运营突发事件下,向城市轨道交通(城轨)乘客有针对性地发布诱导信息,是实现高效疏导、确保城轨运营安全的重要举措。本文考虑乘客异质性,开展突发事件下城轨诱导信息发布策略研究。首先,基于潜在分类模型(Latent Class Model,LCM)构建城...运营突发事件下,向城市轨道交通(城轨)乘客有针对性地发布诱导信息,是实现高效疏导、确保城轨运营安全的重要举措。本文考虑乘客异质性,开展突发事件下城轨诱导信息发布策略研究。首先,基于潜在分类模型(Latent Class Model,LCM)构建城轨乘客在突发事件和诱导信息双重作用下的路径选择行为模型,分析乘客对诱导信息接受程度及路径选择偏好的差异。其次,以线网乘客总出行时间和线网客流分布均衡性基尼系数为优化目标,构建基于路径选择行为分析的信息诱导优化模型,并应用非支配排序遗传算法(Non-dominated Sorting Genetic AlgorithmⅡ,NSGA-Ⅱ)求解,以获得突发事件下受影响起讫点(Origin and Destination,OD)间各有效路径的最优推荐指数。最后,以北京市工作日早高峰城轨区域线网进行案例分析。结果表明:城轨乘客在突发事件下对诱导信息存在“诱导服从型”“诱导中立型”“诱导无视型”这3类不同接受程度的群体。提供诱导信息后,线网乘客总出行时间减少3.906%,线网客流分布均衡性基尼系数下降4.063%,同时减少了高满载率区间数量。事件结束后,诱导信息的继续发布可降低突发事件受影响区间7.08%的满载率,并避免乘客在刚恢复正常运营区间上的再次聚集。展开更多
Porcine reproductive and respiratory syndrome(PRRS)is recognized as one of the most infectious viral diseases of swine.Although Cluster of differentiation 163(CD163)is identified as an essential receptor for mediating...Porcine reproductive and respiratory syndrome(PRRS)is recognized as one of the most infectious viral diseases of swine.Although Cluster of differentiation 163(CD163)is identified as an essential receptor for mediating PRRS virus(PRRSV)infection,the important residues involved in infection on CD163 are still unclear.Therefore,it is very important to identify these key residues to study the mechanism of PRRSV infection and to generate anti-PRRSV pigs.In this study,we first generated immortalized porcine alveolar macrophage(IPAM)cell lines harboring 40-residues(residues 523-562,including R561(arginine(R)at position 561))deletion of CD163.PRRSV infection experiments showed that these IPAM cell lines were completely resistant to PRRSV infection.We then generated cloned pigs carrying CD163-R561A(an arginine(R)to alanine(A)substitution at position 561 of CD163).PRRSV challenge experiments in porcine alveolar macrophages(PAMs)isolated from the CD163-R561A pigs showed significantly lower susceptibility to PRRSV than that of CD163-R561 PAMs.Through this study,we show that CD163523-562 contains essential residues for mediating PRRSV infection,and that CD163 R561 significantly contributes to PRRSV infection but is not essential for infection.These functional sites can therefore serve as new targets for understanding the mechanism of PRRSV infection.Furthermore,CD163-R561A pigs can be used as an important model for improving pig germplasm with resistance against PRRSV.展开更多
Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:...Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.展开更多
文摘运营突发事件下,向城市轨道交通(城轨)乘客有针对性地发布诱导信息,是实现高效疏导、确保城轨运营安全的重要举措。本文考虑乘客异质性,开展突发事件下城轨诱导信息发布策略研究。首先,基于潜在分类模型(Latent Class Model,LCM)构建城轨乘客在突发事件和诱导信息双重作用下的路径选择行为模型,分析乘客对诱导信息接受程度及路径选择偏好的差异。其次,以线网乘客总出行时间和线网客流分布均衡性基尼系数为优化目标,构建基于路径选择行为分析的信息诱导优化模型,并应用非支配排序遗传算法(Non-dominated Sorting Genetic AlgorithmⅡ,NSGA-Ⅱ)求解,以获得突发事件下受影响起讫点(Origin and Destination,OD)间各有效路径的最优推荐指数。最后,以北京市工作日早高峰城轨区域线网进行案例分析。结果表明:城轨乘客在突发事件下对诱导信息存在“诱导服从型”“诱导中立型”“诱导无视型”这3类不同接受程度的群体。提供诱导信息后,线网乘客总出行时间减少3.906%,线网客流分布均衡性基尼系数下降4.063%,同时减少了高满载率区间数量。事件结束后,诱导信息的继续发布可降低突发事件受影响区间7.08%的满载率,并避免乘客在刚恢复正常运营区间上的再次聚集。
基金supported by the Major Scientific Research Tasks for Scientific and Technological Innovation Projects of the Chinese Academy of Agricultural Sciences(CAAS-ZDRW202006)the National Transgenic Breeding Project,China(2018ZX08009-26B)+1 种基金the Shenzhen Science and Technology Plan Project,China(CJGJZD20210408092402006)the Shenzhen Key Technology Projects,China(JSGG20180507182028625).
文摘Porcine reproductive and respiratory syndrome(PRRS)is recognized as one of the most infectious viral diseases of swine.Although Cluster of differentiation 163(CD163)is identified as an essential receptor for mediating PRRS virus(PRRSV)infection,the important residues involved in infection on CD163 are still unclear.Therefore,it is very important to identify these key residues to study the mechanism of PRRSV infection and to generate anti-PRRSV pigs.In this study,we first generated immortalized porcine alveolar macrophage(IPAM)cell lines harboring 40-residues(residues 523-562,including R561(arginine(R)at position 561))deletion of CD163.PRRSV infection experiments showed that these IPAM cell lines were completely resistant to PRRSV infection.We then generated cloned pigs carrying CD163-R561A(an arginine(R)to alanine(A)substitution at position 561 of CD163).PRRSV challenge experiments in porcine alveolar macrophages(PAMs)isolated from the CD163-R561A pigs showed significantly lower susceptibility to PRRSV than that of CD163-R561 PAMs.Through this study,we show that CD163523-562 contains essential residues for mediating PRRSV infection,and that CD163 R561 significantly contributes to PRRSV infection but is not essential for infection.These functional sites can therefore serve as new targets for understanding the mechanism of PRRSV infection.Furthermore,CD163-R561A pigs can be used as an important model for improving pig germplasm with resistance against PRRSV.
基金Guangxi Science and Technology Base and Talent Project (Guike AD20297013)Guangxi Natural Science Foundat ion Project (2021GXNSFBA220036)The second batch of"Qihuang Project"High-Level Talent Team Cultivation Project of Guangxi University of Traditional Chinese Medicine (2021001)。
文摘Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.
