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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui Chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai Jiayun Chen Xinzhou Zhang Sheng Nie Chunbo Chen yulin feng Jigang Wang National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China 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 TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and function.The natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or dysfunction.In this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels.Our results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer cells.These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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Revealing the Distribution of Aggregation-Induced Emission Nanoparticles via Dual-Modality Imaging with Fluorescence and Mass Spectrometry

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Research 2021年第1期2021卷 826-834页

作者： Liucheng Mao Yuming Jiang Hui Ouyang yulin feng Ruoxin Li Xiaoyong Zhang Zongxiu Nie Yen Wei The Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 100084China Beijing National Laboratory for Molecular Sciences Key Laboratory of Analytical Chemistry for Living BiosystemsInstitute of ChemistryChinese Academy of SciencesBeijing 100190China State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment Jiangxi University of Traditional Chinese MedicineNanchang 330006China Department of Chemistry Nanchang University999 Xuefu AvenueNanchang 330031China

Aggregation-induced emission nanoparticles(AIE NPs)are widely used in the biomedical field.However,understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth.Herein,we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging(LDI MSI)to map and quantify the biodistribution of AIE NPs(TPAFN-F127 NPs)by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule.We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen,and most gradually excreted from the body after 5 days.The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model.As a proof of concept,the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI,and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone.The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure.This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.

关键词： spleen distribution retention

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Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

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Journal of Pharmaceutical Analysis 2021年第1期11卷 96-107页

作者： Lu Wang Sen Li Jiaxin Li Zhongzhe Cheng yulin feng Hui Ouyang Zhifeng Du Hongliang Jiang Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhanChina Department of Pharmacy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Jiangxi University of Traditional Chinese Medicine NanchangChina School of Pharmacy Weifang Medical UniversityWeifangChina

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

关键词： Alismatis rhizoma Triterpenes Metabolites HPLC-QTOF-MS/MS

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Dynamic Analyses of a Simply Supported Double-Beam System Subject to a Moving Mass with Fourier Transform Technique

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Computer Modeling in Engineering & Sciences 2019年第10期121卷 291-314页

作者： Lizhong Jiang Xilin Chai Zhihua Tan Wangbao Zhou yulin feng Zhipeng Lai Lan Zheng School of Civil Engineering Central South UniversityChangsha410075China National Engineering Laboratory for High Speed Railway Construction Central South UniversityChangsha410075China

In order to study the dynamic characteristics of a simply supported double-beam system under a moving mass,the system of fourth-order dynamic partial differential equations of a simply supported double-beam system was transformed into a system of second-order dynamic ordinary differential equations relative to time coordinates by performing the finite sin-Fourier Transform relative to space coordinates.And the analytical solution of the dynamic response of the simply supported double-beam system under a moving mass was obtained by solving the system of dynamic ordinary differential equations.The analytical method and ANSYS numerical method were used to calculate the dynamic responses of several simply supported double-beam systems under a moving mass at different speeds.The influences of inertial effect,mass movement speed,and Winkler-layer spring stiffness and damping on the dynamic responses of simply supported double-beam systems were analyzed.According to the study results,the analytical calculation results in this paper fit well with the ANSYS finite element numerical calculation results,demonstrating the rationality of the analytical method.The inertial effect has a significant influence on the dynamic response characteristics of the simply supported double-beam system.The simply supported double-beam system underwent several resonant speeds under a moving mass,and the Winkler-layer spring stiffness has a relatively significant effect on the vibration of the first beam.

关键词： Double-beam system moving mass dynamic response analytical method finite sin-Fourier Transform

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鸦胆子苷B与肠道菌群相互作用及对人肺癌A549细胞的抑制作用

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中国实验方剂学杂志 2024年第13期30卷 160-166页

作者：石凌钰王文敏冯育林杨世林万阳陈道峰温泉江西中医药大学南昌330006 江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室南昌330006 复旦大学药学院上海201203

目的:分析鸦胆子苷B和肠道菌群相互作用,以及其代谢产物对人肺癌A549细胞的抑制活性,探讨鸦胆子苷B对非小细胞肺癌(NSCLC)治疗的价值。方法:采用肠道菌群体外温孵培养法,将鸦胆子苷B与人肠道菌群体外共孵育,通过超高效液相色谱-四极杆-... 详细信息

目的:分析鸦胆子苷B和肠道菌群相互作用,以及其代谢产物对人肺癌A549细胞的抑制活性,探讨鸦胆子苷B对非小细胞肺癌(NSCLC)治疗的价值。方法:采用肠道菌群体外温孵培养法,将鸦胆子苷B与人肠道菌群体外共孵育,通过超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS)分析代谢转化产物。采用细胞增殖与活性检测法(CCK-8法)检测原型物鸦胆子苷B及其代谢产物对人肺癌A549细胞增殖的影响并计算半数抑制浓度(IC_(50))。取健康雄性大鼠5只,经灌胃给药鸦胆子苷B药液(2 mg·kg^(-1)),连续7 d,分别采集大鼠给药前和给药后的粪便,基于16S rRNA高通量测序分析鸦胆子苷B给药前后肠道菌群变化。结果:鸦胆子苷B可被人肠道菌群经脱糖基水解代谢为鸦胆子苦醇,原型物和转化产物对A549细胞的IC50分别为1755.50、19.57μmol·L^(-1),代谢产物对A549细胞增殖的抑制活性显著优于鸦胆子苷B。肠道菌群分析结果显示,与给药前比较,给药后大鼠肠道菌群α多样性和β多样性未发生明显变化。物种丰度方面,门水平上,鸦胆子苷B降低了放线菌门、变形菌门的物种相对丰度,增加了厚壁菌门、髌骨菌门、蓝细菌门的物种相对丰度;属水平上,鸦胆子苷B降低了葡萄球菌属、气球菌属、嗜冷菌属的物种相对丰度,增加了罗姆布茨菌属、乳杆菌属、狭义梭菌属1、Norank-f-norank-o-Clostridia-UCG-014、苏黎世杆菌属、异杆菌属、糖杆菌念珠菌属的物种相对丰度。功能预测结果显示,与给药前比较,给药后大鼠肠道功能均未发生显著变化。结论:鸦胆子苷B可在肠道菌群作用下脱糖基,转化为苷元鸦胆子苦醇,抗肿瘤活性显著提高。服用鸦胆子苷B不会使肠道菌群结构和功能发生显著变化,造成肠道微生态平衡失调,且给药鸦胆子苷B后出现对NSCLC患者有益的肠道菌群变化。

关键词：鸦胆子鸦胆子苷B 鸦胆子苦醇肠道菌群代谢转化人肺癌A549细胞非小细胞肺癌(NSCLC) 16S rRNA高通量测序

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边墩沉降致连续简支桥段纵连线桥系统层间联结劣化规律

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防灾减灾工程学报 2024年第3期44卷 623-631页

作者：冯玉林何帅蒋丽忠周旺保颜建伟华东交通大学土木建筑学院江西南昌330013 华东交通大学轨道交通基础设施性能监测与保障国家重点实验室江西南昌330013 中南大学高速铁路建造技术国家工程研究中心湖南长沙410075

为研究边墩沉降致纵连板式无砟轨道-连续梁桥系统(纵连线桥系统)层间联结劣化状态,在考虑边墩沉降与层间接触不连续影响的基础上,建立纵连线桥系统非线性空间模型,采用前期提出的理论模型对其进行验证,据此分析边墩沉降下纵连线桥系统... 详细信息

为研究边墩沉降致纵连板式无砟轨道-连续梁桥系统(纵连线桥系统)层间联结劣化状态,在考虑边墩沉降与层间接触不连续影响的基础上,建立纵连线桥系统非线性空间模型,采用前期提出的理论模型对其进行验证,据此分析边墩沉降下纵连线桥系统典型变形模式,层间联结失效的演化过程、发展规律及出现位置等。结果表明:建立的空间模型准确可靠;边墩沉降下,线桥系统会产生跟随变形、自重变形和悬停分离三种变形模式;沉降墩、与沉降墩临近的简支梁墩及连续梁桥另一侧边墩上方会出现层间联结失效,与沉降墩临近的简支梁墩、连续梁桥全部桥墩上的支座均会发生破坏;边墩沉降处板底脱空高度可用边墩沉降值减去连续梁桥变形限值进行描述;各脱空区长度均随边墩沉降幅值增加而增大,与沉降墩临近的简支梁墩左、右两侧区域脱空长度成正对称分布,连续梁另一边墩处脱空长度值只与连续梁变形有关,始终维持在2.56 m。

关键词：高速铁路桥墩沉降损伤演化悬停分离连续梁桥

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藏药“叶格兴”的基原及化学成分、药理活性研究进展

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世界科学技术-中医药现代化 2024年第3期26卷 675-690页

作者：杨安南冯艳李志峰李亚荣缐杨王琦冯育林钟国跃江西中医药大学药学院南昌330000 中药固体制剂制造技术国家工程研究中心南昌330000

目的澄清常用藏药“叶格兴”的基原,考察其化学成分与药理活性,为规范临床用药、质量控制及资源的合理利用等提供依据。方法采用文献考证、植物分类学鉴定、化学成分考察、药理活性鉴定,结合资源分布及临床使用现状调查分析。结果藏药... 详细信息

目的澄清常用藏药“叶格兴”的基原,考察其化学成分与药理活性,为规范临床用药、质量控制及资源的合理利用等提供依据。方法采用文献考证、植物分类学鉴定、化学成分考察、药理活性鉴定,结合资源分布及临床使用现状调查分析。结果藏药“叶格兴”涉及2科4属7种,即忍冬科接骨木属,菊科千里光属、合耳菊属、风毛菊属,文献记载的基原植物中最早使用的“叶格兴嘎保”即“白”者应是双花千里光、川西千里光;“叶格兴那保”即“黑”应为柳叶菜风毛菊及血满草;莱菔叶千里光(异叶千里光)、菊叶千里光(菊状千里光)、接骨草为云南、甘肃、川西习用、市场流通的主要代用品。叶格兴主要含萜类、黄酮类、生物碱类、酚酸等化学成分;叶格兴黑者主要用于“愈创”,白者主要用于“消炎”与现代药理研究抗炎、抗氧化、抗菌等活性相对应。结论鉴于“叶格兴”的基原涉及到多种不同科属的植物,“叶格兴”已成为这些植物类药材的统称;据考证结果及化学成分、药理活性研究进展,从有利于规范临床用药、保证疗效和药材质量的角度,其名称和基原宜规范为:“■/叶格兴嘎保”(即白者),来源为双花千里光(红缨合耳菊)、川西千里光(川西合耳菊);“■/叶格兴那保”(即黑者),来源为柳叶菜风毛菊、血满草,莱菔叶千里光(异叶千里光)、菊叶千里光(菊状千里光)为各地代用品;接骨草作为独立药物。应加强各地方代用品的资源与使用现状调查、不同资源物种的药效物质基础及生物活性等的比较研究,规范其品种-名称-基原,以合理利用其资源。

关键词：叶格兴藏药本草考证化学成分药理活性

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基于修正Archard模型非连续接触的浮动球密封结构磨损行为研究

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流体机械 2024年第4期52卷 20-27页

作者：高俊峰赵嘉逸冯玉林杨玲玲李伟明友合肥通用机械研究院有限公司合肥230031 合肥通用机电产品检测院有限公司合肥230031

针对不连续接触磨损问题,以硬密封浮动球阀中浮动球密封结构为研究对象,将欧拉-拉格朗日耦合法(CEL)、全局网络重构法(ALE)、修正Archard模型与硬密封条件下的数值计算模型相结合,利用Abaqus子程序UMESHMOTION,实现对非连续接触密封结... 详细信息

针对不连续接触磨损问题,以硬密封浮动球阀中浮动球密封结构为研究对象,将欧拉-拉格朗日耦合法(CEL)、全局网络重构法(ALE)、修正Archard模型与硬密封条件下的数值计算模型相结合,利用Abaqus子程序UMESHMOTION,实现对非连续接触密封结构的磨损仿真分析,探究流体介质压力、启闭速度及密封面宽度等对密封面磨损特性的影响规律,揭示不连续接触条件下的磨损机制;提出密封结构接触面全局磨损量均值(GWA)的评价方法。结果表明:非连续接触形式下,磨损较大位置出现应力集中;启闭速度和密封面宽度对密封面磨损影响较小;当V_(oc)为2 mm/s时GWA最小;当b_(m)为3.0 mm时GWA最小;流体介质压力对密封面磨损影响较大;非连续接触的磨损机理主要是磨粒磨损和疲劳磨损。研究结果可为不连续接触结构的优化设计提供理论基础和技术支撑。

关键词： Archard磨损模型非连续接触浮动球密封结构磨损特性欧拉-拉格朗日耦合全局网络重构

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Impacts of pancreatic exocrine insufficiency on gut microbiota

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 271-279页

作者： yulin GUO feng CAO Fei LI Department of General Surgery Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Acute Pancreatitis Clinical Center of Capital Medical University Beijing 100053China

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal p H as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

关键词： Pancreatic exocrine insufficiency Gut microbiota Gut microbiome Pancreatic enzyme replacement therapy

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酸藤子的化学成分研究

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中草药 2024年第9期55卷 2868-2874页

作者：李婉亭李志强曾祥昊余惠敏钟国跃冯育林何明珍江西中医药大学江西南昌330006 中药固体制剂制造技术国家工程研究中心江西南昌330006

目的研究酸藤子Embelia laeta的化学成分。方法利用硅胶、Sephadex LH-20、HP-20大孔吸附树脂、半制备高效液相等各种方法进行分离纯化,通过核磁共振波谱、质谱等对化合物的结构进行表征和解析。结果从酸藤子70%乙醇提取物的正丁醇萃取... 详细信息

目的研究酸藤子Embelia laeta的化学成分。方法利用硅胶、Sephadex LH-20、HP-20大孔吸附树脂、半制备高效液相等各种方法进行分离纯化,通过核磁共振波谱、质谱等对化合物的结构进行表征和解析。结果从酸藤子70%乙醇提取物的正丁醇萃取部位中分离得到19个化合物,分别鉴定为淫羊藿次苷D2(1)、山柰酚-3-O-β-D-葡萄糖-7-O-α-L-鼠李糖苷(2)、反式对羟基桂皮酸(3)、咖啡酸(4)、槲皮素-3-O-α-L-鼠李糖吡喃糖基-7-O-β-D-吡喃葡萄糖苷(5)、4-(β-吡喃葡萄糖基氧基)-苯甲醛(6)、1-O-对羟基肉桂酰单甘油酯(7)、山柰酚-3-O-β-D-(2''-O-β-D-呋喃糖基)-吡喃葡萄糖苷-7-O-α-L-鼠李糖吡喃糖苷(8)、绿原酸(9)、反式咖啡酸(10)、对羟基肉桂酸甲酯(11)、反式-3-O-香豆酰奎宁酸(12)、5-对反式香豆酰奎宁酸甲酯(13)、1-(3',4'-二羟基肉桂酰基)-环戊二烯二醇(14)、槲皮素-3-O-β-D-呋喃芹糖-(1→2)-β-D-吡喃葡萄糖-7-O-α-L吡喃鼠李糖苷(15)、槲皮素-3-O-吡喃葡萄糖苷(16)、柽柳黄素3-O-β-D-葡萄糖苷-7-O-α-L-鼠李糖苷(17)、N-(3-((3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基)氧基)丙基)肉桂酰胺(18)、D-去氢南天竹啡碱(19)。结论其中化合物18为新化合物,命名为酸藤子碱苷,化合物1~3、5~8、11~15、17和19首次从酸藤子植物中分离得到。

关键词：酸藤子淫羊藿次苷D2 反式对羟基桂皮酸槲皮素-3-O-α-L-鼠李糖吡喃糖基-7-O-β-D-吡喃葡萄糖苷 D-去氢南天竹啡碱

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