Although 2D MoS2 alone shows excellent gas-sensing performance, it is prone to stacking when used as the sensitive layer, resulting in insufficient contact with the target gas and lower sensitivity. To solve this, a 2D-MoS2/1D-CuPc heterojunction was prepared with different weight ratios of MoS2 nanosheets to CuPc micro-nanowires, and its room-temperature gas-sensing properties were studied. The response of the 2D-MoS2/1D-CuPc heterojunction to a target gas was related to the weight ratio of MoS2 to CuPc. When the weight ratio of MoS2 to CuPc was 20:7 (7-CM), the gas sensitivity of MoS2/CuPc composites was the best. Compared with the pure MoS2 sensor, the responses of 7-CM to 1000 ppm formaldehyde (CH2O), acetone (C3H6O), ethanol (C2H6O), and 98% RH increased by 122.7, 734.6, 1639.8, and 440.5, respectively. The response of the heterojunction toward C2H6O was twice that of C3H6O and 13 times that of CH2O. In addition, the response time of all sensors was less than 60 s, and the recovery time was less than 10 s. These results provide an experimental reference for the development of high-performance MoS2-based gas sensors.

Grinding-assisted liquid-phase exfoliation is a widely used method for the preparation of two-dimensional nanomaterials. In this study, N-methylpyrrolidone and acetonitrile, two common grinding solvents, were used during the liquid-phase exfoliation for the preparation of MoS2 nanosheets. The morphology and structure of MoS2 nanosheets were analyzed via scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. The effects of grinding solvents on the gas-sensing performance of the MoS2 nanosheets were investigated for the first time. The results show that the sensitivities of MoS2 nanosheet exfoliation with N-methylpyrrolidone were 2.4-, 1.4-, 1.9-, and 2.7-fold higher than exfoliation with acetonitrile in the presence of formaldehyde, acetone, and ethanol and 98% relative humidity, respectively. MoS2 nanosheet exfoliation with N-methylpyrrolidone also has fast response and recovery characteristics to 50–1000 ppm of CH2O. Accordingly, although N-methylpyrrolidone cannot be removed completely from the surface of MoS2, it has good gas sensitivity compared with other samples. Therefore, N-methylpyrrolidone is preferred for the preparation of gas-sensitive MoS2 nanosheets in grinding-assisted liquid-phase exfoliation. The results provide an experimental basis for the preparation of two-dimensional materials and their application in gas sensors.

Reduning Injection (RDNI) is a traditional Chinese medicine formula indicated for the treatment of inflammatory diseases. However, the molecular mechanism of RDNI is unclear. The information of RDNI ingredients was collected from previous studies. Targets of them were obtained by data mining and molecular docking. The information of targets and related pathways was collected in UniProt and KEGG. Networks were constructed and analyzed by Cytoscape to identify key compounds, targets, and pathways. Data mining and molecular docking identified 11 compounds, 84 targets, and 201 pathways that are related to the anti-inflammatory activity of RDNI. Network analysis identified two key compounds (caffeic acid and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) which would play critical roles in the treatment of inflammatory diseases by RDNI. The cross-talks among pathways provided a deeper understanding of anti-inflammatory effect of RDNI. RDNI is capable of regulating multiple biological processes and treating inflammation at a systems level. Network pharmacology is a practical approach to explore the therapeutic mechanism of TCM for complex disease.

Objectives: Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work, but the roles of metabonomics biomarkers in the pathogenesis of psoriasis is unclear. Methods: The metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. The binding affinity between each metabonomics biomarker and target was calculated by molecular docking. A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways. Results: long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers. Most key enzymes belonged hydrolase, thioesterase and acyltransferase. Six proteins (TNF-alpha, MAPK3, iNOS, eNOS, COX2 and mTOR) were extensively involved in inflammatory reaction, immune response and cell proliferation, and might be drug targets for psoriasis. PI3K-Akt signaling pathway and five other pathways had dose correlation with the pathogenesis of psoriasis and could deserve further research. Conclusions: The inflammatory reaction, immune response and cell proliferation are mainly involved in psoriasis. Network pharmacology provide a new insight into the relationships between metabonomics biomarkers and the pathogenesis of psoriasis.

Objective:To explore the multi-target effects of Bushen Zhuangjin decoction(BSZJD)in delaying cataplasia of articular cartilage from the molecular level, and give a pharmacodynamic illustration for the theory of "treatment for flaccidity aims at the origin". Methods:Based on the simulation platforms of molecular docking and biological network, the targets of cataplasia of articular cartilage including matrix metalloproteinase(MMP)-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-11 and MMP-13 were chosen as subject, their active-sites were built by respectively original ligand. The interaction between targets and compounds in BSZJD was studied by molecular docking. BSZJD compound-target network of delaying cataplasia of articular cartilage was constructed. The functional characteristic of BSZJD was studied by biological network. Results:Total of potential active compounds was 106, which mainly belong to saponins, and 33 compounds among them had good interaction with one target, while 40 and 33 compounds had good interaction with two targets and more than two targets, respectively. The average number of targets was 2.3 in each compound contained in compound-target network model, and every target was related to 13.2 compounds on average. Moreover, the majority of compounds acted on few targets, while three compounds acted on a large number of targets, up to a maximum of seven. The relations between BSZJD compounds and targets followed the power function p(k)=k-1.6429, which revealed the interaction between BSZJD compounds and targets existed the nonlinear regulation pattern of "one to many, many to one". Conclusion:BSZJD effects for delaying cataplasia of articular cartilage exist multi-target effects. Furthermore, the compounds in BSZJD work mainly by ways of promiscuous drug in the therapy of OA. This comes up an explanation about BSZJD therapeutical effect for OA based on the theory of "treatment for flaccidity aims at the origin". The results also provide a certain reference and inspiration for discovering new drugs from BSZJD for treatment of OA.

"网络药理学与生物医药发展国际论坛"于2018年8月23-25日在江苏省连云港市召开。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局和连云港市人民政府共同主办,中国药理学会网络药理学专业委员会承办,江苏康缘药业股份有限公司协办,中国药理学会网络药理学专业委员会主任委员周文霞教授和常务委员、江苏康缘药业股份有限公司董事长肖伟教授共同担任论坛主席。有来自美国、澳大利亚、奥地利、中国大陆和中国澳门等多个国家和地区的97名代表出席本次论坛。国家卫生健康委员会科技教育司监察刘登峰专员应邀参会。论坛针对国际、国内网络药理学研究的现状、最新进展和发展前沿等有关问题进行了综合讨论,展示了该研究领域的新技术、新进展和新应用。为促进国内外学术交流,本文对部分专家的观点和意见进行了整理,以期为促进我国网络药理学和生物医药研究与发展起到积极的推动作用。

目的:从分子水平揭示白芍治疗类风湿关节炎的作用.方法:从北京大学天然产物库中搜索白芍的化学成分,通过分子对接和生物网络技术,研究白芍化合物与类风湿关节炎相关通路重要靶点的相互作用.结果:模拟筛选出来白芍有效成分群25个化合物,为苷类、多酚类、黄酮类和有机酸类化合物,能与p38 MAPK、JNK和PI3K-AKT信号通路中重要靶点p38、JNK-1、JNK-3、PI3Kα、PI3Kβ 和PI3Kδ有相互作用.结论:网络药理学直观显示了白芍治疗类风湿关节炎的多成分、多靶点和多通路作用,为后续从白芍中开发出治疗类风湿关节炎的新药提供了依据.

Abstract Introduction: Psoriasis is a refractory skin disorder, and usually requires a lifetime control. Traditional Chinese medicine (TCM) is effective and safe for this disease. However, the cellular and molecular mechanisms of TCM remedies for psoriasis are still not fully understood. TCM contains numerous natural products. Natural products have historically been invaluable as a resource of therapeutic agents. Yet, there is no integrated information about active compounds of TCM for psoriasis. Method: We use systems pharmacology methods to develop the Psoriasis Database of Traditional Chinese Medicine (PDTCM). The database covered a number of psoriasis-related information (formulas, TCM, compounds, target proteins, diseases and biomarkers). With these data information, an online platform was constructed Results: PDTCM comprises 38 empirical therapeutic formulas, 34373 compounds from 1424 medicinal plants, 44 psoriasis-related proteins and 76 biomarkers from 111 related diseases. On this platform, users can screen active compounds for a psoriasis-related target and explore molecular mechanisms of TCM. Accordingly, users can also download the retrieved structures and data information with a defined value set. In addition, it helps to get a better understanding of Chinese prescriptions in disease treatment. Conclusion: With the systems pharmacology-based data, PDTCM would become a valuable resource for TCM in psoriasis-related research. Key messages PDTCM platform comprises a great deal of data on TCM and psoriasis. On this platform, users can retrieve and get needed information with systems pharmacology methods, such as active compounds screening, target prediction and molecular mechanisms exploration. It is a tool for psoriasis-related research on natural drugs systematically.

Objective:To investigate analgesic functional chemome characteristics of Radix Saposhnikoviae (RS), and provide information on molecular basis for clinical application of RS in Bi syndrome therapy.Methods:The chemical components of RS were retrieved from the Handbook of the Constituents in Chinese Herb Original Plants and other literatures, and the molecular dataset of RS was constructed for computer simulation. Tumor necrosis factor alpha (TNF-α), p38, inducible nitric oxide synthase (iNOS) and phosphodiesterase 4A (PDE-4A) were considered as analgesic targets. The analgesic functional chemome of RS was identified by molecular docking. The drug/drug-like molecules correlated to p38, TNF-α, iNOS and PDE-4A were retrieved from therapeutic targets database (TTD). The analgesic functional chemome characteristics of RS were dissected by comparing the chemical space and compound-target network characteristics of the RS analgesic functional chemome to those of drug/drug-like molecules.Results:49 compounds, which mainly contained glycosides, flavonoids, coumarins, organic acids, etc., composed pharmacodynamic material basis of RS. These compounds had discrete chemical space, and most of them had similar chemical space with drug/drug-like molecules. The average target number correlated with each compound within the compound-target network was 1.20 in the analgesic functional chemome of RS and 1.05 in the drug/drug-like molecules, and each average target number was correlated with 12.25 compounds and 5.50 compounds, respectively. The number of compounds interacted with≥2 targets was eight in the analgesic functional chemome of RS and one in the drug/drug-like molecules.Conclusion:Computer simulation could intuitively trace out the analgesic function of RS. The functional chemome of RS had better multi-target effects compared with drug/drug-like molecules, and became an important source on mining promiscuous drugs from RS.

Neurodegenerative diseases, referring to as the progressive loss of structure and function of neurons, constitute one of the major challenges of modern medicine. Traditional Chinese herbs have been used as a major preventive and therapeutic strategy against disease for thousands years. The numerous species of medicinal herbs and Traditional Chinese Medicine (TCM) compound formulas in nervous system disease therapy make it a large chemical resource library for drug discovery. In this work, we collected 7362 kinds of herbs and 58,147 Traditional Chinese medicinal compounds (Tcmcs). The predicted active compounds in herbs have good oral bioavailability and central nervous system (CNS) permeability. The molecular docking and network analysis were employed to analyze the effects of herbs on neurodegenerative diseases. In order to evaluate the predicted efficacy of herbs, automated text mining was utilized to exhaustively search in PubMed by some related keywords. After that, receiver operator characteristic (ROC) curves was used to estimate the accuracy of predictions. Our study suggested that most herbs were distributed in family of Asteraceae, Fabaceae, Lamiaceae and Apocynaceae. The predictive model yielded good sensitivity and specificity with the AUC values above 0.800. At last, 504 kinds of herbs were obtained by using the optimal cutoff values in ROC curves. These 504 herbs would be the most potential herb resources for neurodegenerative diseases treatment. This study would give us an opportunity to use these herbs as a chemical resource library for drug discovery of anti-neurodegenerative disease.

Inflammation is a protective biological response to body/tissue damage that involves immune cells, blood vessels and molecular mediators. In this work, we constructed the pathway network of inflammation, including 11 sub-pathways of inflammatory factors. Pathway-based network efficiency and network flux were adopted to evaluate drug efficacy. By using approved and experimentally validated anti-inflammatory drugs as training sets, a predictive model was built to screen potential anti-inflammatory drugs from approved drugs in DrugBank. This drug repositioning approach would bring a fast and cheap way to find new indications for approved drugs. Moreover, molecular phenomics profiles of the expression of inflammatory factors will provide new insight into the drug mechanism of action.

目的:研究元胡止痛胶囊治疗头痛和痛经的药效物质和分子作用机制.方法:采用分子对接、分子-靶蛋白网络特征分析以及靶蛋白-生物通路信息挖掘的方法研究元胡止痛胶囊中分子与靶蛋白的相互作用.结果:分子对接与网络分析发现元胡止痛胶囊中有63个活性成分,且大部分具有良好的生物利用度和血脑屏障通透性,其中Coptisine,Protopine,Berberine等17个为其主要活性成分,可通过与GluA2,iNOS,AKR1 C2,ROCK1等28个靶蛋白相互作用,一方面降低疼痛信号的感知和传递,另一方面调控血管/子宫平滑肌的舒张与收缩,进而达到缓解疼痛的治疗作用.结论:通过数据分析确定了元胡止痛胶囊止痛的分子作用机制和主要活性成分,有助于减少后续药效物质基础和分子作用机制实验研究的盲目性.

Huatan Tongluo Fang (HTTLF) is a traditional herbal formula that can resolve phlegm and dredge collaterals. HTTLF has also been used to treat rheumatoid arthritis (RA); however, the mechanism underlying the therapeutic effects of HTTLF on RA has not been clearly elucidated at the molecular level. In the present study, an integrated model of system pharmacology containing chemical space analysis, potential active compound prediction and compound-target-disease network was constructed to investigate the molecular mechanisms of HTTLF. The compounds from HTTLF dispersed well in the chemical space. Most of the compounds from HTTLF had similar chemical spaces to drug/drug-like compounds associated with RA, according to the MDL Drug Data Report. A total of 127 potentially active compounds and 17 targets of RA were identified. Among them, 50 compounds interacted with ≥2 targets, while 77 compounds interacted with only one target. In addition, 17 targets were associated with 82 diseases that belonged to 26 categories. These results indicate that HTTLF has diverse chemical spaces and polypharmacology with regards to the treatment of RA. In addition, HTTLF demonstrated therapeutic potential against diverse diseases other than RA, including osteoarthritis, atherosclerosis and brain cancer. This study provides a novel platform for understanding how HTTLF treats RA; this is beneficial for explaining the diverse functions of HTTLF with regards to RA, and may help develop novel compounds with desirable therapeutic targets to treat RA.

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.

目的 探索桂枝茯苓胶囊治疗痛经、子宫肌瘤和盆腔炎的分子作用机制和潜在活性成分群.方法 通过文献挖掘、多个数据库联用检索与痛经、盆腔炎以及子宫肌瘤疾病相关的130个靶蛋白基础上,利用分子计算结合网络特征分析获得桂枝茯苓胶囊的主要活性成分和潜在的靶点蛋白,并将其投射到KEGG数据库阐释桂枝茯苓胶囊的分子作用机制.结果 数据分析结果表明,与蛋白相互作用较强的115个活性分子主要分布在桂枝和茯苓中,进一步的网络特征分析发现高网络度和介数的分子主要为五环三萜类和甾醇类化合物;与化合物作用的绝大部分靶蛋白(78.57％)分布在与痛经、盆腔炎及子宫肌瘤密切相关的15条生物通路中,而这些通路涉及到子宫平滑肌的增殖和收缩,子宫内的血管形成和血液循环,雌激素和黄体酮等多种激素的分泌,以及前列腺素等炎症因子合成或释放和相关钙通道的调控等.结论 桂枝茯苓胶囊主要是由其所含的五环三萜类和甾醇类化合物与多个靶点蛋白作用,调控多条生物通路(如arachidonic acid metabolism,calcium signaling pathway,GnRH signaling pathway,complement and coagulation cascades,progesterone-mediated oocyte maturation)来抑制子宫平滑肌收缩和增殖、改善微循环、降低激素分泌和炎症反应(如PGE2,PGF2α,leukotriene B4),从而起到缓解痛经和盆腔炎引起的疼痛、改善子宫肌瘤患者的生活质量的作用.

G-quadruplexes have been reported to exist both in human genome and transcriptome and are of great interests due to their important biological functions. Up to now, the formation and property of G-quadruplex in human mature microRNAs has not been explored yet. In this study, we discovered that hsa-miR-3620-5p, a guanine rich human mature microRNA, could fold into a stable parallel G-quadruplex in near physiological condition for the first time. We explored the formation, folding pattern and binding affinity of the miR-3620-5p G-quadruplex by ESI-MS, CD, NMR and SPR. The results indicated that its high-order structure was comprised of three G-quartets with two bases in each parallel loop stretching outward and two bases flanking at each end. In addition, sanguinarine, a natural alkaloid screened from traditional Chinese medicine was characterized to have high binding affinity and thermodynamic stabilization effects through π–π stacking interaction with the external G-quartets. Furthermore, the potent interaction of sanguinarine with miR-3620-5p G-quadruplex could block the base pairing between miR-3620-5p and its target sequence. Therefore, our study revealed the possibility of regulating microRNA functions using potent G-quadruplex binders, and could provide a new approach to affect the microRNA:mRNA interactions.

Objective: To explore pharmacodynamic material basis and molecular mechanism of Wutou Tang in pain relief. Methods: Based on the simulation platform of Discovery Studio, the molecular set of Wutou Tang was built and compared with drug set of anti-inflammatory and analgesic actions from DrugBank database in chemical space. After that, network pharmacology based on molecular docking was used to explore the interactions of Wutou Tang and targets related to pain. Results: The molecular sets of Wutou Tang and drugs had better overlaps in chemical space. The main pharmacodynamic material basis of Wutou Tang contains alkaloids, flavonoids, saponins. They could act on six targets including inducible nitric oxide synthase (iNOS), p38, C-Jun N-terminal Kinase 1 (JNK-1), tumor necrosis factor-α (TNF-α), phosphodiesterase 4A (PDE-4A) and Kappa-type opioid receptor. Conclusion: Wutou Tang can mainly act on p38 MAPK and JNK signaling pathways, and has multiple analgesic actions including the inhibition of NO release, the reduction of mechanical hyperalgesia, and the prevention of algesia impulsion conduction and transmission, etc. It has an effect of multi-ingredients, multi-targets and multi-pathways.

Objective To establish a method for directional separation of dehydrotumulosic acid from the extracts of Guizhi Fuling Capsule with molecular imprinting technique(MIT). Methods Molecular imprinting polymer(MIP) was prepared by sol-gel process with dehydrotumulosic acid as molecular template to study the absorption property. The dehydrotumulosic acid was achieved from Guizhi Fuling Capsule by one-step separation with polymer as filler. The structure of dehydrotumulosic acid was identified on the basis of the spectral data and physicochemical property. Results The maximum binding capacity(Qmax) of MIP was 9.10 mg/g measured by Scatchard equation and the purity of dehydrotumulosic acid was 90.76% by HPLC. Conclusion The established MIT for the directional separation of dehydrotumulosic acid from Guizhi Fuling Capsule is simple and benefit to reducing the solvent use during the separation process, which could offer a novel method for the separation and purification of dehydrotumulosic acid.

Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmcological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine.