Li-S batteries have been considered as one of advanced next-generation energy storage systems owing to their remarkable theoretical capacity(1672 m Ah g^(-1))and high energy density(2600 Wh kg^(-1)).However,critical i...Li-S batteries have been considered as one of advanced next-generation energy storage systems owing to their remarkable theoretical capacity(1672 m Ah g^(-1))and high energy density(2600 Wh kg^(-1)).However,critical issues,mainly pertaining to lithium polysulfide shuttle and slow sulfur reaction kinetics,have posed a fatal threat to the electrochemical performances of Li-S batteries.The situation is even worse for high sulfur-loaded and flexible cathodes,which are the essential components for practical Li-S batteries.In response,the use of metal compounds as electrocatalysts in Li-S systems have been confirmed as an effective strategy to date.Particularly,recent years have witnessed many progresses in phosphidesoptimized Li-S chemistry.This has been motivated by the superior electron conductivity and high electrocatalytic activity of phosphides.In this tutorial review,we offer a systematic summary of active metal phosphides as promoters for Li-S chemistry,aiming at helping to understanding the working mechanism of phosphide electrocatalysts and guiding the construction of advanced Li-S batteries.展开更多
The burgeoning demand for modern electronic devices and electric vehicles has driven the development of efficient,reliable,and environmentally friendly batteries[1,2].Lithium–sulfur(Li–S)batteries with high theoreti...The burgeoning demand for modern electronic devices and electric vehicles has driven the development of efficient,reliable,and environmentally friendly batteries[1,2].Lithium–sulfur(Li–S)batteries with high theoretical capacity(1672 mA h g1)and energy density(2600 W h kg1),have garnered significant interest in both academic and industrial research[3,4].However,the widespread production and commercialization of Li–S batteries are impeded by the inherent characteristics of sulfur and lithium,along with their complex electrochemical behaviors.Notably,challenges such as the polysulfide shuttle effect and the slow kinetics of the sulfur nucleation/decomposition reaction hinder capacity utilization and cycling stability.To overcome these challenges,innovative electrocatalyst strategies aimed at enhancing activity have been explored.展开更多
Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit V...Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases.It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms.Using comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed.Mechanistically,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor growth.Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway.Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.展开更多
Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits thei...Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits their clinical benefits.To overcome such resistance,new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR.However,much less effort has been put into alternative strategies,such as targeting the intrinsic protective responses to EGFR TKIs.In this study,we found that EGFR TKIs,including gefitinib and AZD9291,impaired lysosome-dependent degradation of SQSTM1,thus compromising their anti-cancer efficiency.By accumulating in the lysosome lumen,gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity.As a result,SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance.Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo.Furthermore,a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells.Therefore,targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy.展开更多
As an innovative maintenance technology of asphalt pavement,encapsulated rejuvenator used to improve its self-healing performance has been widely investigated by researchers in recent years.In this work,the selfhealin...As an innovative maintenance technology of asphalt pavement,encapsulated rejuvenator used to improve its self-healing performance has been widely investigated by researchers in recent years.In this work,the selfhealing properties of asphalt mixture with and without encapsulations were comparatively studied considering these parameters:Healing time,healing cycles and microwave heating.Three-point bending strength recovery test and fatigue loading cycles recovery test were conducted for two kinds of encapsulations containing the healing agents present inside the asphalt mixture,namely compartmented Ca-alginate/SiO_(2) fiber and compartmented Ca-alginate/graphene oxide fiber.The results showed that the optimum healing time was three days.After the 30 s of microwave heating,the recovery of fatigue loading cycles of asphalt mixture with compartmented Ca-alginate/graphene oxide fiber was four times larger than that of control asphalt mixture.Compared with the single effect related to the encapsulated healing agent or temperature,the synergistic effect of temperature and encapsulation could further significantly improve the self-healing properties of asphalt mixture.The compartmented Ca-alginate/graphene oxide fiber not only could soften asphalt through the encapsulated healing agent to improve self-healing properties of asphalt,but also could repeatedly and quickly heal cracks thanks to microwave action.The synthesis of the fiber breaks the current boundary between the two technologies(capsules healing method and induction healing method)and opens up a new horizon for the asphalt self-healing technology.展开更多
Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has bee...Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.展开更多
基金supported by the Project of State Key Laboratory of Environment-Friendly Energy Materials(SWUST,China,Grant Nos.19FKSY16 and 18ZD320304)。
文摘Li-S batteries have been considered as one of advanced next-generation energy storage systems owing to their remarkable theoretical capacity(1672 m Ah g^(-1))and high energy density(2600 Wh kg^(-1)).However,critical issues,mainly pertaining to lithium polysulfide shuttle and slow sulfur reaction kinetics,have posed a fatal threat to the electrochemical performances of Li-S batteries.The situation is even worse for high sulfur-loaded and flexible cathodes,which are the essential components for practical Li-S batteries.In response,the use of metal compounds as electrocatalysts in Li-S systems have been confirmed as an effective strategy to date.Particularly,recent years have witnessed many progresses in phosphidesoptimized Li-S chemistry.This has been motivated by the superior electron conductivity and high electrocatalytic activity of phosphides.In this tutorial review,we offer a systematic summary of active metal phosphides as promoters for Li-S chemistry,aiming at helping to understanding the working mechanism of phosphide electrocatalysts and guiding the construction of advanced Li-S batteries.
基金supported by the National Natural Science Foundation of China(52172239)the Project of State Key Laboratory of Environment-Friendly Energy Materials(18ZD320304 and 22fksy23).
文摘The burgeoning demand for modern electronic devices and electric vehicles has driven the development of efficient,reliable,and environmentally friendly batteries[1,2].Lithium–sulfur(Li–S)batteries with high theoretical capacity(1672 mA h g1)and energy density(2600 W h kg1),have garnered significant interest in both academic and industrial research[3,4].However,the widespread production and commercialization of Li–S batteries are impeded by the inherent characteristics of sulfur and lithium,along with their complex electrochemical behaviors.Notably,challenges such as the polysulfide shuttle effect and the slow kinetics of the sulfur nucleation/decomposition reaction hinder capacity utilization and cycling stability.To overcome these challenges,innovative electrocatalyst strategies aimed at enhancing activity have been explored.
基金This study is supported by the State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,and Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou 510060,P.R.Chinathe National Natural Science Foundation of China(82150710555 and 82220108016 to X.Li,81970823 to Jin Yao and 81830013 to J.O.)+4 种基金a Key Research and Development Plan of Shandong Province(2016GSF201100)the Fundamental Research Funds for the Central Universities(19ykpy151)the long-term structural Methusalem funding by the Flemish Government,Belgiumthe Deutsche Forschungsge-meinschaft(Project No.:394046768-SFB1366)the DZHK partner site Mannheim/Heidelberg to H.F.L.,an ERA PerMed 2020 JTC grant“PROGRESS”.
文摘Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases.It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms.Using comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed.Mechanistically,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor growth.Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway.Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
基金This work was supported by the National Natural Science Foundation of China#1 under grant no.91740106the Natural Science Foundation of Zhejiang Province under grant nos.LR19H160003,LQ18H160004,and Q18H160015the High Level Innovative Talents Program and 151 Talents program in Zhejiang.
文摘Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits their clinical benefits.To overcome such resistance,new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR.However,much less effort has been put into alternative strategies,such as targeting the intrinsic protective responses to EGFR TKIs.In this study,we found that EGFR TKIs,including gefitinib and AZD9291,impaired lysosome-dependent degradation of SQSTM1,thus compromising their anti-cancer efficiency.By accumulating in the lysosome lumen,gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity.As a result,SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance.Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo.Furthermore,a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells.Therefore,targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy.
基金funded by Foshan Self-Finance Science and Technology Project(No.2020001005441)the National Key R&D Program of China(No.2018YFB1600200)the National Natural Science Foundation of China(No.51978547).
文摘As an innovative maintenance technology of asphalt pavement,encapsulated rejuvenator used to improve its self-healing performance has been widely investigated by researchers in recent years.In this work,the selfhealing properties of asphalt mixture with and without encapsulations were comparatively studied considering these parameters:Healing time,healing cycles and microwave heating.Three-point bending strength recovery test and fatigue loading cycles recovery test were conducted for two kinds of encapsulations containing the healing agents present inside the asphalt mixture,namely compartmented Ca-alginate/SiO_(2) fiber and compartmented Ca-alginate/graphene oxide fiber.The results showed that the optimum healing time was three days.After the 30 s of microwave heating,the recovery of fatigue loading cycles of asphalt mixture with compartmented Ca-alginate/graphene oxide fiber was four times larger than that of control asphalt mixture.Compared with the single effect related to the encapsulated healing agent or temperature,the synergistic effect of temperature and encapsulation could further significantly improve the self-healing properties of asphalt mixture.The compartmented Ca-alginate/graphene oxide fiber not only could soften asphalt through the encapsulated healing agent to improve self-healing properties of asphalt,but also could repeatedly and quickly heal cracks thanks to microwave action.The synthesis of the fiber breaks the current boundary between the two technologies(capsules healing method and induction healing method)and opens up a new horizon for the asphalt self-healing technology.
基金supported by the National Natural Science Foundation of China (Nos. 21773169, 21973069, 21805144)Natural Science Foundation of Zhejiang Province (No. LY18B020016)the PEIYANG Young Scholars Program of Tianjin University (No. 2018XRX-0007)。
文摘Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.
