Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibi...Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 pathway.We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their in-teraction.Results showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM co-culture.Additionally,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by TAMs.The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity observed.Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture system.Importantly,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway.Overall,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.展开更多
基金supported by the National Natural Science Foundation of China(No.82274512)Guangzhou Science and Technology Project(No.202201020327)+1 种基金Collaborative basic and clinical Innovation project between Guangdong Hospital of Chinese Medicine and the School of Biomedical Sciences of the Chinese University of Hong Kong(No.YN2018HK02)Guangdong basic and Applied basic Research Fund(No.2023A1515110708).
文摘Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 pathway.We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their in-teraction.Results showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM co-culture.Additionally,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by TAMs.The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity observed.Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture system.Importantly,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway.Overall,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.
文摘随着移动边缘计算(mobile edge computing,MEC)技术的不断演进发展,大量的用户设备分散在边缘服务器密集部署的各个区域内。然而,在任务时延与资源受限的前提下,如何选择合适的服务器进行任务卸载,仍然是一个具有挑战性的难题。研究用户-服务器关联、卸载比例以及资源分配的联合优化问题,在考虑需求和服务异构性下最小化系统能耗。该问题被建模为混合整数非线性规划问题,并分解为用户-服务器关联子问题、卸载率和资源分配子问题进行求解。对于第一个子问题,在同时考虑通信质量与服务类型条件下,利用改良的带权匈牙利算法(Kuhn-Munkres matching algorithm,K-M)实现用户-服务器关联。为了处理第二个高度非凸问题,提出一种有效的双层算法,内层采用拉格朗日对偶法得到计算与通信资源分配;外层采用一维搜索方法得到卸载比例。最后,利用块坐标下降技术交替求解两个子问题,直到收敛。仿真结果表明,与随机算法、贪婪算法和带权匈牙利匹配-本地计算(Kuhn-Munkres matching and local computing,KM-LC)算法相比,文中所提出的算法能有效降低系统能耗。
