Analysis of Lavandulyl Flavonoids from Sophora flavescens with Antiinflammatory Activity Based on Molecular Network Technology

[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.

Chemical diversity of scleractinian corals revealed by untargeted metabolomics and molecular networking

The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.

Comprehensive profiling of Lingzhihuang capsule by liquid chromatography coupled with mass spectrometry-based molecular networking and target prediction

Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.

Deciphering bioactive compounds of complex natural products by tandem mass spectral molecular networking combined with an aggregation-induced emission based probe

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 mech ANism 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 activities,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 uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.

A Novel 3D Supramolecular Network Constructed from [Cu(4,4'-bipyridine)(O_2CMe)_2]_2 Molecular Ladders by Hydrogen Bonding

The title complex, {[Cu2（4,4＇-bipyridine）2（μ-O2CMe）2（O2CMe）2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474（5）, b = 11.7566（2）, c = 19.5380（6）A, β = 92.930（2）°, V = 3084.84（16） A^3, Z = 4, Cu2C28N409H30, Mr = 693.64, Dc = 1.494 g/cm^3, F（000） = 1424 and μ（MoKα） = 1.436 mm^-1. With the use of 2062 observed reflections （I 〉 2σ（I））, the structure was refined to R = 0.0769 and wR = 0.2154. In complex 1, the dimeric copper acetate units are linked through 4,4’-bipyridine to yield ID molecular ladders. These ladders are connected via O-H…O hydrogen bonds to generate 2D layers, which are further linked through C-H…O hydrogen bonds to give a 3D supramolecular network.

Understanding biological functions through molecular networks

染色体序列并且分子的网络的随后的高产量的印射的结束允许我们从网络观点学习生物学。试验性、统计、数学的当模特儿的途径被采用了学习分子的网络的结构，函数和动力学，并且开始揭示各种各样的网络性质的重要连接到生物系统的函数。与这些功能的连接一致，一个网络的进化选择是显然基于功能，而非直接在网络的结构上。动态模块化是分子的网络的突出的特征之一。利用如此的一个特征可以通过过程特定的模块化的网络的建设简化基于网络的生物研究并且提供连接 genotypic 变化到复杂特点或疾病的功能、机械学的卓见，它是可能的是在理解建筑群人疾病的下一个波浪的一条关键途径。与 ready-to-use 网络分析和当模特儿的工具的开发，网络途径在不久的将来将被灌输进日常生物研究。

Molecular network using molecular circuit for drug delivery use

A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can be trapped and moved (transported) dynamically within the wavelength router and bus networks, in which the required drug delivery can perform within the wavelength router before reaching the required destination. PANDA ring is a modified optical add/drop filter. It is a name of Chinese bear, which is used to name the device by the authors. The advantage of the proposed system is that the drug delivery networks can perform within the tiny system (thin film device), where the large molecular drug networks such as ring, star and bus networks are also proposed, in which the applications such as Alzheimers’ and Parkinson diagnosis, blood circulation networks and in situ surgery operation are discussed.

Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog,asperpyrroindotide A,using LC–MS/MS-based molecular networking

Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.

Sarcaglarols A-D, Lindenane-Monoterpene Heterodimers from Sarcandra glabra Based on Molecular Networks

Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.

A survey on biomarker identification based on molecular networks

Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. Results： In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. Conclusions： The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of hiomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.

Acetylcholinesterase inhibitors and antioxidants mining from marine fungi:bioassays,bioactivity coupled LC-MS/MS analyses and molecular networking

Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around China.Their bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/ml.Six strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum TBG1-17.From the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH incubation.Furthermore,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone I.aspernolide E,a phenolic derivative and possibly unknown compounds 8-10 and 12.

Rapid identification of stigmastane-type steroid saponins from Vernonia amygdalina leaf based onα-glucosidase inhibiting activity and molecular networking

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,pneumonia.The current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in V.amygdalina.First,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes.Furthermore,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this plant.Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V.amygdalina leaf.

Practice and Prospect:HIV-1 Molecular NetworkBased Studies in China

Identification of human immunodeficiency virus(HIV)transmission networks is a critical step in the public health response;however,it is challenging to achieve this through traditional epidemiological surveys alone.The molecular network approach can provide more accurate information for understanding HIV outbreaks and bring targeted interventions into reality.Based on the current global development of the concept of the molecular network,Chinese scientists have in recent years explored the applications of molecular networks for understanding the HIV-1 transmission trends,for identifying the population acquiring priority interventions,and for evaluating the targeted intervention effectiveness.In this review,we focus on research progress by Chinese scientists in the field of molecular networks and put forward some suggestions for future research of molecular networks.

Self-assembled supramolecular networks at interfaces: Molecular immobilization and recognition using nanoporous templates

In this review a series of organic-based open porous networks are discussed, in which hydrogen bonds play an important role in network formation. Using these open networks as molecular templates: 1) a wealth of functional guest species can be immo- bilized; 2) fullerene molecules can be separated and recognized; 3) photoisomerization reactions can be observed by STM; 4) 1D molecular arrays can be constructed; and 5) heterogeneous bilayer structures can be formed. It is envisioned that these su- pramolecular networks might be developed into a new family of useful soft frameworks for studies toward shape-selective ca- talysis, molecular recognition and host-guest supramolecular chemistry.

Use of Network Pharmacology and Molecular Docking to Investigate the Mechanism by Which Ginseng Ameliorates Hypoxia

Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the

Analysis of mechanism on Indigo Naturalis in treating chronic myelocytic leukemia based on two-dimentional model of protein-protein interaction network-moleculardocking technique

运用分子对接技术探讨青黛干预CMLK562细胞的有效分子学机制.使用在线人类孟德尔遗传数据库（OMIM）筛选CML相关基因,使用String10.0用于进一步文本挖掘并构建CML可视化蛋白质相互作用网络,将数据读入Cytoscape3.4.0,通过插件CentiScaPe2.1实现网络拓扑分析.青黛活性小分子物质从第三方数据库获取,运用Chemoffice8.0与Sybyl8.1对其再构建和优化,得到青黛小分子配体结构库,通过SurflexDock模块与受体革巴点进行分子对接,打分后得到关键靶标.构建了由425个节点（蛋白质）和2799条边（相互作用）组成的蛋白质相互作用网络,分析得出关键靶标JAK2.CML是一个受多基因调控的复杂疾病,JAK2很可能是其关键节点.

Exploration on Shufeng Jiedu Capsule for Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ&middot;mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.

不同光源条件下与花生株高变化相关基因的转录组分析

【目的】为了探究不同光源条件下与花生株高变化相关的基因。【方法】以冀花5号(直立型)和开选01-6(匍匐型)品种为研究材料,分别在LED光和自然光两种培养条件进行盆栽试验。【结果】冀花5号在强光条件下株高显著变矮,而开选01-6变化幅度不大,表明冀花5号对光照反应相对敏感。转录组的PCA结果显示LED光源下冀花5号和开选01-6距离相对较近,自然光源下冀花5号和开选01-6距离较近,说明光照对基因表达的影响大于基因型间的差异影响。GO和KEGG注释分析发现不论在差异表达数目、基因类型或主要响应的调控网络上,冀花5号和开选01-6对不同光源的响应存在显著差异,尤其差异基因在植物昼夜节律相关的通路上显著富集,暗示着植物昼夜节律调控网络对株型的形态建成至关重要。进一步分析发现分别有16个和19个植物昼夜节律相关基因在开选01-6和冀花5号中特异响应,分别有6个和17个植物激素信号转导相关基因在开选01-6和冀花5号中特异响应,表明这些基因在花生株型形态建成中起着关键调控作用。【结论】昼夜节律调控途径是调控株高变化的主要途径,植物生长激素信号在其中也起了关键作用。以上研究结果对育种家深入理解不同光源条件下花生株型的形态建成具有重要的参考价值。

RETRACTED:Exploring the Mechanism of Wu Ling San plus Flavor for the Treatment of Diabetic Macular Edema Based on Network Pharmacology and Molecular Docking Techniques

Short Retraction Notice The paper does not meet the standards of “Chinese Medicine ". This article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. The aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. Editor guiding this retraction: Prof. Maythem Saeed (EiC of CM) The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

The Molecular Mechanism of Xinyi San for the Treatment of Senile Rhinitis Based on Network Pharmacology

Objective: To study the molecular mechanism of Xinyi San for the treatment of senile rhinitis by applying network pharmacological analysis technology. Methods: The effective components and corresponding targets of Xinyi San were collected by TCMSP. The targets of senile rhinitis were collected by the Genecards database. The potential target of Xinyi San in the treatment of senile rhinitis was obtained by Venn analysis. Cytoscape 3.7.2 the software constructs the relationship network model of “disease-single drug-active ingredient-action target”. Protein protein interaction (PPI) network was constructed by using a string database. R4.1.1 software was used for GO function enrichment analysis and KEGG pathway enrichment analysis. Results: In this study, we obtained 158 active ingredients, 40 potential therapeutic targets, 74 GO projects, and 99 pathways. Major pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Pathways of neurodegeneration-multiple diseases, etc. Conclusion: Xinyi San has the characteristics of multi-component, multi-target, and multi-channel in the treatment of senile rhinitis. This study provides a basis for the in-depth study of Xinyi San.