Characteristics of HIV-1 CRF01_AE molecular network in Yunnan Province / 中华微生物学和免疫学杂志

Objective:To investigate the molecular network of HIV-1 CRF01_AE in Yunnan Province and the factors influencing it.Methods:Demographic data and plasma samples of HIV/AIDS patients in Yunnan drug resistance monitoring database from 2018 to 2021 were collected. HIV-1 pol gene fragments (protease and reverse transcriptase region) were amplified using RT-PCR and then sequenced. The optimal gene distance was selected and a molecular network was constructed based on the sequences of CRF01_AE genotype. Results:In this study, a total of 967 sequences of CRF01_AE genotype were obtained by sequencing. At the optimal gene distance threshold of 1.75%, a total of 320 sequences were involved in the network with a rate of 33.1%, and 84 clusters were identified. In the regional distribution, one cluster dominated by multiple regions, one cluster dominated by Zhaotong, one cluster dominated by Honghe and five clusters dominated by Wenshan were formed in the network. In the network, 75.8% of heterosexual men were connected with other heterosexual men and 54.1% were connected with heterosexual women. There was potential transmission among 66.7% of men who have sex with men (MSM). HIV/AIDS patients in Chuxiong, Dali, Dehong, Honghe, Lincang, Pu′er, Wenshan, Yuxi and Zhaotong were more likely to be involved in the network that those in Kunming. People who were 50 years old and above were more likely to be involved in the network than those less than 25 years old. Factors influencing HIV/AIDS patients with HIV-1 CRF01_AE infection to become high-risk transmitters in Yunnan were not found and further study on this subject was needed.Conclusions:HIV-1 CRF01_AE strains had spread actively in different regions of Yunnan Province and the transmission network was complex. Dynamic monitoring of CRF01_AE strains should be strengthened and a precise intervention for high-risk transmitters should be performed to reduce new infections.

Rapid identification of the chemical compounds in the leaves of Solanum nigrum L. based on UHPLC-Q Exactive MS and molecular network technology / 药学学报

The whole herb of Solanum nigrum L. can be used as the herbal drug. In this study, UHPLC-Q Exactive high resolution mass combined with GNPS molecular network was used for the rapid characterization of the components in the leaves of S. nigrum L. A total of 157 compounds were identified, including 30 steroid alkaloids, 61 steroid saponins, 35 flavonoids, and 31 other compounds (amino acids and organic acids), by comparison with the data reported in the literature, and mass fragmentation characteristics analysis, as well as the correlation of known and unknown nodes in the GNPS molecular network. Compared with the fruits and stems, the leaves of S. nigrum L was rich in a variety of steroidal saponins, steroidal alkaloids, and flavonoids, and the results lay the foundation for the precise resources utilization of S. nigrum L.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS / 中国中药杂志

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.

Bioprospecting as a strategy for conservation and sustainable use of the Brazilian Flora / Bioprospecção como estratégia para a conservação e uso sustentável da Flora Brasileira

Abstract In Brazil, research with natural products had a strong impulse when FAPESP supported the creation of the Laboratory of Chemistry of Natural Products of the Institute of Chemistry of USP (1966). In 1999, FAPESP launched the Research Program in the Characterization, Conservation, Restoration and Sustainable Use of Biodiversity (BIOTA-FAPESP), which intensified the sustainable exploitation of biodiversity, and which evolved to form the Biota Network for Bioprospection and Bioassays (BIOprospecTA), which integrates groups from all over the country, optimizing the use of the skills already installed for the bioprospecting of microorganisms, plants, invertebrates, vertebrates and marine organisms. Of the 104 projects related to plant sciences, 35 carried out bioprospection of Brazilian flora, belonging to the areas of Chemistry, Botany, Genetics, Plant Physiology, Plant Morphology, Plant (Chemo)taxonomy, Ecosystem Ecology, Plant Genetics. Physical Sciences, Forest Resources, Forestry Engineering, Agronomy, leading to thousands of publications, engagement of hundreds of students and a deeper understanding of natural products in different biological models through macromolecules analysis aided by computational and spectrometric strategies, in addition to pharmacological evaluations. The development of omics approaches led to a more comprehensive view of the chemical profile of an organism, and enabled integrated and concomitant studies of several samples, and faster annotation of known molecules, through the use of hyphenated and chemometric techniques, and molecular networking. This also helped to overcome the lack of information on the safety and efficacy of herbal preparations, in projects dealing with the standardization of herbal products, according to international standards. The BIOTA-FAPESP program has also focused on environmental aspects, in accordance with the principles of Green Chemistry and has had positive effects on international collaboration, on the number and impact of scientific publications and on partnership with companies, a crucial step to add value and expand the production chain of bioproducts. Also, the compilation, systematization and sharing of data were contemplated with the creation of the NUBBEDB database, of free access, and that integrates with international databases (ACD/labs, American Chemical Society - ACS), helping researchers and companies in the development from different areas of science, technology, strengthening the bioeconomy and subsidizing public policies.

Resumo No Brasil, as pesquisas com produtos naturais tiveram um forte impulso quando a FAPESP apoiou a criação do Laboratório de Química de Produtos Naturais do Instituto de Química da USP (1966). Em 1999, a FAPESP lançou o Programa de Pesquisa em Caracterização, Conservação, Restauração e Uso Sustentável da Biodiversidade (BIOTA-FAPESP), que intensificou a exploração sustentável da biodiversidade, e que evoluiu para formar a Rede Biota de Bioprospecção e Bioensaios (BIOprospecTA), que integra grupos de todo o país, otimizando o aproveitamento das competências já instaladas para a bioprospecção de microrganismos, plantas, invertebrados, vertebrados e organismos marinhos. Dos 104 projetos relacionados às ciências vegetais, 35 realizaram a bioprospecção da flora brasileira, em diversas áreas como Química, Botânica, Fisiologia e Morfologia Vegetal, (Quimio)taxonomia Vegetal, Ecologia de Ecossistemas, Genética Vegetal, Recursos Florestais, Engenharia Florestal, dentre outros, levando a milhares de publicações, ao engajamento de centenas de estudantes e ao entendimento mais profundo dos produtos naturais em diferentes modelos biológicos por meio da análise de micromoléculas auxiliada por estratégias computacionais e espectrométricas, além de avaliações farmacológicas. O desenvolvimento de abordagens ômicas ampliou a visão sobre perfil químico dos organismos, possibilitou o estudo integrado e concomitante de várias amostras, e a anotação mais rápida de moléculas conhecidas, por meio do uso de técnicas hifenadas, quimiométricas e redes moleculares. Isso também contribuiu para superar a falta de informação sobre a segurança e eficácia dos fitopreparados, em projetos que tratam da padronização de produtos fitoterápicos, de acordo com normas internacionais. O programa BIOTA-FAPESP também tem focado em aspectos ambientais, de acordo com os princípios da Química Verde e teve reflexos positivos na colaboração internacional, no número e no impacto das publicações científicas e na parceria com empresas, etapa crucial para agregar valor e expandir a cadeia produtiva de bioprodutos. Ainda, a compilação, sistematização e compartilhamento de dados foram contemplados com a criação da base de dados NUBBEDB, de livre acesso, e que se integra com bases internacionais (ACD/labs, American Chemical Society - ACS), auxiliando pesquisadores e empresas no desenvolvimento de diferentes áreas da ciência, tecnologia, fortalecendo a bioeconomia e subsidiando políticas públicas.

Deciphering bioactive compounds of complex natural products by tandem mass spectral molecular networking combined with an aggregation-induced emission based probe / 药物分析学报

Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD's ACE inhibitory ac-tivities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to un-cover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.

Rapid identification of chemical constituents in the dried stem bark of Asparagus officinalis L. based on UPLC-Q-TOF-MS/MS / 药学学报

Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with a molecular network analysis strategy was used to identify the chemical constituents of the stem bark of two kinds of asparagus. The chemical constituents were identified by determining an accurate molecular weight, the fragmentation pathway, and comparison with the mass spectrometry data from the references. A molecular network was established based on the similarity of MS/MS fragmentation patterns. A total of 107 compounds were identified or tentatively deduced, which included 46 saponins, 13 flavonoids, and 48 other compounds. The chemical compounds identified in the stem bark of white and green asparagus differed greatly: the white asparagus was rich in saponins, while the green asparagus was rich in flavonoids. In conclusion, the chemical constituents of asparagus stem bark were characterized rapidly using UPLC-Q-TOF-MS/MS and molecular network analysis, with 10 compounds and 45 targets determined from the HIT 2.0 herbal ingredients' targets platform. This work will provide a theoretical basis for the resource utilization of asparagus.

Influencing factors of molecular network transmission clusters of HIV/AIDS in Huzhou / 预防医学

Objective @#To analyze the influencing factors for the molecular network transmission clusters of HIV/AIDS, and to provide scientific evidence for the precise prevention and control of AIDS. @*Methods@#A case-control study was conducted. The HIV/AIDS cases reported from January 2017 to June 2019 in Huzhou with strong clustering of HIV molecular transmission were recruited as the case group, and the residents with same gender, similar age ( ±three years ) and HIV negative in the same community and period were matched ( 1∶4 ) as the control group. Demographic characteristics, AIDS related knowledge and sexual behaviors were collected by a questionnaire survey. The Cox regression model was used to analyze the influencing factors for HIV/AIDS molecular network transmission cluster.@*Results @#There was 100 people in the case group and 400 people in the control group, the differences between them in age, sex, marital status, place of residence and educational level were not statistically significant ( P>0.05 ) . The results of multivariate Cox regression analysis showed that awareness of AIDS related knowledge ( HR=0.145, 95%CI: 0.059-0.352 ) was a protective factor for molecular network transmission clusters of HIV/AIDS; men who have sex wth men ( MSM, HR=9.614, 95%CI: 4.645-19.901) , seeking homosexual partners through the internet (HR=16.321, 95%CI: 7.016-32.968) and having syphilis ( HR=3.314, 95%CI: 1.073-10.232 ) were risk factors for molecular network transmission clusters of HIV/AIDS.@*Conclusions@#The awareness of AIDS related knowledge, MSM, seeking homosexual partners through the internet and suffering from syphilis are the influencing factors for molecular network transmission clusters of HIV/AIDS.

Identification on triterpenoid saponins of Clematis species by UPLC-LTQ-Orbitrap combined with molecular network / 中草药

Objective: To construct molecular network and analyze rapidly the saponins of six species of Clematis plants. Methods: The mass spectral data, acquired with UHPLC-LTQ Orbitrap MS, were uploaded to the GNPS analysis platform to build molecular network, visualized by Cytoscape software. On the other hand, the triterpenoid saponins from six plants were identified on the basis of the fragmentation regularity of the standard and the reported literature. Results: Twenty-five triterpenoid saponins, including 16 hederagenin saponins and nine oleanolic acid-type saponins, were determined from six kinds of plants. The distribution of the triterpenoid saponins in the six kinds of plants were profiled by the pie chart of each node in molecular network. Twenty compounds were found in at least two species of Clematis. Clematichinenoside A and oleanolic acid 3-O-ribopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside were the common constituents in five species. Six saponins were distributed in in single species of Clematis. Conclusion: Compared with traditional phytochemical methods, the molecular network technology of UPLC-LTQ-Orbitrap MS can quickly and visually distinguish different triterpenoid saponins in six kinds of plants. There are similarities and differentiates among the triterpenoid saponins in the six kinds of plants, which provides the basis for the substitution of medicinal materials.

Progress in research on the transmission characteristics of HIV-infected persons based on molecular network method / 中华流行病学杂志

HIV molecular network is a recently reported method for studying the transmission characteristics of HIV-infected people. Countries have used this method to conduct a large number of researches on transmission relations, transmission hotspots and epidemic surveillance for the purpose of providing evidence for precise AIDS intervention and control. At present, there are three major methods for constructing molecular networks in the world, i.e. genetic distance method based on pairwise alignment, phylogenetic node support method, and joint parameter method based on the two methods. This paper reviews the progress of the three methods for constructing HIV molecular network to study the transmission characteristics of HIV-infected patients, in order to provide data support for the prevention and control of HIV. Since the emergence of the molecular network method, Beijing, Shanghai, Zhejiang, Sichuan and other provinces in China have reported relevant research results using molecular network analysis, which provided scientific data for further precise AIDS prevention and control. Recent international studies have also predicted that molecular network based transmission cluster detection is expected to become a new method to stop AIDS epidemic.

Molecular mechanism of Shuguan Granules in treating angina based on integrative pharmacology / 中国中药杂志

The paper analyzed the combined administration of traditional Chinese medicine Shuguan Granules, and studied its six plant herbs, namely Polygoni Multiflori Radix, Salviae Miltiorrhizae Radix et Rhizoma, Polygonati Rhizoma, Chuanxiong Rhizoma, Epomedii Folium, and Carthami Flos by network pharmacology analysis, in order to define chemical constituents and drugs targets through integrated pharmacology platform. Based on the results, indications of Shuguan Granules were collected through the ETCM database. Therefore, the present study could determine the potential optimal indications of the drug. The results showed that chest apoplexy was the main traditional Chinese medicine(TCM) symptom treated by Shuguan Granules, whose monarch drug was Salviae Miltiorrhizae Radix et Rhizoma. Network pharmacology analysis found that the target enrichment results of Shuguan Granules were related to the indications of coronary heart disease, angina and atherosclerosis. According to the indications, angina may be the best indication for Shuguan Granules. The 229 components in Shuguan Granules involved a total of 109 core targets, of which TNF and MMP9 were the direct targets to the angina disease. In addition, Shuguan Granules could also indirectly intervene in the progression of angina through MAPK, NFKB, GF and other targets. The main pathways involving angina pectoris are PI3 K-Akt signaling pathway, RAS signaling pathway, TNF signaling pathway, Estrogen signaling pathway and glycolysis/gluconeogenesis, which can intervene in many aspects of angina, such as inflammatory reaction, blood lipid metabolism and vasodilation.

Advances in treatment of atrial fibrillation with Chinese materia medica and biological molecular network analysis of ginsenoside in treating atrial fibrillation / 中草药

Atrial fibrillation (AF) is the most common type of arrhythmia in clinic. At present, the therapies of AF by western medicine are fewer with obvious side effects. It is expected to improve the curative effect and reduce side effects by the combination of traditional Chinese medicine (TCM) and western medicine. The research progresses of Chinese materia medica (CMM) treatment for AF were summarized, and the biological molecular network was carried out for the analysis of blood components of ginsenoside from the key CMM Panax ginseng in AF treatment. The blood components of ginsenoside in network analysis including targets searching, network construction, and GO biological processes analysis were selected to explore the possible mechanism in treating AF. It indicated that the possible mechanism might be related to apoptosis regulation, cell membrane potassium ion flow, and so on.

Topological characteristics of postoperative survival rate-related molecules in hepatocellular carcinoma-associated complex networks / 军事医学

Objective To explore the network structure of genes and microRNA(miRNA) at the system level and to study topological characteristics of survival rate related molecules by means of survival analysis.Methods Regulatory networks were established with genes of hepatocellular carcinoma( HCC) and with the expression profiling data of miRNA. Survival knowledge in nodes was studied.Results All the nodes in gene co-expression networks conformed to power-law distribution.In a network, high-degree nodes were called Hub, which enriched more survival related genes than lower degree ones.Conclusion Hub nodes in gene regulatory networks promise to be potential features for molecular subtyping.

Exploring molecular networks using MONET ontology

The description of the complex molecular network responsible for cell behavior requires new tools to integrate large quantities of experimental data in the design of biological information systems. These tools could be used in the characterization of these networks and in the formulation of relevant biological hypotheses. The building of an ontology is a crucial step because it integrates in a coherent framework the concepts necessary to accomplish such a task. We present MONET (molecular network), an extensible ontology and an architecture designed to facilitate the integration of data originating from different public databases in a single- and well-documented relational database, that is compatible with MONET formal definition. We also present an example of an application that can easily be implemented using these tools.

Formula Western Drug Maybe One of Final Strategic Aims of Modernization of Traditional Chinese Medicine / 中国生物工程杂志

Systems Biology including Systems Biomedicine is emerging internationally and providing opportunities for revolutions of Traditional Chinese Medicine (TCM) and conventional western drugs (WD), while the latter has been taking more advantages because WD has much stronger research basis at molecular levels than TCM. Thorough understanding of molecular network including gene network would automatically induces design of WD into formula western drugs equipped with TCM philosophy, but such molecular formula drug is eventually one of the final aims of modernization of TCM. So TCM is facing big threats it never met. This situation requires a nationwide and international strategy with intelligence and resolution.