目的:基于网络药理学和分子对接技术,探讨经验方归元膏的活性成分防治慢性疲劳综合征(CFS)的潜在机制。方法:从TCMSP数据库、BATMAN数据库筛选归元膏的化学成分和靶点,通过GeneCards、OMIM、DisGenet数据库检索收集CFS靶点,将归元膏作...目的:基于网络药理学和分子对接技术,探讨经验方归元膏的活性成分防治慢性疲劳综合征(CFS)的潜在机制。方法:从TCMSP数据库、BATMAN数据库筛选归元膏的化学成分和靶点,通过GeneCards、OMIM、DisGenet数据库检索收集CFS靶点,将归元膏作用靶点和疾病靶点取交集,使用Cytoscape Version 3.9.1制做药物和疾病靶点韦恩图,运用STRING数据库构建蛋白质与蛋白质相互作用的PPI网络作用图,并通过Cytoscape3.8.2软件中的插件CytoNCA筛选关键靶点,并将交集靶点导入David数据库,利用微生信程序进行基因本体(GO)和京都和基因组百科全书(KEGG)富集分析,并通过Cytoscape3.8.2构建归元膏药物–有效成分–靶点和归元膏药物–成分–靶点–通路网络,最后用AutoDock vinna软件进行分子对接验证。结果:检索出归元膏活性成分有111个,其中quercetin,isoflavanone,poriferasta-7,22E-dien-3beta-ol,hancinol,orchinol等为归元膏防治CFS的关键成分,CFS相关靶点507个,其中IL-6 (白细胞介素-6),TNF (肿瘤坏死因子),STAT3 (信号转导及转录激活因子3),JUN,BCL2 (B细胞淋巴瘤/白血病-2),HIF1A (缺氧诱导因子1α亚单位),AKT1 (AKT丝氨酸/苏氨酸激酶1),CASP3 (caspase-3),MMP9 (基质金属蛋白酶9),NFKB1 (核因子kappa B亚基1)为防治CFS的关键靶点,GO富集分析示生物学过程方面可能通过对凋亡过程的负调控、细胞增殖的正调控、蛋白质磷酸化的正调控、内皮细胞增殖的正调控等,分子功能主要包括酶结合、受体结合、蛋白酶结合等;细胞功能主要包含线粒体、蛋白质复合物、细胞内膜结合的细胞器等。KEGG富集分析一共得到186条信号通路,主要与PI3K-Akt通路、卡波西肉瘤相关疱疹病毒感染、丝裂原活化蛋白激酶信号通路等有关。分子对接结果表明归元膏中的核心作用靶点和主要活性成分具备稳定性的结合活性。结论:归元膏将quercetin、poriferasta-7,22E-dien-3beta-ol、orchinol、isoflavanone等关键活性成分与IL6、TNF、STAT3、JUN、BCL2、HIF1A、AKT1和CASP3等靶点结合,通过对PI3K/Akt、MAPK、NF-κB等多条信号通路的调控,调节了CFS患者的免疫反应、细胞凋亡、代谢紊乱等多个生物学过程。通过激活抗凋亡通路、抑制促炎因子的产生和调节能量代谢,验证了该方多靶点多线路的调控,发挥了多靶点、多通路的协同作用,显著改善了CFS的症状。Objective: Based on network pharmacology and molecular docking technology, this study explores the potential mechanisms of active ingredients in the empirical formula Guiyuan Ointment for the prevention and treatment of chronic fatigue syndrome (CFS). Methods: Chemical components and targets of Guiyuan Ointment were screened from the TCMSP database and BATMAN database. CFS targets were collected through GeneCards, OMIM, and DisGenet databases. The intersection of Guiyuan Ointment’s action targets and disease targets was taken. Cytoscape Version 3.9.1 was used to create a Venn diagram of drug and disease targets. The STRING database was employed to construct a protein-protein interaction (PPI) network diagram, and key targets were screened using the CytoNCA plugin in Cytoscape 3.8.2 software. The intersection targets were imported into the David database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the microbioinformatics program. Cytoscape 3.8.2 was used to construct the Guiyuan Ointment drug-effective component-target and drug-component-target-pathway networks. Finally, molecular docking validation was conducted using AutoDock Vina software. Results: A total of 111 active components of Guiyuan Ointment were retrieved, among which quercetin, isoflavanone, poriferasta-7,22E-dien-3beta-ol, hancinol, and orchinol are key components for the prevention and treatment of CFS by Guiyuan Ointment. There are 507 CFS-related targets, with IL-6 (interleukin-6), TNF (tumor necrosis factor), STAT3 (signal transducer and activator of transcription 3), JUN, BCL2 (B-cell lymphoma/leukemia-2), HIF1A (hypoxia-inducible factor 1α subunit), AKT1 (AKT serine/threonine kinase 1), CASP3 (caspase-3), MMP9 (matrix metallopeptidase 9), and NFKB1 (nuclear factor kappa B subunit 1) being key targets for the prevention and treatment of CFS. GO enrichment analysis showed that in terms of biological processes, it may involve negative regulation of apoptosis, positive regulation of cell proliferation, positive regulation of protein phosphorylation, and positive regulation of endothelial cell proliferation, etc. The main molecular functions include enzyme binding, receptor binding, and protease binding, etc. The main cellular functions involve mitochondria, protein complexes, and cell organelles bound to the intracellular membrane, etc. KEGG enrichment analysis yielded a total of 186 signaling pathways, mainly related to the PI3K-Akt pathway, Kaposi’s sarcoma-associated herpesvirus infection, and mitogen-activated protein kinase signaling pathway, etc. The molecular docking results indicated that the core action targets and main active components in Guiyuan Ointment have stable binding activity. Conclusion: Guiyuan Ointment combines key active components such as quercetin, poriferasta-7,22E-dien-3beta-ol, orchinol, and isoflavanone with targets like IL6, TNF, STAT3, JUN, BCL2, HIF1A, AKT1, and CASP3. By regulating multiple signaling pathways such as PI3K/Akt, MAPK, and NF-κB, it modulates various biological processes in CFS patients, including immune response, cell apoptosis, and metabolic disorders. Through activating anti-apoptotic pathways, inhibiting the production of pro-inflammatory factors, and regulating energy metabolism, it verifies the multi-target and multi-pathway regulation of this formula, exerting synergistic effects on multiple targets and pathways, and significantly improving the symptoms of CFS.展开更多
Hu Junhui,president of Tianfu Association(Singapore)and recipient of the Public Service Medal(PBM),has been leading community efforts to help new Chinese immigrants integrate into Singaporean society.Originally from H...Hu Junhui,president of Tianfu Association(Singapore)and recipient of the Public Service Medal(PBM),has been leading community efforts to help new Chinese immigrants integrate into Singaporean society.Originally from Hebei Province in China,Hu arrived in Singapore in 1994 as one of the first technical professionals dispatched by China.Since then,he has built a life and career firmly rooted in Singapore.Over more than four years at China Construction(South Pacific)Development Co Pte Ltd,he rose through the ranks from project engineer to site manager and eventually project director.In 1999,he left the company to start his own business,setting up a construction firm with several partners.His focus shifted to real estate in 2007,when he co-founded JVA Venture Pte Ltd.展开更多
Marine heatwaves(MHWs),which can exert devastating socioeconomic and ecological impacts,have attracted much public interest in recent years.In this study,we evaluate the sub-seasonal forecast skill of MHWs based on th...Marine heatwaves(MHWs),which can exert devastating socioeconomic and ecological impacts,have attracted much public interest in recent years.In this study,we evaluate the sub-seasonal forecast skill of MHWs based on the Nanjing University of Information Science&Technology Climate Forecast System version 1.1(NUIST CFS1.1)and analyze the related physical processes.Our results show that the model can accurately forecast the occurrence of MHWs on a global scale out to a lead time of 25 days.Notably,even at lead times of 51–55 days,the forecast skill in most tropical regions,as well as in the northeastern and southeastern Pacific,is superior to both random forecasts and persistence forecasts.Accurate predictions of sea level pressure,zonal currents,and mixed-layer depth are important for MHW forecasting.Furthermore,we also conduct forecast skill assessments for two well-documented MHW events.Due to its ability to correctly forecast the changes in heat flux anomalies at a lead time of 25 days,the model can accurately forecast the strong MHW event that occurred in the South China Sea in May–October 2020.However,the forecasting results were less than optimal for the strong MHW event that occurred along the Australian west coast in January–April 2011.Although the model accurately forecasts its occurrence,the forecast of its intensity is poor.Additionally,when the lead time exceeds 10 days,forecasts of the relevant physical processes of this MHW event are also inaccurate.展开更多
当地震波在地层中传播时,能量的衰减是传播介质非弹性性质的反映.这种介质所固有的衰减特性通常用品质因子(Quality Factor,Q)来描述.本文基于地震波在传播过程中主频降低的衰减特性,利用质心频率偏移法(Centrold Frequency Shift,简称C...当地震波在地层中传播时,能量的衰减是传播介质非弹性性质的反映.这种介质所固有的衰减特性通常用品质因子(Quality Factor,Q)来描述.本文基于地震波在传播过程中主频降低的衰减特性,利用质心频率偏移法(Centrold Frequency Shift,简称CFS)对零偏VSP正演模型进行Q值计算,分析薄层、上下行波场、频带宽度、反演波速、震源位置等因素的影响.模型结果显示:CFS法比频谱比法、振幅衰减法能更加准确识别薄层界面,可准确反演出厚度10m的地层;上行波场的加入降低反演结果准确度,尤其对高Q值层;当有效波频带增宽时,高频部分衰减明显,Q值反演结果接近理论值;反演波速误差对反演准确性影响很大.最后,利用CFS对实际井旁地面地震资料进行Q值反演,反Q滤波后其主频由25Hz提高到35Hz,分辨率得到改善,证明了CFS方法的实用性.展开更多
本文提出了一种新型的基于CFS特征选择和神经网络的高效入侵检测模型。通过使用该模型对经过特征提取后的攻击数据的训练学习,可以有效地识别各种入侵。在经典的KDD Cup 1999入侵检测数据集上的测试说明,该模型能够高效地对攻击模式进...本文提出了一种新型的基于CFS特征选择和神经网络的高效入侵检测模型。通过使用该模型对经过特征提取后的攻击数据的训练学习,可以有效地识别各种入侵。在经典的KDD Cup 1999入侵检测数据集上的测试说明,该模型能够高效地对攻击模式进行训练学习,从而正确有效地检测网络攻击。展开更多
文摘目的:基于网络药理学和分子对接技术,探讨经验方归元膏的活性成分防治慢性疲劳综合征(CFS)的潜在机制。方法:从TCMSP数据库、BATMAN数据库筛选归元膏的化学成分和靶点,通过GeneCards、OMIM、DisGenet数据库检索收集CFS靶点,将归元膏作用靶点和疾病靶点取交集,使用Cytoscape Version 3.9.1制做药物和疾病靶点韦恩图,运用STRING数据库构建蛋白质与蛋白质相互作用的PPI网络作用图,并通过Cytoscape3.8.2软件中的插件CytoNCA筛选关键靶点,并将交集靶点导入David数据库,利用微生信程序进行基因本体(GO)和京都和基因组百科全书(KEGG)富集分析,并通过Cytoscape3.8.2构建归元膏药物–有效成分–靶点和归元膏药物–成分–靶点–通路网络,最后用AutoDock vinna软件进行分子对接验证。结果:检索出归元膏活性成分有111个,其中quercetin,isoflavanone,poriferasta-7,22E-dien-3beta-ol,hancinol,orchinol等为归元膏防治CFS的关键成分,CFS相关靶点507个,其中IL-6 (白细胞介素-6),TNF (肿瘤坏死因子),STAT3 (信号转导及转录激活因子3),JUN,BCL2 (B细胞淋巴瘤/白血病-2),HIF1A (缺氧诱导因子1α亚单位),AKT1 (AKT丝氨酸/苏氨酸激酶1),CASP3 (caspase-3),MMP9 (基质金属蛋白酶9),NFKB1 (核因子kappa B亚基1)为防治CFS的关键靶点,GO富集分析示生物学过程方面可能通过对凋亡过程的负调控、细胞增殖的正调控、蛋白质磷酸化的正调控、内皮细胞增殖的正调控等,分子功能主要包括酶结合、受体结合、蛋白酶结合等;细胞功能主要包含线粒体、蛋白质复合物、细胞内膜结合的细胞器等。KEGG富集分析一共得到186条信号通路,主要与PI3K-Akt通路、卡波西肉瘤相关疱疹病毒感染、丝裂原活化蛋白激酶信号通路等有关。分子对接结果表明归元膏中的核心作用靶点和主要活性成分具备稳定性的结合活性。结论:归元膏将quercetin、poriferasta-7,22E-dien-3beta-ol、orchinol、isoflavanone等关键活性成分与IL6、TNF、STAT3、JUN、BCL2、HIF1A、AKT1和CASP3等靶点结合,通过对PI3K/Akt、MAPK、NF-κB等多条信号通路的调控,调节了CFS患者的免疫反应、细胞凋亡、代谢紊乱等多个生物学过程。通过激活抗凋亡通路、抑制促炎因子的产生和调节能量代谢,验证了该方多靶点多线路的调控,发挥了多靶点、多通路的协同作用,显著改善了CFS的症状。Objective: Based on network pharmacology and molecular docking technology, this study explores the potential mechanisms of active ingredients in the empirical formula Guiyuan Ointment for the prevention and treatment of chronic fatigue syndrome (CFS). Methods: Chemical components and targets of Guiyuan Ointment were screened from the TCMSP database and BATMAN database. CFS targets were collected through GeneCards, OMIM, and DisGenet databases. The intersection of Guiyuan Ointment’s action targets and disease targets was taken. Cytoscape Version 3.9.1 was used to create a Venn diagram of drug and disease targets. The STRING database was employed to construct a protein-protein interaction (PPI) network diagram, and key targets were screened using the CytoNCA plugin in Cytoscape 3.8.2 software. The intersection targets were imported into the David database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the microbioinformatics program. Cytoscape 3.8.2 was used to construct the Guiyuan Ointment drug-effective component-target and drug-component-target-pathway networks. Finally, molecular docking validation was conducted using AutoDock Vina software. Results: A total of 111 active components of Guiyuan Ointment were retrieved, among which quercetin, isoflavanone, poriferasta-7,22E-dien-3beta-ol, hancinol, and orchinol are key components for the prevention and treatment of CFS by Guiyuan Ointment. There are 507 CFS-related targets, with IL-6 (interleukin-6), TNF (tumor necrosis factor), STAT3 (signal transducer and activator of transcription 3), JUN, BCL2 (B-cell lymphoma/leukemia-2), HIF1A (hypoxia-inducible factor 1α subunit), AKT1 (AKT serine/threonine kinase 1), CASP3 (caspase-3), MMP9 (matrix metallopeptidase 9), and NFKB1 (nuclear factor kappa B subunit 1) being key targets for the prevention and treatment of CFS. GO enrichment analysis showed that in terms of biological processes, it may involve negative regulation of apoptosis, positive regulation of cell proliferation, positive regulation of protein phosphorylation, and positive regulation of endothelial cell proliferation, etc. The main molecular functions include enzyme binding, receptor binding, and protease binding, etc. The main cellular functions involve mitochondria, protein complexes, and cell organelles bound to the intracellular membrane, etc. KEGG enrichment analysis yielded a total of 186 signaling pathways, mainly related to the PI3K-Akt pathway, Kaposi’s sarcoma-associated herpesvirus infection, and mitogen-activated protein kinase signaling pathway, etc. The molecular docking results indicated that the core action targets and main active components in Guiyuan Ointment have stable binding activity. Conclusion: Guiyuan Ointment combines key active components such as quercetin, poriferasta-7,22E-dien-3beta-ol, orchinol, and isoflavanone with targets like IL6, TNF, STAT3, JUN, BCL2, HIF1A, AKT1, and CASP3. By regulating multiple signaling pathways such as PI3K/Akt, MAPK, and NF-κB, it modulates various biological processes in CFS patients, including immune response, cell apoptosis, and metabolic disorders. Through activating anti-apoptotic pathways, inhibiting the production of pro-inflammatory factors, and regulating energy metabolism, it verifies the multi-target and multi-pathway regulation of this formula, exerting synergistic effects on multiple targets and pathways, and significantly improving the symptoms of CFS.
文摘Hu Junhui,president of Tianfu Association(Singapore)and recipient of the Public Service Medal(PBM),has been leading community efforts to help new Chinese immigrants integrate into Singaporean society.Originally from Hebei Province in China,Hu arrived in Singapore in 1994 as one of the first technical professionals dispatched by China.Since then,he has built a life and career firmly rooted in Singapore.Over more than four years at China Construction(South Pacific)Development Co Pte Ltd,he rose through the ranks from project engineer to site manager and eventually project director.In 1999,he left the company to start his own business,setting up a construction firm with several partners.His focus shifted to real estate in 2007,when he co-founded JVA Venture Pte Ltd.
基金supported by National Natural Science Foundation of China(Grant Nos.42030605 and 42088101)National Key R&D Program of China(Grant No.2020YFA0608004)High Performance Computing of Nanjing University of Information Science&Technology for their support of this work。
文摘Marine heatwaves(MHWs),which can exert devastating socioeconomic and ecological impacts,have attracted much public interest in recent years.In this study,we evaluate the sub-seasonal forecast skill of MHWs based on the Nanjing University of Information Science&Technology Climate Forecast System version 1.1(NUIST CFS1.1)and analyze the related physical processes.Our results show that the model can accurately forecast the occurrence of MHWs on a global scale out to a lead time of 25 days.Notably,even at lead times of 51–55 days,the forecast skill in most tropical regions,as well as in the northeastern and southeastern Pacific,is superior to both random forecasts and persistence forecasts.Accurate predictions of sea level pressure,zonal currents,and mixed-layer depth are important for MHW forecasting.Furthermore,we also conduct forecast skill assessments for two well-documented MHW events.Due to its ability to correctly forecast the changes in heat flux anomalies at a lead time of 25 days,the model can accurately forecast the strong MHW event that occurred in the South China Sea in May–October 2020.However,the forecasting results were less than optimal for the strong MHW event that occurred along the Australian west coast in January–April 2011.Although the model accurately forecasts its occurrence,the forecast of its intensity is poor.Additionally,when the lead time exceeds 10 days,forecasts of the relevant physical processes of this MHW event are also inaccurate.
文摘当地震波在地层中传播时,能量的衰减是传播介质非弹性性质的反映.这种介质所固有的衰减特性通常用品质因子(Quality Factor,Q)来描述.本文基于地震波在传播过程中主频降低的衰减特性,利用质心频率偏移法(Centrold Frequency Shift,简称CFS)对零偏VSP正演模型进行Q值计算,分析薄层、上下行波场、频带宽度、反演波速、震源位置等因素的影响.模型结果显示:CFS法比频谱比法、振幅衰减法能更加准确识别薄层界面,可准确反演出厚度10m的地层;上行波场的加入降低反演结果准确度,尤其对高Q值层;当有效波频带增宽时,高频部分衰减明显,Q值反演结果接近理论值;反演波速误差对反演准确性影响很大.最后,利用CFS对实际井旁地面地震资料进行Q值反演,反Q滤波后其主频由25Hz提高到35Hz,分辨率得到改善,证明了CFS方法的实用性.
