Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensivel...Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.展开更多
Development of new metal-free heterogeneous catalysts has long been the focus of intense research interest.The integration of multifunctional monomers into the skeletons of porous organic polymers(POPs)provides an eff...Development of new metal-free heterogeneous catalysts has long been the focus of intense research interest.The integration of multifunctional monomers into the skeletons of porous organic polymers(POPs)provides an efficient pathway to achieve this goal.Herein,we rationally designed and successfully prepared a new Troger’s base(TB)-derived POPs by insertion of pillar[5]arene macrocycle as a positively auxiliary group.Combined the both merits of pillar[5]arene macrocycle and TB moiety,the as-prepared polymer was further explored as an effective metal-free heterogeneous catalyst and exhibited promoted catalytic performance in Knoevenagel condensation and CO_(2)conversion.This work provides a new strategy to fabricate metal-free heterogeneous catalysts based on macrocyclic POPs.展开更多
Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they ...Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they also face challenges,including low capacity,unsatisfactory rate performance,and limited cycling stability,which pose the primary obstacles to their practical use.Herein,a pyrenoimidazole-based COF,denoted as PyIm-COF,has been synthesized as a novel electrode material for highperformance SIBs using an efficient synthetic strategy.With extended fully conjugated backbones and readily accessible redox-active sites,PyIm-COF demonstrates remarkable high-rate performance,delivering around 250 m Ah g^(−1)and excellent cycling stability,retaining 97.2%of its capacity even after 2500 cycles at 5 A g^(−1),which is higher than that of most previously reported COF-based SIBs.This work provides valuable insights into the development of nitrogen-rich conjugated COF electrode materials for rechargeable SIBs.展开更多
Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogeno...Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.展开更多
Uridine diphosphate(UDP)-glucuronosyltransferases(UGTs)are enzymes involved in the biotransformation of important endogenous compounds such as steroids,bile acids,and hormones as well as exogenous substances including...Uridine diphosphate(UDP)-glucuronosyltransferases(UGTs)are enzymes involved in the biotransformation of important endogenous compounds such as steroids,bile acids,and hormones as well as exogenous substances including drugs,environmental toxicants,and carcinogens.Here,a novel fluorescent probe BDMP was developed based on boron-dipyrromethene(BODIPY)with high sensitivity for the detection of UGT1A8.The glucuronidation of BDMP not only exhibited a redemission wavelength(lex/lem=500/580 nm),but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration.Based on this perfect biocompatibility and cell permeability,BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines(LoVo and HCT15)in real time.In addition,BDMP could also be used to visualize UGT1A8 in tumor tissues.These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.展开更多
A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholi...A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.展开更多
Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological ...Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.展开更多
Currently,the development of selective fluorescent probes toward targeted enzymes is still a great challenge,due to the existence of numerous isoenzymes that share similar catalytic capacity.Herein,a double-filtering ...Currently,the development of selective fluorescent probes toward targeted enzymes is still a great challenge,due to the existence of numerous isoenzymes that share similar catalytic capacity.Herein,a double-filtering strategy was established to effectively develop isoenzyme-specific fluorescent probe(s)for cytochrome P450(CYP)which are key enzymes involving in metabolism of endogenous substances and drugs.In the first-stage of our filtering approach,near-infrared(NIR)fluorophores with alkoxyl group were prepared for the screening of CYP-activated fluorescent substrates using a CYPs-dependent incubation system.In the second stage of our filtering approach,these candidates were further screened using reverse protein-ligand docking to effectively determine CYP isoenzyme-specific probe(s).Using our double-filtering approach,probes S9 and S10 were successfully developed for the real-time and selective detection of CYP2C9 and CYP2J2,respectively,to facilitate high-throughput screening and assessment of CYP2C9-mediated clinical drug interaction risks and CYP2J2-associated disease diagnosis.These observations suggest that our strategy could be used to develop the isoform-specific probes for CYPs.展开更多
Sulfur dioxide and its derivative sulfite widely existed in air,water as the environment pollutant.Sulfite is also commonly used as preservative and additive in fresh fruits,vegetables,wines and pharmaceutical materia...Sulfur dioxide and its derivative sulfite widely existed in air,water as the environment pollutant.Sulfite is also commonly used as preservative and additive in fresh fruits,vegetables,wines and pharmaceutical materials.Due to sulfite is closely related with human diseases,it is very urgent for the sensitive and rapid quantification of sulfite in various samples.In our study,a turn-on near infrared(NIR)fluorescent probe(MDQ)was developed for sulfite detection based on a Michael addition reaction,with high sensitivity(LOD 4.16 nmol/L),selectivity and fast response time(400 s).Using MDQ,a quantify method for sulfite in traditional Chinese medicines(TCMs)was developed with the advantages of high precision,accuracy and convenient operation.Furthermore,according to the photophysical property of MDQ,a portable fluorescence detector is designed to quantify sulfite for TCMs and surface water in Dalian city of China.Therefore,the developed fluorescent probe MDQ and portable fluorescent detector as a rapid inspection instrument were successfully used to real-time monitor the sulfite in various complex samples.展开更多
Carbazole-based conjugated microporous polymers(CMPs)as a new type of advanced porous material have created tremendous research curiosities in the area of photocatalysis.Besides,introducing boron-containing dyes into ...Carbazole-based conjugated microporous polymers(CMPs)as a new type of advanced porous material have created tremendous research curiosities in the area of photocatalysis.Besides,introducing boron-containing dyes into the CMPs framework was rare but will be rather promising due to their unique properties,including strong electron-accepting capability,efficient catalytic behaviour,significant absorption coefficient and high quantum.Herein,we rationally designed and prepared two new CMPs,i.e.Cz-BF_(2)-CMP and Cz-BPh2-CMP with the combination of carbazole and boron-containing dye as electron donor and acceptor motifs,respectively.Due to the efficient D-A effect between carbazole and boron-dye which not only accelerated the interfacial charge transfer efficiency but also improved the separation capability of photogenerated electron-hole pairs,both CMPs exhibited excellent photocatalytic performances in organic transformations such as green synthesis of benzimidazole in aqueous solution and aerobic oxidation of thioether in EtOH.展开更多
基金the National Natural Science Foundation of China(Nos.81930112 and 82225048)Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University for support(No.2021YB07)Research on National Reference Material and Product Development of Natural Products(No.SG030801,Beijing Polytechnic)。
文摘Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.
基金the National Natural Science Foundation of China(No.U1808210)the Natural Science Foundation of Liaoning province(No.2019-MS-046).
文摘Development of new metal-free heterogeneous catalysts has long been the focus of intense research interest.The integration of multifunctional monomers into the skeletons of porous organic polymers(POPs)provides an efficient pathway to achieve this goal.Herein,we rationally designed and successfully prepared a new Troger’s base(TB)-derived POPs by insertion of pillar[5]arene macrocycle as a positively auxiliary group.Combined the both merits of pillar[5]arene macrocycle and TB moiety,the as-prepared polymer was further explored as an effective metal-free heterogeneous catalyst and exhibited promoted catalytic performance in Knoevenagel condensation and CO_(2)conversion.This work provides a new strategy to fabricate metal-free heterogeneous catalysts based on macrocyclic POPs.
基金the Natural Science Foundation of Liaoning province(grant no.2019-MS-046)W.Zhang thanks the University of Colorado Boulder for financial support of this work+1 种基金W.Huang acknowledges the support from the National Natural Science Foundation of China(grant no.21875206)The authors acknowledge the assistance of the Dalian University of Technology Instrumental Analysis Center.
文摘Covalent organic frameworks(COFs)have garnered increasing attention as promising electrode materials for sodium-ion batteries(SIBs)due to their ordered backbones,uniform pore sizes,and high surface areas.However,they also face challenges,including low capacity,unsatisfactory rate performance,and limited cycling stability,which pose the primary obstacles to their practical use.Herein,a pyrenoimidazole-based COF,denoted as PyIm-COF,has been synthesized as a novel electrode material for highperformance SIBs using an efficient synthetic strategy.With extended fully conjugated backbones and readily accessible redox-active sites,PyIm-COF demonstrates remarkable high-rate performance,delivering around 250 m Ah g^(−1)and excellent cycling stability,retaining 97.2%of its capacity even after 2500 cycles at 5 A g^(−1),which is higher than that of most previously reported COF-based SIBs.This work provides valuable insights into the development of nitrogen-rich conjugated COF electrode materials for rechargeable SIBs.
基金supported by the National Natural Science Foundation of China(Nos. 21572029, 31600641,81703604, 81773687, 81672961 and 81573501)the National Key Research and Development Program of China (Nos. 2017YFC1700200 and 2017YFC1702000)+2 种基金Program of Shanghai Academic/Technology Research Leader(No. 18XD1403600)Shuguang Program (No. 18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission and the Innovative Entrepreneurship Program of High-level Talents in Dalian (Nos. 2016RQ025 and 2017RQ121)
文摘Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.
基金the Natural Science Foundation of Liaoning Province 2020-MS-252the National Key R&D Program of China(Grant No.2018YFC1603001).
文摘Uridine diphosphate(UDP)-glucuronosyltransferases(UGTs)are enzymes involved in the biotransformation of important endogenous compounds such as steroids,bile acids,and hormones as well as exogenous substances including drugs,environmental toxicants,and carcinogens.Here,a novel fluorescent probe BDMP was developed based on boron-dipyrromethene(BODIPY)with high sensitivity for the detection of UGT1A8.The glucuronidation of BDMP not only exhibited a redemission wavelength(lex/lem=500/580 nm),but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration.Based on this perfect biocompatibility and cell permeability,BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines(LoVo and HCT15)in real time.In addition,BDMP could also be used to visualize UGT1A8 in tumor tissues.These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.
基金supported financially by National Key R&D Program of China (No. 2018YFC1603001)
文摘A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.
基金financially supported by National Natural Science Foundation of China(Nos.81930112 and 82004211)State Key Laboratory of Fine Chemicals KF1912,Distinguished professor of Liaoning Province,Dalian Science and Technology Leading Talents Project(2019RD15,China)the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University(2021YB07)。
文摘Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.
基金The authors thank the National Natural Science Foundation of China(81930112,82174228 and 82004211)National Key R&D program of China(2018YFC1705900)+3 种基金Distinguished Professor of Liaoning Province(XLYC2002008,China)“1+X”program for Clinical Competency enhancement-Interdisciplinary Innovation Project of Second Hospital of Dalian Medical University,Dalian Science and Technology Leading Talents Project(2019RD15,China)High-level Talents of Dalian(2020RQ066 and 2020RQ076,China)the Open Research Fund of the School of Chemistry and Chemical Engineering,and Henan Normal University for support(2020ZD01 and 2021YB07,China)for financial support.T.D.J.wishes to thank the Royal Society for a Wolfson Research Merit Award.
文摘Currently,the development of selective fluorescent probes toward targeted enzymes is still a great challenge,due to the existence of numerous isoenzymes that share similar catalytic capacity.Herein,a double-filtering strategy was established to effectively develop isoenzyme-specific fluorescent probe(s)for cytochrome P450(CYP)which are key enzymes involving in metabolism of endogenous substances and drugs.In the first-stage of our filtering approach,near-infrared(NIR)fluorophores with alkoxyl group were prepared for the screening of CYP-activated fluorescent substrates using a CYPs-dependent incubation system.In the second stage of our filtering approach,these candidates were further screened using reverse protein-ligand docking to effectively determine CYP isoenzyme-specific probe(s).Using our double-filtering approach,probes S9 and S10 were successfully developed for the real-time and selective detection of CYP2C9 and CYP2J2,respectively,to facilitate high-throughput screening and assessment of CYP2C9-mediated clinical drug interaction risks and CYP2J2-associated disease diagnosis.These observations suggest that our strategy could be used to develop the isoform-specific probes for CYPs.
基金supported financially by Distinguished Professor Program of Liaoning Province(No.XLYC2002008)Dalian Science and Technology Leading Talents Project(Nos.2019RD15,2020RJ09 and 2020RQ076)+2 种基金Liaoning Provincial Natural Science Foundation(No.20180550761)Liaoning Revitalization Talents Program(No.XLYC1907017)the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University(No.2021YB07).
文摘Sulfur dioxide and its derivative sulfite widely existed in air,water as the environment pollutant.Sulfite is also commonly used as preservative and additive in fresh fruits,vegetables,wines and pharmaceutical materials.Due to sulfite is closely related with human diseases,it is very urgent for the sensitive and rapid quantification of sulfite in various samples.In our study,a turn-on near infrared(NIR)fluorescent probe(MDQ)was developed for sulfite detection based on a Michael addition reaction,with high sensitivity(LOD 4.16 nmol/L),selectivity and fast response time(400 s).Using MDQ,a quantify method for sulfite in traditional Chinese medicines(TCMs)was developed with the advantages of high precision,accuracy and convenient operation.Furthermore,according to the photophysical property of MDQ,a portable fluorescence detector is designed to quantify sulfite for TCMs and surface water in Dalian city of China.Therefore,the developed fluorescent probe MDQ and portable fluorescent detector as a rapid inspection instrument were successfully used to real-time monitor the sulfite in various complex samples.
基金We are grateful for financial support from the National Natural Science Foundation of China(No.U1808210)the Natural Science Foundation of Liaoning Province(No.2019-MS-046)the Open Sharing Fund for the Large-scale Instruments and Equipment of Dalian University of Technology(Nos.DUTKFJJ2021086 and DUTKFJJ2021122).
文摘Carbazole-based conjugated microporous polymers(CMPs)as a new type of advanced porous material have created tremendous research curiosities in the area of photocatalysis.Besides,introducing boron-containing dyes into the CMPs framework was rare but will be rather promising due to their unique properties,including strong electron-accepting capability,efficient catalytic behaviour,significant absorption coefficient and high quantum.Herein,we rationally designed and prepared two new CMPs,i.e.Cz-BF_(2)-CMP and Cz-BPh2-CMP with the combination of carbazole and boron-containing dye as electron donor and acceptor motifs,respectively.Due to the efficient D-A effect between carbazole and boron-dye which not only accelerated the interfacial charge transfer efficiency but also improved the separation capability of photogenerated electron-hole pairs,both CMPs exhibited excellent photocatalytic performances in organic transformations such as green synthesis of benzimidazole in aqueous solution and aerobic oxidation of thioether in EtOH.
