The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the divers...The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the diverse oxidation states and structural tunability of cerium-based metal-organic frameworks(Ce-MOFs),this study employed a competitive coordination strategy utilizing a single carboxylate functional group ligand to construct a series of MOF-808-X(X=-NH_(2),-OH,-Br,and-NO_(2))featuring rich solid-state FLPs for hydrogenation of unsaturated olefins.The-X functional group serves as a microenvironment,enhancing hydrogenation activity by modulating the electronic properties and acid-base characteristics of the FLP sites.The unique redox properties of elemental cerium facilitate the exposure of unsaturated Ce sites(Ce-CUS,Lewis acid(LA))and adjacent Ce-OH(Lewis base(LB))sites within the MOFs,generating abundant solid-state FLP(Ce-CUS/Ce-OH)sites.Experimental results demonstrate that Ce-CUS and Ce-OH interact with theσandσ^(*)orbitals of H-H,and this"push-pull"synergy promotes heterolytic cleavage of the H-H bond.The lone pair electrons of the electron-donating functional group are transmitted through the molecular backbone to the LB site,thereby increasing its strength and reducing the activation energy required for H_(2)heterolytic cleavage.Notably,at 100℃and 2 MPa H_(2),MOF-808-NH_(2)achieves complete conversion of styrene and dicyclopentadiene,significantly outperforming MOF-808.Based on in-situ analysis and density functional theory calculations,a plausible reaction mechanism is proposed.This research enriches the theoretical framework for unsaturated olefin hydrogenation catalysts and contributes to the development of efficient catalytic systems.展开更多
Spinal cord injury （SCI） currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neu...Spinal cord injury （SCI） currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neurological structures damaged, and secondary pathophysiological changes of surviving tissues （Yezierski, 2005; D＇Angelo et al., 2013）.展开更多
Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment...Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment modulation strategy was used to construct the nitrogen-doped hollow carbon sphere encapsulated with Pd(Pd@NHCS-X,X:600–800)nanoreactors for catalytic HDO of biomass-derived vanillin in water.The specific surface microenvironments of Pd@NHCS catalysts including the electronic property of active Pd centers and the surface wettability and porous structure of NHCS supports could be well-controlled by the calcination temperature of catalysts.Intrinsic kinetic evaluations demonstrated that the Pd@NHCS-600 catalyst presented a high turnover frequency of 337.77 h^(–1)and a low apparent activation energy of 18.63 kJ/mol.The excellent catalytic HDO performance was attributed to the unique surface microenvironment of Pd@NHCS catalyst based on structure-performance relationship analysis and DFT calculations.It revealed that pyridinic N species dominated the electronic property regulation of Pd sites through electronic metal-support interaction(EMSI)and produced numerous electron-rich active Pd centers,which not only intensified the dissociation and activation of H2 molecules,but also substantially improved the activation capability of vanillin via the enhanced adsorption of–C=O group.The fine hydrophilicity and abundant porous structure promoted the uniform dispersion of catalyst and ensured the effective access of reactants to catalytic active centers in water.Additionally,the Pd@NHCS-600 catalyst exhibited excellent catalytic stability and broad substrate applicability for the selective aqueous phase HDO of various biomass-derived carbonyl compounds.The proposed surface microenvironment modulation strategy will provide a new consideration for the rational design of high-performance nitrogen-doped carbon-supported metal catalysts for catalytic biomass transformation.展开更多
Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-mo...Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-modified,pH and reactive oxygen species(ROS) sequential-responsive,transformable dualimmunofunction nanoprodrug(MpRTNP).This nanoprodrug encapsulates a transforming growth factor-β(TGF-β) receptor inhibitor SD-208(MpRTNP@SD),to simultaneously alleviate the immunosuppressive effects of TGF-β and tumor-associated macrophages(TAMs).In the weakly acidic tumor microenvironment(TME),the vesicle-micelle morphology transformation occurs owing to the protonation of PC7A,which is accompanied by SD-208 release to inhibit cancer-associated fibroblasts and regulatory T cells.The transformed micelles then target TAMs via mannose receptor-media ted endocytosis.Upon laser irradiation,the thioketal linker is cleaved,releasing conjugated chlorin e6 and generating ROS,which facilitates TAM polarization.The PC7A^(+) segment activates the stimulator of the interferon gene in TAMs with elevated phosphorylation of TANK binding kinase 1 and interferon regulatory factor 3,and type I interferon secretion.MpRTNP@SD displays superior abscopal effects and robust antitumor immunity,as evidenced by increased CD8^(+)/CD4^(+) T cell infiltration and reduced regulatory T cell(Treg) ratios.Mouse survival time is prolonged after combination with the CD47 antibody.This study provides a novel strategy for potent antitumor immunotherapy through pH and ROS sequential-gated spatiotemporal regulation of the TME.展开更多
Photocatalytic CO_(2) reduction to fuels and chemicals has been considered as the promising avenue to realize carbon resource recycling.Covalent organic frameworks(COFs)with pre-designed and tailorable structures are ...Photocatalytic CO_(2) reduction to fuels and chemicals has been considered as the promising avenue to realize carbon resource recycling.Covalent organic frameworks(COFs)with pre-designed and tailorable structures are promising platforms for studying the influence of the microenvironment of catalysts on photocatalytic CO_(2) reduction.Herein,we report three isomorphic COFs(TPHH-COF,TPPD-COF and TPBD-COF)as heterogeneous photocatalysts for CO_(2) reduction and investigate the different levels of conjugation and planarity of COFs effect on the catalytic activity.Photoelectrochemical measurements show that TPPD-COF has a narrower band gap and faster photocurrent response compared to TPHH-COF and TPBD-COF,probably due to the moderate conjugation and planarity.As the photocatalyst,TPPD-COF showed the most outstanding photocatalytic activity with the production rates of 951 and 157μmol·g^(–1)·h^(–1) for CO and H2,respectively.This study illustrates the close relation between microenvironment and photocatalytic activity and provides new insights for designing high-performance.展开更多
Although the potential of microenvironment modulation to enhance electricity-driven CO_(2)reduction has been recognized,substantial challenges remain,particularly in effectively integrating multiple favorable microenv...Although the potential of microenvironment modulation to enhance electricity-driven CO_(2)reduction has been recognized,substantial challenges remain,particularly in effectively integrating multiple favorable microenvironments.Herein,we synthesize CeO_(2)with abundant oxygen vacancies to effectively disperse and anchor small-sized Ag_(2)O nanoparticles(Ag_(2)O/Vo-CeO_(2)).Vo-CeO_(2)acts as a multifunctional modulator,regulating both the reaction microenvironment and the electronic structure of Ag sites,thereby boosting CO_(2)reduction(CO_(2)RR)efficiency.Its strong CO_(2)adsorption and H_(2)O dissociation capabilities facilitate the supply of CO_(2)and active^(*)H species to Ag sites.The electron-withdrawing effect of VoCeO_(2)induces polarization at interfacial Ag sites,generating Agd+species that enhance CO_(2)affinity and activation.Moreover,the electronic coupling between Vo-CeO_(2)and Ag upshifts the d-band center of Ag,optimizing COOH binding and lowering the thermodynamic barrier of the potential-determining step.Ag_(2)O/Vo-CeO_(2)delivers a consistently high Faraday efficiency(FE)of over 99% for CO production even at industrially current density(up to 365 mA cm^(-2)herein),and the operational potential window spans an astonishing 1700 m V(FE>95%).The unprecedented activity,which overcomes the trade-off between the selectivity and current density for CO_(2)RR,outperforms state-of-the-art Ag-based catalysts reported to date.These findings offer a promising pathway to develop robust CO_(2)RR catalysts and present an engineering strategy for constructing the optimal microenvironment of active sites via the synergistic effects of multifunctional modulation.展开更多
The electronic structure of catalytic active sites can be influenced by modulating the coordination bonding of the central single metal atom,but it is difficult to achieve.Herein,we reported the single Zn-atom incorpo...The electronic structure of catalytic active sites can be influenced by modulating the coordination bonding of the central single metal atom,but it is difficult to achieve.Herein,we reported the single Zn-atom incorporated dual doped P,N carbon framework(Zn-N_(4)P/C)for ORR via engineering the surrounding coordination environment of active centers.The Zn-N_(4)P/C catalyst exhibited comparable ORR activity(E_(1/2)=0.86 V)and significantly better ORR stability than that of Pt/C catalyst.It also shows respectable performance in terms of maximum peak power density(249.6 mW cm^(-2)),specific capacitance(779 mAh g^(-1)),and charge-discharge cycling stability for 150 hours in Zn-air battery.The high catalytic activity is attributed to the uniform active sites,tunable electronic/geometric configuration,optimized intrinsic activity,and faster mass transfer during ORR-pathway.Further,theoretical results exposed that the Zn-N_(4)P configuration is more electrochemically active as compared to Zn-N_(4) structure for the oxygen reduction reaction.展开更多
Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a co...Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.展开更多
Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we su...Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we summarize recent advances in design of aggregatable nanoparticles by different stimuli.Internal(pH and enzyme)and external(light,temperature and ROS)stimuli are introduced for a comprehensive description.Moreover,the aggregated nanoparticles usually exhibit photothermal,photoacoustic,PET and enhanced MRI contrast,which is also described.In the end,we discuss about the potential applications and challenges for the future clinical translation.展开更多
Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during c...Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.展开更多
Ruthenium(Ru)has been recognized as a prospective candidate to substitute platinum catalysts in water-splitting-based hydrogen production.However,minimizing the Ru contents,optimizing the water dissociation energy of ...Ruthenium(Ru)has been recognized as a prospective candidate to substitute platinum catalysts in water-splitting-based hydrogen production.However,minimizing the Ru contents,optimizing the water dissociation energy of Ru sites,and enhancing the long-term stability are extremely required,but still face a great challenge.Here,we report on creating tungsten oxide-anchored Ru clusters(Ru-WO_(x))with electron-rich and anti-corrosive microenvironments for efficient and robust seawater splitting.Benefiting from the abundant oxygen vacancy structure in tungsten oxide support,the Ru-WO_(x)exhibits strong Ru-O and Ru-W bonds at the interface.Our study elucidates that the strong Ru-O bonds in Ru-WO_(x)may accelerate the water dissociation kinetics,and the Ru-W bonds will lead to the strong metal-support interaction and electrons transfer fromWto Ru.The optimal Ru-WO_(x)catalysts exhibit a low overpotential of 29 and 218mVat the current density of 10 mA cm^(−2) in alkaline and seawater media,respectively.The outstanding long-term stability discloses that the Ru-WO_(x)catalysts own efficient corrosion resistance in seawater electrolysis.We believe that thiswork offers new insights into the essential roles of electron-rich and anti-corrosivemicroenvironments in Ru-based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.展开更多
Micro/nanomotors(MNMs)have recently emerged as highly promising drug delivery vehicles,showing great potential for biomedical applications.MNMs are typically classified based on their driving mechanisms,and one notabl...Micro/nanomotors(MNMs)have recently emerged as highly promising drug delivery vehicles,showing great potential for biomedical applications.MNMs are typically classified based on their driving mechanisms,and one notable category is gas-driven MNMs,which are self-propelled at the micro/nano scale by gases generated through chemical reactions.These motors can effectively overcome various physiological barriers by utilizing unique physiological actions and driving forces in vivo,gas-driven MNMs offer significant advantages in treating diseases such as tumors and thrombosis.This review first explores the underlying mechanisms of gas-driven MNMs,then discusses their recent applications in overcoming physiological barriers.Finally,it analyses their future prospects and advantages,aiming to inspire further research and accelerate clinical translation in the biomedical field.展开更多
Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly kill...Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.展开更多
Development of heterogeneous molecular photocatalysts for promising light-driven hydrogen evolution reaction(HER)is highly demanding but still challenging.Here,we report the blue-greenish emitting dinuclear metal–org...Development of heterogeneous molecular photocatalysts for promising light-driven hydrogen evolution reaction(HER)is highly demanding but still challenging.Here,we report the blue-greenish emitting dinuclear metal–organic halides as photocatalyst by incorporating site-specific single copper(Ⅰ)atoms that exhibit an efficient carbon-negative H_(2) production.Interestingly,the electronic properties,including the spin and charge density of central Cu(Ⅰ)active site,can be triggered by substituent modulation in metal–organic halides,which greatly affect the exciton dissociation kinetics and thus the HER reactivity.The optimized spin density in these heterogeneous photocatalysts drastically boosts the hydrogen production rate from 1250 to 3130μmol·g^(–1)·h^(–1).Our molecular strategy provides a platform that rationally facilitates electronic modulation of copper(Ⅰ)atoms,tunes the macroscopic optoelectronic properties of photocatalysts and boosts carbon-negative HER activity,extending the boundaries of conventional molecular-based photocatalysts.展开更多
Insurmountable blood-brain barrier(BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease(AD).Poor accumulation of drugs in lesion sites and undesired effectivene...Insurmountable blood-brain barrier(BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease(AD).Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing Aβ deposition or TAU protein need to be resolved urgently.Herein,a nanocleaner is designed with a rapamycin-loaded ROS-responsive PLGA core and surface modification with KLVFF peptide and acid-cleavable DAG peptide [R@(ox-PLGA)-KcD].DAG can enhance the targeting and internalization effect of nanocleaner towards neurovascular unit endothelial cells in AD lesions,and subsequently detach from nanocleaner in response to acidic microenvironment of endosomes to promote the transcytosis of nanocleaner from endothelial cells into brain parenchyma.Then exposed KLVFF can capture and carry Aβ to microglia,attenuating Aβ-induced neurotoxicity.Strikingly,rapamycin,an autophagy promoter,is rapidly liberated from nanocleaner in the high ROS level of lesions to improve Aβ degradation and normalize inflammatory condition.This design altogether accelerates Aβ degradation and alleviates oxidative stress and excessive inflammatory response.Collectively,our finding offers a strategy to target the AD lesions precisely and multi-pronged therapies for clearing the toxic proteins and modulating lesion microenvironment,to achieve efficient AD therapy.展开更多
文摘The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the diverse oxidation states and structural tunability of cerium-based metal-organic frameworks(Ce-MOFs),this study employed a competitive coordination strategy utilizing a single carboxylate functional group ligand to construct a series of MOF-808-X(X=-NH_(2),-OH,-Br,and-NO_(2))featuring rich solid-state FLPs for hydrogenation of unsaturated olefins.The-X functional group serves as a microenvironment,enhancing hydrogenation activity by modulating the electronic properties and acid-base characteristics of the FLP sites.The unique redox properties of elemental cerium facilitate the exposure of unsaturated Ce sites(Ce-CUS,Lewis acid(LA))and adjacent Ce-OH(Lewis base(LB))sites within the MOFs,generating abundant solid-state FLP(Ce-CUS/Ce-OH)sites.Experimental results demonstrate that Ce-CUS and Ce-OH interact with theσandσ^(*)orbitals of H-H,and this"push-pull"synergy promotes heterolytic cleavage of the H-H bond.The lone pair electrons of the electron-donating functional group are transmitted through the molecular backbone to the LB site,thereby increasing its strength and reducing the activation energy required for H_(2)heterolytic cleavage.Notably,at 100℃and 2 MPa H_(2),MOF-808-NH_(2)achieves complete conversion of styrene and dicyclopentadiene,significantly outperforming MOF-808.Based on in-situ analysis and density functional theory calculations,a plausible reaction mechanism is proposed.This research enriches the theoretical framework for unsaturated olefin hydrogenation catalysts and contributes to the development of efficient catalytic systems.
文摘Spinal cord injury （SCI） currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neurological structures damaged, and secondary pathophysiological changes of surviving tissues （Yezierski, 2005; D＇Angelo et al., 2013）.
文摘Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment modulation strategy was used to construct the nitrogen-doped hollow carbon sphere encapsulated with Pd(Pd@NHCS-X,X:600–800)nanoreactors for catalytic HDO of biomass-derived vanillin in water.The specific surface microenvironments of Pd@NHCS catalysts including the electronic property of active Pd centers and the surface wettability and porous structure of NHCS supports could be well-controlled by the calcination temperature of catalysts.Intrinsic kinetic evaluations demonstrated that the Pd@NHCS-600 catalyst presented a high turnover frequency of 337.77 h^(–1)and a low apparent activation energy of 18.63 kJ/mol.The excellent catalytic HDO performance was attributed to the unique surface microenvironment of Pd@NHCS catalyst based on structure-performance relationship analysis and DFT calculations.It revealed that pyridinic N species dominated the electronic property regulation of Pd sites through electronic metal-support interaction(EMSI)and produced numerous electron-rich active Pd centers,which not only intensified the dissociation and activation of H2 molecules,but also substantially improved the activation capability of vanillin via the enhanced adsorption of–C=O group.The fine hydrophilicity and abundant porous structure promoted the uniform dispersion of catalyst and ensured the effective access of reactants to catalytic active centers in water.Additionally,the Pd@NHCS-600 catalyst exhibited excellent catalytic stability and broad substrate applicability for the selective aqueous phase HDO of various biomass-derived carbonyl compounds.The proposed surface microenvironment modulation strategy will provide a new consideration for the rational design of high-performance nitrogen-doped carbon-supported metal catalysts for catalytic biomass transformation.
基金supported by National Natural Science Foundation of China(Nos.52103190 and 52103191)Special Program for Supporting Innovative Youth Talent Teams(No.32320683)+1 种基金Start-up Grant(Nos.32340311 and 35220151) from Zhengzhou UniversityNatural Science Foundation of Henan Province(No.242300420127)。
文摘Nanomaterials that can sequentially respond to internal and external stimuli,functioning as a sequential gate,have great potential for targeting different aspects of antitumor immunity.Herein,we construct a mannose-modified,pH and reactive oxygen species(ROS) sequential-responsive,transformable dualimmunofunction nanoprodrug(MpRTNP).This nanoprodrug encapsulates a transforming growth factor-β(TGF-β) receptor inhibitor SD-208(MpRTNP@SD),to simultaneously alleviate the immunosuppressive effects of TGF-β and tumor-associated macrophages(TAMs).In the weakly acidic tumor microenvironment(TME),the vesicle-micelle morphology transformation occurs owing to the protonation of PC7A,which is accompanied by SD-208 release to inhibit cancer-associated fibroblasts and regulatory T cells.The transformed micelles then target TAMs via mannose receptor-media ted endocytosis.Upon laser irradiation,the thioketal linker is cleaved,releasing conjugated chlorin e6 and generating ROS,which facilitates TAM polarization.The PC7A^(+) segment activates the stimulator of the interferon gene in TAMs with elevated phosphorylation of TANK binding kinase 1 and interferon regulatory factor 3,and type I interferon secretion.MpRTNP@SD displays superior abscopal effects and robust antitumor immunity,as evidenced by increased CD8^(+)/CD4^(+) T cell infiltration and reduced regulatory T cell(Treg) ratios.Mouse survival time is prolonged after combination with the CD47 antibody.This study provides a novel strategy for potent antitumor immunotherapy through pH and ROS sequential-gated spatiotemporal regulation of the TME.
基金supported by the NSFC of China(Nos.21971032,21801038,21771035).
文摘Photocatalytic CO_(2) reduction to fuels and chemicals has been considered as the promising avenue to realize carbon resource recycling.Covalent organic frameworks(COFs)with pre-designed and tailorable structures are promising platforms for studying the influence of the microenvironment of catalysts on photocatalytic CO_(2) reduction.Herein,we report three isomorphic COFs(TPHH-COF,TPPD-COF and TPBD-COF)as heterogeneous photocatalysts for CO_(2) reduction and investigate the different levels of conjugation and planarity of COFs effect on the catalytic activity.Photoelectrochemical measurements show that TPPD-COF has a narrower band gap and faster photocurrent response compared to TPHH-COF and TPBD-COF,probably due to the moderate conjugation and planarity.As the photocatalyst,TPPD-COF showed the most outstanding photocatalytic activity with the production rates of 951 and 157μmol·g^(–1)·h^(–1) for CO and H2,respectively.This study illustrates the close relation between microenvironment and photocatalytic activity and provides new insights for designing high-performance.
基金the support of this research by the Nat ional Natural Science Foundation of China(22179035)the Hei-longjiang Provincial Natural Science Foundation Joint Fund Cultivation Project(PL2024B012)the Fundamental Research Funds for the Universities of Heilongjiang Province(2023-KYYWF-1440)。
文摘Although the potential of microenvironment modulation to enhance electricity-driven CO_(2)reduction has been recognized,substantial challenges remain,particularly in effectively integrating multiple favorable microenvironments.Herein,we synthesize CeO_(2)with abundant oxygen vacancies to effectively disperse and anchor small-sized Ag_(2)O nanoparticles(Ag_(2)O/Vo-CeO_(2)).Vo-CeO_(2)acts as a multifunctional modulator,regulating both the reaction microenvironment and the electronic structure of Ag sites,thereby boosting CO_(2)reduction(CO_(2)RR)efficiency.Its strong CO_(2)adsorption and H_(2)O dissociation capabilities facilitate the supply of CO_(2)and active^(*)H species to Ag sites.The electron-withdrawing effect of VoCeO_(2)induces polarization at interfacial Ag sites,generating Agd+species that enhance CO_(2)affinity and activation.Moreover,the electronic coupling between Vo-CeO_(2)and Ag upshifts the d-band center of Ag,optimizing COOH binding and lowering the thermodynamic barrier of the potential-determining step.Ag_(2)O/Vo-CeO_(2)delivers a consistently high Faraday efficiency(FE)of over 99% for CO production even at industrially current density(up to 365 mA cm^(-2)herein),and the operational potential window spans an astonishing 1700 m V(FE>95%).The unprecedented activity,which overcomes the trade-off between the selectivity and current density for CO_(2)RR,outperforms state-of-the-art Ag-based catalysts reported to date.These findings offer a promising pathway to develop robust CO_(2)RR catalysts and present an engineering strategy for constructing the optimal microenvironment of active sites via the synergistic effects of multifunctional modulation.
文摘The electronic structure of catalytic active sites can be influenced by modulating the coordination bonding of the central single metal atom,but it is difficult to achieve.Herein,we reported the single Zn-atom incorporated dual doped P,N carbon framework(Zn-N_(4)P/C)for ORR via engineering the surrounding coordination environment of active centers.The Zn-N_(4)P/C catalyst exhibited comparable ORR activity(E_(1/2)=0.86 V)and significantly better ORR stability than that of Pt/C catalyst.It also shows respectable performance in terms of maximum peak power density(249.6 mW cm^(-2)),specific capacitance(779 mAh g^(-1)),and charge-discharge cycling stability for 150 hours in Zn-air battery.The high catalytic activity is attributed to the uniform active sites,tunable electronic/geometric configuration,optimized intrinsic activity,and faster mass transfer during ORR-pathway.Further,theoretical results exposed that the Zn-N_(4)P configuration is more electrochemically active as compared to Zn-N_(4) structure for the oxygen reduction reaction.
基金supported by National Natural Science Foundation of China(Project No.81872805,82073771,82104085)Guangdong Basic and Applied Basic Research Foundation(Project No.2020A1515110147,2021A1515011418,2021A1515012025)。
文摘Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.
基金supported by the National Natural Science Foundation of China(No.81961138009)the Young Elite Scientists Sponsorship Program by CAST(No.2017QNR001)+1 种基金the Fundamental Research Funds for the Central Universities,111 Project(No.B18035)RFBR and National Natural Science Foundation of China Collaboration Project(No.19-58-55001)。
文摘Recent days,aggregatable nanoparticles,which can specifically respond to certain stimulus,have shown great potential in tumor-targeted drug delivery with prolonged retention and deeper penetration.In this review,we summarize recent advances in design of aggregatable nanoparticles by different stimuli.Internal(pH and enzyme)and external(light,temperature and ROS)stimuli are introduced for a comprehensive description.Moreover,the aggregated nanoparticles usually exhibit photothermal,photoacoustic,PET and enhanced MRI contrast,which is also described.In the end,we discuss about the potential applications and challenges for the future clinical translation.
基金partially supported by the National Natural Science Foundation of China(51802209,22077093,51761145041,51525203)the National Research Programs from Ministry of Science and Technology(MOST)of China(2016YFA0201200)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20180848)the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.
基金National Natural Science Foundation of China,Grant/Award Number:52273269Sichuan Science and Technology Program,Grant/Award Numbers:2023YFH0027,2023YFH0008+3 种基金Fundamental Research Funds for the Central UniversitiesState Key Laboratory of Polymer Materials Engineering,Grant/Award Numbers:sklpme2022-3-07,sklpme2021-4-02GRF,Grant/Award Number:CityU11308923The Basic Research Project from Shenzhen Science and Technology Innovation Committee,Grant/Award Number:JCYJ20210324134012034。
文摘Ruthenium(Ru)has been recognized as a prospective candidate to substitute platinum catalysts in water-splitting-based hydrogen production.However,minimizing the Ru contents,optimizing the water dissociation energy of Ru sites,and enhancing the long-term stability are extremely required,but still face a great challenge.Here,we report on creating tungsten oxide-anchored Ru clusters(Ru-WO_(x))with electron-rich and anti-corrosive microenvironments for efficient and robust seawater splitting.Benefiting from the abundant oxygen vacancy structure in tungsten oxide support,the Ru-WO_(x)exhibits strong Ru-O and Ru-W bonds at the interface.Our study elucidates that the strong Ru-O bonds in Ru-WO_(x)may accelerate the water dissociation kinetics,and the Ru-W bonds will lead to the strong metal-support interaction and electrons transfer fromWto Ru.The optimal Ru-WO_(x)catalysts exhibit a low overpotential of 29 and 218mVat the current density of 10 mA cm^(−2) in alkaline and seawater media,respectively.The outstanding long-term stability discloses that the Ru-WO_(x)catalysts own efficient corrosion resistance in seawater electrolysis.We believe that thiswork offers new insights into the essential roles of electron-rich and anti-corrosivemicroenvironments in Ru-based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.
基金supported by the National Natural Science Foundation of China(Nos.82222067,and 82102936)Outstanding Youth Foundation of Henan Province Henan(No.222300420020)+3 种基金China Postdoctoral Science Foundation(No.2023M743232)the Postdoctoral Fellowship Program of CPSF under Grant Number(No.GZB20230676)Scientific and Technological Innovation Talent in Central Plains,Key Projects of Advantageous disciplines in Henan Province(No.222301420011)Scientific and Technological Project of Henan Province(No.242102310450).
文摘Micro/nanomotors(MNMs)have recently emerged as highly promising drug delivery vehicles,showing great potential for biomedical applications.MNMs are typically classified based on their driving mechanisms,and one notable category is gas-driven MNMs,which are self-propelled at the micro/nano scale by gases generated through chemical reactions.These motors can effectively overcome various physiological barriers by utilizing unique physiological actions and driving forces in vivo,gas-driven MNMs offer significant advantages in treating diseases such as tumors and thrombosis.This review first explores the underlying mechanisms of gas-driven MNMs,then discusses their recent applications in overcoming physiological barriers.Finally,it analyses their future prospects and advantages,aiming to inspire further research and accelerate clinical translation in the biomedical field.
基金supported by National Natural Science Foundation of China(No.81961138009)the Fundamental Research Funds for the Central Universities(Nos.SCU2017A001,2018SCUH0024,China)+1 种基金111 Project(No.B18035,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2020YFS0570,China)
文摘Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.
基金supported by the National Natural Science Foundation of China(92161121).
文摘Development of heterogeneous molecular photocatalysts for promising light-driven hydrogen evolution reaction(HER)is highly demanding but still challenging.Here,we report the blue-greenish emitting dinuclear metal–organic halides as photocatalyst by incorporating site-specific single copper(Ⅰ)atoms that exhibit an efficient carbon-negative H_(2) production.Interestingly,the electronic properties,including the spin and charge density of central Cu(Ⅰ)active site,can be triggered by substituent modulation in metal–organic halides,which greatly affect the exciton dissociation kinetics and thus the HER reactivity.The optimized spin density in these heterogeneous photocatalysts drastically boosts the hydrogen production rate from 1250 to 3130μmol·g^(–1)·h^(–1).Our molecular strategy provides a platform that rationally facilitates electronic modulation of copper(Ⅰ)atoms,tunes the macroscopic optoelectronic properties of photocatalysts and boosts carbon-negative HER activity,extending the boundaries of conventional molecular-based photocatalysts.
基金supported by National Natural Science Foundation of China (No. 81872806)111 Project (No. B18035, China)the Fundamental of Research Funds for the Central University (China)。
文摘Insurmountable blood-brain barrier(BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease(AD).Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing Aβ deposition or TAU protein need to be resolved urgently.Herein,a nanocleaner is designed with a rapamycin-loaded ROS-responsive PLGA core and surface modification with KLVFF peptide and acid-cleavable DAG peptide [R@(ox-PLGA)-KcD].DAG can enhance the targeting and internalization effect of nanocleaner towards neurovascular unit endothelial cells in AD lesions,and subsequently detach from nanocleaner in response to acidic microenvironment of endosomes to promote the transcytosis of nanocleaner from endothelial cells into brain parenchyma.Then exposed KLVFF can capture and carry Aβ to microglia,attenuating Aβ-induced neurotoxicity.Strikingly,rapamycin,an autophagy promoter,is rapidly liberated from nanocleaner in the high ROS level of lesions to improve Aβ degradation and normalize inflammatory condition.This design altogether accelerates Aβ degradation and alleviates oxidative stress and excessive inflammatory response.Collectively,our finding offers a strategy to target the AD lesions precisely and multi-pronged therapies for clearing the toxic proteins and modulating lesion microenvironment,to achieve efficient AD therapy.
