Fe single-atom catalysts(Fe-SACs)have been extensively studied as a highly efficient electrocatalyst toward the oxygen reduction reaction(ORR).Nonetheless,they suffer from stability issue induced by dissolution of Fe ...Fe single-atom catalysts(Fe-SACs)have been extensively studied as a highly efficient electrocatalyst toward the oxygen reduction reaction(ORR).Nonetheless,they suffer from stability issue induced by dissolution of Fe metal center and the OH^(−)blocking.Herein,a surface molecular engineering strategy is developed by usingβ-cyclodextrins(CDs)as a localized molecular encapsulation.The CD-modified Fe-SAC(Fe-SNC-β-CD)shows obviously improved activity toward the ORR with 0.90 V,4.10 and 4.09 mA cm^(-2)for E_(1/2),J_(0)and Jk0.9,respectively.Meanwhile,the Fe-SNC-β-CD shows the excellent long-term stability against aggressive stress and the poisoning.It is confirmed through electrochemical investigation that modification ofβ-CD can,on one hand,regulate the atomic Fe coordination chemistry through the interaction between the CD and FeN_(x) moiety,while on the other mitigate the strong adsorption of OH^(−)and function as protective barrier against the poisoning molecules leading to enhanced ORR activity and stability for the Fe-SACs.The molecular encapsulation strategy demonstrates the uniqueness of post-pyrolysis surface molecular engineering for the design of single-atom catalyst.展开更多
As a vital negative regulator of Wnt signaling pathway,human Notum(hNotum)plays a crucial regulatory role in the progression of many human diseases.Deciphering the relevance of h Notum to human diseases requires pract...As a vital negative regulator of Wnt signaling pathway,human Notum(hNotum)plays a crucial regulatory role in the progression of many human diseases.Deciphering the relevance of h Notum to human diseases requires practical and reliable tools for visualizing h Notum activity in living systems.Herein,an enzyme-activatable fluorogenic tool(IR-783 octanoate)was rationally engineered for sensing and imaging h Notum activity in living systems by integrating computer-aided molecular design and biochemical assays.IR-783 octanoate showed good optical properties,excellent specificity and high binding-affinity towards h Notum(K_(m)=0.98μmol/L).IR-783 octanoate could be well up-taken into the cancerous cells or tumors that over-expressed organic anion transporting polypeptides(OATPs),and then hydrolyzed by cellular h Notum to release free IR-783 ketone,which created brightly fluorescent signals around 646 nm.Further investigations showed that IR-783 octanoate achieved a good performance for in-situ functional imaging of h Notum in both living cells,cancerous tissues and organs.It was also found that some SW620cells with multipolar spindles could be stained by IR-783 octanoate to emit extremely bright signals,suggesting that this agent could be used as a novel visualizing tool for tracing the cells undergoing abnormal cell mitoses.Collectively,this study devises a highly specific fluorogenic tool for in-situ functional imaging of hNotum in living systems,which offers a practical and reliable tool to dynamically track the changes in h Notum activity under various conditions.展开更多
As an alternative energy,hydrogen can be converted into electrical energy via direct electrochemical conversion in fuel cells.One important drawback of full cells is the sluggish oxygen reduction reaction(ORR)promoted...As an alternative energy,hydrogen can be converted into electrical energy via direct electrochemical conversion in fuel cells.One important drawback of full cells is the sluggish oxygen reduction reaction(ORR)promoted by the high-loading of platinum-group-metal(PGM)electrocatalysts.Fe-N-C family has been received extensive attention because of its low cost,long service life and high oxygen reduction reaction activity in recent years.In order to further enhance the ORR activity,the synthesis method,morphology regulation and catalytic mechanism of the active sites in Fe-N-C catalysts are investigated.This paper reviews the research progress of Fe-N-C from nanoparticles to single atoms.The structure-activity relationship and catalytic mechanism of the catalyst are studied and discussed,which provide a guidance for rational design of the catalyst,so as to promote the more reasonable design of Fe-N-C materials.展开更多
Dual-metal single-atom catalysts(DACs),featuring high atomic utilization efficiency,excellent selectivity,and stability originating from the atomically dispersed nature,have emerged as a new frontier in heterogeneous ...Dual-metal single-atom catalysts(DACs),featuring high atomic utilization efficiency,excellent selectivity,and stability originating from the atomically dispersed nature,have emerged as a new frontier in heterogeneous electrocatalysis due to the synergistic effect between diversified metal active sites in promoting their catalytic activity.In this review,the recent progress and development on the syntheses,characterizations,theoretical uniqueness,and applications for various catalytic reactions and devices(oxygen reduction reaction,oxygen evolution reaction,hydrogen evolution reaction,CO_(2) reduction reaction,N2 reduction reaction,proton exchange membrane fuel cells)are summarized and reviewed.Specifically,the synergistic effect between the two metal centers and electronic structures of catalysts is systematically discussed.Moreover,the future challenges and prospects in developing practical DACs are proposed as a possible direction for further investigation.展开更多
The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-C...The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included:(1) selection of herbal drugs of target based on TCMs knowledge base;(2) chemome profiling of TCMs extract library by LC-MS;(3) cytological profiling of TCMs extract library by high-content cell-based imaging;(4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes;(5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs(Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.展开更多
The aryl hydrocarbon receptor(AhR)plays a crucial role in regulating many physiological processes.Activating the AhReCYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases.Here,a...The aryl hydrocarbon receptor(AhR)plays a crucial role in regulating many physiological processes.Activating the AhReCYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases.Here,a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators,via functional sensing of CYP1A1 activities in live cells.Firstly,a cell-permeable,isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems,which was subsequently used for discovering the efficacious modulators of the AhReCYP1A1 axis.Following screening of a compound library,LAC-7 was identified as an efficacious activator of the AhReCYP1A1 axis,which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines.LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages.Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice,and markedly reduced the levels of multiple inflammatory factors.Collectively,an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems,which strongly facilitated the discovery of efficacious modulators of the AhReCYP1A1 axis as novel antiinflammatory agents.展开更多
基金the National Natural Science Foundation of China(52171199)for the financial support.
文摘Fe single-atom catalysts(Fe-SACs)have been extensively studied as a highly efficient electrocatalyst toward the oxygen reduction reaction(ORR).Nonetheless,they suffer from stability issue induced by dissolution of Fe metal center and the OH^(−)blocking.Herein,a surface molecular engineering strategy is developed by usingβ-cyclodextrins(CDs)as a localized molecular encapsulation.The CD-modified Fe-SAC(Fe-SNC-β-CD)shows obviously improved activity toward the ORR with 0.90 V,4.10 and 4.09 mA cm^(-2)for E_(1/2),J_(0)and Jk0.9,respectively.Meanwhile,the Fe-SNC-β-CD shows the excellent long-term stability against aggressive stress and the poisoning.It is confirmed through electrochemical investigation that modification ofβ-CD can,on one hand,regulate the atomic Fe coordination chemistry through the interaction between the CD and FeN_(x) moiety,while on the other mitigate the strong adsorption of OH^(−)and function as protective barrier against the poisoning molecules leading to enhanced ORR activity and stability for the Fe-SACs.The molecular encapsulation strategy demonstrates the uniqueness of post-pyrolysis surface molecular engineering for the design of single-atom catalyst.
基金supported by National Natural Science Foundation of China(Nos.81922070,81973286,82273897,U23A20516,81801818)Shanghai Municipal Health Commission’s TCM research project(No.2022CX005)+4 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTDD-202004)Three-year Action Plan for Shanghai TCM Development and Inheritance Program(No.ZY(2021-2023)-0401)Department of Science&Technology of Liaoning Province Grant(No.2022JH2/20200056)supported by the State Key Laboratory of Fine ChemicalsDalian University of Technology(No.KF 2202)。
文摘As a vital negative regulator of Wnt signaling pathway,human Notum(hNotum)plays a crucial regulatory role in the progression of many human diseases.Deciphering the relevance of h Notum to human diseases requires practical and reliable tools for visualizing h Notum activity in living systems.Herein,an enzyme-activatable fluorogenic tool(IR-783 octanoate)was rationally engineered for sensing and imaging h Notum activity in living systems by integrating computer-aided molecular design and biochemical assays.IR-783 octanoate showed good optical properties,excellent specificity and high binding-affinity towards h Notum(K_(m)=0.98μmol/L).IR-783 octanoate could be well up-taken into the cancerous cells or tumors that over-expressed organic anion transporting polypeptides(OATPs),and then hydrolyzed by cellular h Notum to release free IR-783 ketone,which created brightly fluorescent signals around 646 nm.Further investigations showed that IR-783 octanoate achieved a good performance for in-situ functional imaging of h Notum in both living cells,cancerous tissues and organs.It was also found that some SW620cells with multipolar spindles could be stained by IR-783 octanoate to emit extremely bright signals,suggesting that this agent could be used as a novel visualizing tool for tracing the cells undergoing abnormal cell mitoses.Collectively,this study devises a highly specific fluorogenic tool for in-situ functional imaging of hNotum in living systems,which offers a practical and reliable tool to dynamically track the changes in h Notum activity under various conditions.
基金W.X.C.acknowledges the National Natural Science Foundation of China(No.21801015)W.X.C.acknowledges the Beijing Institute of Technology Research Fund Program for Young Scholars(No.3090012221909).
文摘As an alternative energy,hydrogen can be converted into electrical energy via direct electrochemical conversion in fuel cells.One important drawback of full cells is the sluggish oxygen reduction reaction(ORR)promoted by the high-loading of platinum-group-metal(PGM)electrocatalysts.Fe-N-C family has been received extensive attention because of its low cost,long service life and high oxygen reduction reaction activity in recent years.In order to further enhance the ORR activity,the synthesis method,morphology regulation and catalytic mechanism of the active sites in Fe-N-C catalysts are investigated.This paper reviews the research progress of Fe-N-C from nanoparticles to single atoms.The structure-activity relationship and catalytic mechanism of the catalyst are studied and discussed,which provide a guidance for rational design of the catalyst,so as to promote the more reasonable design of Fe-N-C materials.
基金National Natural Science Foundation of China,Grant/Award Number:52171199。
文摘Dual-metal single-atom catalysts(DACs),featuring high atomic utilization efficiency,excellent selectivity,and stability originating from the atomically dispersed nature,have emerged as a new frontier in heterogeneous electrocatalysis due to the synergistic effect between diversified metal active sites in promoting their catalytic activity.In this review,the recent progress and development on the syntheses,characterizations,theoretical uniqueness,and applications for various catalytic reactions and devices(oxygen reduction reaction,oxygen evolution reaction,hydrogen evolution reaction,CO_(2) reduction reaction,N2 reduction reaction,proton exchange membrane fuel cells)are summarized and reviewed.Specifically,the synergistic effect between the two metal centers and electronic structures of catalysts is systematically discussed.Moreover,the future challenges and prospects in developing practical DACs are proposed as a possible direction for further investigation.
基金supported by National Key R&D Program of China (2022YFC3500302)National Natural Science Foundation of China (No. 82173963)+1 种基金Key R&D Project of Shandong Province (No. 2021CXGC010507, China)Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory Southwestern Chinese Medicine Resources (No. 2022ZYXK2011015, China)。
文摘The chemical complexity of traditional Chinese medicines(TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform(TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included:(1) selection of herbal drugs of target based on TCMs knowledge base;(2) chemome profiling of TCMs extract library by LC-MS;(3) cytological profiling of TCMs extract library by high-content cell-based imaging;(4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes;(5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs(Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.
基金supported by National Natural Science Foundation of China(Nos.U23A20516,81922070,82273897 and 52303191)National Key Research and Development Program of China(No.2022YFC3502000)+5 种基金Shanghai Science and Technology Innovation Action Plans(21S21900600,China)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02,China)Shanghai Municipal Health Commission’s TCM research project(No.2022CX005,China)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTDD-202004,China)the State Key Laboratory of Fine Chemicals,Dalian University of Technology(No.KF 2202,China)Shanghai University of Traditional Chinese Medicine(No.2021LK023,China).
文摘The aryl hydrocarbon receptor(AhR)plays a crucial role in regulating many physiological processes.Activating the AhReCYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases.Here,a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators,via functional sensing of CYP1A1 activities in live cells.Firstly,a cell-permeable,isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems,which was subsequently used for discovering the efficacious modulators of the AhReCYP1A1 axis.Following screening of a compound library,LAC-7 was identified as an efficacious activator of the AhReCYP1A1 axis,which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines.LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages.Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice,and markedly reduced the levels of multiple inflammatory factors.Collectively,an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems,which strongly facilitated the discovery of efficacious modulators of the AhReCYP1A1 axis as novel antiinflammatory agents.
