Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production...Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.展开更多
为了寻求合理简化的流域地形指数水文模型TOPMODEL(Topographic Index model)用于大尺度的陆面模式,推导了土壤表层饱和导水率k0、衰减因子f和地下水补给速率R空间都可变的扩展的TOPMODEL,并将f空间非均匀分布的TOPMODEL与陆面模式SSiB...为了寻求合理简化的流域地形指数水文模型TOPMODEL(Topographic Index model)用于大尺度的陆面模式,推导了土壤表层饱和导水率k0、衰减因子f和地下水补给速率R空间都可变的扩展的TOPMODEL,并将f空间非均匀分布的TOPMODEL与陆面模式SSiB4耦合(SSiB4/GTOP)。通过耦合模型在f空间非均匀条件下进行实际流域的水文模拟,分析f空间非均匀对流域土壤湿度、蒸散发、地表径流、基流和总径流的影响。主要结论有:(1)k0和R的空间变化并不改变经典TOPMODEL原有关系式,只要定义新的地形指数,k0和R空间非均匀TOPMODEL与空间均匀的TOPMODEL并无区别;(2) f空间变化条件下由于局地的地下水埋深还与局地的f值有关,地形指数相同的区域具有水文相似性这一结论不再成立;(3)与f空间均匀的模拟结果相比较,f随海拔高度h i增加而线性减小使模拟的流域土壤湿度、地表径流和流域蒸散减小但使基流和总径流增加;(4) f空间非均匀对流域水文模拟结果有影响,但其影响明显小于流域地形因子的影响。展开更多
单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,...单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,提出直接表征DAB-DC/AC变换器效率的物理量:效率敏感因子。通过研究效率敏感因子对系统损耗的影响机理,实现变换器效率最优的硬件参数设计,为多参数耦合的单级式DAB-DC/AC变换器效率优化提供理论指导。最后通过一台450 W样机验证所提理论的正确性。展开更多
文摘Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.
文摘单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,提出直接表征DAB-DC/AC变换器效率的物理量:效率敏感因子。通过研究效率敏感因子对系统损耗的影响机理,实现变换器效率最优的硬件参数设计,为多参数耦合的单级式DAB-DC/AC变换器效率优化提供理论指导。最后通过一台450 W样机验证所提理论的正确性。
