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国际医学放射学杂志 2024年第1期 128-129页

作者： J.Wang x.zhu J.Zeng C.Liu W.Shen x.J.Sun 刘莹莹

摘要目的建立基于影像学特征的机器学习模型，以预测食管鳞状细胞癌（ESCC）病人新辅助化放疗（nCRT）的病理临床缓解（pCR）。方法招募2008年1月—2018年12月期

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Expression and functions of transient receptor potential channels in liver diseases

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Acta Pharmaceutica Sinica B 2023年第2期13卷 445-459页

作者： Wenhui Wang Pengyu Liu Yalin Zhang Li Yan Michael x.zhu Jin Wang Ye Yu Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Medical Genetics and Developmental Biology School of Medicinethe Key Laboratory of Developmental Genes and Human DiseasesMinistry of EducationSoutheast UniversityNanjing 210009China School of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Department of Integrative Biology and Pharmacology McGovern Medical Schoolthe University of Texas Health Science Center at HoustonHoustonTX 77030USA

Liver diseases constitute a major healthcare burden globally,including acute hepatic injury resulted from acetaminophen overdose,ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis,alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD)and hepatocellular carcinoma(HCC).Attainable treatment strategies for most liver diseases remain inadequate,highlighting the importance of substantial pathogenesis.The transient receptor potential(TRP)channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver.It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels.Here,we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults,to inflammation,subsequent fibrosis and hepatoma.We also explore expression levels of TRPs in liver tissues of ALD,NAFLD and HCC patients from Gene Expression Omnibus(GEO)or The Cancer Genome Atlas(TCGA)database and survival analysis estimated by Kaplan-Meier Plotter.At last,we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases.The aim is to provide a better understanding of the implications of TRP channels in liver diseases,contributing to the discovery of novel therapeutic targets and efficient drugs.

关键词： TRP Liver disease Liver injury ALD NAFLD Fibrosis Inflammation HCC

Regulation of lysosomal ion homeostasis by channels and transporters

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Science China(Life Sciences) 2016年第8期59卷 777-791页

作者： Jian xiong Michael x.zhu Department of Integrative Biology and Pharmacology Mc Govern Medical School Program of Cell and Regulatory Biology Graduate School of Biomedical Sciences The University of Texas Health Science Center at Houston

Lysosomes are the major organelles that carry out degradation functions. They integrate and digest materials compartmentalized by endocytosis, phagocytosis or autophagy. In addition to more than 60 hydrolases residing in the lysosomes, there are also ion channels and transporters that mediate the flux or transport of H^+, Ca^(2+), Na^+, K^+, and Cl^- across the lysosomal membranes. Defects in ionic exchange can lead to abnormal lysosome morphology, defective vesicle trafficking, impaired autophagy, and diseases such as neurodegeneration and lysosomal storage disorders. The latter are characterized by incomplete lysosomal digestion and accumulation of toxic materials inside enlarged intracellular vacuoles. In addition to degradation, recent studies have revealed the roles of lysosomes in metabolic pathways through kinases such as mechanistic target of rapamycin(m TOR) and transcriptional regulation through calcium signaling molecules such as transcription factor EB(TFEB) and calcineurin. Owing to the development of new approaches including genetically encoded fluorescence probes and whole endolysosomal patch clamp recording techniques, studies on lysosomal ion channels have made remarkable progress in recent years. In this review, we will focus on the current knowledge of lysosome-resident ion channels and transporters, discuss their roles in maintaining lysosomal function, and evaluate how their dysfunction can result in disease.

关键词： lysosomal storage disease(LSD) ion homeostasis calcium lysosome acidification

A novel TRPC6-dependent mechanism of TGF-β-induced migration and invasion of human hepatocellular carcinoma cells

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Science China(Life Sciences) 2018年第9期61卷 1120-1122页

作者： Yun Tian Michael x.zhu College of Bioscience and Biotechnology Hunan Agricultural University Department of Integrative Biology and Pharmacology McGovern Medical School The University of Texas Health Science Center at Houston

Mechanisms on cancer cell migration and invasion have been major topics of cancer research and anti-cancer therapy development. Among the multiple cell signaling pathways involved in cell migration, those elicited by transforming growth factorβ(TGF-β) have attracted tremendous attention. The TGF-βpolypeptide cytokines include four isoforms:TGF-β1, TGF-β2, TGF-β3, and TGF-β4, which are secreted mainly from cells of white blood cell lineage, such as macrophages, T cells and platelets. However, TGF-βcan also be synthesized and released from fibroblasts and

关键词：癌症治疗房间移植 cytokines TGF-β 制导生长因素血小板

The local structure of binary solutions of diethylamine acetate ionic liquid

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The local structure of binary solutions of diethylamine acet...

The hills and valleys of calcium signaling

第十七届全国化学热力学和热分析学术会议

作者： H.Zhang x.zhu School of Chemistry and Chemical Engineering Qufu Normal University

As an extremely hot topic, Ionic liquids（ILs） have attracted world-wide attentions due to their many outstanding properties, such as negligible vapor pressure, high thermal stability and properties-adjustable. Recently ammonium-based ionic liquids are showing enormous potentials with many advantages compared to imidazolium-based ILs, such as low-cost, easy to prepare, smaller toxicity. Their excellent performances have been revealed in electrochemistry1, catalysis2, wastewater treatment3, and CO2 adsorptions4. However their special behaviors in solutions due to the influence of molecular solvents have seldom been discussed. In this paper, diethylamine acetate ionic liquid（IL） was synthesized using acetic acid and diethylamine. And the acetone/IL and water/IL binary solutions were prepared at different concentrations. Then 1H NMR chemical shifts of every solution were measured. Using the following local composition（LC） model5, the chemical shifts of certain group could be well correlated:σ1,cal=σ01φ11+σ∞1φ21（1） where φ11 and φ21 are local volume fractions of molecules 1 and 2 around the central molecule 1, respectively. σ01 and σ∞1are pure substance and infinitely dilute chemical shifts of a certain proton of molecule 1, respectively. The local molar volume fractions can be defined as following: φ11=x1/（x1+∧21+x2）（2） φ21=∧21x2/（x1+∧21+x2）（3）∧21=v2/v1exp[-（g21-g11）/RT]（4） where g21 and g11 are proportional to the 1-2 and 1-1 interaction energies, respectively, where V1 and V2 are the mole volumes of molecule 1 and 2 which are calculated by division of molecular weight and density（the measured density of IL, water and acetone at 298.15 K are 0.9625 g·cm-3, 0.9970 g·cm-3 and 0.7845 g·cm-3 respectively using the pycnometer method）. With the help of interaction energies（g21-g11）, the local mole fraction of IL x11 and solvents x21 could be calculated using the eq.（5）-（6）: x21/x11=x2exp（-g21/RT）/x1exp（-g11/RT）=x2/x1exp[-（g21-g11）/RT]（5）x11+x21=1（6） where x11 and x21 denote the local mole fraction of IL and solvent around

关键词： ammonium-based ILs binary solutions 1H NMR chemical shifts local composition

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Science China(Life Sciences) 2016年第8期59卷 743-748页

作者： Michael x.zhu Biguang Tuo Jenny J.Yang Department of Integrative Biology and Pharmacology Mc Govern Medical School The University of Texas Health Science Center at Houston Department of Gastroenterology Affiliated Hospital Zunyi Medical College and Digestive Disease Institute of Guizhou Province Department of Chemistry Center for Diagnostics and Therapeutics Georgia State University

Calcium is important for life.Studies over the last several decades have gradually revealed the critical involvement of calcium,especially its ionic form(Ca^(2+)),in every aspect of life forms on earth.Among them,a great deal of work has been done to illustrate how Ca2+levels are regulated in the cytoplasm and how many of the cytosolic enzymes and sig-

关键词： Ca The hills and valleys of calcium signaling

基于乳腺x线检查深度学习模型预测间隔性和筛查检出的乳腺癌:6369名女性的对照研究

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国际医学放射学杂志 2022年第1期 109-109页

作者： x.zhu T.K.Wolfgruber L.Leong M.Jensen C.Scott S.Winham 白雪

摘要深度学习（DL）模型区分女性筛检出的乳腺癌及间隔性乳腺癌（乳腺x线检查未发现）风险的能力文献中未见报道。目的研究DL模型在评估有无临床危险因素的间隔性

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索拉非尼联合肝动脉灌注化疗治疗肝细胞癌伴门静脉癌栓与单纯索拉非尼治疗比较：一项随机试验

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国际医学放射学杂志 2022年第4期 480-480页

作者： K.Zheng x.zhu S.Fu G.Cao W.Li L.xu 胡静怡

摘要目的比较索拉非尼联合肝动脉灌注化疗（HAIC）与单独索拉非尼治疗晚期肝细胞癌（HCC）伴门静脉癌栓（PVTT）的疗效和安全性。资料与方法这项Ⅱ期试验纳入了

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CD4 + CD25 + REGULATORY T CELL PRODUCTION CAN BE INDUCED IN INFECTION WITH SCHISTOSOMA JAPONICUM IN MURINE MODEL

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CD4 + CD25 + REGULATORY T CELL PRODUCTION CAN BE INDUCED IN ...

Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2x3 receptors

第十九届国际动物学大会

作者： x.P.Cai Y.Wang M.J.Ji x.zhu L.Zhang G.F.Li x.J.Wang Z.S.Zhang H.W.Wu C.Su G.L.Wu Department of Pathogenic Biology Nanjing Medical University Nanjing 210029 China

In recent years, growing evidences have been presented to support the pivotal roles of CD4 + CD25 + regulatory T cells in autoimmunity and transplantation. In some parasitic diseases such as malaria and leishmaniasis,...

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Science Bulletin 2018年第24期63卷 1616-1625页

作者： Bin Li Jin Wang xiaoyang Cheng Yan Liu Yang Yang xiaona Yang Changrun Guod Youya Niu Peng Cao xiangyang Lu Michael x.zhu Yun Tian Ye Yu College of Biosdence and Biotechnology.Hunan Agricultural University Changsha 410128China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical ScienceGuangxi Normal UniversityGuilin 541004China Department of Pharmacology and Chemical Biology Institute of Medical SciencesShanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medicine and Clinical Pharmacy China Pharmaceutical UniversityNanjing 210009China Department of Cell Biology and Genetics Hunan University of MedicineHuaihua 418000China Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese MedicineNanjing 210023China

P2x receptors are a family of extracellular ATP-gated trimeric cation channels that is widely distributed in human tissues. Quite some drug candidates targeting P2x receptors have entered into preclinical or main phases of clinical trials, but many of them failed due to low subtype-selectivity or species differences in pharmacological activities between human and experimental animals. Here, we identified the distinct inhibitory efficacies of NF110, a competitive inhibitor, between the rat(rP2x3) and human(hP2x3) P2x3 receptors. We demonstrated that this difference is determined by two amino acids located in the dorsal fin(DF) domain of P2x3 receptors. As revealed by mutagenesis, metadynamics, and covalent modification, NF110-mediated rP2x3 inhibition may be through a filling in the cavity formed by the DF,left flipper(LF) and lower body(LB) to partially, rather than fully, occupy the ATP-binding pocket.Moreover, substitution of residues located in the DF and/or LF domains of the rP2x2 receptor, a NF110-insensitive subtype, with the equivalent amino acids of rP2x3, bestowed the sensitivity of rP2x2 to NF110. The critical roles of the DF and LF domains in channel gating of P2x and low conservativity in residue sequences of those two domains raise the possibility that small molecules differentially interacting with the residues of the DF and LF domains of different P2x receptors may modulate channel's activity in a subtype-selective manner. However, the possible species-specificity of P2x inhibitors/modulators makes it more complex when interpreting the preclinical data into clinical researches.Nevertheless, our data provide new insights into the subtype-selectivity of competitive inhibitors and their distinct potencies in the human and experimental animals, both of which are extremely important in the drug discovery of P2x receptors.

关键词： P2x receptors Competitive inhibitors NF110 Species-specificity Subtype-selectivity