The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, p...The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.展开更多
Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocy...Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstrated that protein kinase B(AKT) activation,as well as reduced CCAAT enhancer-binding protein beta(C/EBPβ) and increased CBP/p300-interacting transactivators with E(glutamic acid)/D(aspartic acid)-rich-carboxylterminal domain 4(CITED4),contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation.Conclusion:Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation,and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis.These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.展开更多
Atherosclerosis(AS)is a complex cardiovascular disease characterized by the buildup of plaque in the arteries.The development of effective diagnostic and therapeutic strategies is crucial for the management of AS.Poly...Atherosclerosis(AS)is a complex cardiovascular disease characterized by the buildup of plaque in the arteries.The development of effective diagnostic and therapeutic strategies is crucial for the management of AS.Polymeric nanomaterials,due to their unique properties such as biocompatibility,versatility,and ease of functionalization,have emerged as promising materials for the diagnosis and treatment of AS.This review summarizes the pathogenesis,mechanisms,and microenvironment features changes in AS,as well as the polymeric nanomaterial treatment strategies targeting these changes.It also provides a detailed overview of the applications of polymeric nanomaterials in various imaging techniques and therapy strategies for AS.In addition,this review discusses the biosafety evaluation systems for polymeric nanomaterials,encompassing in vivo distribution and metabolism assessment,biological evaluation,immunological evaluation,and toxicological evaluation.It aims to compile the current state of research and applications of polymeric nanomaterials in AS diagnosis and treatment,highlighting their potential for translation into clinical practice.展开更多
Single-atom alloy catalysts represent a novel and advanced category of materials in heterogeneous catalysis,attracting considerable interest in electrochemical power storage and utilization because of the distinctive ...Single-atom alloy catalysts represent a novel and advanced category of materials in heterogeneous catalysis,attracting considerable interest in electrochemical power storage and utilization because of the distinctive structural attributes and remarkable catalytic capabilities.By establishing atomically precise arrangements of catalytic centers on metallic surfaces,single-atom alloy create highly efficient active sites with near-perfect atomic utilization.The robust electronic coupling and geometric interactions between the atomic-scale precision sites and the supporting metal matrix impart exceptional catalytic properties,such as improved kinetic performance,precise molecular recognition,and prolonged operational durability.In essence,the structural integrity of the isolated metal active sites in single-atom alloy,combined with their precisely tunable coordination environments,substantially boosts the electrochemical performance and catalytic efficiency.This review begins by introducing and discussing the fundamental concepts and inherent attributes of single-atom alloy.The methodological framework for single-atom alloy development was systematically examined,encompassing architectural design principles,fabrication methodologies,and analytical characterization techniques.Following this,the comprehensive summarization was conducted regarding the implementation of single-atom alloy catalysts in energy transformation technologies,with specific emphasis on fuel cells and environmentally electrochemical processes.Finally,forward-looking insights and perspectives are presented on the current challenges facing the development of single-atom alloy catalysts.展开更多
Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion(I/R)injury.MiR-210 is regulated in the adaptation process induced by exercise;however,its impact on exerc...Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion(I/R)injury.MiR-210 is regulated in the adaptation process induced by exercise;however,its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear.We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury.Here,we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice.Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases.In 8-week swimming model in wild-type(WT)and miR-210 knockout(KO)rats,we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity.In neonatal rat cardiomyocytes,miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size.Additionally,miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes(hESC-CMs)and AC16 cell line,indicating its functional roles in human cardiomyocytes.We further identified miR-210 target genes,cyclin-dependent kinase 10(CDK10)and ephrin-A3(EFNA3),that regulate cardiomyocyte proliferation and apoptosis.Finally,miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury.We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury.In summary,this study elucidates the role of miR-210,an exercise-responsive miRNA,in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth.Furthermore,miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury.Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210,which can alleviate I/R injury and promote cardioprotection.展开更多
The energy dissipation pathways of a photosensitizer for phototherapies,including photodynamic therapy(PDT)and photothermal therapy(PTT),compete directly with that of itsfluorescence(FL)emission.Enriching heavy atoms o...The energy dissipation pathways of a photosensitizer for phototherapies,including photodynamic therapy(PDT)and photothermal therapy(PTT),compete directly with that of itsfluorescence(FL)emission.Enriching heavy atoms on theπ-conjugated systems and aggregation-caused quenching are two effective methods to turn off the FL emission of photosensitizers,which is expected to boost the inter-system crossing(for PDT)and nonradiative transition(for PTT)of photosensitizers for maximized phototherapeutic efficacy.Following this approach,an all-iodine-substituted polydiacetylene aggregate poly(diiododiacetylene)(PIDA)has been developed,which shows a superior near infrared absorption(ε_(808nm)=26.1 g^(-1) cm^(-1) L)with completely blocked FL,as well as high efficiency of reactive oxygen species generation(nearly 45 folds of indocyanine green)and photothermal conversion(33.4%).To make the insolublefibrillar PIDA aggregates favorable for systemic administration,they are converted into nanospheres through a pre-polymerization morphology transformation strategy.The in vivo study on a 4T1 tumor-bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days,validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition.展开更多
文摘The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.
基金supported by the grants from National Key Research and Development Project(2018YFE0113500 to JX)National Natural Science Foundation of China(82020108002 and 81911540486 to JX,81970335 and 82170285 to YB)+4 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX)Science and Technology Commission of Shanghai Municipality(20DZ2255400 and 18410722200 to JX)the“Dawn”Program of Shanghai Education Commission(19SG34 to JX)the Shanghai Rising-Star Program(19QA1403900 to YB)the Science and Technology Commission of Shanghai Municipality(21SQBS00100 to YB).
文摘Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstrated that protein kinase B(AKT) activation,as well as reduced CCAAT enhancer-binding protein beta(C/EBPβ) and increased CBP/p300-interacting transactivators with E(glutamic acid)/D(aspartic acid)-rich-carboxylterminal domain 4(CITED4),contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation.Conclusion:Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation,and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis.These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.
基金supported by the National Natural Science Foundation of China(52325304,22077038,21877042 and 52403184)Nature Science Foundation of Hubei Province of China(2025CFB479)the Fundamental Research Funds for the Central Universities.
文摘Atherosclerosis(AS)is a complex cardiovascular disease characterized by the buildup of plaque in the arteries.The development of effective diagnostic and therapeutic strategies is crucial for the management of AS.Polymeric nanomaterials,due to their unique properties such as biocompatibility,versatility,and ease of functionalization,have emerged as promising materials for the diagnosis and treatment of AS.This review summarizes the pathogenesis,mechanisms,and microenvironment features changes in AS,as well as the polymeric nanomaterial treatment strategies targeting these changes.It also provides a detailed overview of the applications of polymeric nanomaterials in various imaging techniques and therapy strategies for AS.In addition,this review discusses the biosafety evaluation systems for polymeric nanomaterials,encompassing in vivo distribution and metabolism assessment,biological evaluation,immunological evaluation,and toxicological evaluation.It aims to compile the current state of research and applications of polymeric nanomaterials in AS diagnosis and treatment,highlighting their potential for translation into clinical practice.
基金supported by the National Natural Science Foundation of China(Grant No.22208322)the Natural Science Foundation of Henan,China(Grant No.242300421230)the fund from the State Key Laboratory of Powder Metallurgy,China(Grant No.Sklpm-KF-021).
文摘Single-atom alloy catalysts represent a novel and advanced category of materials in heterogeneous catalysis,attracting considerable interest in electrochemical power storage and utilization because of the distinctive structural attributes and remarkable catalytic capabilities.By establishing atomically precise arrangements of catalytic centers on metallic surfaces,single-atom alloy create highly efficient active sites with near-perfect atomic utilization.The robust electronic coupling and geometric interactions between the atomic-scale precision sites and the supporting metal matrix impart exceptional catalytic properties,such as improved kinetic performance,precise molecular recognition,and prolonged operational durability.In essence,the structural integrity of the isolated metal active sites in single-atom alloy,combined with their precisely tunable coordination environments,substantially boosts the electrochemical performance and catalytic efficiency.This review begins by introducing and discussing the fundamental concepts and inherent attributes of single-atom alloy.The methodological framework for single-atom alloy development was systematically examined,encompassing architectural design principles,fabrication methodologies,and analytical characterization techniques.Following this,the comprehensive summarization was conducted regarding the implementation of single-atom alloy catalysts in energy transformation technologies,with specific emphasis on fuel cells and environmentally electrochemical processes.Finally,forward-looking insights and perspectives are presented on the current challenges facing the development of single-atom alloy catalysts.
基金supported by grants from the National Key Research and Development Project(2022YFA1104500 to J.X.)National Natural Science Foundation of China(82020108002 and 82225005 to J.X.,81970335 and 82170285 to Y.B.,82000253 and 82370277 to H.W.,and 81772444 to L.W.)+2 种基金Science and Technology Commission of Shanghai Municipality(23410750100,20DZ2255400,and 21XD1421300 to J.X.,23010500300 and 21SQBS00100 to Y.B.,and 20YF1414000 and 23ZR1422900 to H.W.)“Dawn”Program of Shanghai Education Commission(19SG34 to J.X.)“Chenguang”Program of Shanghai Education Commission(20CG46 to H.W.).
文摘Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion(I/R)injury.MiR-210 is regulated in the adaptation process induced by exercise;however,its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear.We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury.Here,we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice.Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases.In 8-week swimming model in wild-type(WT)and miR-210 knockout(KO)rats,we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity.In neonatal rat cardiomyocytes,miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size.Additionally,miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes(hESC-CMs)and AC16 cell line,indicating its functional roles in human cardiomyocytes.We further identified miR-210 target genes,cyclin-dependent kinase 10(CDK10)and ephrin-A3(EFNA3),that regulate cardiomyocyte proliferation and apoptosis.Finally,miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury.We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury.In summary,this study elucidates the role of miR-210,an exercise-responsive miRNA,in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth.Furthermore,miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury.Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210,which can alleviate I/R injury and promote cardioprotection.
基金National Natural Science Foundation of China,Grant/Award Numbers:22077038,52325304,21877042Huazhong University Supportive Fund for Fundamental Research。
文摘The energy dissipation pathways of a photosensitizer for phototherapies,including photodynamic therapy(PDT)and photothermal therapy(PTT),compete directly with that of itsfluorescence(FL)emission.Enriching heavy atoms on theπ-conjugated systems and aggregation-caused quenching are two effective methods to turn off the FL emission of photosensitizers,which is expected to boost the inter-system crossing(for PDT)and nonradiative transition(for PTT)of photosensitizers for maximized phototherapeutic efficacy.Following this approach,an all-iodine-substituted polydiacetylene aggregate poly(diiododiacetylene)(PIDA)has been developed,which shows a superior near infrared absorption(ε_(808nm)=26.1 g^(-1) cm^(-1) L)with completely blocked FL,as well as high efficiency of reactive oxygen species generation(nearly 45 folds of indocyanine green)and photothermal conversion(33.4%).To make the insolublefibrillar PIDA aggregates favorable for systemic administration,they are converted into nanospheres through a pre-polymerization morphology transformation strategy.The in vivo study on a 4T1 tumor-bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days,validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition.
