The mixing and combustion characteristics in a cavity flameholding combustor under inlet Mach number 2.92 are numerically investigated with ethylene injection.Dimensionless distance is defined as the ratio of the actu...The mixing and combustion characteristics in a cavity flameholding combustor under inlet Mach number 2.92 are numerically investigated with ethylene injection.Dimensionless distance is defined as the ratio of the actual distance to the height of the combustor entrance.The cavity shear-layer mode,the lifted cavity shear-layer mode,and jet wake mode with upstream separation are observed respectively with dimensionless distance equals to 1.5,4.5,and 7.5.In both non-reacting and reacting flow fields,the numerical results are essentially in agreement with the schlieren photography,flame chemiluminescence images,and wall pressure,which verify the reliability of the numerical method.The results of non-reacting flow fields show that the BackwardFacing Step(BFS)can promote the flow separation downstream at a fixed distance.The more forward the separation position is,the larger the separation zone is in the non-reacting flow field.Furthermore,the larger the separation zone is,the higher the intensity of combustion in the reacting flow field is.A reasonable distance can reduce the total pressure loss generated by the shock waves in the combustor.The flame presents remarkable three-dimensional characteristics in the reacting flow fields.When dimensionless distance equals to 4.5,there are flames near the side wall above the cavity and it is difficult for the flame stabilization in the center of the combustor,while the combustion intensity in the center of the combustor is higher than that near the side wall when dimensionless distance equals to 7.5.In the cavity flameholding combustors with a backward-facing step,the higher combustion intensity may bring much total pressure loss to the combustor.Thus,it is a good choice to achieve better thrust performance when dimensionless distance equals to 4.5 compared to the other two combustors.展开更多
Human epidermal growth factor receptor 2 positive(HER2+)breast cancer,as a subtype with high invasiveness and poor prognosis,faces issues of intertumoral heterogeneity and signaling pathway dysregulation leading to tr...Human epidermal growth factor receptor 2 positive(HER2+)breast cancer,as a subtype with high invasiveness and poor prognosis,faces issues of intertumoral heterogeneity and signaling pathway dysregulation leading to trastuzumab resistance in clinical treatment.Therefore,innovative therapeutic strategies are urgently needed to enhance treatment efficacy and improve patient prognosis.In this study,we proposed an antibody-targeted nanoplatform responsive to the tumor microenvironment,aiming to induce ferroptosis in HER2+breast can-cer cells and thereby enhance the sensitivity to HER2-targeted drugs.Fe-MOF@Erastin@Herceptin(FEH)was prepared by loading Erastin onto mesoporous Fe-MOF and modifying it with trastuzumab(a HER2+breast cancer cell-specific antibody).This platform gradually releases trastuzumab,Erastin,and Fe3+in the tumor microenvironment.The modification of trastuzumab enhances tumor cell targeting while reducing toxicity to non-target cells and tissues.Erastin inhibits system XCto reduce glutathione(GSH)synthesis.Fe3+consumes glutathione and reduces itself to Fe2+via a reduction reaction,which further enhances the catalytic effect of H2O2 and triggers the Fenton reaction to generate large amounts of reactive oxygen species(ROS).In the antibody-targeted cascade reaction,decreased intracellular GSH content and increased Fe2+and ROS can further promote lipid peroxidation and down-regulation of glutathione peroxidase 4(GPX4)in breast cancer cells,inducing ferroptosis.The experimental results indicate that FEH can significantly improve the tumor microen-vironment by enhancing ferroptosis effects,providing a potential new strategy for precision therapy of HER2+breast cancer cells.展开更多
基金supported by the National Natural Science Foundation of China(Nos.11925207 and 12002381)the Scientific Research Plan of the National University of Defense Technology in 2019,China(No.ZK19-02)the Science and Technology Foundation of State Key Laboratory,China(No.6142703200311).
文摘The mixing and combustion characteristics in a cavity flameholding combustor under inlet Mach number 2.92 are numerically investigated with ethylene injection.Dimensionless distance is defined as the ratio of the actual distance to the height of the combustor entrance.The cavity shear-layer mode,the lifted cavity shear-layer mode,and jet wake mode with upstream separation are observed respectively with dimensionless distance equals to 1.5,4.5,and 7.5.In both non-reacting and reacting flow fields,the numerical results are essentially in agreement with the schlieren photography,flame chemiluminescence images,and wall pressure,which verify the reliability of the numerical method.The results of non-reacting flow fields show that the BackwardFacing Step(BFS)can promote the flow separation downstream at a fixed distance.The more forward the separation position is,the larger the separation zone is in the non-reacting flow field.Furthermore,the larger the separation zone is,the higher the intensity of combustion in the reacting flow field is.A reasonable distance can reduce the total pressure loss generated by the shock waves in the combustor.The flame presents remarkable three-dimensional characteristics in the reacting flow fields.When dimensionless distance equals to 4.5,there are flames near the side wall above the cavity and it is difficult for the flame stabilization in the center of the combustor,while the combustion intensity in the center of the combustor is higher than that near the side wall when dimensionless distance equals to 7.5.In the cavity flameholding combustors with a backward-facing step,the higher combustion intensity may bring much total pressure loss to the combustor.Thus,it is a good choice to achieve better thrust performance when dimensionless distance equals to 4.5 compared to the other two combustors.
基金supported by the National Natural Science Founda-tion of China(52171243 to Yu Wang and 52371256 to Yu Wang)Beijing Natural Science Foundation(2252058 to Zhiguang Fu).
文摘Human epidermal growth factor receptor 2 positive(HER2+)breast cancer,as a subtype with high invasiveness and poor prognosis,faces issues of intertumoral heterogeneity and signaling pathway dysregulation leading to trastuzumab resistance in clinical treatment.Therefore,innovative therapeutic strategies are urgently needed to enhance treatment efficacy and improve patient prognosis.In this study,we proposed an antibody-targeted nanoplatform responsive to the tumor microenvironment,aiming to induce ferroptosis in HER2+breast can-cer cells and thereby enhance the sensitivity to HER2-targeted drugs.Fe-MOF@Erastin@Herceptin(FEH)was prepared by loading Erastin onto mesoporous Fe-MOF and modifying it with trastuzumab(a HER2+breast cancer cell-specific antibody).This platform gradually releases trastuzumab,Erastin,and Fe3+in the tumor microenvironment.The modification of trastuzumab enhances tumor cell targeting while reducing toxicity to non-target cells and tissues.Erastin inhibits system XCto reduce glutathione(GSH)synthesis.Fe3+consumes glutathione and reduces itself to Fe2+via a reduction reaction,which further enhances the catalytic effect of H2O2 and triggers the Fenton reaction to generate large amounts of reactive oxygen species(ROS).In the antibody-targeted cascade reaction,decreased intracellular GSH content and increased Fe2+and ROS can further promote lipid peroxidation and down-regulation of glutathione peroxidase 4(GPX4)in breast cancer cells,inducing ferroptosis.The experimental results indicate that FEH can significantly improve the tumor microen-vironment by enhancing ferroptosis effects,providing a potential new strategy for precision therapy of HER2+breast cancer cells.
