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CD226 maintains regulatory T cell phenotype stability and metabolism by the mTOR/Myc pathway under inflammatory conditions

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CELL REPORTS 2023年第10期42卷 113306页

作者： Ma, Jingchang Hu, Wei Liu, Yitian Duan, Chujun Zhang, Dongliang Wang, Yuling Cheng, Kun Yang, Lu wu, shuwen Jin, Boquan Zhang, Yuan Zhuang, Ran Fourth Mil Med Univ Dept Immunol 169 West Changle Rd Xian 710032 Shaanxi Peoples R China Chinese Peoples Liberat Army Gen Hosp Med Ctr 5 Dept Emergency 100 Western 4th Ring Rd Beijing 100039 Peoples R China Northwestern Polytech Univ Inst Med Res 127 West Youyi Rd Xian 710072 Shaanxi Peoples R China

Regulatory T (Treg) cells exhibit immunosuppressive phenotypes and particular metabolic patterns with certain degrees of plasticity. Previous studies of the effects of the co-stimulatory molecule CD226 on Treg cells are controversial. Here, we show that CD226 primarily maintains the Treg cell stability and metabolism phenotype under inflammatory conditions. Conditional deletion of CD226 within Foxp3+ cells exacerbates symptoms in murine graft versus host disease models. Treg cell-specific deletion of CD226 increases the Treg cell percentage in immune organs but weakens their immunosuppressive function with a T helper 1-like phenotype conversion under inflammation. CD226-deficient Treg cells exhibit reduced oxidative phosphorylation and increased glycolysis rates, which are regulated by the adenosine 50-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/myelocytomatosis oncogene (Myc) pathway, and inhibition of Myc signaling restores the impaired functions of CD226-deficient Treg cells in an inflammatory disease model of colitis. This study reveals an Myc-mediated CD226 regulation of Treg cell phenotypic stability and metabolism, providing potential therapeutic strategies for targeted interventions of Treg cell-specific CD226 in inflammatory diseases.

关键词： CD226 Treg cells metabolism inflammatory diseases Research topic(s)CP: Immunology

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The genetic association between osteoprotegerin gene polymorphisms and fracture risk in Chinese Han population

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JOURNAL OF CELLULAR PHYSIOLOGY 2019年第11期234卷 20603-20607页

作者： wu, shuwen Li, Zhiyong Zhang, Jian Rui, Yanxiang Baodi Peoples Hosp Dept Orthoped Tianjin Peoples R China Baodi Peoples Hosp Dept Spinal Joint Surg Tianjin 301800 Peoples R China Baodi Peoples Hosp Dept Hand & Foot Surg Tianjin 301800 Peoples R China

This article put the genetic association exploration of osteoprotegerin (OPG) gene polymorphisms in promoter region (A-163G, T-245G) and fracture risk first and hoped to explain the ethology of fracture. The genotyping of OPG gene polymorphisms was conducted with the method of polymerase chain reaction-restriction fragment length polymorphism in 125 fracture patients and 138 relative controls. The genotype frequencies of selected controls based on OPG gene polymorphisms were checked by the chi(2) test whether conformed to Hardy-Weinberg equilibrium (HWE). The relative risk was represented with odds ratio (OR) and 95% confidence interval (95% CI) between gene polymorphism and disease. The linkage disequilibrium (LD) and haplotype were also analyzed. The genotypes distributions of selected controls in OPG polymorphisms conformed to HWE. The G allele of A-163G polymorphism carriers had the tendency to suffer from fracture in the same condition, compared with A allele carriers (OR=1.63, 95% CI=1.04-2.55). TG and TG/GG genotypes of OPG T-245G polymorphism also showed the increased risk of fracture development, but not TT genotype (OR=2.22, 95% CI=1.15-4.28;OR=2.45, 95% CI=1.28-4.68). Likely, the mutant allele G had an abnormally higher frequency in cases than controls (14.00% and 6.16%). These two polymorphisms existed the LD and the haplotype G (-163)-G (-245) obviously increased the risk of fracture. OPG A-163G, T-245G polymorphisms were associated with the onset of fracture and both the independent risk factors.

关键词： fracture haplotype OPG polymorphism

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Interleukin-6 absence triggers intestinal microbiota dysbiosis and mucosal immunity in mice

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CYTOKINE 2022年 153卷 155841-155841页

作者： wu, shuwen Zhang, Yuan Ma, Jingchang Liu, Yongming Li, Wenpeng Wang, Tingting Xu, Xuexue Wang, Yuling Cheng, Kun Zhuang, Ran Northwestern Polytech Univ Inst Med Res 127 West Youyi Rd Xian 710072 Shaanxi Peoples R China Fourth Mil Med Univ Dept Immunol 169 West Changle Rd Xian 710032 Shaanxi Peoples R China Fourth Mil Med Univ Orthoped Dept Tangdu Hosp 1 Xinsi Rd Xian 710032 Shaanxi Peoples R China

Interleukin-6 (IL-6) in mucosal immune cells is involved in post-injury intestinal regeneration, inflammation responses, and gastric homeostasis. However, the interaction between IL-6 and the dynamic balance of gut microbiota (GM) remains unexplored. Intestinal pathology was assessed by hematoxylin and eosin and periodic acid-Schiff staining in wild-type (WT) and IL-6 gene knockout (KO) C57BL/6J mice. GM profiles were established via high-throughput sequencing of the fecal bacterial 16S rRNA gene. Intestinal alpha-and beta-defensins were measured by quantitative real-time PCR;further, flow cytometry was performed to analyze isolated intraepithelial lymphocytes (IELs). Compared with the WT, IL-6 KO did not obviously change gut structures, but significantly reduced GM diversity, resulting in reduced metabolic pathways with decreased gram-positive but elevated gram-negative bacteria. More taxa alterations included differences at the phyla (e.g., increased Verrucomicrobia and decreased Firmicutes) and genera (e.g., increased Akkermansia and decreased Lactobacillus) levels. Absence of IL-6 also significantly increased intestinal expression of defensins alpha 3 and alpha 4 (Defa3 and Defa4) and the percentage of natural TCR gamma delta(+) IELs, providing a molecular basis for triggering mucosal immune response. Therefore, IL-6 loss remodels GM composition and alters IEL maintenance, identifying IL-6 as a crucial cytokine for GM dysbiosis and mucosal immunity.

关键词： Interleukin-6 Intestine Gut microbiota Intraepithelial lymphocytes Paneth cells alpha-defensins

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Inter-X: Towards Versatile Human-Human Interaction Analysis

Inter-X: Towards Versatile Human-Human Interaction Analysis

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Conference on Computer Vision and Pattern Recognition (CVPR)

作者： Liang Xu Xintao Lv Yichao Yan Xin Jin shuwen wu Congsheng Xu Yifan Liu Yizhou Zhou Fengyun Rao Xingdong Sheng Yunhui Liu Wenjun Zeng Xiaokang Yang Shanghai Jiao Tong University Eastern Institute of Technology Ningbo WeChat Tencent Inc. Lenovo

ISBN: (数字)9798350353006

ISBN: (纸本)9798350353013

The analysis of the ubiquitous human-human interactions is pivotal for understanding humans as social beings. Existing human-human interaction datasets typically suffer from inaccurate body motions, lack of hand gestures and fine- grained textual descriptions. To better perceive and generate human-human interactions, we propose Inter-X, a currently largest human-human interaction dataset with accurate body movements and diverse interaction patterns, together with detailed hand gestures. The dataset includes

关键词： Computer vision Accuracy Annotations Semantics Benchmark testing Pattern recognition Task analysis

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湿地植物香蒲根系抗氧化酶活性和根系分泌物对阿特拉津胁迫的响应

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农业环境科学学报 2021年第12期40卷 2751-2760页

作者：武淑文侯磊刘云根范黎明叶敏云南农业大学植物保护学院昆明650201 西南林业大学生态与环境学院昆明650224

为探明阿特拉津胁迫下水生植物根系的生理响应特征,以典型湿地植物香蒲(Typhaangustifolia L.)为研究对象,采用水培实验,研究阿特拉津(0、0.2、0.4 mg·L^(-1)和2.0 mg·L^(-1))胁迫45 d对香蒲根系阿特拉津积累、抗氧化酶活性... 详细信息

为探明阿特拉津胁迫下水生植物根系的生理响应特征,以典型湿地植物香蒲(Typhaangustifolia L.)为研究对象,采用水培实验,研究阿特拉津(0、0.2、0.4 mg·L^(-1)和2.0 mg·L^(-1))胁迫45 d对香蒲根系阿特拉津积累、抗氧化酶活性以及根系分泌物的影响。结果表明:阿特拉津可以在香蒲根系积累且显著降低香蒲生物量。随阿特拉津胁迫的提升,根系丙二醛(MDA)含量持续升高;超氧化物歧化酶(SOD)活性显著降低(P<0.05),过氧化氢酶(CAT)活性呈先增加再降低趋势(P<0.05),且在0.4 mg∙L^(-1)时达到最大值,较对照提高123.7%;阿特拉津胁迫对谷胱甘肽(GSH)活性无明显影响。香蒲根系分泌物中检出的化合物种类随着阿特拉津质量浓度的升高而增多,主要包括烷烃、烯烃、酯、胺、醇、酚、酮和有机酸类化合物,其中烷烃类化合物种类最多且相对含量最大;高浓度阿特拉津胁迫(2 mg∙L^(-1))抑制酯类和醇类化合物的分泌,而提高酚类和有机酸类化合物的分泌量;根系阿特拉津含量、MDA含量分别与酚类和有机酸类的相对含量呈正相关关系。研究发现,阿特拉津胁迫诱导的氧化应激激活了香蒲根系的抗氧化防御系统,植物通过调节分泌物的组成和含量应对胁迫,最终降低了生物量的积累。

关键词：阿特拉津香蒲根系分泌物抗氧化酶活性

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Long-term monitoring and characterization of resistance to chlorfenapyr in Plutella xylostella (Lepidoptera: Plutellidae) from China

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PEST MANAGEMENT SCIENCE 2019年第3期75卷 591-597页

作者： Wang, Xingliang Wang, Jing Cao, Xiaowei Wang, Falong Yang, Yihua wu, shuwen wu, Yidong Nanjing Agr Univ Dept Entomol Coll Plant Protect Nanjing 210095 Jiangsu Peoples R China

BACKGROUND Plutella xylostella (L.) is a worldwide pest of crucifer crops. Chlorfenapyr has been used extensively to manage several insect pests in vegetables, including P. xylostella. In this study, 48 field populations were collected from 11 geographic locations of China from 2008 to 2017 for resistance monitoring to chlorfenapyr. Inheritance and synergism of chlorfenapyr resistance were characterized in a field-derived population. RESULTS Compared with the susceptible SZ strain, 33 of 39 populations collected from Eastern China were susceptible or developed low levels of resistance to chlorfenapyr (< 10-fold), five populations developed mid-level resistance (11-33-fold), and only one population had high level resistance (208-fold). However, seven of nine populations sampled from Southern China evolved 136-334-fold resistance. Interestingly, the dynamic of the median lethal concentration (LC50) values from four continuous sampling sites (NJ, HF, JN and KS) showed a sharp increase in 2009, which implies that adults may have immigrated from chlorfenapyr-resistant regions. A highly resistant field population (GZ15) was further studied. By crossing the GZ15 and susceptible SZ strains we showed that resistance to chlorfenapyr was autosomally inherited and incompletely dominant. Synergism bioassays revealed that metabolic detoxification might not be responsible for chlorfenapyr resistance in the GZ15 population. CONCLUSIONS Some field populations of P. xylostella from China have evolved high levels of resistance to chlorfenapyr. Field-evolved resistance to chlorfenapyr is autosomal and dominant in the GZ15 population. These findings provide useful information for the design of effective resistance management strategies against P. xylostella in the field. (c) 2018 Society of Chemical Industry

关键词： diamondback moth chlorfenapyr resistance inheritance synergism

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A sheepherder with a severe diarrhea caused by Trichostrongylus colubriformis

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TRAVEL MEDICINE AND INFECTIOUS DISEASE 2022年 48卷 102325-102325页

作者： Du, Bing Zhang, Lei Dang, Wenqiang Sun, Xiaoli wu, shuwen Zhang, Ling Mo, Tingjun Xu, Jun Liu, Yong Wang, Lifu Harbin Med Univ Affiliated Hosp 2 Dept Gastroenterol & Hepatol Harbin Heilongjiang Peoples R China Guangzhou Kingmed Ctr Clin Lab Guangzhou Peoples R China Guangzhou Med Univ KingMed Sch Lab Med Guangzhou Key Lab Clin Rapid Diag & Early Warning Guangzhou Peoples R China Guangzhou Kingmed Ctr Clin Lab Guangzhou Guangdong Peoples R China

In heavy infections, T. colubriformis can cause severe enteritis with crypt hypertrophy, extensive villous atrophy, infiltration of leukocytes, intestinal epithelium erosion and high intestinal lumen serum protein exudation [3]. Under the microscope, the stool specimen revealed the presence of worm and oval eggs (Fig. 1). Mitochondrial DNA analysis of the COX-1 gene sequence identified the worm as—T. colubriformis based on comparisons with homologous sequences in GenBank (accession no. [...]albendazole therapy was continued for six days.

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The mirid bug Apolygus lucorum deploys a glutathione peroxidase as a candidate effector to enhance plant susceptibility

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JOURNAL OF EXPERIMENTAL BOTANY 2020年第9期71卷 2701-2712页

作者： Dong, Yumei Jing, Maofeng Shen, Danyu Wang, Chenyang Zhang, Meiqian Liang, Dong Nyawira, Karani T. Xia, Qingyue Zuo, Kairan wu, shuwen wu, Yidong Dou, Daolong Xia, Ai Nanjing Agr Univ Coll Plant Protect Nanjing Peoples R China

The mirid bug Apolygus lucorum has become a major agricultural pest since the large-scale cultivation of Bt-cotton. It was assumed that A. lucorum, similarly to other phloem sap insects, could secrete saliva that contains effector proteins into plant interfaces to perturb host cellular processes during feeding. However, the secreted effectors of A. lucorum are still uncharacterized and unstudied. In this study, 1878 putative secreted proteins were identified from the transcriptome of A. lucorum, which either had homology with published aphid effectors or shared common features with plant pathogens and insect effectors. One hundred and seventy-two candidate effectors were used for cell death-inducing/suppressing assays, and a putative salivary gland effector, Apolygus lucorum cell death inhibitor 6 (AI6), was characterized. The mRNAs of AI6 were enriched at feeding stages (nymph and adult) and, in particular, in salivary glands. Moreover, we revealed that the secreted AI6 encoded an active glutathione peroxidase that reduced reactive oxygen species (ROS) accumulation induced by INF1 or FIg22. Expression of the AI6 gene in planta altered insect feeding behavior and promoted plant pathogen infections. Inhibition of cell death and enhanced plant susceptibility to insect and pathogens are dependent on glutathione peroxidase activity of AI6. Thus, this study shows that a candidate salivary gland effector, AI6, functions as a glutathione peroxidase and suppresses ROS induced by pathogen-associated molecular pattern to inhibit pattern-triggered immunity (PTI)-induced cell death. The identification and molecular mechanism analysis of the AI6 candidate effector in A. lucorum will provide new insight into the molecular mechanisms of insect-plant interactions.

关键词： Apolygus lucorum cell death effector glutathione peroxidase plant-insect interaction ROS

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Colorimetric quantification and discrimination of phenolic pollutants based peroxidase-like Fe3O4 nanoparticles

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SENSORS AND ACTUATORS B-CHEMICAL 2020年 303卷 127225-000页

作者： wu, shuwen Guo, Danzhao Xu, Xuechao Pan, Jianming Niu, Xiangheng Jiangsu Univ Sch Food & Biol Engn Zhenjiang 212013 Jiangsu Peoples R China Jiangsu Univ Sch Chem & Chem Engn Inst Green Chem & Chem Technol Zhenjiang 212013 Jiangsu Peoples R China

Given the great harm of toxic phenolic pollutants toward the environment and human health, exploring efficient and low-cost methods for their monitoring becomes strongly necessary. Herein, we propose a facile and high-performance sensor array for colorimetric quantification and discrimination of phenolic pollutants by employing Fe3O4 nanoparticles (Fe3O4 NPs) as a peroxidase mimic. The small-size Fe3O4 NPs exhibit favorable catalytic activity to promote the reaction of 4-aminoantipyrine, phenolic species and H2O2, giving a remarkable color change to indicate the level of the target. As a result, the approach provided linear response for phenol in the concentration range from 1.67 mu M to 1.2 mM, offering a limit of detection down to 3.79 mu M. By integrating the colorimetric array with principal component analysis, common phenolic compounds, including phenol, o-chlorophenol, m-chlorophenol, p-chlorophenol, m-aminophenol and o-nitrophenol, were well discriminated even at a very low concentration. These results suggest our sensor array as an effective tool to rapidly detect and differentiate phenolic contaminants in environmental and food matrices.

关键词： Nanozyme Phenol Fe3O4 nanoparticles Colorimetric detection Discrimination Sensor array

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Discovery of aminothiazole derivatives as novel human enterovirus A71 capsid protein inhibitors

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BIOORGANIC CHEMISTRY 2022年 122卷 105683-105683页

作者： Xu, Zhichao Tang, Qi Xu, Ting Cai, Yang Lei, Ping Chen, Yinuo Zhou, Wenting Dong, Chune Lan, Ke wu, shuwen Zhou, Hai-Bing Wuhan Univ Wuhan Univ Sch Pharmaceut Sci Hubei Prov Engn & Technol Res Ctr Fluorinated Phar Hubei Prov Key Lab Dev Originated DisKey Lab Comb Wuhan 430071 Peoples R China Wuhan Univ Coll Life Sci State Key Lab Virol Wuhan 430072 Peoples R China Wuhan Univ Med Res Inst Frontier Sci Ctr Immunol & Metab Wuhan 430071 Peoples R China Anhui Med Univ Key Lab Zoonoses High Inst Anhui Sch Basic Med Sci Dept MicrobiolKey Lab Microbiol & Parasitol Anhui Hefei Peoples R China

Enterovirus A71 (EV-A71), one of the major pathogens that causes hand, foot and mouth disease (HFMD), has seriously threatened the health and safety of young children. In this study, aminothiazole derivatives were synthesized and screened against EV-A71 in Rhabdomyosarcoma (RD) cells. The best compound (12s), with a biphenyl group, showed activity against EV-A71 (EC50: 0.27 mu M) but also against a series of different human enteroviruses without significant cytotoxicity (CC50 > 56.2 mu M). Mechanistic studies including time-of-drug-addition assays, viral entry assays and microscale thermophoresis (MST) experiments, showed that 12s binds to EV-A71 capsid and blocks the binding between the viral protein VP1 and the relevant human scavenger receptor class B member 2 (hSCARB2).

关键词： EV-A71 Capsid protein Aminothiazole analogs Structure-activity relationship MST assay HSCARB2

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