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Inhibition of Farnesoid-x-receptor signaling during abdominal sepsis by dysbiosis exacerbates gut barrier dysfunction

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CELL COMMUNICATION AND SIGNALING 2025年第1期23卷 1-25页

作者： qian, shuwen Su, Zehua Lin, Jiaqi Hou, qianhao Wang, Xiaomei Li, Yuling Wang, Jieying Huang, Changchun Wang, Zetian Cubero, Francisco Javier Wang, Xiangrui Liao, Lijun Tongji Univ Yangpu Hosp Sch Med Dept Anesthesiol & Pain Management Shanghai 200090 Peoples R China Tongji Univ Shanghai East Hosp Sch Med Dept Pain Management Shanghai 200120 Peoples R China Tongji Univ Jian Hosp Shanghai East Hosp Sch Med Nanchang 343006 Jiangxi Peoples R China Shanghai Jiao Tong Univ Renji Hosp Clin Ctr Invest Sch Med Shanghai 200127 Peoples R China Ningbo First Hosp Dept Anesthesiol Ningbo 315010 Zhejiang Peoples R China Univ Complutense Madrid Sch Med Dept Immunol Ophthalmol & ENT Madrid Spain Tongji Univ Shanghai East Hosp Inst Pain Med Sch Med Shanghai 200120 Peoples R China

Background and aimsBacterial translocation and intestinal dysbiosis due to gut barrier dysfunction are widely recognized as major causes of the initiation and development of intra-abdominal sepsis. Systemic bacterial translocation and hepatic activation of the myeloid differentiation primary response gene 88 (Myd88) can disturb bile acids (BAs) metabolism, further exacerbating intestinal dysbiosis. The farnesoid X receptor (FXR) and fibroblast growth factor (FGF) 15/19 are well known to be involved in the control of BAs synthesis and enterohepatic circulation. However, the influence of intestinal microbiota on intestinal Myd88 signaling, the FXR/FGF15 axis, as well as gut-liver crosstalk during sepsis remains unclear. The present study aims to decipher the role of intestinal Myd88 in abdominal sepsis, its impact on intestinal FXR signaling and FGF15-mediated gut-liver *** levels of FXR and FGF15 in the liver and intestines, alongside assessments of gut barrier function, were evaluated in septic wild-type (WT) mice 24 h post-cecal ligation and puncture (CLP) surgery. Subsequently, the FXR agonist INT-747 was administered to explore the relationship between FXR activation and gut barrier function. Further investigations involved Myd88-deficient mice with specific deletion of Myd88 in intestinal epithelial cells (Myd88 triangle IEC), subjected to CLP to examine the interplay among intestinal Myd88, FXR, gut barrier function, microbiota, and BA composition. Additionally, fecal microbiota transplantation (FMT) from septic mice to Myd88 triangle IEC mice was conducted to study the impact of dysbiosis on intestinal Myd88 expression during sepsis, using floxed (Myd88fl/fl) mice as controls. Finally, the effects of the probiotic intervention on gut barrier function and sepsis outcomes in CLP mice were *** of sepsis via CLP led to hepatic cholestasis, suppressed FXR-FGF15 signaling, altered gut microbiota composition, and comp

关键词： Sepsis Gut microbiota Myd88 FXR FGF15 Probiotics Bile acids

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DNAzyme-Immobilizing Microgel Magnetic Beads Enable Rapid, Specific, Culture-Free, and Wash-Free Electrochemical Quantification of Bacteria in Untreated Urine

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ACS SENSORS 2022年第4期7卷 985-994页

作者： Pandey, Richa Lu, Yang Osman, Enas Saxena, Survanshu Zhang, Zijie qian, shuwen Pollinzi, Angela Smieja, Marek Li, Yingfu Soleymani, Leyla Hoare, Todd McMaster Univ Dept Engn Phys Hamilton ON L8S 4L8 Canada Univ Calgary Dept Biomed Engn Calgary AB Canada McMaster Univ Sch Biomed Engn Hamilton ON L8S 4L8 Canada McMaster Univ Dept Biochem & Biomed Sci Hamilton ON Canada McMaster Univ Dept Chem Engn Hamilton ON L8S 4L7 Canada McMaster Univ Res St Josephs Hamilton Dept Med Pathol & Mol Med Hamilton ON L8S 4L8 Canada

Rapid, ultrasensitive, and specific detection and identification of bacteria in unprocessed clinical specimens is critically needed to enable point-of-care diagnosis of infectious diseases. However, existing systems require sample processing and/or analyte enrichment for direct bacterial analysis in clinical samples, which significantly adds to the assay time and complexity. Herein, we integrate RNA-cleaving DNAzymes specifictoEscherichia coli(***) and programmed for electrochemical signal transduction,multifunctional microgel magnetic beads for immobilizing theDNAzyme into a hydrated and three-dimensional scaffold, andhierarchical electrodes for ultrasensitive electrochemical readout toachieve rapid bacterial analysis in undiluted and unprocessed urinecollected from symptomatic patients suspected of having urinarytract infections (UTIs). The microgel magnetic bead assay enables highly efficient conjugation and hydration of the immobilizedDNAzymes, resulting in low limits-of-detection of 6 CFU/mL in buffer and 138 CFU/mL in unprocessed urine with high specificityagainst multiple urinary pathogens within a 1 hour assay time. The assay successfully identifies which patients are infected withE. colias the causative organism for their UTI symptoms, indicating the clinical relevance of this assay

关键词： microgel magnetic beads POEGMA polymer DNAzyme electrochemical biosensor bacteria detection

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Adipose tissue plasticity and the pleiotropic roles of BMP signaling

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JOURNAL OF BIOLOGICAL CHEMISTRY 2021年第1期296卷 100678页

作者： qian, shuwen Tang, Yan Tang, Qi-Qun Fudan Univ Sch Basic Med Sci Dept Biochem & Mol Biol Key Lab Metab & Mol MedMinist Educ Shanghai Peoples R China Fudan Univ Dept Endocrinol & Metab Zhongshan Hosp Shanghai Peoples R China

Adipose tissues, including white, beige, and brown adipose tissue, have evolved to be highly dynamic organs. Adipose tissues undergo profound changes during development and regeneration and readily undergo remodeling to meet the demands of an everchanging metabolic landscape. The dynamics are determined by the high plasticity of adipose tissues, which contain various cell types: adipocytes, immune cells, endothelial cells, nerves, and fibroblasts. There are numerous proteins that participate in regulating the plasticity of adipose tissues. Among these, bone morphogenetic proteins (BMPs) were initially found to regulate the differentiation of adipocytes, and they are being reported to have pleiotropic functions by emerging studies. Here, in the first half of the article, we summarize the plasticity of adipocytes and macrophages, which are two groups of cells targeted by BMP signaling in adipose tissues. We then review how BMPs regulate the differentiation, death, and lipid metabolism of adipocytes. In addition, the potential role of BMPs in regulating adipose tissue macrophages is considered. Finally, the expression of BMPs in adipose tissues and their metabolic relevance are discussed.

关键词： BMPs adipogenesis plasticity adipocyte beige macrophage

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复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的半数有效剂量

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临床麻醉学杂志 2024年第1期40卷 61-64页

作者：钱淑雯郭旋沈耘张马忠上海市杨浦区中心医院同济大学附属杨浦医院麻醉科 200090 上海交通大学医学院附属上海儿童医学中心麻醉科儿童临床药理研究室

目的探讨复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的半数有效剂量(ED_(50))。方法选择择期在鼻咽通气道下完成白内障手术的老年患者38例,年龄≥65岁,BMI 18~25 kg/m^(2),ASAⅠ—Ⅲ级。患者依次静脉注射舒芬太尼0.1μg/kg,... 详细信息

目的探讨复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的半数有效剂量(ED_(50))。方法选择择期在鼻咽通气道下完成白内障手术的老年患者38例,年龄≥65岁,BMI 18~25 kg/m^(2),ASAⅠ—Ⅲ级。患者依次静脉注射舒芬太尼0.1μg/kg,3 min后静脉注射瑞马唑仑,2 min后置入鼻咽通气道。首例患者给予瑞马唑仑0.2 mg/kg,采用改良Dixon序贯法确定下一例患者瑞马唑仑的剂量,若前一例患者鼻咽通气道置入时出现以下任意一种阳性反应(摇头、呛咳、体动、HR增快幅度>基础值的20%、SBP或DBP升高幅度>基础值的20%),则下一例麻醉诱导时瑞马唑仑剂量增加0.01 mg/kg,反之则减少0.01 mg/kg,直到出现7次折返后停止。采用Probit回归分析计算复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的ED_(50)、95%有效剂量(ED95)及95%可信区间(CI)。结果复合舒芬太尼时瑞马唑仑抑制鼻咽通气道置入反应的ED_(50)为0.193 mg/kg(95%CI 0.191~0.195 mg/kg),ED95为0.209 mg/kg(95%CI 0.205~0.213 mg/kg)。结论复合舒芬太尼时瑞马唑仑抑制老年患者鼻咽通气道置入反应的ED_(50)为0.193 mg/kg(95%CI 0.191~0.195 mg/kg)。

关键词：瑞马唑仑半数有效剂量鼻咽通气道老年

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Detecting Legionella pneumophila in Cooling Tower Water Samples with a DNAzyme/Bead-Based Fluorescence Assay

ANALYSIS & SENSING

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ANALYSIS & SENSING 2023年第6期3卷

作者： qian, shuwen McConnell, Erin M. Rothenbroker, Meghan Gu, Jimmy Alungulesa, Simina Godbout, Louis Li, Yingfu McMaster Univ Dept Biochem & Biomed Sci 1280 Main St West Hamilton ON L8S 4K1 Canada Technol Propres TGWT inc 452 rue Jean Neveu Longueuil PQ J4G 1N8 Canada McMaster Univ Michael G DeGroote Inst Infect Dis Res 1280 Main St West Hamilton ON L8S 4K1 Canada McMaster Univ Sch Biomed Engn 1280 Main St West Hamilton ON L8S 4K1 Canada McMaster Univ Biointerfaces Inst 1280 Main St West Hamilton ON L8S 4K1 Canada

Legionella pneumophila is the causative agent behind the deadly waterborne disease Legionnaires', which is commonly transmitted by the spread of contaminated droplets from cooling tower water samples. The lack of effective detection methods presents a challenge for L. pneumophila outbreak control. Previously, an RNA-cleaving DNAzyme called LP1 was reported to specifically target L. pneumophila. In this study, LP1 was immobilized onto agarose beads via streptavidin-biotin interaction to develop a bead-based fluorescence assay for L. pneumophila detection. This bead-based assay demonstrated excellent stability and functionality in various cooling tower water samples. To improve L. pneumophila monitoring in real-world samples, a lysozyme treatment was used to enhance L. pneumophila recognition. The limit of detection of this DNAzyme-based bead assay can reach 10(3) CFUs in cell-spiked cooling tower water samples without cell culturing or signal amplification steps.

关键词： Bead-based assay Biosensor DNAzyme Fluorescence detection Legionella pneumophila

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Intestinal dysbiosis exacerbates gut barrier dysfunction via inhibiting FXR-FGF15 in intra-abdominal sepsis

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JOURNAL OF HEPATOLOGY 2023年第Sup1期78卷 S347-S347页

作者： qian, shuwen Wang, Xiaomei Hou, Qiaohao Su, Zehua Shi, Haobing Liao, Lijun Wang, Xiangrui Tongji Univ Yangpu Cent Hosp Shanghai Peoples R China Tongji Univ Shanghai East Hosp Sch Med Shanghai Peoples R China

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基于柔性传感器的绳驱动连续体机器人反馈控制

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传感器与微系统 2024年第8期43卷 87-90页

作者：钱书文郑天江沈雯钧杨桂林中国科学院宁波材料技术与工程研究所浙江宁波315201 中国科学院大学北京100049 浙江省机器人与智能制造装备技术重点实验室浙江宁波315201

鉴于绳驱动连续体机器人独特的柔顺性使得其骨架变形难以通过传统的刚性传感器测量,另一方面,基于分段常曲率假设建立的运动学模型开环控制存在位置精度低的问题。本文以模块化设计的绳驱动连续体机器人为研究对象,利用了一种弹性磁电... 详细信息

鉴于绳驱动连续体机器人独特的柔顺性使得其骨架变形难以通过传统的刚性传感器测量,另一方面,基于分段常曲率假设建立的运动学模型开环控制存在位置精度低的问题。本文以模块化设计的绳驱动连续体机器人为研究对象,利用了一种弹性磁电应变传感器并建立了多元回归模型实现机器人形状感知。通过一种运动空间映射方法实现了机器人柔性臂在三维空间内的闭环反馈控制。最终搭建了机器人样机平台并进行实验验证。结果有力地证明了基于柔性传感器的反馈控制方法的可行性和准确性。

关键词：绳驱动连续体机器人柔性传感器运动空间映射反馈控制

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Slit3 secreted from M2-like macrophages increases sympathetic activity and thermogenesis in adipose tissue

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NATURE METABOLISM 2021年第11期3卷 1536-1551页

作者： Wang, Yi-Na Tang, Yan He, Zhihui Ma, Hong Wang, Linyuan Liu, Yang Yang, Qiqi Pan, Dongning Zhu, Cuiqing qian, shuwen Tang, Qi-Qun Fudan Univ Key Lab Metab & Mol Med Dept Biochem & Mol Biol Sch Basic Med SciZhongshan HospMinist Educ Shanghai Peoples R China Fudan Univ Zhongshan Hosp Dept Endocrinol & Metab Shanghai Peoples R China Fudan Univ Inst Biomed Sci Minist Educ Key Lab Metab & Mol Med Shanghai Peoples R China Fudan Univ State Key Lab Med Neurobiol Inst Brain Sci Shanghai Peoples R China Fudan Univ MOE Frontier Ctr Brain Sci Inst Brain Sci Shanghai Peoples R China

Slit3 is shown to be secreted from M2-like macrophages resident in adipose tissue, where it enables cold adaptation by stimulating norepinephrine release from sympathetic neurons. Beiging of white adipose tissue (WAT) is associated with an increase of anti-inflammatory M2-like macrophages in WAT. However, mechanisms through which M2-like macrophages affect beiging are incompletely understood. Here, we show that the macrophage cytokine Slit3 is secreted by adipose tissue macrophages and promotes cold adaptation by stimulating sympathetic innervation and thermogenesis in mice. Analysing the transcriptome of M2-like macrophages in murine inguinal WAT (iWAT) after cold exposure, we identify Slit3 as a secreted cytokine. Slit3 binds to the ROBO1 receptor on sympathetic neurons to stimulate Ca2+/calmodulin-dependent protein kinase II signalling and norepinephrine release, which enhances adipocyte thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT promotes beiging and thermogenesis, whereas mice that lack Slit3 in myeloid cells are cold-intolerant and gain more weight. Our findings shed new light on the integral role of M2-like macrophages for adipose tissue homeostasis and uncover the macrophage-Slit3-sympathetic neuron-adipocyte signalling axis as a regulator of long-term cold adaptation.

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A single-cell sequence analysis of mouse subcutaneous white adipose tissue reveals dynamic changes during weaning

COMMUNICATIONS BIOLOGY

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COMMUNICATIONS BIOLOGY 2024年第1期7卷 787页

作者： qian, shuwen Zhang, Chenyang Tang, Yan Dai, Mengyuan He, Zhihui Ma, Hong Wang, Linyuan Yang, Qiqi Liu, Yang Xu, Wei Zhang, Zhao Tang, Qi-qun Fudan Univ Dept Biochem & Mol Biol Key Lab Metab & Mol Med Minist EducSch Basic Med SciZhongshan Hosp Shanghai 200032 Peoples R China Fudan Univ Zhongshan Hosp Dept Endocrinol & Metab Shanghai 200032 Peoples R China Fudan Univ Shanghai Med Coll Dept Immunol Shanghai 200032 Peoples R China

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGF beta ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning. A single-cell sequence on mouse subcutaneous white adipose tissue analyses the dynamics of preadipocytes and immune cells populations in early life time and suggests potential changes involved in the beige-like remodeling during weaning.

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Cable-Driven Continuum Robot Perception Using Skin-Like Hydrogel Sensors

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ADVANCED FUNCTIONAL MATERIALS 2022年第34期32卷 2203241-2203241页

作者： Yan, Huizhen Wang, Yi Shen, Wenjun Li, Famin Gao, Guorong Zheng, Tianjiang Xu, Zhenyu qian, shuwen Chen, Chin-yin Zhang, Chi Yang, Guilin Chen, Tao Chinese Acad Sci Ningbo Inst Mat Technol & Engn Zhejiang Key Lab Marine Mat & Protect Technol Key Lab Marine Mat & Related Technol Ningbo 315201 Peoples R China Chinese Acad Sci Ningbo Inst Mat Technol & Engn Zhejiang Key Lab Robot & Intelligent Mfg Equipmen Ningbo 315201 Peoples R China Univ Chinese Acad Sci Sch Chem Sci Beijing 100049 Peoples R China

The cable-driven continuum robot (CDCR) is a highly significant soft robot that exhibits a lightweight structure, intrinsic safety properties, and a considerable degree of freedom;therefore, it can work well in confined and complex environments. However, commonly used fiber Bragg grating sensors in CDCR systems are ultra-stiff, extremely low in elongation, and lack an adhesion mechanism;this significantly restricts the movement of the robot and tends to delaminate from it, which makes it unsuitable for integrated systems. In this study, a new strategy is developed to enable CDCR perception via skin-like hydrogel sensors made from ionic conductive polyacrylamide/alginate/nanoclay polymeric composite hydrogels;it exhibits a fracture strain of 1840% and adheres to a CDCR backbone with an adhesion strength of 6.6 kPa. The sensors are sensitive, stable, and reliable, and they can be manually operated to draw portraits using sensing curves as painted lines. Through these sensors, the CDCR acquires proprioception for sensing movements and exteroception for sensing barriers and traps. The hydrogel sensors are further employed to build a closed-loop control system for regulating the bending of the CDCR. This study establishes effective routes for designing sensors and closed-loop systems that can be applied to soft robots.

关键词： adhesion continuum robots flexible sensors hydrogels ionic conductors

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