链路预测是通过已知的网络拓扑和节点属性挖掘未来时刻节点潜在关系的重要手段,是预测缺失链路和识别虚假链路的有效方法,在研究社会网络结构演化中具有现实意义.传统的链路预测方法基于节点信息或路径信息相似性进行预测,然而,前者考...链路预测是通过已知的网络拓扑和节点属性挖掘未来时刻节点潜在关系的重要手段,是预测缺失链路和识别虚假链路的有效方法,在研究社会网络结构演化中具有现实意义.传统的链路预测方法基于节点信息或路径信息相似性进行预测,然而,前者考虑指标单一导致预测精度受限,后者由于计算复杂度过高不适合在规模较大网络中应用.通过对网络拓扑结构的分析,本文提出一种基于节点交互度(interacting degree of nodes,IDN)的社会网络链路预测方法.该方法首先根据网络中节点间的路径特征,引入了节点效率的概念,从而提高对于没有公共邻居节点之间链路预测的准确性;为了进一步挖掘节点间共同邻居的相关属性,借助分析节点间共同邻居的拓扑结构,该方法还创新性地整合了路径特征和局部信息,提出了社会网络节点交互度的定义,准确刻画出节点间的相似度,从而增强网络链路的预测能力;最后,本文借助6个真实网络数据集对IDN方法进行验证,实验结果表明,相比于目前的主流算法,本文提出的方法在AUC和Precision两个评价指标上均表现出更优的预测性能,预测结果平均分别提升22%和54%.因此节点交互度的提出在链路预测方面具有很高的可行性和有效性.展开更多
Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possi...Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, D-galactosamine/LPS(GalN/LPS)-treated mice and cycloheximide/TNFα(CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell(HSC)activation/proliferation and prevented fibrosis. Elevated bile acid(BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.展开更多
文摘链路预测是通过已知的网络拓扑和节点属性挖掘未来时刻节点潜在关系的重要手段,是预测缺失链路和识别虚假链路的有效方法,在研究社会网络结构演化中具有现实意义.传统的链路预测方法基于节点信息或路径信息相似性进行预测,然而,前者考虑指标单一导致预测精度受限,后者由于计算复杂度过高不适合在规模较大网络中应用.通过对网络拓扑结构的分析,本文提出一种基于节点交互度(interacting degree of nodes,IDN)的社会网络链路预测方法.该方法首先根据网络中节点间的路径特征,引入了节点效率的概念,从而提高对于没有公共邻居节点之间链路预测的准确性;为了进一步挖掘节点间共同邻居的相关属性,借助分析节点间共同邻居的拓扑结构,该方法还创新性地整合了路径特征和局部信息,提出了社会网络节点交互度的定义,准确刻画出节点间的相似度,从而增强网络链路的预测能力;最后,本文借助6个真实网络数据集对IDN方法进行验证,实验结果表明,相比于目前的主流算法,本文提出的方法在AUC和Precision两个评价指标上均表现出更优的预测性能,预测结果平均分别提升22%和54%.因此节点交互度的提出在链路预测方面具有很高的可行性和有效性.
基金supported by National Natural Science Foundation of China (grants 81430091, 81720108032, 81421005, 91429308 and 81603194)the Project for Major New Drug Innovation and Development (grant 2015ZX09501010 and 2017ZX09101003-002-003, China)+3 种基金Overseas Expertise Introduction Project for Discipline Innovation (G20582017001, China)"Double First Class" Initiative Project (CPU2018GF01 and CPU2018GF09, China)State Key Laboratory of Natural Medicines at China Pharmaceutical University (SKLNMZZCX201610 and SKLNMZZCX201801, China)China Postdoctoral Science Foundation (grants 2016M600455 and 2017T100423)
文摘Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, D-galactosamine/LPS(GalN/LPS)-treated mice and cycloheximide/TNFα(CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell(HSC)activation/proliferation and prevented fibrosis. Elevated bile acid(BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.
