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Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2056-2070页

作者： Hongjuan Zhang Ying chen Yu Zhang Luyao Qiao Xiangyin Chi Yanxing Han Yuan Lin shuyi Si Jiandong Jiang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Tuberculosis(TB)is one of the deadly diseases caused by Mycobacterium tuberculosis(Mtb),which presents a significant public health *** of TB relies on the combination of several anti-TB drugs to create shorter and safer ***,new anti-TB agents working by different mechanisms are urgently ***,a tubulin-like protein with GTPase activity,forms a dynamic Z-ring in cell *** of FtsZ inhibitors are designed to inhibit GTPase *** Mtb,the function of Z-ring is modulated by SepF,a FtsZ binding *** FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of ***,we established a yeast twohybrid based screening system to identify inhibitors of FtsZ/SepF interaction in *** this system,we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and ***,we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down,fluorescence polarization(FP),surface plasmon resonance(SPR)and CRISPRi knockdown ***,T0349 can inhibit bacterial cell division by inducing filamentation and abnormal *** data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

关键词： Anti-Mycobacterium tuberculosis FtsZ SepF Bacterial division Yeast two-hybrid CRISPRi Protein—protein interaction Inhibitor

Flotation performance of a novel Gemini collector for kaolinite at low temperature

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International Journal of Mining Science and Technology 2021年第6期31卷 1145-1152页

作者： Shiyong Zhang Zhiqiang Huang Hongling Wang Rukuan Liu chen cheng shuyi Shuai Yajing Hu Zhiqun Guo Xinyang Yu Guichun He Weng Fu School of Resource and Environment Engineering Jiangxi University of Science and TechnologyGanzhou 34100China Guangdong Institute of Resources Comprehensive Utilization Guangzhou 510650China Hunan Academy of Forestry Changsha 410004China School of Chemical Engineering The University of QueenslandBrisbane 4072Australia

How to sustainably produce bauxite by effective reverse froth flotation of kaolinite at low temperature is an urgent problem to be solved in the field of mineral *** this work,a novel amino-based Gemini surfactant butadiyl-1,4-bis(dimethyl dodecylammonium bromide)(BBDB) was prepared and first utilized as a novel collector for kaolinite *** flotation performance for kaolinite was compared with that of the common monomolecular surfactant 1-dodecylamine(DDA) by micro-flotation *** tests results indicated that 95% kaolinite recovery was obtained using 2.0×10^(-4) mol/L BBDB at 25℃ which was half of the dosage when DDA obtained the maximum kaolinite recovery of81%.At extremely low temperature(0℃),3.0×10^(-4) mol/L BBDB could still collect 91% kaolinite,while DDA showed a frustrating *** contact angle tests indicated that BBDB could still significantly improve the hydrophobicity of the kaolinite surface(contact angle 71.7°) than DDA(contact angle only25.8°) at 0℃.The Krafft point comparison tests indicated that BBDB had a much lower Krafft point(below0℃) than *** transform infrared spectroscopy(FTIR)-spectrum analysis and zeta potential measurements showed that BBDB was physically adsorbed on the surface of kaolinite through electrostatic interaction.

关键词： Kaolinite Bauxite Gemini surfactant Flotation collector Low temperature

CPTA treatment reveals potential transcription factors associated with carotenoid metabolism in flowers of Osmanthus fragrans

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Horticultural Plant Journal 2021年第5期7卷 479-487页

作者： Wan Xi Yanhong He Linlin Zhu Shiyang Hu shuyi Xiong Yi Zhang Jingjing Zou Hongguo chen Caiyun Wang Riru Zheng Key Laboratory of Horticultural Plant Biology Ministry of EducationCollege of Horticulture and Forestry SciencesHuazhong Agricultural UniversityWuhan 430070China Key Laboratory of Urban Agriculture in Central China Ministry of Agriculture and Rural AffairsWuhan 430070China Hubei Engineering Research Center for Fragrant Plants Hubei University of Science and TechnologyXianningHubei 430070China

Osmanthus fragrans is one of the top ten traditional flowers in *** is divided into three different groups according to its color.α-Carotene and β-carotene are the main determinants to distinguish the color differences between three ***,the dominant genes and transcription factors involved in carotenoid metabolism remain *** treatment(0.7mmol·L−1)remarkably promoted lycopene,α-carotene and β-carotene contents in *** sequencing analysis revealed that CPTA treatment could trigger chain reactions in carotenoid metabolism pathway *** up-regulated and 10 down-regulated transcription factors which have close association with carotenoid variation were significantly induced by CPTA *** up-regulated TFs such as MYB43,MYB123,HSF,were further subjected to transcript expression determination in different cultivars with drastic *** them,transcript expression of four up-regulated TFs coincided with the carotenoid accumulation in different *** selected up-regulated OfMYB43 to verify its function,which is related to stress tolerance and transcriptional *** overexpression of OfMYB43 in *** flowers showed that it could remarkably promote the expression of PDS,ZISO,LCYE and CCD4,leading to increased accumulation of β-branch ***43 was a potential positive regulator of carotenoid biosynthesis in *** *** study provides insight into the molecular mechanism of carotenoid metabolism in ***.

关键词： Osmanthus fragrans CPTA Carotenoid Transcriptome sequencing Transcription factor OfMYB43

Innovative strategies for photodynamic therapy against hypoxic tumor

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Asian Journal of Pharmaceutical Sciences 2023年第1期18卷 44-71页

作者： Xiaotong Li Lei chen Miaoting Huang Shaoting Zeng Jiayi Zheng shuyi Peng Yuqing Wang Hong cheng Shiying Li Department of Anesthesiology the Second Clinical School of Guangzhou Medical UniversityGuangzhou 510182China Department of Anesthesiology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology the NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China Biomaterials Research Center School of Biomedical EngineeringSouthern Medical UniversityGuangzhou 510515China

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor *** which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor *** worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of *** enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to ***,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) ***,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of *** addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia *** this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic ***,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

关键词： Photodynamic therapy Hypoxia Tumor Nanomaterials

Rongchang and Xifeng capsules suppress pentylenetetrazole-induced seizures and change rest/wake behavior in zebrafish larvae

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Journal of Traditional Chinese Medicine 2019年第6期39卷 875-884页

作者： Zhang Shuhui Xu Jia Wang Chao Feng Daofu Dai Liangti Kuang Xiangyu Zhu shuyi Fang Yongchun chen Dongyan He Xianghui Feng Xizeng State Key Laboratory of Medicinal Chemical Biology The Key Laboratory of Bioactive MaterialsMinistry of Education/College of Life ScienceNankai UniversityTianjin 300071China Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation Department of Histology and EmbryologySchool of MedicineNankai UniversityTianjin 300071China The Institute of Robotics and Automatic Information Systems Tianjin Key Laboratory of Intelligent RoboticsNankai UniversityTianjin 300071China Department of General Surgery Tianjin Medical University General HospitalTianjin300052China

OBJECTIVE:To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazoleinduced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their ***:We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects.c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the ***/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng ***:Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole(PTZ)-induced seizures were ***(500μg/m L)and Xifeng(200μg/m L)rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae,which indicated antiepileptic *** rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the *** on correlation between the actions of the two capsules and known compounds,we predicted that they might change rest/wake behaviors by affecting serotonin,GABAergic and histamine signaling ***:The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was *** study provides insight into the capsules'effect on epilepsy.

关键词： Zebrafish Larva Anticonvulsants Rongchang capsule Xifeng capsule Rest/wake behavior

Do wearing masks and preservatives have a combined effect on skin health?

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Eco-Environment & Health 2024年第1期3卷 107-115页

作者： Yu Liu Leijian chen shuyi Zhang Xiaoxiao Wang Yuanyuan Song Hongwen Sun Zongwei Cai Lei Wang MOE Key Laboratory of Pollution Processes and Environmental Criteria College of Environmental Science and EngineeringNankai UniversityTianjin 300350China State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China

Chemical exposure and local hypoxia caused by mask-wearing may result in skin physiology *** effects of methylparaben(MeP),a commonly used preservative in personal care products,and hypoxia on skin health were investigated by HaCaT cell and ICR mouse *** exposure resulted in lipid peroxidation and interfered with cellular glutathione metabolism,while hypoxia treatment disturbed phenylalanine,tyrosine,and tryptophan biosynthesis pathways and energy metabolism to respond to oxidative stress.A hypoxic environment increased the perturbation of MeP on the purine metabolism in HaCaT cells,resulting in increased expression of proinflammatory *** synergistic effects were further validated in a mouse model with MeP dermal exposure and“mask-wearing”***,PPARG,and MMP2 were identified as possible key gene targets associated with skin health risks posed by MeP and *** toxicity analysis suggested a synergistic effect,indicating the risk of skin inflammation and skin barrier aging.

关键词： MeP Hypoxia Synergistic effect Skin metabolomics Network toxicology

Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3508-3526页

作者： shuyi Wang Jun Tao Huaguo chen Machender R.Kandadi Mingming Sun Haixia Xu Gary D.Lopaschuk Yan Lu Junmeng Zheng Hu Peng Jun Ren Department of Emergency Shanghai Tenth People's HospitalSchool of Medicine Tongji UniversityShanghai 200072China Shanghai University School of Medicine Shanghai 200044China University of Wyoming College of Health Sciences LaramieWY 82071USA Department of Cardiovascular Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510000China Medprime Health Services LLC ParisTX 75460USA Department of Cardiology Shanghai Institute of Cardiovascular DiseasesZhongshan Hospital Fudan UniversityShanghai 200032China Department of Cardiology Affiliated Hospital of Nantong UniversityNantong 226001China Cardiovascular Research Centre University of AlbertaEdmontonAlberta T6G 2S2Canada Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationDepartment of Endocrinology and MetabolismZhongshan Hospital Fudan UniversityShanghai 200032China Department of Laboratory Medicine and Pathology University of WashingtonSeattleWA 98195USA

Given the opposing effects of Akt and AMP-activated protein kinase(AMPK)on metabolic homeostasis,this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic ***2–Ampkα2 double knockout(DKO)mice were placed on high fat diet for 5 *** metabolism,energy homeostasis,cardiac function,lipid accumulation,and hepatic steatosis were *** mice were lean without anthropometric *** fat intake led to adiposity and decreased respiratory exchange ratio(RER)in wild-type(WT)mice,which were ablated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** fat intake increased blood and hepatic triglycerides and cholesterol,promoted hepatic steatosis and injury in WT *** effects were eliminated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** diet promoted fat accumulation,and enlarged adipocyte size,the effect was negated in DKO *** intake elevated fatty acid synthase(FAS),carbohydrate-responsive element-binding protein(CHREBP),sterol regulatory element-binding protein 1(SREBP1),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),peroxisome proliferator-activated receptor-α(PPARα),PPARγ,stearoyl-CoA desaturase 1(SCD-1),phosphoenolpyruvate carboxykinase(PEPCK),glucose 6-phosphatase(G6Pase),and diglyceride O-acyltransferase 1(DGAT1),the effect was absent in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** diet dampened mitophagy,promoted inflammation and phosphorylation of forkhead box protein O1(FoxO1)and AMPKα1(Ser^(485)),the effects were eradicated by *** of Parkin effectively nullified DKO-induced metabolic benefits against high fat *** samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B(LC3B),Pink1,Parkin,as well as enhanced phosphorylation of Akt,AMPK(Ser^(485)),and FoxO1,which were consolidated by RNA sequencing(RNAseq)and mass spectrometry analyses from rodent and human *** data suggest that concurrent de

关键词： Akt2 AMPK Parkin High fat intake Obesity Steatosis Mitophagy FoxO1

Organometallic perovskite single crystals grown on lattice-matched substrate for photodetection

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Nano Materials Science 2020年第3期2卷 292-296页

作者： Xin Wang Yuwei Li Yubing Xu Yuzhu Pan Yao Wua Guanwen Li Wei Zhang shuyi Ding Jing chen Wei Lei Dewei Zhao Joint International Research Laboratory of Information Display and Visualization School of Electronic Science and EngineeringSoutheast UniversityNanjing210096China Shenzhen China Star Optoelectronics Semiconductor Display Technology Co.Ltd. ShenZhen518132China School of Information Engineering Nanjing Normal University Taizhou CollegeTaizhouChina Department of Physics and Astronomy and Wright Center for Photovoltaics Innovation and Commercialization The University of ToledoToledoOH43606United States

In this work,we demonstrate that an organometallic perovskite(OP)single crystal for effective photodetection can be grown on a gold(Au)-decorated substrate using liquid phase *** covered gold could both control the shape of the epitaxial layer and act as its *** MAPbCl3 single crystal and an MAPbBr1.5Cl1.5 single crystal were used as the substrate and the epitaxial layer,*** device,with an Au-perovskite-Au structure,can be fully *** to the high-quality epitaxial layer,the maximum external quantum efficiency(EQE)value is over 60%under the voltage of20 *** addition,the response speed can reach 200 and 500 ns(ns)rise and fall,*** work provides an effective and promising method to fabricate efficient perovskite-based photodetectors.

关键词： Perovskite single crystals Liquid phase epitaxy Ultraviolet detection

Robust Anti⁃swing Control for Unmanned Helicopter Slung⁃Load System with Prescribed Performance

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Transactions of Nanjing University of Aeronautics and Astronautics 2021年第2期38卷 193-205页

作者： SHAO shuyi LIU Nan LI Chunru chen Mou College of Automation Engineering Nanjing University of Aeronautics and AstronauticsNanjing 211106P.R.China College of Aerospace Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210016P.R.China

A robust anti-swing control method based on the error transformation function is proposed,and the problem is handled for the unmanned helicopter slung-load system(HSLS)deviating from the equilibrium state due to the disturbances in the lifting ***,the nonlinear model of unmanned HSLS is ***,the errors of swing angles are constructed by using the two ideal swing angle values and the actual swing angle values for the unmanned HSLS under flat flight,and the error transformation functions are investigated to guarantee that the errors of swing angles satisfy the prescribed ***,the nonlinear disturbance observers are introduced to estimate the bounded disturbances,and the robust controllers of the unmanned HSLS,the velocity and the attitude subsystems are designed based on the prescribed performance method,the output of disturbance observer and the sliding mode backstepping strategy,***,the Lyapunov function is developed to prove the stability of the closed-loop ***,the simulation studies are shown to demonstrate the effectiveness of the control strategy.

关键词： unmanned helicopter slung-load system prescribed performance anti-swing control disturbance observer sliding mode controller