiang hospitalZhejiang University School of MedicineHangzhouChina School of Medicine Zhejiang University City CollegeHangzhouZhejiang 310015China School of MOE Key Laboratory of Biosystems Homeostasis&Protection and Innovation Center for Cell Signaling Network Life Sciences InstituteZhejiang UniversityHangzhouZhejiang 310058China Institutes of Biology and Medical Science Soochow UniversitySuzhou 215123P.R.China Department of Orthopaedic Surgery the Third Affiliated Hospital of Wenzhou Medical UniversityRui’anJiangsu 325000P.R.China

The hallmark of tumorigenesis is the successful circumvention of cell death regulation for achieving unlimited replication and *** is a newly identified type of cell death dependent on lipid peroxidation which differs from classical programmed cell death in terms of morphology,physiology and *** broad spectrum of injury and tumor tolerance are the main reasons for radiotherapy and chemotherapy *** effective rate of tumor immunotherapy as a new treatment method is less than 30%.Ferroptosis can be seen in radiotherapy,chemotherapy,and tumor immunotherapy;therefore,fer-roptosis activation may be a potential strategy to overcome the drug resistance mechanism of traditional cancer *** this review,the characteristics and causes of cell death by lipid peroxidation in ferroptosis are briefly *** addition,the three metabolic regulations of ferroptosis and its crosstalk with classical signaling pathways are ***,these findings sug-gest the vital role of ferroptosis in immunotherapy based on the interaction of ferroptosis with tumor immunotherapy,chemotherapy and radiotherapy,thus,indicating the remarkable potential of ferroptosis in cancer treatment.

关键词： cancer ferroptosis immunotherapy

The way of SARS-CoV-2 vaccine development:success and challenges

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3421-3434页

作者： Yetian Dong Tong Dai Bin Wang Lei Zhang Ling-hui Zeng Jun Huang Haiyan Yan Long Zhang fangfang zhou School of Medicine Zhejiang University City CollegeHangzhou 310015 ZhejiangChina Life Sciences Institute and Innovation Center for Cell Signaling Network Zhejiang UniversityHangzhouZhejiang 310058China Department of Orthopaedic Surgery The Third Affiliated Hospital of Wenzhou Medical UniversityRui‘anChina Institutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout *** novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious ***,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced ***,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and *** have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different ***,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.

关键词： immunity vaccine respiratory

Reliable knowledge graph fact prediction via reinforcement learning

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Visual Computing for Industry,Biomedicine,and Art 2023年第1期6卷 304-317页

作者： fangfang zhou Jiapeng Mi Beiwen Zhang Jingcheng Shi Ran Zhang Xiaohui Chen Ying Zhao Jian Zhang School of Computer Science and Engineering Central South UniversityChangshaHunan 410083China School of Target and Data Information Engineering UniversityZheng ZhouHenan 450001China

Knowledge graph(KG)fact prediction aims to complete a KG by determining the truthfulness of predicted *** learning(RL)-based approaches have been widely used for fact ***,the existing approaches largely suffer from unreliable calculations on rule confidences owing to a limited number of obtained reasoning paths,thereby resulting in unreliable decisions on prediction ***,we propose a new RL-based approach named EvoPath in this *** features a new reward mechanism based on entity heterogeneity,facilitating an agent to obtain effective reasoning paths during random *** also incorporates a new postwalking mechanism to leverage easily overlooked but valuable reasoning paths during *** mechanisms provide sufficient reasoning paths to facilitate the reliable calculations of rule confidences,enabling EvoPath to make precise judgments about the truthfulness of prediction *** demonstrate that EvoPath can achieve more accurate fact predictions than existing approaches.

关键词： Knowledge graph Fact prediction Reinforcement learning Entity heterogeneity Postwalking mechanism

基于数据挖掘的中药复方治疗宫颈HR-HPV感染的用药规律分析

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实用妇科内分泌电子杂志 2024年第10期11卷 4-6,14页

作者：杨雅伊桂涛仇影影周方芳万贵平南京中医药大学附属中西医结合医院妇产科江苏南京210000 江苏省中医药研究院江苏南京210000

目的运用数据挖掘技术分析中药复方治疗宫颈高危型人乳头瘤病毒(HR-HPV)感染的用药规律。方法检索收集治疗宫颈HR-HPV感染的中药复方,根据纳入、排除标准进行筛选后建立数据库,运用R语言进行频数、证型、性味、关联规则及相关性分析。... 详细信息

目的运用数据挖掘技术分析中药复方治疗宫颈高危型人乳头瘤病毒(HR-HPV)感染的用药规律。方法检索收集治疗宫颈HR-HPV感染的中药复方,根据纳入、排除标准进行筛选后建立数据库,运用R语言进行频数、证型、性味、关联规则及相关性分析。结果共纳入83个方剂,包含183味中药,高频药物多为清热药与补益药,药味以苦、甘、寒为主,多入肝经;通过关联分析筛选出50条常用药对组合;通过相关性分析,发现“柴胡-白芍”“白术-党参”“白花蛇舌草-薏苡仁”和“牡丹皮-赤芍”具有较强相关性。结论宫颈HR-HPV感染本虚标实,以健脾祛湿,清热解毒为治疗原则,辅以疏肝理气、活血化瘀。

关键词：高危型人乳头瘤病毒中药用药规律数据挖掘

长疗程逆灸对急性脑梗死患者预防卒中后抑郁的效果观察

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国际医药卫生导报 2024年第2期30卷 239-243页

作者：赵丹徐传伟周芳芳陈德仁林颖汪燕玲江苏省海滨康复医院医疗事业部连云港222042 南京中医药大学连云港附属医院康复科连云港210019 南京医科大学康达学院附属连云港中医院康复科连云港222001

目的观察长疗程逆灸对急性脑梗死患者预防卒中后抑郁发生的效果。方法本研究为随机对照试验,前瞻性选取2021年1月至2022年12月江苏省海滨康复医院及连云港市中医院收治的80例急性脑梗死患者为研究对象,按照随机数字表法分为治疗组(40例... 详细信息

目的观察长疗程逆灸对急性脑梗死患者预防卒中后抑郁发生的效果。方法本研究为随机对照试验,前瞻性选取2021年1月至2022年12月江苏省海滨康复医院及连云港市中医院收治的80例急性脑梗死患者为研究对象,按照随机数字表法分为治疗组(40例)及对照组(40例)。治疗组男21例、女19例,年龄(64.55±9.37)岁;对照组男22例、女18例,年龄(64.58±8.89)岁。对照组给予卒中规范化治疗,主要包括抗血小板聚集,降脂,合并有高血压、糖尿病以及冠心病患者均给予相应对症治疗;治疗组在对照组基础上采用长疗程逆灸治疗,20 min/次,1次/d,5 d/周,持续24周。对比两组患者治疗前及治疗4周、8周、12周、24周的汉密尔顿抑郁量表(HAMD)、简易智力状态检查量表(MMSE)、Barthel指数(BI)、美国国立卫生研究院卒中量表(NIHSS)评分及卒中后抑郁发生率。采用独立样本t检验、χ^(2)检验。结果治疗组患者治疗4周、8周、12周、24周卒中后抑郁发生率均低于对照组[2.5%(1/40)比17.5%(7/40)、5.0%(2/40)比20.0%(8/40)、10.0%(4/40)比27.5%(11/40)、17.5%(7/40)比37.5%(15/40)],差异均有统计学意义(χ^(2)=5.000、4.114、4.021、4.013,均P<0.05)。治疗组治疗4周、8周、12周HAMD评分均低于对照组[(7.25±2.88)分比(9.07±4.21)分、(9.70±2.74)分比(11.28±3.58)分、(12.17±2.76)分比(13.85±3.54)分],差异均有统计学意义(t=2.261、2.210、2.358,均P<0.05)。治疗组治疗12周、24周MMSE评分均高于对照组[(23.60±1.89)分比(22.70±1.83)分、(24.93±1.46)分比(23.75±1.63)分],差异均有统计学意义(t=2.163、3.400,均P<0.05)。治疗组治疗4周、8周、12周、24周BI评分均高于对照组[(66.13±6.84)分比(62.88±10.35)分、(69.25±4.88)分比(65.75±5.26)分、(73.13±4.63)分比(70.38±4.58)分、(74.63±3.47)分比(71.75±4.46)分],差异均有统计学意义(t=2.091、3.087、2.671、3.216,均P<0.05)。治疗后,治疗组NIHSS评分低于对照组[(7.20±2.43)分比(11.03±2.70)分],差异有统计学意义(t=6.655,P<0.05)。结论长疗程逆灸急性脑梗死患者百会、大椎穴,可促进脑梗死患者神经功能恢复,改善认知功能,降低卒中后抑郁发生率。

关键词：卒中后抑郁脑梗死逆灸长疗程预防