Exploring the mechanism of action of herb pair Pinellia Ternata-Magnolia Officinalis in the treatment of liver cancer based on network pharmacology and molecular docking

Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.

Characteristics of Magnetic Tribology on High Flux Pair of Magnetic Driving Mechanism

The rectangle-like pulsed magnetic field acted on the rubbing pair was presented through analyzing the exciting property in the reciprocating travel. The test of wear in NG-x tester shows that the wear between the electromagnetic core and down magnetic board distributes in the high velocity slip region of reciprocating travel, and the adhesive wear in the low velocity slip region nearby up and down dead points is depressed owing to the presence of high flux magnetic field. The lubrication by magnetic fluid with high permeability effectively reduces the friction and wear of high flux rubbing pair, and improves the conducting property of magnetic circuit constructed by the rubbing pair, which is beneficial to increase the operation performance of magnetic driving mechanism.

Effects of carrier density and interactions on pairing symmetry in a t_(2g) model

By utilizing the fluctuation exchange approximation method,we perform a study on the superconducting pairing symmetry in a t_(2g) three-orbital model on the square lattice.Although the tight-binding parameters of the model are based on Sr_(2)RuO_(4),we have systematically studied the evolution of superconducting pairing symmetry with the carrier density and interactions,making our findings relevant to a broader range of material systems.Under a moderate Hund’s coupling,we find that spin fluctuations dominate the superconducting pairing,leading to a prevalent spin-singlet pairing with a d_(x^(2)-y^(2))-wave symmetry for the carrier density within the range of n=1.5-4 per site.By reducing the Hund’s coupling,the charge fluctuations are enhanced and play a crucial role in determining the pairing symmetry,leading to a transition of the pairing symmetry from the spin-singlet d_(x^(2)-y^(2))-wave to the spin-triplet p-wave.Furthermore,we find that the superconducting pairings are orbital dependent.As the carrier density changes from n=4 to n=1.5,the active orbitals for superconducting pairing shift from the quasi-two-dimensional orbital dxy to the quasi-one-dimensional orbitals d_(xz) and d_(yz).

Mechanism of Magnoliae Flos and Xanthii Fructus herb pair in treatment of allergic rhinitis based on network pharmacology

Objective: To explore the molecular mechanism of Magnoliae Flos and Xanthii Fructus herb pair for allergic rhinitis based on network pharmacology. Methods: From the Traditional Chinese Medicine Systems Pharmacology database, Uniprot database, and Gene Cards database, the relevant chemical constituents information, pharmacokinetic information and hub target of allergic rhinitis were obtained. The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. The screened target information was analyzed by the Metascape database for Gene Ontology biological function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Results: Main components of Magnoliae Flos and Xanthii Fructus herb pair, such as aloe-emodin, stigmasterol, beta-sitosterol and Yangambin, depend on the interaction of Nitric Oxide Synthase 3, Tumor Necrosis Factor, Caspase-3 and other functions involve G protein-coupled (amine) receptor activity, RNA polymerase II basic transcription factor binding, protease binding, heme binding, and integrin binding;can regulate calcium signal pathway, serotonergic synapse, Kyoto Encyclopedia of Genes and Genomes signal pathway, tryptophan inflammatory mediator regulation pathway, estrogen signal pathway alone or in combination, and play a role in the treatment of allergic rhinitis. Conclusion: Magnoliae Flos combined with Xanthii Fructus can regulate biomolecular network in multiple targets and pathways to treat allergic rhinitis.

Reaction mechanism of hydrogen activation by frustrated Lewis pairs

Typically, a Lewis acid and a Lewis base can react with each other and form a classical Lewis adduct. The neutralization reaction can however be prevented by ligating the acid and base with bulky substituents and the resulting complex is known as a "frustrated Lewis pair"(FLP). Since the Lewis acid and base reactivity remains in the formed complex, FLPs can display interesting chemical activities, with promising applications in catalysis. For example, FLPs were shown to function as the first metal-free catalyst for molecular hydrogen activation. This, and other recent applications of FLPs, have opened a new thriving research field. In this short-review, we recapitulate the computational and experimental studies of the H_2 activation by FLPs. We discuss the thus-far uncovered mechanistic aspects, including pre-organization of FLPs,the reaction paths for the activation, the polarization of He H bond and other factors affecting the reactivity. We aim to provide a rather complete mechanistic picture of the H_2 activation by FLPs, which has been under debate for decades since the first discovery of FLPs. This review is meant as a starting point for future studies and a guideline for industrial applications.

DFT Study on Reaction Mechanism of DNA Base Pair with Hydroxyl Radical

In order to elucidate the indirect effect by radiation on DNA base pairs, we investigate the mechanism for the attacking reaction of a hydroxyl radical (·OH-radical) to the G-C and A-T base pairs, by the density functional theory (DFT) calculations. The effect of solvation on the mechanism is also revealed by performing the same DFT calculations under the continuum solvation approximation. We find the stable structures for the dehydrogenated G-C and A-T base pairs, in which the hydrogen atom of NH2 group of G or A base is abstracted by the ·OH-radical. The solvation around the base pairs stabilizes the dehydrogenated structures significantly, indicating the acceleration of the attacking reaction by ·OH-radical to the base pairs in water. Therefore, we conclude that the hydrogen atom of the NH2 group of G or A base in the G-C and A-T base pairs is the most preferably abstracted by the ·OH-radical in living cells.

A Method for Automatically Establishing a Mathematical Model of Kinematic Analysis to a Planar Mechanism with a Multiple Joint and Prismatic Pair

A method for automatically establishing a mathematical model of kinematic analysis to a planar mechanism with multiple joint and prismatic pair is presented. The breadth （ or depth ） first search spanning tree can be obtained based on an adjacency matrix of the mechanism. Then the kinematic chain （or mechanism）＇s basic loops can be obtained. On the basis of these basic loops, a mathematical model of kinematic analysis can be established and solved automatically. In the sense of a calculative mechanism, structural analysis of the kinematic chain relates to the kinematic analysis of a mechanism. Thus, an effective way is supplied to the given mechanism＇s kinematic analysis for automatic modeling and solving, and a method is supplied to the structural type to optimize kinematic synthesis.

Study on the mechanism of two related Chinese herbs Chenpi-Banxia in the treatment of coronary microvascular dysfunction based on network pharmacology

Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction(CMD).Methods:Obtaining potential active compounds of Chenpi-Banxia from TCMSP,while the targets for CMD were obtained from DrugBank and OMIM databases.Using UniProt database to query the corresponding gene name.The key target of Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction can be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG Pathway analyses of major targets were performed by using the DAVID database and use Binformatics to draw bubble map.Finally,the ingredient-major arget-key pathway network was constructed by Cytoscape3.7.1.Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and 56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3K-Akt signaling pathway),Vascular endothelial growth factor signaling pathway(VEGF signaling pathway),Apoptosis related pathways(Apoptosis)and Hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the Compounds-Target-Pathway network.Conclusion:The study verified the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology.It predicted that Chenpi-Banxia couldtreat Coronary Microvascular Dysfunction mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.

Mechanism of "Epimedium-Cistanche deserticola" in the treatment of breast cancer with bone metastasis

Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mechanism has not been fully clarified. Methods: In this study, the network pharmacology and bioinformatics technology were used to explore the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis. TCMSP, TCM database@Taiwan and TCMID databases were used to screen the main effective components of the drug. Swiss Target Prediction and STITCH databases were used to search the potential target of action of Epimedium and Cistanche deserticola. Genecards, OMIN and Drugbank databases were used to search the cause of bone metastasis of breast cancer. The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis, A visualized network of "drug - component - target - signaling pathway" was constructed by using the software of Cytoscape 3.6.0, and the core genes were screened out. Results: The study found that there are 30 main effective components of Epimedium and Cistanche deserticola, and 544 genes are involved in the potential therapeutic targets, among which 101 genes are potential targets of Epimedium and Cistanche deserticola in the treatment of breast cancer bone metastasis. Through the analysis of GO and KEGG pathways, we found that the mechanisms involved in antitumor, osteoblast differentiation, osteoclast apoptosis and regulation of bone microenvironment, such as apoptosis, osteoclast differentiation, PI3K-Akt, HIF-1 signaling pathway, T cell receptor signaling pathway, etc. TP53, VEGFA, AKT1, EGFR, SRC, CCND1, MAPK3, ESR1 may be the key genes in the treatment of breast cancer bone metastasis. Conclusion: In this study, the network of "drug - component - target- signaling pathway" was constructed through network pharmacology, and it was found that the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis involves multiple targets and pathways, which is conducive to guiding clinical medication.

The Kinematics Analysis of Heald Selecting Mechanism of Rotary Electronic Dobby

In order to improve the reliability of the mechanical movement of the rotary electronic dobby, the kinematics analysis of the heald selection mechanism is carried out and the simulation is carried out with Matlab. Firstly, the operation mechanism of the heald selection mechanism is analyzed in detail. The conjugate cam is mapped. The cam profile curve is fitted with cubic spline interpolation. Secondly, based on the overall analysis method and the complex vector method, the kinematics analysis of the key components after the high pair low generation is performed, and the angular displacement and angular velocity of each component are calculated with the rotation of the active cam. Finally, the movement curve diagram is drawn with Matlab, which lays the foundation for the dynamic analysis and in-depth study of the selection mechanism in the future.

考虑润滑间隙效应的空间并联机构动力学优化

为了改善润滑间隙效应引起的空间并联机构动态性能的渐变劣化问题,以3-RRPaR冗余并联机构为研究对象,提出一种考虑润滑间隙效应的空间并联机构动力学优化方法。建立了考虑润滑转动副间隙的3-RRPaR冗余并联机构动力学模型;以优化末端执行器的动力学响应误差和优化间隙关节处的约束反力为目的设置目标函数,通过优化末端执行器质量以及转动惯量的方式来缓解运动副间隙导致的劣化效应,建立了考虑润滑间隙效应3-RRPaR冗余并联机构动力学优化模型;试验验证了所建动力学模型的有效性,对比分析两种目标函数对优化效果的影响以选择最佳优化方式,并分析优化前后考虑润滑间隙效应的空间并联机构动力学特性,结果表明动力学优化使润滑间隙转动副处约束反力峰值降低16.16%,为改善间隙效应提高空间并联机构动态性能提供了理论支撑。

丹参-当归治疗缺血性脑卒中作用机制网络药理学研究

目的探讨丹参-当归治疗缺血性脑卒中(CIS)的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Swiss TargetPrediction数据库获取丹参和当归的活性成分及作用靶点,并通过检索PubMed、中国知网相关文献进行补充;通过GeneCards、人类孟德尔遗传数据库(OMIM)、DisGeNET数据库获取CIS的潜在靶点;将丹参-当归治疗CIS的共有靶点导入String 11.0平台,构建活性成分与疾病靶点蛋白的蛋白相互作用(PPI)网络,利用Cytoscape 3.8.2软件构建疾病-药物-活性成分-靶点可视化网络;将共有靶点导入DAVID数据库进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,并利用Cytoscape 3.8.2软件构建活性成分-核心靶点-通路网络;利用AutoDock软件对疾病-药物-活性成分-靶点网络中度值排名前6的核心靶点和活性成分进行分子对接验证。结果共检索到82种活性成分,其中丹参65个、当归17个,潜在作用靶点787个,疾病靶点671个,共有靶点76个。度值排名前6的活性成分为丹参醇B、丹参新醌D、木犀草素、阿魏酸、藁本内酯、丹参酮ⅡA,核心靶点为MAPK14,MAPK1,AKT1,PTGS2,EGFR,JAK2。共获得GO功能条目2545个,其中生物学过程2244个,细胞组成128个,分子功能173个,分别涉及对脂多糖的反应、膜筏、内肽酶活性等;KEGG信号通路152条,主要涉及PI3K-Akt信号通路、脂质和动脉粥样硬化、钙信号通路等。分子对接结果证明了6种活性成分与其相应核心靶点均有较好的结合活性。结论丹参-当归治疗CIS具有多成分-多靶点-多通路的调控特点,其作用机制可能与抗炎、抗氧化应激、抗神经细胞凋亡、调节自噬功能等有关。

基于硬质WC涂层的不同摩擦副间的摩擦磨损特性及损伤机制研究

目的探究硬质WC-12Co涂层与摩擦副间的力学性能、摩擦磨损特性的对应关系。方法采用超音速火焰喷涂(HVOF)技术制备WC-12Co硬质涂层,利用SEM、XRD、EDS等分析涂层的微观形貌、物相组成和元素分布规律等,研究该涂层与不同对偶配副的摩擦学性能及摩擦磨损机理等。结果采用HVOF技术制备的WC-12Co涂层中各元素及物相分布均匀,涂层的显微硬度约为1103.8HV0.3,纳米硬度约为20.47GPa。涂层和不同对偶配副的干摩擦因数均在0.80以上,磨损率在10^(-6)mm^(3/)(N·m)量级,其中与Al_(2)O_(3)对偶球配副时摩擦因数(约0.81)最低,与WC-6Co对偶球配副时摩擦因数(约0.85)最大,在与Al_(2)O_(3)配副时磨损率最大,约为11.09×10^(-6)mm^(3)/(N·m),与GCr15配副时磨损率最小,约为1.60×10^(-6)mm^(3)/(N·m)。结论硬质WC-12Co涂层致密均匀,其力学性能优异,与不同材质对偶球配副时其磨损机制有所不同,导致摩擦副间的摩擦因数和磨损率略有差异,但其耐磨性均良好,可以根据实际应用工况特点选择不同的摩擦副,以保证硬质碳化钨涂层的安全稳定长效服役。

中药单味药、药对及复方治疗睡眠障碍的研究进展

睡眠是人类不可或缺的生理活动,约占人生中1/3的时间。人体需要借助适当的睡眠来完成身体机能及大脑认知学习的恢复等关键生理功能。近年来,睡眠障碍的发病率呈上升趋势,西医治疗睡眠障碍虽取得一定疗效,但仍存在诸多问题,而中药以其不良反应小、疗效显著的优势受到广泛关注。对中药单味药、药对、复方治疗睡眠障碍的研究进展和作用机制进行归纳总结,以期为中药防治睡眠障碍的临床应用研究提供参考。

融合边界处理机制的学习型麻雀搜索算法

为改善麻雀搜索算法(SSA)初始化阶段种群分布不充分,寻优过程中容易受到局部最优解干扰的不足,提出融合边界处理机制的学习型麻雀搜索算法(HSSA)。使用Piecewise map初始化种群,提高种群的分散程度;使用排序配对学习与竞争学习策略分别更新跟随者和警戒者,确保各代的最优解信息能够引导下一代的位置更新;自适应的警戒者数量使得警戒者作用被强调,提供灵活的应变机制;根据不同阶段的寻优特点制定多策略边界处理机制,保留住种群数量的同时,为超出边界的个体提供更加合理的搜索位置。经过12个基准函数的仿真实验,并借助消融实验、Wilcoxon秩和检验等证明了HSSA在收敛速度上的稳定性和寻优的高效性。

从网络药理学分析马齿苋-地锦草药对配伍治疗溃疡性结肠炎作用机制

目的运用网络药理学技术探讨马齿苋-地锦草药对治疗溃疡性结肠炎(UC)作用机制。方法通过TCMSP数据库获取马齿苋-地锦草的有效活性成分,利用Uniprot3.7.2数据库预测活性成分作用靶点,通过Gene-Cards数据库、OMIM数据库获取疾病基因,将药物与疾病基因取交集后利用STRING数据库研究二者相关性,并根据结果分析其潜在作用机制。结果经过筛选得到目标药对关键靶点蛋白61个和分子信号通路169条,基因本体(GO)功能富集分析显示主要有炎症反应、凋亡过程的负调控、脂多糖的细胞反应等生物过程;京都基因和基因组百科全书(KEGG)富集分析显示马齿苋-地锦草治疗UC主要通过肿瘤坏死因子(TNF)信号通路、核因子κB信号通路、Toll样受体信号通路、NOD样受体信号通路等发挥作用。结论马齿苋-地锦草药对治疗UC具有多靶点、通路复杂、层次分明的特点,马齿苋-地锦草潜在作用机制为日后临床治疗UC提供理论依据,并拓展了临床运用中医药治疗UC的思路。

基于网络药理学探讨“麦冬-五味子”药对治疗心肌纤维化的机制

目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共同靶点;通过Cytoscape软件构建“药物活性成分-疾病-靶点”网络模型;利用微生信平台进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用STRING数据库构建蛋白互作网络;通过Auto Dock Tools1.5.6软件进行分子对接验证。结果“麦冬-五味子”药对中共筛选得到戈米辛M2、五味子酚乙、麦冬二氢高异黄酮B等85个活性成分,主要作用于HSP90AA1、AKT1、SRC等163个心肌纤维化靶点上,主要富集在脂质与动脉粥样硬化信号通路、糖尿病并发症中的age-rage信号通路、癌症发病途径信号通路等相关通路上。结论“麦冬-五味子”药对主要通过调控炎性反应、氧化应激、脂质沉积、细胞增殖凋亡等多种生物过程来抑制心肌纤维化。

最近对寻址的专利实体关系抽取方法

针对专利领域没有公开数据集的问题,标注一个中文专利实体关系抽取数据集PERD(patent entity relation dataset)。为完成实体关系抽取任务,提出最近对寻址的实体关系抽取模型NPAM(nearest pair addressing entity relationship extraction model),实体位置信息获取方法的改进、注意力机制建模矩阵和实体抽取方法的创新,使该模型在PERD上F1值达到72.74%,相比模型PRGC提升12.64个百分点。实验结果验证了该模型的有效性。

药对何首乌-牛膝抗骨质疏松的作用机制研究

目的:利用网络药理学研究牛膝何首乌联用抗骨质疏松的作用机制。方法:运用中药系统药理学数据库与分析平台(TCMSP)与文献检索筛选何首乌、牛膝两味中药所含的活性成分。利用Disgent数据库搜索与骨质疏松相关的蛋白靶点;利用Pubchem平台,预测何首乌、牛膝所含活性成分所作用的人类蛋白靶点。分析牛膝何首乌药的交集靶点,并将交集靶点进行蛋白网络分析,构建药物-成分-靶点的网络图。通过微生信平台对关键基因作用的靶向细胞进行富集分析。结果:确定何首乌成分5个,牛膝成分10个,二者共有成分1个,获得药对与疾病交集基因35个;PPI蛋白分析获得10个主要作用成分;绘制GO分析可视图、KEGG分析可视图并对其进行解析,解析结果表明何首乌牛膝主要成分通过抑制骨吸收,诱导骨形成等通路来减轻骨质疏松症的发展。结论:牛膝何首乌药对抗骨质疏松的作用机制可能是通过靶点与共有通路完成的,并且该药对可通过多通路、多靶点、多成分、多层次发挥对骨质疏松症的治疗作用。