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MiR-186-5p carried by M2 macrophage-derived exosomes downregulates TRPP2 expression in airway smooth muscle to alleviate asthma progression

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INTERNATIONAL IMMUNOPHARMACOLOGY 2025年 148卷 114107页

作者： Wang, Zunyun Ren, Yan Li, Yicong Zhang, Yuxin Bai, suwen Hou, Wenxuan Zhang, Wenjun Yao, Yanheng zhao, Hongxian Wang, Minghua Luo, Yumei Pang, Gang Du, Juan Chinese Univ Hong Kong Ciechanover Inst Precis & Regenerat Med Sch Med Shenzhen Guangdong Peoples R China Anhui Med Univ Sch Basic Med Sci Hefei Anhui Peoples R China Chinese Univ Hong Kong Shenzhen Affiliated Hosp 2 Sch Med Shenzhen Guangdong Peoples R China Longgang Dist Peoples Hosp Shenzhen Shenzhen Guangdong Peoples R China

Bronchial asthma (asthma) is a chronic inflammatory disease of the airways that remains an unresolved problem. Reportedly M2 macrophages and exosomes play a role in inflammation, including asthma. We investigated the roles of M2 macrophage-derived exosomes (M2-Exos) effect in asthmatic progression by using ovalbumin (OVA) induced asthmatic mice model. M2-Exos significantly ameliorated the pulmonary inflammatory response and airway hyperresponsiveness in asthmatic mice and suppressed aberrant proliferation and transient receptor potential polycystic protein 2(TRPP2) expression in LPS-stimulated primary airway smooth muscle cells (ASMCs). Then, we found that miR-186-5p of M2-Exos could target TRPP2 through online database analysis. However, miR-186-5p downregulation by miR-186-5p inhibitors decreased the protective effect of M2-Exos in asthmatic mouse and cellular models. miR-186-5p was identified and selectively combined with the polycystin-2 gene encoding TRPP2 protein, inhibited TRPP2 protein production, and downregulated TRPP2 expression. A reduction in the number of TRPP2 calcium (Ca) channels formed on the cell membrane leads to a decreased intracellular Ca2+ concentration ([Ca2+] i), causing reduced ASMC contraction and proliferation, thereby improving airway hyperresponsiveness and airway remodeling in asthma. Collectively, we conclude that M2 exosomal miR-186-5p to alleviate asthma progression and airway hyperresponsiveness though downregulating TRPP2 expression. These results may offer a novel insight to the treatment and drug delivery of asthma.

关键词： M2 macrophages Exosomes Transient receptor potential polycystic protein MiR-186-5p Asthma

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Down-regulated FTO and ALKBH5 co-operatively activates FOXO signaling through m6A methylation modification in HK2 mRNA mediated by IGF2BP2 to enhance glycolysis in colorectal cancer

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CELL AND BIOSCIENCE 2023年第1期13卷 1页

作者： Ye, Mujie Chen, Jinhao Lu, Feiyu zhao, Minghui Wu, suwen Hu, Chunhua Yu, Ping Kan, Jingbao Bai, Jianan Tian, Ye Tang, Qiyun Nanjing Med Univ Affiliated Hosp 1 Jiangsu Prov Hosp Inst Neuroendocrine Tumor 300 Guangzhou Rd Nanjing 210029 Peoples R China Nanjing Med Univ Jiangsu Prov Hosp Dept Radiat Oncol Affiliated Hosp 1 Nanjing Peoples R China Fudan Univ Obstet & Gynaecol Hosp Shanghai Peoples R China

BackgroundN6-methyladenosine (m6A) modification is the most abundant reversible methylation modification in eukaryotes, and it is reportedly closely associated with a variety of cancers progression, including colorectal cancer (CRC). This study showed that activated lipid metabolism and glycolysis play vital roles in the occurrence and development of CRC. However, only a few studies have reported the biological mechanisms underlying this *** and mRNA levels of FTO and ALKBH5 were measured using western blot and qRT-PCR. The effects of FTO and ALKBH5 on cell proliferation were examined using CCK-8, colony formation, and EdU assays, and the effects on cell migration and invasion were tested using a transwell assay. m6A RNA immunoprecipitation (MeRIP) and RNA-seq was used to explore downstream target gene. RIP was performed to verify the interaction between m6A and HK2. The function of FTO and ALKBH5 in vivo was determined by xenograft in nude *** this study, FTO and ALKBH5 were significantly down-regulated in CRC patients and cells both in vivo and in vitro in a high-fat environment. Moreover, FTO and ALKBH5 over-expression hampered cell proliferation both in vitro and in vivo. Conversely, FTO and ALKBH5 knockdown accelerated the malignant biological behaviors of CRC cells. The mechanism of action of FTO and ALKBH5 involves joint regulation of HK2, a key enzyme in glycolysis, which was identified by RNA sequencing and MeRIP-seq. Furthermore, reduced expression of FTO and ALKBH5 jointly activated the FOXO signaling pathway, which led to enhanced proliferation ability in CRC cells. IGF2BP2, as a m6A reader, positively regulated HK2 mRNA in m6A dependent manner. Additionally, down-regulation of FTO/ALKBH5 increased METTL3 and decreased METTL14 levels, further promoting CRC *** conclusion, our study revealed the FTO-ALKBH5/IGF2BP2/HK2/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in C

关键词： Colorectal cancer N6-methyladenosine RNA demethylase Glycolysis

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浅谈跨国海洋油气钻探项目界面管理风险与对策

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国际石油经济 2020年第8期28卷 39-44页

作者：邓玉明赵建臣刘正礼赵苏文赵维青金立平张星星中海油能源发展股份有限公司中国海洋石油国际有限公司中海石油(中国)有限公司深圳分公司

跨国海洋油气钻探项目的参与方较多,需要进行界面管理。目前各大石油公司界面管理的普遍做法是建立桥接文件。文化冲突是项目界面管理的一个重要问题,而且项目管理运营的决策风险可能导致项目运行出现问题。清晰的责任分摊或界定,对项... 详细信息

跨国海洋油气钻探项目的参与方较多,需要进行界面管理。目前各大石油公司界面管理的普遍做法是建立桥接文件。文化冲突是项目界面管理的一个重要问题,而且项目管理运营的决策风险可能导致项目运行出现问题。清晰的责任分摊或界定,对项目风险处理与管控具有重要意义。桥接文件使得项目各方的多种管理体系共存,在澄清不同体系存在的冲突的同时,填补了项目权益主体多体系间的缺口,为项目提供了一个良好的管理界面。桥接文件是项目界面管理风险触发后的指导体系,及早识别隐患、评估可能的风险是制定桥接文件的关键。

关键词：桥接文件界面管理风险管理海洋油气钻探国际合作

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Intrinsically Disordered Proteins Link Alternative Splicing and Post-Translational Modifications to Complex Cell Signaling and Reulation

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BIOPHYSICAL JOURNAL 2018年第3期114卷 79A-79A页

作者： Zhou, Jinhong zhao, suwen Dunker, A. K. Shanghai Tech IHuman Inst Shanghai Peoples R China Indiana Univ Biochem & Mol Biol Indianapolis IN 46204 USA

408-Pos

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Establishment and Application of Small Batch Material Production Arrangement Model Based on Time Series

Establishment and Application of Small Batch Material Produc...

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作者： Li zhao Xudong Sha Hui Lv suwen Sun Department of Mathematics and Physics Zibo Normal College School of marxism BinZhou Medical University

The inventory management of multi-variety and small-batch material production is one of the important bases to maintain normal operation of manufacturing *** paper introduces a method of setting up the weekly forecast model of material demand to help enterprises make reasonable arrangement of material *** model takes into account the comprehensive factors such as the predicted value of demand, the characteristics of demand, inventory and shortage quantity, so as to avoid the possible large inventory or shortage problem, improve the production efficiency and customer satisfaction, reduce the inventory cost, and bring economic benefits and competitive advantages for enterprises.

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Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole

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NATURE COMMUNICATIONS 2018年第1期9卷 4224页

作者： Liu, Dazhi Wei, Yifeng Liu, Xuyang Zhou, Yan Jiang, Li Yin, Jinyu Wang, Feifei Hu, Yiling Urs, Ankanahalli N. Nanjaraj Liu, Yanhong Ang, Ee Lui zhao, suwen zhao, Huimin Zhang, Yan Tianjin Univ Sch Pharmaceut Sci & Technol Collaborat Innovat Ctr Chem Sci & Engn Tianjin Key Lab Modern Drug Delivery & High Effic Tianjin 300072 Peoples R China ASTAR Inst Chem & Engn Sci Metab Engn Res Lab Singapore 138669 Singapore ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201202 Peoples R China Chinese Acad Sci Tech Inst Phys & Chem Beijing 100190 Peoples R China Univ Illinois Dept Chem & Biomol Engn 600 South Mathews Ave Urbana IL 61801 USA

Skatole is a malodorous compound that contributes to the characteristic smell of animal faeces. Although skatole has long been known to originate from bacterial tryptophan fermentation, the enzyme catalysing its formation has so far remained elusive. Here we report the use of comparative genomics for the discovery of indoleacetate decarboxylase, an O-2-sensitive glycyl radical enzyme catalysing the decarboxylation of indoleacetate to form skatole as the terminal step of tryptophan fermentation in certain anaerobic bacteria. We describe its biochemical characterization and compare it to other glycyl radical decarboxylases. Indoleacetate decarboxylase may serve as a genetic marker for the identification of skatole-producing environmental and human-associated bacteria, with impacts on human health and the livestock industry.

关键词： Biochemistry Computational biology and bioinformatics

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Succinate-acetate permease from Citrobacter koseri is an anion channel that unidirectionally translocates acetate

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细胞研究（英文版） 2018年第6期28卷 644-654页

作者： Biao Qiu Bingqing Xia Qingtong Zhou Yan Lu Miaomiao He Kazuya Hasegawa Zhiqiang Ma Fengyu Zhang Lichuan Gu Qionglei Mao Feng Wang suwen zhao zhaobing Gao Jun Liao School of Life Science and Technology ShanghaiTech University Shanghai 201210 China Institute of Biochemistry and Cell Biology Chinese Academy of Sciences 320 Yueyang Road Shanghai 200031 China CAS Key Laboratory of Receptor Research State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China University of Chinese Academy of Sciences 19A Yuquan Road Beijing 100049China iHuman Institute ShanghaiTech University Shanghai 201210 China protein Crystal Analysis Division Japan Synchrotron Radiation Research Institute Hyogo 679-5198 Japan Key Laboratory of Functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical Engineering South China University of Technology Guangzhou Guangdong 510640 China State Key Laboratory of Microbial Technology Shandong University Jinan Shandong 250100 China Wuxi Biortus Biosciences Co. Ltd Wuxi Jiangsu 214437 China School of Life Science and Technology ShanghaiTech University Shanghai 201210 China iHuman Institute ShanghaiTech University Shanghai 201210 China CAS Key Laboratory of Receptor Research State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

Acetate is an important metabolite in metabolism and cell ***-Acetate Permease (SatP) superfamily proteins are known to be responsible for acetate transport across membranes,but the nature of this transport remains ***,we show that the SatP homolog from Citrobacter koseri (SatP_Ck) is an anion channel that can unidirectionally translocate acetate at rates of the order of ～107 ions/*** structures of SatP_Ck in complex with multiple acetates at 1.8 A reveal that the acetate pathway consists of four acetate-binding sites aligned in a single file that are interrupted by three hydrophobic *** bound acetates at the four sites are each orientated *** acetate at the cytoplasmic vestibule is partially dehydrated,whereas those in the main pore body are fully *** residues within the substrate pathway may coordinate translocation of acetates via anion-n ***_Ck reveals a new type of selective anion channel and provides a structural and functional template for understanding organic anion transport.

关键词： Ion channel signalling X-ray crystallography

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明末戲曲家陳情表及其著述輯考

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戏曲与俗文学研究 2018年第2期 107-129页

作者：趙素文復旦大學中國計量大學人文社科學院中文系

明末戲曲家陳情表創作成就頗高,祁彪佳譽之爲“天才豪放”,但他的作品多已散佚,近人曲録均謂其生平事迹不詳。今考陳情表本名陳禘,字聖鑒,又字自嚳,紹興會稽縣人。童生身份。負才不遇,貧病而終。卒年爲崇禎十一年(1638)八月。本文又通... 详细信息

明末戲曲家陳情表創作成就頗高,祁彪佳譽之爲“天才豪放”,但他的作品多已散佚,近人曲録均謂其生平事迹不詳。今考陳情表本名陳禘,字聖鑒,又字自嚳,紹興會稽縣人。童生身份。負才不遇,貧病而終。卒年爲崇禎十一年(1638)八月。本文又通過輯佚梳理陳情表的現存遺作,對他的戲曲、詩詞創作成就做簡單評述。

关键词：陳情表祁彪佳遠山堂曲品遠山堂劇品

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Integrated multi-omics profiling characterizes the crucial role of human dental epithelium during tooth development

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CELL REPORTS 2025年第4期44卷 115437页

作者： Zhang, Ran Shen, Zongshan zhao, Zhenni Gu, Xiuge Yan, Tianxing Wei, Wei Wu, Chuan Xia, Jinxuan Zhang, Yuanyuan Chen, suwen Ma, Linsha Zhang, Dong Wu, Xiaoshan Sharpe, Paul T. Wang, Songlin Capital Med Univ Sch Basic Med Sch Beijing Lab Oral Hlth Beijing Peoples R China Peking Univ Sch & Hosp Stomatol Dept Oral Pathol Beijing Peoples R China Natl Ctr Stomatol Beijing Peoples R China Natl Clin Res Ctr Oral Dis Beijing Peoples R China Natl Engn Res Ctr Oral Biomat & Digital Med Device Beijing Peoples R China Southern Univ Sci & Technol Sch Med Lab Homeostat Med Shenzhen Peoples R China Southern Univ Sci & Technol SUSTech Homeostat Med Inst Shenzhen Peoples R China Sun Yat sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou Peoples R China Capital Med Univ Beijing Friendship Hosp Immunol Res Ctr Oral & Syst Hlth Beijing Peoples R China Cent South Univ Academician Workstat Oral Maxillofacial Regenerat Changsha Peoples R China Kings Coll London Ctr Craniofacial & Regenerat Biol London SE1 9RT England Capital Med Univ Beijing Obstet & Gynecol Hosp Beijing Maternal & Child Hlth Care Hosp Beijing Peoples R China

The development of early human tooth primordia is not well understood. Here, we linked single-cell RNA sequencing, spatial transcriptomics, and secretome analysis to characterize human fetal tooth development over time. A spatiotemporal atlas of human tooth development at multiple levels was mapped, identifying previously uncharacterized epithelial subpopulations with distinct gene expression profiles and spatial localization. Dynamic changes in epithelial-mesenchymal interactions across developmental stages were characterized. Secretome analysis confirmed the extensive paracrine signaling from the epithelial to mesenchymal compartments and uncovered signaling factors produced by dental epithelium (DE) that regulate mesenchymal cell fate and differentiation. Integration of these datasets highlighted the crucial role of the DE in orchestrating tooth morphogenesis. Our multi-omics approach not only provides unprecedented insights into the cellular and molecular mechanisms of ectoderm-derived tissue development but also serves as a valuable resource, which is publicly available online, for future studies on human tooth regeneration and related diseases.

关键词： human fetal tooth development dental epithelium single-cell RNA sequencing spatial transcriptomics secretome CP: Developmental biology

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Statin therapy associated Lactobacillus intestinalis attenuates pancreatic fibrosis through remodeling intestinal homeostasis

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NPJ BIOFILMS AND MICROBIOMES 2025年第1期11卷 1-15页

作者： Sui, Yuhang Zhang, Tao Ou, suwen Li, Guanqun Liu, Liwei Lu, Tianqi Zhang, Can Cao, Yukai Bai, Rui Zhou, Haoxin zhao, Xinbo Yuan, Yue Wang, Gang Chen, Hua Kong, Rui Sun, Bei Li, Le Harbin Med Univ Affiliated Hosp 1 Dept Liver Surg Harbin Peoples R China Minist Educ Key Lab Hepatosplen Surg Harbin Peoples R China Capital Med Univ Beijing Chaoyang Hosp Dept Hepatobiliary & Pancreaticosplen Surg Beijing Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Pancreat & Biliary Surg Harbin Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Minimally Invas Biliary Surg Harbin Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Cardiol Harbin Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Emergency Surg Harbin Peoples R China Harbin Med Univ Affiliated Hosp 1 Dept Oncol Endoscop Surg Harbin Peoples R China

Chronic pancreatitis (CP) is characterized by irreversible fibrotic destruction and impaired pancreatic function. CP disrupts lipid metabolism and causes the imbalance of gut microbiota which in turn exacerbates pancreatic fibrosis. Statins alter gut microbiota and exert anti-inflammatory effects, but its role in CP has not been fully elucidated. Here, we found that statins-associated higher abundance of Lactobacillus intestinalis (***) maintained gut homeostasis that restrained bacteria translocation from gut to the pancreas, which eventually aggravated pancreatic fibrosis through inhibiting CD8+T cells-dependent immunity. Fecal microbiota transplantation (FMT) or *** administration inhibited the infiltration of CD8+T cells and macrophages that delayed CP progression. *** restrained the recruitment of M1 macrophages and limited the release of Ccl2/7 in the colon, which prevented epithelial damage and epithelial barrier dysfunction through blocking Ccl2/7-Ccr1 signaling. Our findings elucidate that the utilization of statin therapy or supplementation of *** can be potential approach for the therapies of CP.

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