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Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation

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Journal of Molecular Cell Biology 2019年第12期11卷 1069-1082页

作者： Yufang Wang Peiliang Shi Qin Chen Zan Huang Dayuan Zou Jingzi Zhang Xiang Gao zhaoyu lin State Key Laboratory of Pharmaceutical Biotechnology Department of Hepatopancreatobiliary SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolMOE Key Laboratory of Model Animals for Disease StudyModel Animal Research CenterNanjing UniversityNanjing 210061China Jiangsu Province Key Laboratory of Gastrointestinal Nutrition and Animal Health Nanjing Agriculture UniversityNanjing 210095China

Disrupted mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation are often associated with macrophage pyroptosis. It remains unclear how these forms of mitochondrial dysfunction relate to inflammasome activation and gasdermin-D (Gsdmd) cleavage, two central steps of the pyroptotic process. Here, we also found MMP collapse and ROS generation induced by Nlrp3 inflammasome activation as previous studies reported. The elimination of ROS alleviated the cleavage of Gsdmd, suggesting that Gsdmd cleavage occurs downstream of ROS release. Consistent with this result, hydrogen peroxide treatment augmented the cleavage of Gsdmd by caspase-1. Indeed, four amino acid residues of Gsdmd were oxidized under oxidative stress in macrophages. The efficiency of Gsdmd cleavage by inflammatory caspase-1 was dramatically reduced when oxidative modification was blocked by mutation of these amino acid residues. These results demonstrate that Gsdmd oxidation serves as a de novo mechanism by which mitochondrial ROS promote Nlrp3 inflammasome-dependent pyroptotic cell death.

关键词： ROS Nlrp3 gasdermin-D oxidation mitochondria

Intratumoral CD103^(+)CD8^(+)T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma

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Cancer Communications 2023年第10期43卷 1143-1163页

作者： Siqi Ren Tianjun Lan Fan Wu Suling Chen Xue Jiang Chuying Huo Zitian Li Shule Xie Donghui Wu Ruixin Wang Yanyan Li lin Qiu Guoxin Huang Shurui Li Xiaojuan Wang Meifeng Cen Tingting Cai zhaoyu lin Jinsong Li Bowen Li Department of Oral and Maxillofacial Surgery Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangdongP.R.China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdongP.R.China Department of Gynecological Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdongP.R.China School of Stomatology Jilin UniversityJilinP.R.China Stomatology Hospital of Haizhu district GuangdongP.R.China

Background Immune cell heterogenicity is known to determine the therapeutic response to cancer progression.Neoadjuvant chemoimmunotherapy(NACI)has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma(HNSCC),but the underlying mechanism behind this clinical response is unknown.The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses.Here,we attempted to identify molecules predicting NACI response in advanced HNSCC.Methods We performed combined single-cell RNA sequencing(scRNA-seq)and multiplex immunofluorescence(mIHC)staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell(TIL)subtype,CD103^(+)CD8^(+)TILs,associated with clinical response,while both in vitro and in vivo assays were carried out to determine its antitumor efficiency.The regulatory mechanism of the CD103^(+)CD8^(+)TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images.Results We established intratumoral CD103^(+)CD8^(+)TILs density as a determinant of NACI efficacy in cancers.Our scRNA-seq results indicated that the population of CD103^(+)CD8^(+)TILs was dramatically increased in the responders of NACI-treated HNSCC patients,while mIHC analysis confirmed the correlation between intratumoral CD103^(+)CD8^(+)TILs density and NACI efficacy in HNSCC patients.Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI.Functional assays showed that CD103^(+)CD8^(+)TILs were tumor-reactive T cells,while programmed cell death protein-1(PD-1)blockade enhanced CD103^(+)CD8^(+)TILs cytotoxicity against tumor growth in vivo.Mechanistically,targeting the triggering receptor expressed on myeloid cells 2-positive(TREM2^(+))macrophages might enhance the population of CD103^(+)CD8^(+)TILs and facilitate antitumor immunity during NACI treatment.Conclusions Our study hig

关键词： CD103 CD8 head and neck squamous cell carcinoma neoadjuvant chemoimmunotherapy predictive marker tumor-infiltrating lymphocyte

GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity

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Journal of Molecular Cell Biology 2019年第6期11卷 496-508页

作者： Qin Chen Peiliang Shi Yufang Wang Dayuan Zou Xiuwen Wu Dingyu Wang Qiongyuan Hu Yujie Zou Zan Huang Jianan Ren zhaoyu lin Xiang Gao State Key Laboratory of Pharmaceutical Biotechnology and Nanjing Drum Tower Hospital Model Animal Research Center Nanjing University Nanjing 210061 China Department of Surgery Jinling Hospital Medical School of Nanjing University Nanjing 210061 China Jiangsu Province Key Laboratory of Gastrointestinal Nutrition and Animal Health Nanjing Agriculture University Nanjing 210095 China

Gasdermin B (GSDMB) has been reported to be associated with immune diseases in humans, but the detailed molecular mechanisms remain unsolved. The N-terminus of GSDMB by itself, unlike other gasdermin family proteins, does not induce cell death. Here, we show that GSDMB is highly expressed in the leukocytes of septic shock patients, which is associated with increased release of the gasdermin D (GSDMD) N-terminus. GSDMB expression and the accumulation of the N-terminal fragment of GSDMD are induced by the activation of the non-canonical pyroptosis pathway in a human monocyte cell line. The downregulation of GSDMB alleviates the cleavage of GSDMD and cell death. Consistently, the overexpression of GSDMB promotes GSDMD cleavage, accompanied by increased LDH release. We further found that GSDMB promotes caspase-4 activity, which is required for the cleavage of GSDMD in non-canonical pyroptosis, by directly binding to the CARD domain of caspase-4. Our study reveals a GSDMB-mediated novel regulatory mechanism for non-canonical pyroptosis and suggests a potential new strategy for the treatment of inflammatory diseases.

关键词： GSDMB GSDMD pyroptosis sepsis

CD4+T cells memorize obesity and promote weight regain

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Cellular & Molecular Immunology 2018年第6期15卷 630-639页

作者： Jianghuan Zou Beibei Lai Mingzhu Zheng Qin Chen Shujun Jiang Anying Song Zan Huang Peiliang Shi Xin Tu Di Wang linrong Lu zhaoyu lin Xiang Gao State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study Model Animal Research CenterNanjing Biomedical Research InstituteNanjing University12 Xuefu RoadPukou DistrictNanjingJiangsu 210061China Institute of Immunology Program in Molecular and Cellular BiologyZhejiang University School of MedicineHangzhouZhejiang 310058China

Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown.In this study,we report that immune cells,especially CD4+T cells,mediate the‘memory’of previous obese status.In a weight gain-loss-regain model,we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain.This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice.Surprisingly,such obesity memory was abrogated by dexamethasone treatment,whereas immunodeficient Rag1−/−and H2A−/−mice failed to establish such memory.Rag1−/−mice repossessed the obesity memory when immune cells or CD4+T cells isolated from previously obese mice were transferred.Furthermore,depletion of CD4+T cells led to obesity memory ablation.Taken together,we conclude that CD4+T cells mediate obesity memory and promote weight regain.

关键词： CD4+T cell immunodeficiency metabolism obesity memory weight regain

The Design of Digital Excitation Regulator

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Journal of Northeast Agricultural University(English Edition) 2001年第1期8卷 49-54页

作者： TIZong－li zhaoyu－lin 等 NortheastAgriculturalUniversity HeilongjiangHarbin150030PRC

The digital excitation regulator is very popular in the small electric plant. This kind of regulator can im- prove the working condition of generator and its working efficiency. It is on the base of the 80C51 Micro-con- troller. The regulator can automatically finish some functions through the combination of software and hard- ware. Through the experiment we can know it is more intellectual than the traditional analog excitation regu- lator.

关键词： Digital excitation regulator 80C51 Micro-controller analog

基于人工智能的深度学习技术在胃癌领域应用的研究进展

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消化肿瘤杂志（电子版） 2024年第2期16卷 223-230页

作者：张秋盛林祺李广华林昭宇王昭中山大学附属第一医院胃肠外科中心广东广州510080

近年来人工智能(artificial intelligence,AI)技术发展迅速,是目前各大行业的研究热点,尤其是在医学方面,其中深度学习已广泛应用于医学图像处理和临床肿瘤学分析。根据10年来的研究结果,AI与医学结合能够极大提升医生的工作效率,减轻... 详细信息

近年来人工智能(artificial intelligence,AI)技术发展迅速,是目前各大行业的研究热点,尤其是在医学方面,其中深度学习已广泛应用于医学图像处理和临床肿瘤学分析。根据10年来的研究结果,AI与医学结合能够极大提升医生的工作效率,减轻工作负担,对疾病诊断和分级有更高的敏感度和准确度,对指导手术治疗和提高患者生存率具有重要临床意义。在影像组学方面,AI可以从标准医疗成像中提取并分析图像的向量特征,用于胃癌的淋巴结转移和早期复发情况的预测。同样的,在数字病理学方面,AI也可以通过计算机扫描标准的苏木精-伊红染色组织切片,进行数字化处理,进而运用卷积神经网络来处理图像特征,用于胃癌的病理诊断和治疗前的疗效预测等。内镜技术和AI结合近年来也表现出良好的前景,AI能从内镜视频流和静止图片抓取病变特征和确定病变部位。总而言之,目前在肿瘤领域,AI技术可以协助医生更准确地进行诊断,减少人为误差;也可以判断患者是否能从某种治疗中获益,减轻治疗负担。AI的出现对于医生和患者来说都是一种福音。

关键词：人工智能深度学习胃癌诊断预测

Research on Mechanism of Overcurrent and Overvoltage When Contactless Tap Changer Switch Regulates Voltage on Load

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Journal of Northeast Agricultural University(English Edition) 2003年第1期10卷 60-65页

作者： zhaoyu-lin DONGShou-tian LIJia-hui NIJing YUEHong-bin NortheastAgriculturalUniversity HarbinHeilongiiang150030PRC HarbinSuburanElectricCompany HarbinHeilongjiang150001PRC

Analyzes the mechanism of overvoltage when contactless tap changer switch which is applied in distributing transformer converted directly.When the device convert the tap off,it employs the way that the SSR is switched on when voltage through zero and switched off when current through zero.But in the experiment we found that overvoltage will occur in the process of changing tap changer.The paper illustrates the mechanism of overvoltage in theory by analyzing the equivalent circuit and using analytic method of transition process.

关键词： load ratio control tap joint switch,solid state relay overvoltage mechanism

The Role of CD4+ T cells in Obesogenic Memory

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The Role of CD4+ T cells in Obesogenic Memory

腮腺良性肿瘤诊断、手术方式及常见并发症的预防与处理

第四届中国生物物理学会代谢生物学分会学术研讨会

作者： zhaoyu lin

＜正＞Obesity is a serious chronic disease and worldwide public health problem associated with many complex diseases, such as diabetes, hepatic steatosis,cardiovascular diseases. Unfortunately, few effective remedies are available for obesity. The major problem is that most patients suffered from weight regain in2-3 years after obesity treatments, such as obesity drugs, lifestyle intervention and bariatric surgery. This phenomenon has been defined as "obesogenic memory". The underlying mechanism of obesogenic memory remains largely unknown.

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口腔疾病防治 2022年第11期30卷 761-768页

作者：潘朝斌林钊宇中山大学孙逸仙纪念医院口腔颌面外科广东广州510120

腮腺良性肿瘤是头颈部较为常见的肿瘤,手术切除是其最主要的治疗方式。针对腮腺不同部位的良性肿瘤,可根据肿瘤的类型、大小、位置、与面神经的关系及患者对美观的要求等因素综合考虑采用不同的手术入路设计及切除方式,如改良耳周切口... 详细信息

腮腺良性肿瘤是头颈部较为常见的肿瘤,手术切除是其最主要的治疗方式。针对腮腺不同部位的良性肿瘤,可根据肿瘤的类型、大小、位置、与面神经的关系及患者对美观的要求等因素综合考虑采用不同的手术入路设计及切除方式,如改良耳周切口、改良面部除皱切口等,以达到最佳的治疗效果。在腮腺良性肿瘤切除术中,应尽可能保护面神经、耳大神经及腮腺导管,以保留面神经及腺体功能、降低术后并发症。此外,针对腮腺肿瘤切除术后常见的并发症,如面神经损伤、涎瘘、Frey综合征、术后面部凹陷、耳周感觉异常、复发等,应在术中积极预防,并在术后早期干预,在确保完整切除肿瘤的前提下尽量减少术后并发症对患者生活质量的影响。

关键词：腮腺良性肿瘤诊断手术切除手术入路 Blair切口改良耳周切口改良面部除皱切口腮腺浅叶切除腮腺浅叶部分切除并发症