The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ab...The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.展开更多
Carbon dioxide(CO2) is an important greenhouse gas that influences regional climate through disturbing the earth’s energy balance. The CO2concentrations are usually prescribed homogenously in most climate models and ...Carbon dioxide(CO2) is an important greenhouse gas that influences regional climate through disturbing the earth’s energy balance. The CO2concentrations are usually prescribed homogenously in most climate models and the spatiotemporal variations of CO2are neglected. To address this issue,a regional climate model(RegCM4) is modified to investigate the non-homogeneous distribution of CO2and its effects on regional longwave radiation flux and temperature in East Asia. One-year simulation is performed with prescribed surface CO2fluxes that include fossil fuel emission, biomass burning, air-sea exchange, and terrestrial biosphere flux. Two numerical experiments(one using constant prescribed CO2concentrations in the radiation scheme and the other using the simulated CO2concentrations that are spatially non-homogeneous) are conducted to assess the impact of non-homogeneous CO2on the regional longwave radiation flux and temperature. Comparison of CO2concentrations from the model with the observations from the GLOBALVIEW-CO2network suggests that the model can well capture the spatiotemporal patterns of CO2concentrations. Generally, high CO2mixing ratios appear in the heavily industrialized eastern China in cold seasons, which probably relates to intensive human activities. The accommodation of non-homogeneous CO2concentrations in the radiative transfer scheme leads to an annual mean change of -0.12 W m-2in total sky surface upward longwave flux in East Asia. The experiment with non-homogeneous CO2tends to yield a warmer lower troposphere.Surface temperature exhibits a maximum difference in summertime, ranging from -4.18 K to 3.88 K, when compared to its homogeneous counterpart. Our results indicate that the spatial and temporal distributions of CO2have a considerable impact on regional longwave radiation flux and temperature, and should be taken into account in future climate modeling.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant Nos. 81703382 and 81673567)
文摘The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.
基金Supported by the National Natural Science Foundation of China(41575145,41621005,and 91544230)National Key Basic Research and Development Program of China(2016YFC0203303 and 2014CB441203)EU 7th Framework Marie Curie Actions IRSES Project:REQUA(PIRSES-GA-2013-612671)
文摘Carbon dioxide(CO2) is an important greenhouse gas that influences regional climate through disturbing the earth’s energy balance. The CO2concentrations are usually prescribed homogenously in most climate models and the spatiotemporal variations of CO2are neglected. To address this issue,a regional climate model(RegCM4) is modified to investigate the non-homogeneous distribution of CO2and its effects on regional longwave radiation flux and temperature in East Asia. One-year simulation is performed with prescribed surface CO2fluxes that include fossil fuel emission, biomass burning, air-sea exchange, and terrestrial biosphere flux. Two numerical experiments(one using constant prescribed CO2concentrations in the radiation scheme and the other using the simulated CO2concentrations that are spatially non-homogeneous) are conducted to assess the impact of non-homogeneous CO2on the regional longwave radiation flux and temperature. Comparison of CO2concentrations from the model with the observations from the GLOBALVIEW-CO2network suggests that the model can well capture the spatiotemporal patterns of CO2concentrations. Generally, high CO2mixing ratios appear in the heavily industrialized eastern China in cold seasons, which probably relates to intensive human activities. The accommodation of non-homogeneous CO2concentrations in the radiative transfer scheme leads to an annual mean change of -0.12 W m-2in total sky surface upward longwave flux in East Asia. The experiment with non-homogeneous CO2tends to yield a warmer lower troposphere.Surface temperature exhibits a maximum difference in summertime, ranging from -4.18 K to 3.88 K, when compared to its homogeneous counterpart. Our results indicate that the spatial and temporal distributions of CO2have a considerable impact on regional longwave radiation flux and temperature, and should be taken into account in future climate modeling.
