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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue wenshi li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province Key Laboratory of Allergy&Immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated pathways.Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by ERVW-1.In conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

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Silent Speech Interface Design Methodology and Case Study

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Chinese Journal of Electronics 2016年第1期25卷 88-92页

作者： li wenshi Department of Microelectronics Soochow University

Silent speech interfaces(SSI) will face unable talking or silent cell phoning ones, or used in military scenarios. The best sensors and their positions glued information sources of imagined words will be reviewed under decoding model and Figure of merits(FOM) with new features toward multimodal Brain-brain interface(BBI) fitting consciousness communication. The data probing channels of known SSIs can be outlined into three logic categories of traditional articulators, intrinsic brain and neurovascular pathways. Eight kinds of corresponding sensors are evaluated importantly with six-axes spider-web charts.Our novel case of NIRS-based SSI showcased is with millisecond resolution. Above works may enhance the base of Brain Health Microelectronics.

关键词： Silent speech interface(SSI) Research paradigm Imagined word recognition Sensor comparison NIRS based SSI Brain-brain interface(BBI) Conscious ness communication

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A Basic Chemical Synaptic Euler Model and Its Triad Trigger Topology

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Chinese Journal of Electronics 2017年第2期26卷 244-249页

作者： li wenshi li Lei SONG Jiajia Department of Microelectronics Soochow University

To deeply understand neuromorphic electronic systems,a basic chemical synapse model is given by logistic Euler inverse mapping and transformation in tandem,3T-MOS triod-trigger-topology(3T3) is designed in sub-threshold region at 100 mV supply for compact synaptic circuit,and the power consumption of synapse in brain-circuitry(ion-bump-city) is compared with its five mimic blocks of HfOx/AlOx typed memristor,modified 2T-MOS-K+-bump circuit,3T3 synaptic circuit and 4T-Schmitt-oscillator based synaptic circuit,and Chua's circuit on Power-delay-products'(PDP) levels.Above works will match searching for novel feature operators during pushing forward brain health microelectronics.

关键词： Chemical synapse Euler model 3T3 synaptic circuit 4T synaptic circuit Scaling PDPs

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Chaos Criteria Design Based on Modified Sign Functions with One or Three-Threshold

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Chinese Journal of Electronics 2019年第2期28卷 364-369页

作者： WU Senlin li Yaotian li wenshi li Lei Department of Microelectronics Soochow University Laboratory of Modern Acoustics of MOE Nanjing University Department of Chemical and Materials Engineering University of Alberta

The complexity measures of chaotic or periodic signals are perpetual topics of interest to data scientists. This work adheres to the framework of the traditional 0-1 test for chaos and replaces sine and cosine functions by modified sign functions. The compressive mapping rules chosen are one-threshold of three-value or three-threshold of five-value. In new criteria for chaos in forms of the 3s plot and Ks metric compared with 0-1 test results, the periodic state of data features a short beeline instead of a big ring in the pq plot and signs the nearest zero mark, while the chaotic state signs a simple curve instead of a random-walking shape in the pq plot, and shows the nearest one mark. By computing the Lorenz equation evolution under the contrast tests of the Poincare section and Lyapunov index, we visualize a new chaoscriteria design in symbolic dynamics and data compression principles, and our work may lay the foundation for further expressing the chaotic appearance of novel signals deep into future brainets.

关键词： Chaos criteria Symbolic dynamics Data compression Simplest 0-1 test Signed compression plot Ks metric Poincare section Lyapunov index

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Two Entropy-Based Criteria Design for Signal Complexity Measures

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Chinese Journal of Electronics 2019年第6期28卷 1139-1143页

作者： CAI Jinwei li Yaotian li wenshi li Lei Department of Microelectronics Soochow University Department of Chemical and Materials Engineering University of Alberta

Signal complexity denotes the intricate patterns hidden in the complicated dynamics merging from nonlinear system concerned. The chaotic signal complexity measuring in principle combines both the information entropy of the data under test and the geometry feature embedded. Starting from the information source of Shannon’s entropy, combined with understanding the merits and demerits of 0-1 test for chaos, we propose new compression entropy criteria for identifying chaotic signal complexity in periodic, quasi-periodic or chaotic state, in mapping results in 3 s-graph with significant different shape of good or bad spring and in Construction creep(CC) rate with distinguishable value-range of [0, 7%],(7%, 50%] or(50%, 84%]. The employed simulation cases are Lorenz,li and He equations’ evolutions, under key information extracting rules of both two-layer compression functions and self-similarity calcu-lation, compared with methods of 0-1 test for chaos, Lyapunov exponent and Spectral Entropy complexity. The research value of this work will provide deep thinking of the concise featureexpressions of chaotic signal complexity measure in feature domain.

关键词： Chaotic signal complexity measure Compression entropies(3s-graph) Construction creep(CC) rate

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STARD5对胃癌的预后影响及机制研究

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中华肿瘤防治杂志 2024年第1期31卷 19-26页

作者：谢蕊西吴歆姝包博文李文诗俞思琦车晓芳中国医科大学附属第一医院肿瘤内科辽宁省肿瘤药物与生物治疗重点实验室沈阳市恶性肿瘤综合治疗临床医学研究中心辽宁沈阳110001

目的采用人类肿瘤基因表达汇编(GEO)及癌症基因组图谱(TCGA)数据分析类固醇敏感性调节蛋白相关脂类转运结构域蛋白5(STARD5)对胃癌预后的影响,通过细胞实验和分子实验验证并探索其相关机制。方法采用GEO胃癌数据集GSE62254及TCGA胃癌数... 详细信息

目的采用人类肿瘤基因表达汇编(GEO)及癌症基因组图谱(TCGA)数据分析类固醇敏感性调节蛋白相关脂类转运结构域蛋白5(STARD5)对胃癌预后的影响,通过细胞实验和分子实验验证并探索其相关机制。方法采用GEO胃癌数据集GSE62254及TCGA胃癌数据集进行单因素和多因素Cox回归分析,筛选STARD家族中的胃癌独立预后因素,并建立基于STARD家族的列线图模型;分析STARD5表达与临床病理特征的关系;使用基因集富集分析(GSEA)预测STARD5影响胃癌预后的相关通路;瞬时沉默STARD5后检测胃癌细胞的迁移、侵袭及黏附能力和胃癌细胞中相关蛋白表达的变化;采用加州大学圣克鲁兹分校(UCSC)gnome browser预测转录因子与靶基因结合位点。生存分析使用Kaplan-Meier和log-rank检验,STARD5与临床病理特征的关系使用χ^(2)检验,组间比较使用Dunnett’s t检验。结果GSE62254及TCGA胃癌数据集均显示STARD5为胃癌的独立保护因素,均P<0.05;纳入STARD5表达与TNM分期所绘制的列线图预测胃癌患者1、3、5年生存率的性能良好,一致性指数及其95%CI为0.701(0.659~0.744);STARD5表达与胃癌肝转移呈负相关,P=0.020。GSEA提示STARD5低表达与Focal adhesion、PI3K/AKT等通路密切相关,均P<0.05。敲减STARD5后,胃癌细胞迁移、侵袭及黏附能力增加,且AKT磷酸化水平升高,Integrinβ1、XBP-1s、ATF4和ATF6α表达上调;经预测XBP-1与ITGB1(Integrinβ1)启动子区域存在6个结合位点。结论STARD5是胃癌的预后保护因素。STARD5在发生肝转移的胃癌患者中表达降低。STARD5下调可通过上调XBP-1来促进Integrinβ1的转录表达并激活PI3K/AKT信号通路,促进胃癌细胞转移。

关键词：胃癌类固醇敏感性调节蛋白相关脂类转运结构域蛋白5 预后转移内质网应激整合素β1

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Domesticated HERV-W env contributes to the activation of the small conductance Ca^(2+)-activated K^(+)type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

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Virologica Sinica 2023年第1期38卷 9-22页

作者： Xiulin Wua Qiujin Yan lianzhong liu Xing Xue Wei Yao Xuhang li wenshi li Shuang Ding Yaru Xia Dongyan Zhang Fan Zhu State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Wuhan Mental Health Center Wuhan430071China Hubei Province Key Laboratory of Allergy&Immunology Wuhan UniversityWuhan430071China

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.

关键词： Human endogenous retroviruses type W(HERV-W) Env Small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2) 5-Hydroxytryptamine receptor 4(5-HT4R) Schizophrenia

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Characterization of VOC emissions from construction machinery and river ships in the Pearl River Delta of China

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Journal of Environmental Sciences 2020年第10期32卷 138-150页

作者： Richao Wang Zibing Yuan Junyu Zheng Cheng li Zhijiong Huang wenshi li Yan Xie Yiran Wang Kaiyang Yu Lejun Duan School ofEnuironment and Energy South China University of TechnologyGuangzhou 510006China Institute for Enironmental and Climate Research Jinan UniuersityGuangzhou 510000China

Speciated characterization of Volatile Organic Compounds (VOCs),including oxygenated VOCs (OVOCs),from construction machinery and river ships in China is currently lacking.In this regard,we conducted field measurement on speciated VOC (including OVOC) emissions from six construction machinery and five river ships in the Pearl River Delta (PRD) region to identify VOC emission characteristics.We noticed that OVOC emissions from construction machinery and ships accounted for more than 50%of the total VOC emissions,followed by alkenes,aromatics and alkanes.Formaldehyde and acetaldehyde were the most emission species,accounting for 61.8%-83.2%of OVOCs.For construction machinery,the fuel-based emission factors of roller,grader and pile driver were 3.12,3.12 and 7.36 g/kg,respectively.With the rigorous restraint by the national emission standards,VOC emissions of construction machinery had decreased considerably,especially during stageⅢ.Ozone formation potential was also significantly reduced due to the significant decrease in emissions of OVOCs and alkenes with higher reactivity.For river ships,the fuel-based emission factors of cargo ships and speedboat were 1.46 and 0.44 g/kg,respectively.VOC emissions from construction machinery and river ships in Guangdong Province in 2017 were 8851.0 and 4361.0 ton,respectively.This study filled the knowledge gaps of reactive gas emissions from different kinds of non-road mobile sources over the PRD,and more importantly,highlighted the necessity in adding OVOC measurement to give a complete and accurate depiction of reactive gas emissions from non-road mobile sources.

关键词： Construction machinery River ship VOC emissions Formaldehyde Emission factor

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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan liu Kuan liu Yao Hou Chunyang li Qiudi li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed patients.However,there are still unmet needs for treating chronic HEV infections.Herein,we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds.Upon screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities.Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection.Pyrazofurin selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV strains.Encouragingly,both drugs exhibited a sizeable therapeutic window against HEV.For instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in patients.Mechanistically,their anti-HEV mode of action depends on the blockage of pyrimidine synthesis.Notably,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral activity.In conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV infections.Based on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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时间序列复杂性自动度量:快速的弹簧测

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电子测量技术 2022年第6期45卷 94-98页

作者：程杰李文石苏州大学电子信息学院苏州215006

提出了时间序列复杂性自动度量的弹簧测试的一种提速方法。弹簧测试包括5阈值压缩空间中的弹簧图,以及该弹簧图的自相似性刻画数值CC。针对其速度较慢的问题,应用峰谷值映射简化弹簧图,提速自相似性度量。测试方程使用小波映射混沌、统... 详细信息

提出了时间序列复杂性自动度量的弹簧测试的一种提速方法。弹簧测试包括5阈值压缩空间中的弹簧图,以及该弹簧图的自相似性刻画数值CC。针对其速度较慢的问题,应用峰谷值映射简化弹簧图,提速自相似性度量。测试方程使用小波映射混沌、统一方程、Rossler超混沌方程。以分岔图为基本的对比判别几何特征,以基于FFT的谱熵复杂度为自动度量金标准,对比改进前后弹簧自相似性度量CC值的结果,给出各测试例的稳定性分析及计算时间比较。结果表明,改进后的弹簧测试能明显区别周期与混沌,增加了超混沌与混沌的辨识度,时间上提升2~20倍。本工作为周期、混沌、随机3分类识别的自动选参的信号复杂性度量贡献了改良的弹簧测试方法,本质是快速提取三维相图(弹簧图)的非对称非线性统计不变量。

关键词：时间序列多阈值压缩自动度量弹簧测试峰谷值

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