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Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium(KATP)

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National Science Review 2021年第6期8卷 34-45页

作者： Zhirong Zhu Qi Wang hongze liao Ming Liu Zhenxing Liu Youheng Zhang Wei-Hong Zhu Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine ChemicalsJoint International Research Laboratory of Precision Chemistry and Molecular EngineeringFeringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Chemistry and Molecular EngineeringEast China University of Science and Technology Research Center for Marine Drugs State Key Laboratory of Oncogene and Related GenesDepartment of PharmacyRen Ji HospitalSchool of MedicineShanghai Jiao Tong University

The current aggregation-induced emission luminogens(AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO3-ER based on the AIE building block of quinoline-malononitrile(QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate(ATP)-sensitive potassium(KATP) on the endoplasmic reticulum(ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens’ targetability.

关键词： aggregation-induced emission amphiphilic AIEgens endoplasmic reticulum targeting specificity high-fidelity tracking

Microalbuminuria sensitive near-infrared AIE probe for point-of-care evaluating kidney diseases

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Aggregate 2024年第3期5卷 421-428页

作者： Zhirong Zhu Xiaoyan Chen hongze liao Li Li Haojian Yang Qi Wang Wei-Hong Zhu Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine ChemicalsJoint International Research Laboratory of Precision Chemistry and Molecular EngineeringFeringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina Department of Pathology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Research Center for Marine Drugs Department of PharmacyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Laboratory Medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Urinary microalbumin(mALB)serves as an exceptionally sensitive indicator for the early detection of kidney damage,playing a pivotal role in identifying chronic renal failure and kidney lesions in ***,the currentfluores-cent methodologies for point-of-care(POC)diagnosis of mALB in real urine still exhibit suboptimal ***,the development and synthesis of QM-N2,an albumin-activated near-infrared(NIR)aggregation-induced emission(AIE)fluorescent probe,are *** strategic incorporation and positioning of quaternary ammonium salts within the quinoline-malononitrile(QM)scaffold sig-nificantly influence solubility and luminescence ***,the quaternary ammonium salt-free variant,QM-OH,and the quaternary ammonium salt integrated at the donor function group(DFG)site,QM-N1,display limited solubility in aqueous solutions while demonstrating a distinctfluorescence ***,the incorporation of quaternary ammonium salt at the conformational functional group(CFG)site in QM-N2 imparts superior dispersibility in water and reduces the ***,the integration of a well-defined D-π-A struc-ture within QM-N2 enables itself with near-infrared emission,which is crucial for mitigating interference from autofluorescence present in urine *** inter-action with albumin,QM-N2 forms a tight bond with the IIA site of the subdomain of human serum albumin(HSA),inducing alterations in protein configuration and constraining the intrinsic motion offluorescent *** interaction inducesfluorescence,facilitating the sensitive detection of trace ***,QM-N2 is applied for POC testing of mALB using portable equipment,particularly in the diagnosis of mALB-related diseases,notably chronic renal *** positioning underscores its potential as an ideal candidate for self-health measurement at home or in community hospitals.

关键词： AIE-active probe kidney disease microalbuminuria point-of-care testing

Sinomenine derivatives with embedment of nitrogen-containing heterocycles exhibiting potent TNF-inhibitory activity

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Science China Chemistry 2012年第12期55卷 2537-2547页

作者： WANG Meng MA LiYan LOU YangTong BIAN Chao ZHOU TingTing ZHOU HaiBin liao hongze MA Zhao YIN DongSheng CHEN AiZhong WANG ShaoZhong YANG ZhenYu SUN Bing YAO ZhuJun State Key Laboratory of Coordination Chemistry and Nanjing National Laboratory of Microstructures Institute of Chemical Biology and Drug InnovationSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210093China Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes of BiologicalSciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China

Inhibitory effect on tumor necrosis factor-c~ （TNF-c0 production by sinomenine derivatives with embedment of small drug-like nitrogen hetereocyclic moieties has been studied in this work. Several new sinomenine derivatives having chlorophenyl sub- stituent have been found to exhibit much more potent TNF-a inhibitory activity than natural sinomenine and other derivatives.

关键词： sinomenine druggability heterocycle tumor necrosis factor-m inhibition

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

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Acta Pharmaceutica Sinica B 2024年第1期14卷 207-222页

作者： Hongrui Zhu Yamin Gao Liyun Liu Mengyu Tao Xiao Lin Yijia Cheng Yaoyao Shen Haitao Xue Li Guan Huimin Zhao Li Liu Shuping Wang Fan Yang Yongjun Zhou hongze liao Fan Sun Houwen Lin Research Center for Marine Drugs Department of PharmacyRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Institute of Marine Drugs Guangxi University of Chinese MedicineNanning 530200China State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Professional and Technical Ser-vice Center for Biological Material Drug-ability EvaluationShanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 200437China Institute of Marine Biomedicine Shenzhen PolytechnicShenzhen 518055China

Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin ***,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin ***,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC ***,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

关键词： Colorectal cancer TNKSeUSP25 interaction Multi-drug resistance TNKS overexpression Wnt pathway Apoptosis Neoantimycin analog

PEG-6000模拟干旱胁迫下10种紫花苜蓿萌发期抗旱性比较

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黑龙江畜牧兽医 2023年第7期 88-93,105页

作者：崔红慧孙曼曼廖宏泽张家口学院河北张家口075000 广西民族大学海洋生物资源保护与利用重点实验室南宁530008 广西特色经济林培育与利用重点实验室南宁530002

为了分析10种紫花苜蓿萌发期的抗旱性,试验采用不同浓度(10%、15%、20%、25%、30%)的聚乙二醇-6000(polyethylene glycol-6000, PEG-6000)溶液模拟干旱胁迫,同时以不加PEG-6000的纯化水为对照(CK),每个浓度3个重复,每个重复50粒种子,发... 详细信息

为了分析10种紫花苜蓿萌发期的抗旱性,试验采用不同浓度(10%、15%、20%、25%、30%)的聚乙二醇-6000(polyethylene glycol-6000, PEG-6000)溶液模拟干旱胁迫,同时以不加PEG-6000的纯化水为对照(CK),每个浓度3个重复,每个重复50粒种子,发芽期为10 d,第4天计算发芽势,第10天计算发芽率、发芽指数、活力指数、胚根长和胚芽长,利用隶属函数法分别计算10种紫花苜蓿的发芽势、发芽率、发芽指数、活力指数、胚根长及胚芽长6个指标的隶属函数值,再计算各指标隶属函数值平均值,作为抗旱性综合值。结果表明:不同浓度的PEG-6000胁迫对紫花苜蓿种子的萌发具有不同程度的影响。低浓度(10%、15%)PEG-6000胁迫,对部分紫花苜蓿品种种子的发芽率、发芽势、胚根长和胚芽长具有促进作用;高浓度(20%、25%、30%)PEG-6000胁迫,对紫花苜蓿种子萌发具有抑制作用,6个指标测定结果大致呈下降趋势。采用隶属函数法对10种紫花苜蓿萌发期的抗旱性进行综合评价,其抗旱性强弱为WL363HQ>WL168HQ>可汗>WL440HQ>中兰2号>草原3号>三得利>大富翁>佰苜202>敖汉。说明随着PEG-6000浓度的增加,10种紫花苜蓿萌发期的6个指标在干旱胁迫下存在一定的差异,其中WL363HQ和WL168HQ的抗旱性优于其他品种。

关键词：紫花苜蓿 PEG-6000 干旱胁迫种子萌发隶属函数抗旱性

基于CNKI数据库的我国紫花苜蓿研究热点与趋势分析

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广西林业科学 2022年第6期51卷 866-871页

作者：崔红慧廖宏泽张家口学院河北张家口075000 广西民族大学海洋生物资源保护与利用重点实验室广西南宁530006 广西特色经济林培育与利用重点实验室广西南宁530002

紫花苜蓿(Medicago sativa)为品质优良的牧草。为了解我国紫花苜蓿的研究现状和发展趋势,基于中国知网(China National Knowledge Internet,CNKI)数据库,以紫花苜蓿为关键词,对2002-2021年我国发表的紫花苜蓿文献进行检索筛选,对检索出... 详细信息

紫花苜蓿(Medicago sativa)为品质优良的牧草。为了解我国紫花苜蓿的研究现状和发展趋势,基于中国知网(China National Knowledge Internet,CNKI)数据库,以紫花苜蓿为关键词,对2002-2021年我国发表的紫花苜蓿文献进行检索筛选,对检索出的论文分别从年度发文量、研究机构和高被引文章进行计量学分析。结果表明,共检索到9363篇相关文献;发文数量稳步上升;研究单位主要集中在农业类高校;研究热点包括紫花苜蓿的品质、产量、耐盐性、抗旱性、抗寒性和秋眠性等方面。

关键词：紫花苜蓿研究热点 CNKI数据库计量学分析

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镉锌复合胁迫下不同品种苜蓿种子萌发特性

草业科学 2023年第10期40卷 2571-2580页

作者：崔红慧郝艳芹李景柱远婷朱昱赵凌鹤廖宏泽张家口学院旅游与环境学院河北张家口075000 广西民族大学海洋与生物技术学院广西南宁530008 广西特色经济林培育与利用重点实验室广西南宁530002

为比较分析镉(Cd)锌(Zn)复合胁迫对不同紫花苜蓿(Medicago sativa)品种种子萌发和幼苗的影响以及各紫花苜蓿品种的耐镉锌性,本研究以紫花苜蓿为研究材料,采用Cd-Zn复合溶液(Cd^(2+)浓度分别为0、5、10、50、100和200mg·L^(-1);除对照Zn... 详细信息

为比较分析镉(Cd)锌(Zn)复合胁迫对不同紫花苜蓿(Medicago sativa)品种种子萌发和幼苗的影响以及各紫花苜蓿品种的耐镉锌性,本研究以紫花苜蓿为研究材料,采用Cd-Zn复合溶液(Cd^(2+)浓度分别为0、5、10、50、100和200mg·L^(-1);除对照Zn^(2+)浓度为0 mg·L^(-1)外,混合液中Zn^(2+)浓度均为50 mg·L^(-1))处理紫花苜蓿种子,并计算发芽势、发芽率、发芽指数、胚根长和胚芽长,最后利用隶属函数法对紫花苜蓿的耐Cd-Zn性进行综合分析。结果表明:Cd-Zn复合胁迫对紫花苜蓿种子的发芽势、发芽率、发芽指数、胚根长和胚芽长5个指标呈不同的影响。随着Cd-Zn复合溶液浓度的增加,‘中草3号’‘巨能2号’和‘大富翁’种子的发芽势、发芽率、发芽指数、胚芽长和胚根长先增大后减小;‘SK3010’‘中兰2号’‘WL363HQ’‘草原3号’‘佰苜202’‘巨能2号’和‘大富翁’种子的胚芽长和胚根长总体呈减小的趋势。Cd^(2+)浓度为200 mg·L^(-1)和Zn^(2+)浓度为50 mg·L^(-1)时对紫花苜蓿种子萌发具有显著的抑制作用。运用隶属函数法综合评价8个紫花苜蓿种子萌发期耐Cd-Zn性强弱为‘草原3号’>‘中草3号’>‘SK3010’>‘佰苜202’>‘WL363HQ’>‘大富翁’>‘中兰2号’>‘巨能2号’。对8个苜蓿品种耐Cd-Zn性进行聚类分析,苜蓿品种的耐Cd-Zn性可以分为强耐Cd-Zn型、中等耐Cd-Zn型和弱耐Cd-Zn型3类。

关键词：紫花苜蓿重金属种子萌发耐Cd-Zn性隶属函数聚类分析

白及炭疽病病原菌的鉴定及其室内防治药剂筛选

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西南大学学报（自然科学版） 2023年第6期45卷 66-75页

作者：侯秀明王晗怡陈婷婷高萌高乞廖宏泽周浩广西民族大学海洋与生物技术学院/广西多糖材料与改性重点实验室南宁530006 广西民族大学海洋生物资源保护与利用重点实验室南宁530006

在广西桂林市白及种植基地调查发现了一种炭疽病,造成白及产量下降.为明确白及炭疽病病原菌并寻找适合的杀菌剂,采用组织分离法和单孢纯化法从染病叶片中分离病原真菌,柯赫氏法则验证病原后,运用形态学和分子生物学方法鉴定病原,同时利... 详细信息

在广西桂林市白及种植基地调查发现了一种炭疽病,造成白及产量下降.为明确白及炭疽病病原菌并寻找适合的杀菌剂,采用组织分离法和单孢纯化法从染病叶片中分离病原真菌,柯赫氏法则验证病原后,运用形态学和分子生物学方法鉴定病原,同时利用菌丝生长速率测定法分析了8种杀菌剂对病原菌的抑制效果.结果表明,结合菌落、显微形态特征以及多基因序列联合分析(ITS,ACT,CHS-1,HIS3,GAPDH,TUB2),鉴定病原菌为Colletotrichum orchidophilum,回接健康白及叶片后能引起明显病斑,病菌在马铃薯葡萄糖琼脂培养基上的生长速度为0.43 cm/d,不同浓度杀菌剂对典型菌株BJ103.2菌丝生长的抑制作用不同,其中肟菌戊唑醇的抑制作用最强,半数有效浓度(EC 50)为7.92μg/mL.研究结果为炭疽病的诊断与防治策略提供了科学的依据.

关键词：白及炭疽病多基因序列联合分析药剂筛选

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低温胁迫对不同品种紫花苜蓿种子萌发的影响

黑龙江畜牧兽医 2024年第8期 84-91页

作者：崔红慧李洁茹孙曼曼黄小娟郝艳芹廖宏泽张家口学院旅游与环境学院河北张家口075000 广西民族大学海洋与生物技术学院南宁530008 广西特色经济林培育与利用重点实验室南宁530002

为了比较低温(4℃)胁迫下15种紫花苜蓿种子在萌发期的抗寒性差异并筛选抗寒品种,试验以15种紫花苜蓿为研究材料,低温(4℃)胁迫处理各品种紫花苜蓿种子,并以25℃为对照,每个处理3个重复。培养第10天时,每个处理随机选取15株苗测量胚根长... 详细信息

为了比较低温(4℃)胁迫下15种紫花苜蓿种子在萌发期的抗寒性差异并筛选抗寒品种,试验以15种紫花苜蓿为研究材料,低温(4℃)胁迫处理各品种紫花苜蓿种子,并以25℃为对照,每个处理3个重复。培养第10天时,每个处理随机选取15株苗测量胚根长和胚芽长,重复测量3次,统计发芽势、发芽率、发芽指数、活力指数,利用隶属函数法计算每个紫花苜蓿品种的3对指标(发芽势和发芽率、发芽指数和活力指数、胚根长和胚芽长)的隶属函数值,研究低温处理对紫花苜蓿种子萌发的影响。结果表明:低温胁迫对WL168HQ、WL363HQ、巨能2和斯贝德的发芽势和发芽率有一定的促进作用;对15种紫花苜蓿种子的发芽指数、活力指数、胚芽长和胚根长呈不同程度的抑制作用。15种紫花苜蓿萌发期的抗寒性表现为大富翁>沃苜1号>斯贝德、驯鹿>巨能2>巨能201>WL440HQ>皇冠>SR4030>要塞>佰苜202>可汗>SK3010>WL168HQ>WL363HQ。15种紫花苜蓿分为强抗寒型(大富翁)、中等抗寒型(WL440HQ、驯鹿、巨能201、巨能2、斯贝德、皇冠、要塞和沃苜1号)和弱抗寒型(可汗、SK3010、SR4030、WL168HQ、WL363HQ和佰苜202)。说明本研究中大富翁在种子萌发期的抗寒性优于其他品种。

关键词：紫花苜蓿低温胁迫种子萌发抗寒性隶属函数聚类分析