The electrocatalytic water splitting technology can generate highpurity hydrogen without emitting carbon dioxide,which is in favor of relieving environmental pollution and energy crisis and achieving carbon neutrality...The electrocatalytic water splitting technology can generate highpurity hydrogen without emitting carbon dioxide,which is in favor of relieving environmental pollution and energy crisis and achieving carbon neutrality.Electrocatalysts can effectively reduce the reaction energy barrier and increase the reaction efficiency.Facet engineering is considered as a promising strategy in controlling the ratio of desired crystal planes on the surface.Owing to the anisotropy,crystal planes with different orientations usually feature facet-dependent physical and chemical properties,leading to differences in the adsorption energies of oxygen or hydrogen intermediates,and thus exhibit varied electrocatalytic activity toward hydrogen evolution reaction(HER)and oxygen evolution reaction(OER).In this review,a brief introduction of the basic concepts,fundamental understanding of the reaction mechanisms as well as key evaluating parameters for both HER and OER are provided.The formation mechanisms of the crystal facets are comprehensively overviewed aiming to give scientific theory guides to realize dominant crystal planes.Subsequently,three strategies of selective capping agent,selective etching agent,and coordination modulation to tune crystal planes are comprehensively summarized.Then,we present an overview of significant contributions of facet-engineered catalysts toward HER,OER,and overall water splitting.In particular,we highlight that density functional theory calculations play an indispensable role in unveiling the structure–activity correlation between the crystal plane and catalytic activity.Finally,the remaining challenges in facet-engineered catalysts for HER and OER are provided and future prospects for designing advanced facet-engineered electrocatalysts are discussed.展开更多
Porous carbons(PCs)are one of the promising electrode materials for supercapacitors attributed to their low cost,superior electronic conductivity,easy availability,and tailored pore structures.Template methods have be...Porous carbons(PCs)are one of the promising electrode materials for supercapacitors attributed to their low cost,superior electronic conductivity,easy availability,and tailored pore structures.Template methods have been explored as the effective strategies for the fabrication of PCs with desirable morphology and highly controllable pore size distribution.Herein,this review firstly focuses on design and synthetic mechanism of various PCs via hard templates,soft templates,and dual-templates.Secondly,an overview of PCs is presented with a detailed discussion of the structure-activity relationship between electrochemical performances and pore structures.Thirdly,the current challenges and prospects of template-assisted synthesis of PCs for supercapacitors are highlighted regarding further researches.展开更多
Liver cancer represents a major global health concern,with projections indicating that the number of new cases could surpass 1 million annually by 2025.Hepatocellular carcinoma(HCC)constitutes around 90%of liver cance...Liver cancer represents a major global health concern,with projections indicating that the number of new cases could surpass 1 million annually by 2025.Hepatocellular carcinoma(HCC)constitutes around 90%of liver cancer cases and is primarily linked to factors incluidng aflatoxin,hepatitis B(HBV)and C(HCV),and metabolic disorders.There are no obvious symptoms in the early stage of HCC,which often leads to delays in diagnosis.Therefore,HCC patients usually present with tumors in advanced and incurable stages.Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation,metastasis,and recurrence of HCC.Beyond the frequently altered and therapeutically targeted receptor tyrosine kinase(RTK)pathways in HCC,pathways involved in cell differentiation,telomere regulation,epigenetic modification and stress response also provide therapeutic potential.Investigating the key signaling pathways and their inhibitors is pivotal for achieving therapeutic advancements in the management of HCC.At present,the primary therapeutic approaches for advanced HCC are tyrosine kinase inhibitors(TKI),immune checkpoint inhibitors(ICI),and combination regimens.New trials are investigating combination therapies involving ICIs and TKIs or anti-VEGF(endothelial growth factor)therapies,as well as combinations of two immunotherapy regimens.The outcomes of these trials are expected to revolutionize HCC management across all stages.Here,we provide here a comprehensive review of cellular signaling pathways,their therapeutic potential,evidence derived from late-stage clinical trials in HCC and discuss the concepts underlying earlier clinical trials,biomarker identification,and the development of more effective therapeutics for HCC.展开更多
Brincidofovir(BCV)and tecovirimat are the only two chemical drugs that have been approved to treat smallpox and can be requested for monkeypox(Mpox)treatment through a single-patient Emergency Investigational New Drug...Brincidofovir(BCV)and tecovirimat are the only two chemical drugs that have been approved to treat smallpox and can be requested for monkeypox(Mpox)treatment through a single-patient Emergency Investigational New Drug(EIND)application.Disappointedly,the efficacy of tecovirimat manifested in recent clinical trials is far from being satisfactory,while the clinical efficacy of BCV is still inconclusive.Given that monkeypox virus(MPXV),variola and other emerging orthopoxviruses are posing serious threats to global health,it is urgent to develop better therapeutics.In this study,we tested the antiviral effects of three novel prodrugs,which were designed based on previously reported parent drugs,either(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine((S)-HPMPC,cidofovir)or(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine((S)-HPMPA).We found that one of the(S)-HPMPA-based prodrugs,ODE-(S)-HPMPA formate,exhibited significantly better anti-orthopoxvirus activity than BCV both in vitro and in vivo,which also inhibited human adenovirus type 2 and type 21 more efficiently than BCV.Most strikingly,the EC50 and EC90 of ODE-(S)-HPMPA formate against MPXV were more than 40-fold lower than those of BCV.In contrast,we observed that the antiherpes simplex virus type 1(HSV-1)activities of the(S)-HPMPA-based prodrugs were less effective than those of the cidofovir-based prodrugs(BCV and BCV formate),especially in vivo.Moreover,we showed for the first time that cytidine and adenine analog combined therapies could provide mice with complete protection against lethal challenges of both vaccinia and HSV-1.Collectively,we propose that both the ODE-(S)-HPMPA formate and the BCV/ODE-(S)-HPMPA formate combination are worth further investigations for their potential clinical applications.展开更多
Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor ...Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor(EGFRTKI)combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression(EGFR^(high)).We present here the results of a single-arm,open-label,exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib(NCT04642547;n=30).Only patients with EGFR^(high) HCC and progressive disease after lenvatinib treatment were recruited in the study.The most frequent adverse events of all grades were fatigue(27 patients;90%),followed by rash(25 patients;83.3%),diarrhea(24 patients;80%),and anorexia(12 patients;40%).Among 30 patients,9(30%)achieved a confirmed partial response and 14(46.7%)had stable disease according to mRECIST criteria.Based on RECIST1.1,5(16.7%)achieved a confirmed partial response and 18(60%)had stable disease.The estimated median progression free survival(PFS)and overall survival(OS)time were 4.4 months(95%CI:2.5 to 5.9)and13.7 months(95%CI:9.0 to NA),respectively.The objective response rate(ORR)of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC(cabozantinib ORR of 4%;regorafenib ORR of 11%).Given that this combination was well-tolerated,a further clinical study of this combination is warranted.展开更多
Developing effective electrodes with commercial-level active mass-loading(>10 mg cm^(−2))is vital for the practical application of supercapacitors.However,high active mass-loading usually requires thick active mass...Developing effective electrodes with commercial-level active mass-loading(>10 mg cm^(−2))is vital for the practical application of supercapacitors.However,high active mass-loading usually requires thick active mass layer,which severely hinders the ion/electron transport and results in poor capacitive performance.Herein,a self-standing biochar electrode with active mass-loading of ca.40 mg cm^(−2) and thickness of 800μm has been developed from basswood.The basswood was treated with formamide to incorporate N/O in the carbon structure,followed by mild KOH activation to ameliorate the pore size and introduce more O species in the carbon matrix.The as-prepared carbon monoliths possess well conductive carbon skeleton,abundant N/O dopant and 3D porous structure,which are favorable for the ion/electron transport and promoting capacitance performance.The self-standing carbon electrode not only exhibits the maximum areal/mass/volumetric specific capacitance of 5037.5 mF cm^(−2)/172.5 F g^(−1)/63.0 F cm^(−3) at 2 mA cm^(−2)(0.05 A g^(−1)),but also displays excellent rate performance with 76%capacitance retention at 500 mA cm^(−2)(12.5 A g^(−1))in a symmetric supercapacitor,surpassing the state-of-art biomass-based thick carbon electrode.The assembled model can power typical electron devices including a fan,a digital watch and a logo made up of 34 light-emitting diodes for a proper period,revealing its practical application potential.This study not only puts forward a commercial-level high active mass-loading electrode from biomass for supercapacitor,but also bridges the gap between the experimental research and practical application.展开更多
基金support from the National Natural Science Foundation of China(No.22005147)Dr.You acknowledges the financial support from the National Key Research and Development Program of China(2021YFA1600800)+1 种基金the Innovation and Talent Recruitment Base of New Energy Chemistry and Device(B21003)the Open Research Fund of Key Laboratory of Material Chemistry for Energy Conversion and Storage(HUST),Ministry of Education(2021JYBKF03).
文摘The electrocatalytic water splitting technology can generate highpurity hydrogen without emitting carbon dioxide,which is in favor of relieving environmental pollution and energy crisis and achieving carbon neutrality.Electrocatalysts can effectively reduce the reaction energy barrier and increase the reaction efficiency.Facet engineering is considered as a promising strategy in controlling the ratio of desired crystal planes on the surface.Owing to the anisotropy,crystal planes with different orientations usually feature facet-dependent physical and chemical properties,leading to differences in the adsorption energies of oxygen or hydrogen intermediates,and thus exhibit varied electrocatalytic activity toward hydrogen evolution reaction(HER)and oxygen evolution reaction(OER).In this review,a brief introduction of the basic concepts,fundamental understanding of the reaction mechanisms as well as key evaluating parameters for both HER and OER are provided.The formation mechanisms of the crystal facets are comprehensively overviewed aiming to give scientific theory guides to realize dominant crystal planes.Subsequently,three strategies of selective capping agent,selective etching agent,and coordination modulation to tune crystal planes are comprehensively summarized.Then,we present an overview of significant contributions of facet-engineered catalysts toward HER,OER,and overall water splitting.In particular,we highlight that density functional theory calculations play an indispensable role in unveiling the structure–activity correlation between the crystal plane and catalytic activity.Finally,the remaining challenges in facet-engineered catalysts for HER and OER are provided and future prospects for designing advanced facet-engineered electrocatalysts are discussed.
基金the financial support from the National Natural Science Foundation of China(No.22005147).
文摘Porous carbons(PCs)are one of the promising electrode materials for supercapacitors attributed to their low cost,superior electronic conductivity,easy availability,and tailored pore structures.Template methods have been explored as the effective strategies for the fabrication of PCs with desirable morphology and highly controllable pore size distribution.Herein,this review firstly focuses on design and synthetic mechanism of various PCs via hard templates,soft templates,and dual-templates.Secondly,an overview of PCs is presented with a detailed discussion of the structure-activity relationship between electrochemical performances and pore structures.Thirdly,the current challenges and prospects of template-assisted synthesis of PCs for supercapacitors are highlighted regarding further researches.
基金funded by grants from the National Natural Science Foundation of China(82222047,82073039)the Science and Technology Commission of Shanghai Municipality(22XD1423100,22S11900500)Shanghai Municipal Health Commission(2022XD057).
文摘Liver cancer represents a major global health concern,with projections indicating that the number of new cases could surpass 1 million annually by 2025.Hepatocellular carcinoma(HCC)constitutes around 90%of liver cancer cases and is primarily linked to factors incluidng aflatoxin,hepatitis B(HBV)and C(HCV),and metabolic disorders.There are no obvious symptoms in the early stage of HCC,which often leads to delays in diagnosis.Therefore,HCC patients usually present with tumors in advanced and incurable stages.Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation,metastasis,and recurrence of HCC.Beyond the frequently altered and therapeutically targeted receptor tyrosine kinase(RTK)pathways in HCC,pathways involved in cell differentiation,telomere regulation,epigenetic modification and stress response also provide therapeutic potential.Investigating the key signaling pathways and their inhibitors is pivotal for achieving therapeutic advancements in the management of HCC.At present,the primary therapeutic approaches for advanced HCC are tyrosine kinase inhibitors(TKI),immune checkpoint inhibitors(ICI),and combination regimens.New trials are investigating combination therapies involving ICIs and TKIs or anti-VEGF(endothelial growth factor)therapies,as well as combinations of two immunotherapy regimens.The outcomes of these trials are expected to revolutionize HCC management across all stages.Here,we provide here a comprehensive review of cellular signaling pathways,their therapeutic potential,evidence derived from late-stage clinical trials in HCC and discuss the concepts underlying earlier clinical trials,biomarker identification,and the development of more effective therapeutics for HCC.
基金supported in part by the National Natural Science Foundation of China(Grant No.32270986)the major project of Study on Pathogenesis and Epidemic Prevention Technology System by the Ministry of Science and Technology of China(Grant No.2021YFC2302500)the National Key Research and Development Program of China(Grant No.2022YFC2009802).
文摘Brincidofovir(BCV)and tecovirimat are the only two chemical drugs that have been approved to treat smallpox and can be requested for monkeypox(Mpox)treatment through a single-patient Emergency Investigational New Drug(EIND)application.Disappointedly,the efficacy of tecovirimat manifested in recent clinical trials is far from being satisfactory,while the clinical efficacy of BCV is still inconclusive.Given that monkeypox virus(MPXV),variola and other emerging orthopoxviruses are posing serious threats to global health,it is urgent to develop better therapeutics.In this study,we tested the antiviral effects of three novel prodrugs,which were designed based on previously reported parent drugs,either(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine((S)-HPMPC,cidofovir)or(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine((S)-HPMPA).We found that one of the(S)-HPMPA-based prodrugs,ODE-(S)-HPMPA formate,exhibited significantly better anti-orthopoxvirus activity than BCV both in vitro and in vivo,which also inhibited human adenovirus type 2 and type 21 more efficiently than BCV.Most strikingly,the EC50 and EC90 of ODE-(S)-HPMPA formate against MPXV were more than 40-fold lower than those of BCV.In contrast,we observed that the antiherpes simplex virus type 1(HSV-1)activities of the(S)-HPMPA-based prodrugs were less effective than those of the cidofovir-based prodrugs(BCV and BCV formate),especially in vivo.Moreover,we showed for the first time that cytidine and adenine analog combined therapies could provide mice with complete protection against lethal challenges of both vaccinia and HSV-1.Collectively,we propose that both the ODE-(S)-HPMPA formate and the BCV/ODE-(S)-HPMPA formate combination are worth further investigations for their potential clinical applications.
基金supported by the National Natural Science Foundation(Nos.82222047,82073039,82330095,81502672,and 82070619)the Program of Shanghai Academic/Technology Research Leader(No.22XD1423100)+2 种基金the National Key Research and Development Program of China(2022YFC2804300)Shanghai Municipal Commission of Health and Family Planning(2022XD057)the Shanghai Committee of Science and Technology(23ZR1439000 and 22S11900500).
文摘Lenvatinib,a multi-kinase inhibitor,has been approved asfirst-line treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is limited.We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor(EGFRTKI)combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression(EGFR^(high)).We present here the results of a single-arm,open-label,exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib(NCT04642547;n=30).Only patients with EGFR^(high) HCC and progressive disease after lenvatinib treatment were recruited in the study.The most frequent adverse events of all grades were fatigue(27 patients;90%),followed by rash(25 patients;83.3%),diarrhea(24 patients;80%),and anorexia(12 patients;40%).Among 30 patients,9(30%)achieved a confirmed partial response and 14(46.7%)had stable disease according to mRECIST criteria.Based on RECIST1.1,5(16.7%)achieved a confirmed partial response and 18(60%)had stable disease.The estimated median progression free survival(PFS)and overall survival(OS)time were 4.4 months(95%CI:2.5 to 5.9)and13.7 months(95%CI:9.0 to NA),respectively.The objective response rate(ORR)of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC(cabozantinib ORR of 4%;regorafenib ORR of 11%).Given that this combination was well-tolerated,a further clinical study of this combination is warranted.
基金the National Natural Science Foundation of China(No.22005147)the Natural Science Foundation of Fujian Province(No.2020J01419,No.2020J05220).
文摘Developing effective electrodes with commercial-level active mass-loading(>10 mg cm^(−2))is vital for the practical application of supercapacitors.However,high active mass-loading usually requires thick active mass layer,which severely hinders the ion/electron transport and results in poor capacitive performance.Herein,a self-standing biochar electrode with active mass-loading of ca.40 mg cm^(−2) and thickness of 800μm has been developed from basswood.The basswood was treated with formamide to incorporate N/O in the carbon structure,followed by mild KOH activation to ameliorate the pore size and introduce more O species in the carbon matrix.The as-prepared carbon monoliths possess well conductive carbon skeleton,abundant N/O dopant and 3D porous structure,which are favorable for the ion/electron transport and promoting capacitance performance.The self-standing carbon electrode not only exhibits the maximum areal/mass/volumetric specific capacitance of 5037.5 mF cm^(−2)/172.5 F g^(−1)/63.0 F cm^(−3) at 2 mA cm^(−2)(0.05 A g^(−1)),but also displays excellent rate performance with 76%capacitance retention at 500 mA cm^(−2)(12.5 A g^(−1))in a symmetric supercapacitor,surpassing the state-of-art biomass-based thick carbon electrode.The assembled model can power typical electron devices including a fan,a digital watch and a logo made up of 34 light-emitting diodes for a proper period,revealing its practical application potential.This study not only puts forward a commercial-level high active mass-loading electrode from biomass for supercapacitor,but also bridges the gap between the experimental research and practical application.
