Network pharmacology to decipher the mechanism of Danggui Longhui Wan against chronic myeloid leukemia

Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway:Network Pharmacology Analysis and Experimental Validation

Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.

Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation

Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.

基于SD-WAN的企业快速组网探究与应用

企业广域网组网技术,具有传输效率不高、网络延迟大等缺陷,不能满足现代企业高效率传输要求。SD-WAN是当前较为先进的企业组网技术,优势颇多,将其应用在企业中,不仅可以和现有的多协议标记交换(Multi-Protocol Lab Switching,MPLS)实现无缝对接,保证业务的连续性,还能在端到端监控网络状态。鉴于此,本文即围绕SD-WAN展开,对基于SD-WAN的企业快速组网深入研究。

SD-WAN结合边缘智能在纸板生产车间的研究和实践

文章研究了软件定义广域网(Software-Defined Wide Area Networking,SD-WAN)结合边缘智能在瓦楞纸板生产车间中的应用。该研究的目标是提升瓦楞纸板生产车间的网络性能、安全性和管理效率。通过使用SD-WAN技术,该车间可以实现网络虚拟化、智能路由和实时监控,从而提高网络通信的可靠性和稳定性。SD-WAN与边缘智能的结合使网络资源得以高效利用,优化路由决策,并实现主动的网络管理。该研究对于推动工业环境中的网络技术发展具有重要意义,为瓦楞纸板制造业提供了提高生产效率、降低成本以及提升运营灵活性的机遇。

SD-WAN技术在图书馆馆际组网中的应用

【目的】分析VPN技术、专线技术及SD-WAN等组网技术特点,选用SD-WAN技术来组建图书馆馆际网络,可实现不同图书馆间的数字资源共建共享、信息系统良好复用。【方法】以国家图书馆、省级图书馆为例,提出组网原则、网络架构、地址规划等,以福建省图书馆为例进行组网实践。【结果】对国家图书馆、福建省图书馆网络连通性进行测试,无网络丢包现象,可相互访问,运行结果正常,组网成功。【结论】SD-WAN技术可用于图书馆馆际间的组网,接入到SDWAN专网的节点间,可实现网络资源的稳定传输。

MEC-Empowered Non-Terrestrial Network for 6G Wide-Area Time-Sensitive Internet of Things

In the upcoming sixth-generation(6G)era,the demand for constructing a wide-area time-sensitive Internet of Things(IoT)continues to increase.As conventional cellular technologies are difficult to directly use for wide-area time-sensitive IoT,it is beneficial to use non-terrestrial infrastructures,including satellites and unmanned aerial vehicles(UAVs).Thus,we can build a non-terrestrial network(NTN)using a cell-free architecture.Driven by the time-sensitive requirements and uneven distribution of IoT devices,the NTN must be empowered using mobile edge computing(MEC)while providing oasisoriented on-demand coverage for devices.Nevertheless,communication and MEC systems are coupled with each other under the influence of a complex propagation environment in the MEC-empowered NTN,which makes it difficult to coordinate the resources.In this study,we propose a process-oriented framework to design communication and MEC systems in a time-division manner.In this framework,large-scale channel state information(CSI)is used to characterize the complex propagation environment at an affordable cost,where a nonconvex latency minimization problem is formulated.Subsequently,the approximated problem is provided,and it can be decomposed into sub-problems.These sub-problems are then solved iteratively.The simulation results demonstrated the superiority of the proposed process-oriented scheme over other algorithms,implied that the payload deployments of UAVs should be appropriately predesigned to improve the efficiency of using resources,and confirmed that it is advantageous to integrate NTN with MEC for wide-area time-sensitive IoT.

基于拥塞及内存感知的SD-WAN故障恢复

在软件定义广域网(SD-WAN)中,链路故障会导致大量丢包,严重时会引起部分网络瘫痪.现有的流量工程方法通过在数据平面提前安装备份路径能够加快故障恢复过程,但在资源受限的情况下难以适应各种网络故障情况,从而使恢复后的网络性能下降.为了保证网络在故障恢复之后的性能并减少备份资源的消耗,本文提出一种基于拥塞及内存感知的主动式故障恢复方案(CAMA),不仅能够将受影响数据流进行快速重定向,还能实现负载均衡避免恢复后潜在的链路拥塞.实验结果表明,与已有方案相比, CAMA能有效利用备份资源,在负载均衡上有较好的性能,且仅需少量备份规则即可覆盖所有单链路故障情况.

Positioning with Wide-Area GNSS Networks: Concept and Application

The use of Global Navigation Satellite Systems (GNSS) for positioning has revolutionized the way location data is be- ing collected. The NAVigation System with Time And Ranging Global Positioning System (GPS), which is a principal component of the global navigation satellite system (GNSS);is a satellite-based radio navigation system that provides positions of points of interest and time information to users. GPS positional accuracy can be improved by using differential corrections obtained through a technique called Differential GPS (DGPS), which is known to provide the most accurate positioning results. Differential correction can be applied in real time at the data collection phase or in the of- fice, at the post-processing phase. DGPS is generally used for positioning purposes through static or kinematics GPS surveys. In static GPS surveys, one receiver is placed at a point whose coordinates are known and the other receiver is placed over a point whose coordinates are desired. In kinematic surveys, one receiver remains at one point (base station) normally with known coordinates, and the other receiver (rover) moves from point to point in the project area. Kinematic surveys in which points positions are computed on-the-fly (OTF) are known as real-time kinematic (RTK). RTK surveys provide real-time locations of points of interest needed in many applications. Positioning with wide-area GNSS networks is basically based on the DGPS and RTK concepts. Observables from a network of a finite number of GPS receivers over an area are processed by a server at a central location (network server) and made available to the users of the network later or in real-time through radio-based, satellite, or wireless communications. This article provides a review of the concept and application of positioning with wide-area GNSS networks.

SD-WAN在企业组网中的运用

随着云计算、物联网等新兴技术的不断发展,传统企业网络已经无法满足大规模数据传输和处理的需求。软件定义广域网络(Software-Defined networking in a Wide Area Network,SD-WAN)作为一种新型的企业网络架构方案,具有较高的可扩展性、灵活性和可管理性,成为企业网络升级的重要选择。通过对SD-WAN技术在不同企业组网中的应用和SD-WAN网络设计关键技术的介绍,深入剖析其优势和特点,并分析SD-WAN应用过程面临的挑战和解决方案,探讨未来SD-WAN技术的趋势和发展方向。

Discussion on the mechanism of Xiaoyao Wan in the treatment of depression and anxiety based on network pharmacology

In order to clarify the targets of Xiaoyao Wan in the treatment of depression and anxiety,the pharmacological database of traditional Chinese medicine system and the analysis platform(TCMSP)were used to search the chemical components and potential targets of Xiaoyao Wan.The databases of Malacards and Genecards were used to mine the targets related to depression and anxiety.With the help of Cytoscape3.2.1 software,the“Xiaoyao Wan-targets-diseases”network is constructed.The PPI network is constructed through String database.Common targets are enriched by cluster Profiler software package in R language.161 active components of Xiaoyao Wan were screened,and 247 targets related to Xiaoyao Wan were predicted(excluding repetitive targets).The related targets of depression and anxiety were 379,337 respectively.Through the intersection of Venny diagram,24 targets of Xiaoyao Wan,depression and anxiety were obtained.24 key targets were screened out by constructing the interaction network of Xiaoyao Wan,depression and anxiety.Pathway enrichment analysis showed that Xiaoyao Wan mainly acts on key targets involves D(2)dopamine receptor(DRD2),Interleukin-6(IL6),5-hydroxytryptamine receptor 2A(HTR2A),Interleukin-1 beta(IL1B),5-hydroxytryptamine receptor 3A(HTR3A),Sodium-dependent dopamine transporter(SLC6A3),D(1A)dopamine receptor(DRD1),Interleukin-10(IL10),Sodium-dependent noradrenaline transporterin(SLC6A2)and other key targets in the treatment of depression and anxiety,and participates in important pathway processes such as Serotonergic synapse,Dopaminergic synapse,Neuroactive ligand-receptor interaction and regulation of neurotransmitter levels.It is speculated that Xiaoyao Wan plays a role in the treatment of depression and anxiety by affecting neurotransmitters 5-HT and DA,participating in hypothalamic-pituitary-adrenal(HPA)and interfering in the process of inflammation.

基于LoRaWAN的机场跑道警戒灯运行状态监视系统的设计与应用

随着物联网技术的快速发展,为解决无法及时监控反馈跑道警戒灯工作状态的问题,切实提高机场的运行安全裕度,完善跑道安全管理,文章在运用LoRaWAN技术手段实时监控远端警示灯工作状态的同时,通过统筹考虑软硬件设计提出充分利用无线广域网技术的解决方案。

基于SD-WAN技术的企业组网研究

企业广域网组网技术,一直受到传输效率低、网络延迟大、组网成本高等问题的制约。为此,该文将软件定义网络和广域网技术结合运用,为企业广域网设计基于SD-WAN(软件定义广域网)的架构模式。在这种架构中,充分运用SD-WAN技术,通过控制器单元、CPE单元、POP单元的配置,实现企业网和公共网络的高效对接。为了进一步提高传输效率,提出一种新的加速方案。实验结果表明,在该文构建的企业广域网架构下,经过该文提出的加速方案处理,视频信息流和文本信息流的传输实时性都得到明显改善。

基于5G网络与SD-WAN技术的政企专线应急保障方案

政企专线是面向政府、企业提供的高价值通信服务,往往具备较高的保障要求。由于市政施工等外部因素对光缆线路的破坏,导致政企专线中断且抢修时长不可控,通过结合5G网络与SD-WAN技术,提出了一种适用多种政企专线业务的应急保障方案,引入云端交换设备与运营商网络对接,并通过VLAN隔离与路由疏导技术实现政企业务的快速抢通。

一种面向SD-WAN的协议无感知快速源路由转发方案

针对OpenFlow协议依赖的局限性,提出一种将协议无感知转发(POF)技术应用在软件定义广域网(SD-WAN)环境下的快速源路由转发方案。该方案利用POF的高可编程性特征,通过重构源路由包头字段来封装完整的转发路径,采用POF提供的流指令集实现交换机的包处理算法,且在多级流表设计中采用流水线的方式。通过抽象和重用相同的匹配逻辑,减少了整个网络中的流表条目数,提高系统的转发效率和扩展性。基于Mininet搭建了POF实验平台并在单链路拓扑和多播树拓扑2种环境下通过泛洪流量进行测试,实验结果表明,将POF技术运用在SD-WAN中能够获得更好的源路由转发性能。

基于网络药理学和分子对接技术探析缩泉丸治疗膀胱过度活动症的作用机制

目的:通过网络药理学和分子对接技术探析缩泉丸治疗膀胱过度活动症(Overactive Bladder,OAB)的分子机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获得缩泉丸活性成分,利用Uniprot数据库获取缩泉丸活性成分对应的靶标基因。从OMIM、Gene Cards、Drug Bank数据库中检索得到OAB有关靶点,并取活性成分靶点和OAB相关靶点的交集以得出共同靶点。Cytoscape 3.9.1软件被用来绘制中药-活性成分-靶点网络图以直观显示活性成分与靶点之间的相互作用,并将共同靶点上传到STRING数据库用来挖掘网络中的核心靶点。采用Metascape数据库对共同靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后运用Auto Dock Tools 1.5.7对缩泉丸的核心成分与核心靶点进行分子对接验证。结果:研究发现缩泉丸通过槲皮素、豆甾醇、β-谷甾醇等核心成分,作用于丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase1,AKT1)、白细胞介素(Interleukin,IL)-6、IL-1B、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等核心靶点,调节缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)信号通路、钙信号通路、环磷酸鸟苷(Cyclic Guanosine Monophosphate,c GMP)-蛋白激酶G(Protein Kinase G,PKG)信号通路等,并且参与对氮化合物、有机环化合物、蛋白质磷酸化等生物学过程以治疗OAB。分子对接结果表明缩泉丸中的豆甾醇、β-谷甾醇与AKT1、肿瘤蛋白p53(Tumor Protein p53,TP53)、IL-6、TNF等核心靶点均具有较好的结合活性。结论:本研究通过网络药理学和分子对接技术阐释了缩泉丸调节OAB的潜在成分、靶点及通路,为进一步研究缩泉丸治疗OAB的具体机制提供了方向。

基于网络药理学、分子对接及细胞实验验证探讨二至丸治疗多发性骨髓瘤的作用机制

【目的】基于网络药理学、分子对接及细胞实验验证探讨二至丸治疗多发性骨髓瘤(MM)的潜在作用机制。【方法】应用网络药理学、分子对接筛选药物-疾病-靶标-通路关键指标。培养多发性骨髓瘤细胞株RPMI-8226,给予二至丸干预,采用膜联蛋白V(Annexin V)-异硫氰酸荧光素(FITC)染色法检测细胞凋亡,Transwell实验测定细胞侵袭能力,实时定量聚合酶链反应(qRT-PCR)法检测蛋白激酶B(Akt)、细胞周期蛋白D1(CCND1)、糖原合酶激酶3β(GSK-3β)、c-MycmRNA表达,Western Blot法检测细胞Akt、磷酸化蛋白激酶B(p-Akt)、CCND1、c-Myc、GSK-3β、磷酸化糖原合酶激酶3β(p-GSK-3β)蛋白表达。【结果】获得二至丸14个有效成分。二至丸治疗MM涉及靶点142个,通路富集分析结果显示关键靶点可能主要集中在癌症通路、脂质与动脉粥样硬化等。分子对接结果显示,木樨草素和槲皮素与GSK-3β有较好的结合活性及稳定性。进一步细胞实验验证发现,与空白组比较,二至丸低、中、高剂量组细胞凋亡率显著升高,细胞侵袭数减少,GSK-3β的mRNA和蛋白水平显著升高,CCND1、Akt和c-Myc的mRNA和蛋白水平显著降低,呈剂量依赖性,其中,中、高剂量组差异均有统计学意义(P<0.05或P<0.01)。【结论】二至丸对MM的治疗作用可能是通过木犀草素和槲皮素等关键活性成分,促进GSK-3β表达,并抑制Akt/GSK-3β/CCND1/c-Myc信号通路来实现的。

基于网络药理学探讨桂枝茯苓丸治疗急性脑梗死的作用机制及体内验证

目的基于网络药理学的研究方法探讨桂枝茯苓丸治疗急性脑梗死的作用机制。方法在中药系统药理数据库及分析平台(TCMSP)数据库中收集桂枝茯苓丸的主要活性成分,设置口服利用度(OB)≥30%,类药性(DL)≥0.18为筛选条件;使用GeneCards、OMIM、DrugBank数据库收集急性脑梗死的作用靶点,获得桂枝茯苓丸与疾病的交集靶点,绘制交集韦恩图;利用BisoGenet构建PPI网络,通过Cytoscape提取核心靶点;获取关键靶点蛋白后利用Metascape进行GO功能及KEGG通路富集分析。结果利用TCMSP检索共获得桂枝茯苓丸有效成分65个,主要为槲皮素、β-谷甾醇、齿孔酸、猪苓酸C、白花素等;筛选出桂枝茯苓丸治疗急性脑梗死的关键靶点135个,包括TP53、MCM2、UBC等;涉及细胞周期信号通路、泛素介导的蛋白降解信号通路、PI3K-Akt信号通路等119条相关信号通路;分子对接结果显示多个化合物与蛋白的结合能≤8 kJ/moL;实验组的tp53、UBC基因表达量较模型组的低,PI3K、P-Akt蛋白表达量较模型组的高(P<0.05)。结论桂枝茯苓丸治疗急性脑梗死具有多通路、多靶点的特点,为今后研究桂枝茯苓丸治疗急性脑梗死的机制提供了科学的理论依据及研究思路。

高效灵活的双WAN口路由器应用详解

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