The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoid ing their side effects.The main challenge lies in the fast and effective release of the parent drugs at the desired s...The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoid ing their side effects.The main challenge lies in the fast and effective release of the parent drugs at the desired site under specific stimuli.Herein,a cooperative prodrug activation approach with exogenous na tive enzyme and endogenous tumor small molecule biomarkers was developed.Chemically,precursor of methylene blue(MB)and resorufin(RSF)react with horseradish peroxidase(HRP)/hydrogen perox ide(H_(2)O_(2))to quickly and quantitatively release parent dyes and drugs containing amines or carboxylic acids.The application of this approach in mammalian cells was demonstrated with cooperative-activated photodynamic therapy based on a precursor of MB.Compared with free MB,much higher selectivity to ward cancer cells was achieved with this approach as evaluated by the selectivity index(SI).This study provides a new method for fast and effective targeted prodrug activation with no need for antibody mod ification compared with traditional enzyme/prodrug therapy.展开更多
Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of...Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of paramount importance in unraveling the intricacies of pathological mechanisms and advancing the development of disease diagnosis.We herein introduce NFCOP,a state-of-the-art near-infrared(NIR)turn-on fluorescence(FL)probe that has been meticulously designed for highly sensitive,swift and selective imaging of CO.The NFCOP response occurred rapidly with CO,within just 10 s,and the calculated detection limit for CO was determined to be 0.32μmol/L.Further investigations conducted at the cellular level and in vivo demonstrated that NFCOP possesses high sensitivity and selectivity for imaging CO.展开更多
China is one of the most populated and rapidly urbanizing countries worldwide and was among the earliest countries to integrate sustainable development into urban construction.To achieve high-quality development and i...China is one of the most populated and rapidly urbanizing countries worldwide and was among the earliest countries to integrate sustainable development into urban construction.To achieve high-quality development and implement the objectives of“Transforming Our World:The 2030 Agenda for Sustainable Development”,it is crucial to measure and analyze the current level of sustainable development of cities in China.Following the principles of relevance,scientific rigor,universality,reliability,and timeliness,this study constructs an assessment index system for sustainable development,covering seven themes corresponding to the UN Sustainable Development Goal 11.Through detailed calculations,we obtained sustainable development indices for 139 Chinese cities from 2016 to 2022 and analyzed them in three dimensions:distribution dynamics,regional differences,and convergence.The key findings are as follows.First,the level of sustainable development showed improvement,with the average score of included cities increasing by 11.88%from 2016 to 2022.Second,the level of sustainable development was relatively balanced,maintaining low Gini coefficients between 0.05 and 0.06.Third,a weak overallσconvergence feature existed,with increased differentiation in 2021.From a regional perspective,aσconvergence feature was observed in the northeastern but not in the western region.Fourth,both overall absoluteβ-convergence and conditionalβeffects were significant.Regional absoluteβ-convergence and conditionalβ-convergence were also significant.This study contributes to the literature by providing evidence of China’s urban sustainable development,offering policy insights for deepening the implementation of development goals in the future,and providing experiential reference for other developing countries to achieve sustainable development.展开更多
An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfor...An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.展开更多
Conventional anti-Stokes materials-involved deep photodynamic therapy(dPDT)requires much high-intensity irradiance due to low photosensitization efficiency.Herein,we proposed a"booster effector"approach to c...Conventional anti-Stokes materials-involved deep photodynamic therapy(dPDT)requires much high-intensity irradiance due to low photosensitization efficiency.Herein,we proposed a"booster effector"approach to construct highly efficient hot band absorption phototherapeutics for low/biosafety power anti-Stokes light-triggered d PDT.Se,as"booster effector",was introduced into hot band absorption luminophores(HBAs),which not only significantly facilitated intersystem crossing,but also simultaneously enhanced hot band excitation efficiency atν808,as a result successfully enabling excellent photogenerated singlet oxygen capability of HBAs under ultra-low power anti-Stokes excitation(10 mW cm^(-2)in vitro).As far as we know,such low laser power-initiated photosensitization activity has never been reported in the existing anti-Stokes material systems.Importantly,FUC-Se ME can self-assemble into uniform nanospheres in water,greatly boosting cellular uptake(>25-fold larger than FUC-Se),and achieve superior cancer-killing effect(808 nm,10 mW cm^(-2),5 min,the half-maximal inhibitory concentration IC50=1.36μM).After further PEGylation with folate-attached polymer,the resultant FUC-Se ME@FA can effectively enrich at the tumor(signal-to-background ratio,10).Under safety irradiation(330 mW cm^(-2)),FUC-Se ME@FA effectively inhibits deep-seated tumor progression(the tumor growth inhibition rate,84%).This work provides a successful paradigm,possibly being more clinically beneficial than conventional anti-Stokes materials.展开更多
基金the National Natural Science Foundation of China(No.22090011)the Fundamental Research Funds for China Central Universities(No.DUT22LAB608)for financial support。
文摘The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoid ing their side effects.The main challenge lies in the fast and effective release of the parent drugs at the desired site under specific stimuli.Herein,a cooperative prodrug activation approach with exogenous na tive enzyme and endogenous tumor small molecule biomarkers was developed.Chemically,precursor of methylene blue(MB)and resorufin(RSF)react with horseradish peroxidase(HRP)/hydrogen perox ide(H_(2)O_(2))to quickly and quantitatively release parent dyes and drugs containing amines or carboxylic acids.The application of this approach in mammalian cells was demonstrated with cooperative-activated photodynamic therapy based on a precursor of MB.Compared with free MB,much higher selectivity to ward cancer cells was achieved with this approach as evaluated by the selectivity index(SI).This study provides a new method for fast and effective targeted prodrug activation with no need for antibody mod ification compared with traditional enzyme/prodrug therapy.
基金supported by the National Key R&D Programs(No.2021YFA0910001)the Shenzhen Science and Technology Program(Nos.JCYJ20210324115804013,JCYJ2022081810160716,JCYJ20220531093604009)+2 种基金the Specific Research Assistant Funding Program of Chinese Academy of Sciences(No.E35902)the National Natural Science Foundation of China(Nos.22005343,32000982)the Guangdong Provincial Key Area R&D Program(No.2020B1111540001).
文摘Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of paramount importance in unraveling the intricacies of pathological mechanisms and advancing the development of disease diagnosis.We herein introduce NFCOP,a state-of-the-art near-infrared(NIR)turn-on fluorescence(FL)probe that has been meticulously designed for highly sensitive,swift and selective imaging of CO.The NFCOP response occurred rapidly with CO,within just 10 s,and the calculated detection limit for CO was determined to be 0.32μmol/L.Further investigations conducted at the cellular level and in vivo demonstrated that NFCOP possesses high sensitivity and selectivity for imaging CO.
基金supported by the National Key Research and Development Program of China under the theme“Research on urban sustainable development evaluation data fusion management technology” [Grant No.2022YFC3802903].
文摘China is one of the most populated and rapidly urbanizing countries worldwide and was among the earliest countries to integrate sustainable development into urban construction.To achieve high-quality development and implement the objectives of“Transforming Our World:The 2030 Agenda for Sustainable Development”,it is crucial to measure and analyze the current level of sustainable development of cities in China.Following the principles of relevance,scientific rigor,universality,reliability,and timeliness,this study constructs an assessment index system for sustainable development,covering seven themes corresponding to the UN Sustainable Development Goal 11.Through detailed calculations,we obtained sustainable development indices for 139 Chinese cities from 2016 to 2022 and analyzed them in three dimensions:distribution dynamics,regional differences,and convergence.The key findings are as follows.First,the level of sustainable development showed improvement,with the average score of included cities increasing by 11.88%from 2016 to 2022.Second,the level of sustainable development was relatively balanced,maintaining low Gini coefficients between 0.05 and 0.06.Third,a weak overallσconvergence feature existed,with increased differentiation in 2021.From a regional perspective,aσconvergence feature was observed in the northeastern but not in the western region.Fourth,both overall absoluteβ-convergence and conditionalβeffects were significant.Regional absoluteβ-convergence and conditionalβ-convergence were also significant.This study contributes to the literature by providing evidence of China’s urban sustainable development,offering policy insights for deepening the implementation of development goals in the future,and providing experiential reference for other developing countries to achieve sustainable development.
基金supported by the National Natural Science Foundation of China(Grant No.11904239,Y.W.W)the Creative Research Initiative of National Research Foundation of Korea(NRF)(CRI project No.2018R1A3B1052702,J.S.K.)+1 种基金Initial support for the work in Austin came from the National Institutes of Health(CA 68682 to J.L.S.)with subsequent funding from the Robert A.Welch Foundation(F-0018 to J.L.S.)supported by Brain Pool Program through the funded by the Ministry of Science and ICT(Grant No.2020H1D3A1A02080172,M.L.).
文摘An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.
基金supported by the National Natural Science Foundation of China (22090011)the NSFC-Liaoning United Fund (U1908202)。
文摘Conventional anti-Stokes materials-involved deep photodynamic therapy(dPDT)requires much high-intensity irradiance due to low photosensitization efficiency.Herein,we proposed a"booster effector"approach to construct highly efficient hot band absorption phototherapeutics for low/biosafety power anti-Stokes light-triggered d PDT.Se,as"booster effector",was introduced into hot band absorption luminophores(HBAs),which not only significantly facilitated intersystem crossing,but also simultaneously enhanced hot band excitation efficiency atν808,as a result successfully enabling excellent photogenerated singlet oxygen capability of HBAs under ultra-low power anti-Stokes excitation(10 mW cm^(-2)in vitro).As far as we know,such low laser power-initiated photosensitization activity has never been reported in the existing anti-Stokes material systems.Importantly,FUC-Se ME can self-assemble into uniform nanospheres in water,greatly boosting cellular uptake(>25-fold larger than FUC-Se),and achieve superior cancer-killing effect(808 nm,10 mW cm^(-2),5 min,the half-maximal inhibitory concentration IC50=1.36μM).After further PEGylation with folate-attached polymer,the resultant FUC-Se ME@FA can effectively enrich at the tumor(signal-to-background ratio,10).Under safety irradiation(330 mW cm^(-2)),FUC-Se ME@FA effectively inhibits deep-seated tumor progression(the tumor growth inhibition rate,84%).This work provides a successful paradigm,possibly being more clinically beneficial than conventional anti-Stokes materials.