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Bailing capsule(百令胶囊) alleviates autoimmune thyroiditis via regulating peroxisome proliferator-activated receptor signaling pathway: a multi-omics analysis

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Journal of Traditional Chinese Medicine 2024年

作者： WANG Qixin XU Liting WU Jiangpeng HE Xueling TANG Huan CHENG Guangqing LU Tianming DAI Chuanhao guo qiuyan WANG Jigang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences School of Chinese Materia Medica and State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese Medicine

OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule (百令胶囊， BL) anti-autoimmune thyroiditis (AIT). METHODS: Based on the AIT rat model， the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine (FT3)， free thyroxine (FT4)， thyroid-stimulating hormone (TSH)， thyroglobulin antibody (TGAb)， thyroid peroxidase antibody (TPOAb)， and inflammatory factors Interferon-gamma (IFN-γ)， Interleukin-4， -10， and -12 (IL-4， IL-10， and IL-12) as well as thyroid tissue Hematoxylin-eosin (HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis， and further verified by Western blot (WB). RESULTS: BL effectively reduced serum FT3， FT4， TGAb， and TPOAb levels in AIT rats， restored TSH balance， inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12， promoted the production of anti-inflammatory cytokines IL-4 and IL-10， and significantly reduced IFN-γ/IL-4 and IL-12/IL-10， improved thyroid follicular structure， and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acid-binding protein 4， acyl-CoA synthetase long-chain family member 1， and acyl-CoA dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway， thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT rats. CONCLUSIONS: BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferator-activated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.

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齿面锈蚀对齿轮磷化质量的影响

电镀与精饰 2024年第7期46卷 107-110页

作者：赵清碧马勇田晓丽孙峰郭秋彦吉利汽车研究院(宁波)有限公司浙江宁波315336 西安交通大学机械工程学院陕西西安710049 宁波吉利罗佑发动机零部件有限公司浙江宁波315336

齿轮磷化是齿轮常用的一种表面处理方式。某型变速器磷化后齿轮在极限性能试验及耐久试验过程中发生了齿轮轮齿折断及齿面剥落的失效现象。通过宏观及微观形貌测试,发现齿面有直径50μm以上,深度50μm左右的凹坑;通过工厂现场调查及后... 详细信息

齿轮磷化是齿轮常用的一种表面处理方式。某型变速器磷化后齿轮在极限性能试验及耐久试验过程中发生了齿轮轮齿折断及齿面剥落的失效现象。通过宏观及微观形貌测试,发现齿面有直径50μm以上,深度50μm左右的凹坑;通过工厂现场调查及后续试验分析,确定是齿轮流转过程中发生锈蚀导致齿面凹坑,继而在磷化过程中保留凹坑,最终导致齿轮试验中失效。

关键词：磷化齿轮失效凹坑锈蚀

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典型热成形零件的显微组织及力学性能

金属热处理 2024年第6期49卷 135-141页

作者：史宝良姜发同刘旭亮宋文斌金玉明乔蒙郭秋彦吉利汽车研究院(宁波)有限公司浙江宁波315336

基于某白车身典型热成形零件,系统研究了不同热成形零件本体的显微组织和力学性能。结果表明,典型热成形零件显微组织主要为板条状马氏体,个别零件局部区域存在少量残留奥氏体组织,模内软区显微组织主要由铁素体、马氏体以及少量的贝氏... 详细信息

基于某白车身典型热成形零件,系统研究了不同热成形零件本体的显微组织和力学性能。结果表明,典型热成形零件显微组织主要为板条状马氏体,个别零件局部区域存在少量残留奥氏体组织,模内软区显微组织主要由铁素体、马氏体以及少量的贝氏体构成,马氏体无明显的板条状特征,且马氏体的比例相对较低。左前/后车门防撞梁脱碳层厚度分布在38.55~45.57μm,左前门防撞梁三点弯曲平均力值达6962 N,最大力值达9709 N;左后车门防撞梁平均力值达8740 N,最大力值达11392 N,三点弯曲后零件表面状态良好,且无裂纹产生,防撞梁性能满足整车安全碰撞测试要求。热成形零件本体平均维氏硬度分布在456~507 HV10;拉伸性能方面,屈服强度>1000 MPa,抗拉强度>1400 MPa,伸长率≥5.5%;软区测点维氏硬度分布在225~243 HV10,拉伸性能方面,屈服强度>470 MPa,抗拉强度>650 MPa,伸长率≥17%,零件性能均满足标准要求。

关键词：白车身热成形显微组织力学性能

Discovery and repurposing of artemisinin

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Frontiers of Medicine 2022年第1期16卷 1-9页

作者： Qiaoli Shi Fei Xia Qixin Wang Fulong Liao qiuyan guo Chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524045China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Geriatrics The Second Clinical Medical College of Jinan UniversityThe First Affiliated Hospital of Southern University of Science and TechnologyShenzhen People’s HospitalShenzhen 518020China

Malaria is an ancient infectious disease that threatens millions of lives globally even *** discovery of artemisinin,inspired by traditional Chinese medicine(TCM),has brought in a paradigm shift and been recognized as the“best hope for the treatment of malaria”by World Health *** its high potency and low toxicity,the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries,including China,to eventually eradicate ***,we will first review the initial discovery of artemisinin,an extraordinary journey that was in stark contrast with many drugs in western *** will then discuss how artemisinin and its derivatives could be repurposed to treat cancer,inflammation,immunoregulation-related diseases,and ***,we will discuss the implications of the“artemisinin story”and how that can better guide the development of TCM *** believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

关键词： artemisinin drug repurposing cancer inflammation COVID-19 traditional Chinese medicine

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基于轻量化设计的复合轮罩挡泥板性能研究

汽车工艺与材料 2024年第4期 1-7页

作者：魏珺儒刘青松张铭洁李文中李振兴郭秋彦吉利汽车研究院(宁波)有限公司宁波315336

针对基于轻量化设计的吸塑工艺复合轮罩挡泥板力学性能、抗石击性能、振动耐久性能、吸音性能、抗风阻变形量进行研究及分析,并与成熟的注塑工艺、模压工艺进行对比分析。研究表明:复合轮罩挡泥板综合性能满足乘用车轮罩挡泥板的技术要... 详细信息

针对基于轻量化设计的吸塑工艺复合轮罩挡泥板力学性能、抗石击性能、振动耐久性能、吸音性能、抗风阻变形量进行研究及分析,并与成熟的注塑工艺、模压工艺进行对比分析。研究表明:复合轮罩挡泥板综合性能满足乘用车轮罩挡泥板的技术要求,与注塑产品相比,抗石冲击性能及吸音性能更优,质量减轻22%,轻量化效果显著;与模压产品相比,可节省开发周期,更具成本优势。

关键词：轮罩挡泥板轻量化吸塑工艺抗石冲击性能吸音性能

Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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药物分析学报:英文版 2023年第7期13卷 817-829页

作者： Jiayun Chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu qiuyan guo Guangqing Cheng Chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

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Journal of Pharmaceutical Analysis 2022年第4期12卷 570-582页

作者： Qian Zhang Piao Luo Liuhai Zheng Jiayun Chen Junzhe Zhang Huan Tang Dandan Liu Xueling He Qiaoli Shi Liwei Gu Jiahao Li qiuyan guo Chuanbin Yang Yin Kwan Wong Fei Xia Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of SingaporeSingapore117543Singapore Department of Geriatrics Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen518020China

Hepatic stellate cells(HSCs)are essential drivers of *** activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in *** the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ *** a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated ***1 knockdown also led to ROS-mediated apoptosis in activated ***,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.

关键词： Glycyrrhetinic acid Hepatic fibrosis Peroxiredoxin Reactive oxygen species Apoptosis

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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药物分析学报:英文版 2023年第8期13卷 908-925页

作者： qiuyan guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin Chen Jie Gong Maobo Du Guangqing Cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang Jiayun Chen Feng Qiu Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of Chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers

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Journal of Pharmaceutical Analysis 2022年第6期12卷 879-888页

作者： Yuqing Meng Jiayun Chen Yanqing Liu Yongping Zhu Yin-Kwan Wong Haining Lyu Qiaoli Shi Fei Xia Liwei Gu Xinwei Zhang Peng Gao Huan Tang qiuyan guo Chong Qiu Chengchao Xu Xiao He Junzhe Zhang Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of Singapore117543Singapore Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing100049China

The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and ***,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in ***,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic *** identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct *** were also more biological processes enriched with these *** applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with *** strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

关键词： Protein corona Nanoparticles Mass spectrometry Proteomic analysis Pharmacodynamic biomarkers