The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approa...The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.展开更多
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....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.展开更多
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...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.展开更多
Microbial activity and regrowth in drinking water distribution systems is a major concern for water service companies.However,previous studies have focused on the microbial composition and diversity of the drinkingwat...Microbial activity and regrowth in drinking water distribution systems is a major concern for water service companies.However,previous studies have focused on the microbial composition and diversity of the drinkingwater distribution systems(DWDSs),with little discussion on microbial molecular ecological networks(MENs)in different water supply networks.MEN analysis explores the potentialmicrobial interaction and the impact of environmental stress,to explain the characteristics of microbial community structures.In this study,the random matrix theory-based network analysis was employed to investigate the impact of seasonal variation including water source switching on the networks of three DWDSs that used different disinfection methods.The results showed that microbial interaction varied slightly with the seasons but was significantly influenced by different DWDSs.Proteobacteria,identified as key species,play an important role in the network.Combined UV-chlorine disinfection can effectively reduce the size and complexity of the network compared to chlorine disinfection alone,ignoring seasonal variations,which may affect microbial activity or control microbial regrowth in DWDSs.This study provides new insights for analyzing the dynamics of microbial interactions in DWDSs.展开更多
Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid ...Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.展开更多
(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified co...(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.展开更多
Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-...Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.展开更多
The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compound...The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.展开更多
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 pro...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.展开更多
Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8...Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.3.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from Daphne altaica Pall.,representing two types of unparalleled meroterpenoid cores.Their struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMR)calcula-tions,DP4+analysis and electronic circular dichroism(ECD)calculations.The plausible biosynthetic path-ways for 1 and 2 were postulated.Biologically,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/L.Moreover,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil.Molecular docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with acetylcholinesterase.The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.展开更多
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 succes...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.展开更多
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 ...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展开更多
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 i...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.展开更多
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 tonsilliti...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.展开更多
[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...[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.展开更多
Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient...Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient to meet regulatory requirements.Objective:To construct a rapid and effective non-targeted screening method for the identification of risk substances,and to provide a high-throughput method for toxicity assessment.Methods:Molecular networking was utilized for the non-targeted screening of risk substances in facial skincare products,and the toxicity of these risk substances was evaluated through molecular docking and quantitative structure-activity relationship(QSAR)models.Results:Through molecular networking,we identified seven known prohibited ingredients,six of which were confirmed using standard substances.In addition,17 potential risk substances were discovered within molecular clusters containing prohibited ingredients,including antibiotics,antihistamines,and phthalates,etc.Notably,chloramphenicol base and N-desmethyl chlorpheniramine exhibited stronger binding affinity to keratin 5/14 than chloramphenicol and chlorpheniramine through molecular docking,respectively.Additionally,toxicity prediction results indicated that the carcinogenicity of antibiotics presented gender differences in mice and rats,and two chlorpheniramine derivatives also showed carcinogenicity in mice.Moreover,of the 24 compounds,11 showed skin sensitization,while 14 caused skin irritation.Furthermore,half of these compounds demonstrated potential developmental toxicity,and only 4-nitrobenzenethiol was found to be mutagenic.Conclusion:In this study,we developed a visualization strategy for non-targeted screening of risk substances and a high-throughput method for initial toxicity assessment of risk substances.展开更多
Pre-metastatic niches(PMNs)are the microenvi-ronments prepared by the interaction of tumor cells and the surrounding microenvironment for the colonization of circulating tumor cells at distant metastatic sites and bef...Pre-metastatic niches(PMNs)are the microenvi-ronments prepared by the interaction of tumor cells and the surrounding microenvironment for the colonization of circulating tumor cells at distant metastatic sites and before metastasis and spreading.The formation of PMNs includes processes such as vascular leakage and permeability changes,coagulation abnor-malities,extracellular matrix remodeling,migration and recruit-ment of bone marrow-derived cells,and immunosuppression,in which tumor-derived exosomes,tumor-derived soluble factors(TDSFs),bone marrow-derived cells(BMDCs),etc.are crucial in this process.This article focuses on the pre-metastasis microen-vironment,in-depth analysis of representative factors such as tumor-derived secretory factors,exosomes,bone marrow-derived cells and myeloid-derived suppressor cells,and other molecular network mechanisms involved in the formation of PMNs,and introduces tumors The characteristics of the metastatic cascade and the selection of organ parts outline the different roles of related molecules in the regulation of metastasis.That provide an effective reference value in order to better understand the mechanisms of tumor metastasis,tumor metastasis look for potential markers and diagnosis and treatment of cancer.展开更多
The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-act...The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-active metabolites in the sauce.To bridge this gap,our study employed metabolomics and webbased computational tools to investigate the dynamic changes of taste-active metabolites during chili sauce fermentation.By leveraging the advantages of the feature-based molecular network(FBMN),we conducted a rapid annotation of metabolites,successfully identifying 205 metabolites,a considerable portion of which were previously unreported.Through the utilization of the Virtual Taste tool,we identified dihydrosphingosine,lactic acid,isoleucine,phytosphingosine,and gluconic acid as potential taste indicators for quality control.Pathway enrichment analysis further supported their primary involvement in key biochemical pathways,including amino acid t RNA biosynthesis,phenylalanine,tyrosine,tryptophan biosynthesis,and sphingolipid metabolism.This investigation provides valuable insights into the underlying mechanisms contributing to the distinctive flavor profile of chili sauce.展开更多
Soil nitrogen(N)cycling is one of the most critical biogeochemical cycles,and N cycling-related microorganisms are the primary driving force behind N cycling in natural environments.The large karst sinkholes in China,...Soil nitrogen(N)cycling is one of the most critical biogeochemical cycles,and N cycling-related microorganisms are the primary driving force behind N cycling in natural environments.The large karst sinkholes in China,known as Tiankengs,harbor abundant unique biological resources due to their particular environmental conditions.However,N cycling-related microorganisms in Tiankeng soils and their connection to ecosystem processes remain poorly studied.In this study,we investigated the distribution patterns and genomic diversity of N cycling-related microorganisms both inside and outside the Luohun cave Tiankeng in Guizhou,China,utilizing high-throughput sequencing and other techniques.The results indicated that the diversities and abundances of denitrifying bacteria,ammonia-oxidizing bacteria,and ammonia-oxidizing archaea communities inside the Tiankeng were higher than those outside the Tiankeng;however,the microbial network relationships were more fragile inside the Tiankeng.The most abundant species of denitrifying bacteria,ammonia-oxidizing bacteria,and ammonia-oxidizing archaea inside the Tiankeng were unclassified_p_Proteobacteria(47.8%),unclassified_k_norank(AOB,OTU121,37.3%),and unclassified_g_norank_f_norank_o_norank_c_environmental_samples(55.7%),respectively;outside the Tiankeng,they were unclassified_k_norank_d_bacteria(54.5%),unclassified_k_norank(AOB,OTU121,48.1%),and unclassified_k_norank(AOA,OTU70,49.6%),respectively.Additionally,the N content inside the Tiankeng was significantly lower(P<0.05)under the influence of these N cycling-related microorganisms,whereas the nutrient contents were higher than that outside the Tiankeng.To the best of our knowledge,this is the first report on the crucial microbial distribution patterns driving N cycling in karst Tiankengs and provides new insights into the structure and potential functions of N cycling-related microorganisms in the unique ecological environment of fragile Tiankeng ecosystems.展开更多
Liver repair and regeneration are crucial physiological responses to hepatic injury and are orchestrated through intricate cellular and molecular networks.This review systematically delineates advancements in the fiel...Liver repair and regeneration are crucial physiological responses to hepatic injury and are orchestrated through intricate cellular and molecular networks.This review systematically delineates advancements in the field,emphasizing the essential roles played by diverse liver cell types.Their coordinated actions,supported by complex crosstalk within the liver microenvironment,are pivotal to enhancing regenerative outcomes.Recent molecular investigations have elucidated key signaling pathways involved in liver injury and regeneration.Viewed through the lens of metabolic reprogramming,these pathways highlight how shifts in glucose,lipid,and amino acid metabolism support the cellular functions essential for liver repair and regeneration.An analysis of regenerative variability across pathological states reveals how disease conditions influence these dynamics,guiding the development of novel therapeutic strategies and advanced techniques to enhance liver repair and regeneration.Bridging laboratory findings with practical applications,recent clinical trials highlight the potential of optimizing liver regeneration strategies.These trials offer valuable insights into the effectiveness of novel therapies and underscore significant progress in translational research.In conclusion,this review intricately links molecular insights to therapeutic frontiers,systematically charting the trajectory from fundamental physiological mechanisms to innovative clinical applications in liver repair and regeneration.展开更多
文摘The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.
基金Financial support for this study is from the"Double First-Class"University project(CPU2018GY08,China)the 111 Project from Ministry of Education of China and the State Administration of Foreign Export Affairs of China(B18056)the National New Drug Innovation Major Project(2018ZX09711-001-007).
文摘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.
基金This work was partly supported by the National Nature Science Foundation of China （Nos. 91530321, 61390513, 61602347 and 61572363）, and the Fundamental Research Funds for the Central Universities.
文摘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.
基金supported by the National Key R&D Program of China (No. 2019YFC0408700)the National Science and Technology Major Projects of China (Nos. 2017ZX07108-002 and 2017ZX07502003)the funds from the National Natural Science Foundation of China (No. 51778323)
文摘Microbial activity and regrowth in drinking water distribution systems is a major concern for water service companies.However,previous studies have focused on the microbial composition and diversity of the drinkingwater distribution systems(DWDSs),with little discussion on microbial molecular ecological networks(MENs)in different water supply networks.MEN analysis explores the potentialmicrobial interaction and the impact of environmental stress,to explain the characteristics of microbial community structures.In this study,the random matrix theory-based network analysis was employed to investigate the impact of seasonal variation including water source switching on the networks of three DWDSs that used different disinfection methods.The results showed that microbial interaction varied slightly with the seasons but was significantly influenced by different DWDSs.Proteobacteria,identified as key species,play an important role in the network.Combined UV-chlorine disinfection can effectively reduce the size and complexity of the network compared to chlorine disinfection alone,ignoring seasonal variations,which may affect microbial activity or control microbial regrowth in DWDSs.This study provides new insights for analyzing the dynamics of microbial interactions in DWDSs.
基金funded by the National Key Research and Development Program of China(No.2022YFC2804101)the Guangdong Provincial Key R&D Program(No.2023B1111050011)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)the Guangzhou Basic and Applied Basic Research Foundation(No.202201010305)the High-Level Talents Special Program of Zhejiang(No.2022R52036)。
文摘Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.
基金supported by the National Key Research and Development Program of China(No.2022YFC2303100)the National Natural Science Foundation of China(Nos.32022002 and 21977113).
文摘(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.
基金supported by the Natural Science Foundation of Hubei Provincial Department of Education(D20232101)Shandong Second Medical University 2024 Affiliated Hospital(Teaching Hospital)Scientific Research Development Fund Project(2024FYQ026)+3 种基金the innovative Research Programme of Xiangyang No.1 People’s Hospital(XYY2023ZY01)Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine(XYY2023D05)Joint supported by Hubei Provincial Natural Science Foundation and Xiangyang of China(2025AFD091)Traditional Chinese Medicine Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025D019).
文摘Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120066 and 2022A1515010010)the National Natural Science Foundation of China[Nos.82293681(82293680)and 82273822]+3 种基金the Science and Technology Key Project of Guangdong Province(No.2020B1111110004)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Fundamental Research Funds for the Central Universitiesthe support of K.C.Wong Education Foundation。
文摘The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.
基金financially supported by the National Key R&D Program of China(Grant No.:2018YFC1704502)the National Natural Science Foundation of China(Grant No.:81603268)the National Natural Science Foundation of China(Grant No.:81822047)
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.82073736,81872766)Science and Technology Planning Project of Liaoning Province(No.2021JH1/10400049)Liaoning revitalization talents program(Nos.XLYC2002066,XLYC2007180).
文摘Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.3.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from Daphne altaica Pall.,representing two types of unparalleled meroterpenoid cores.Their struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMR)calcula-tions,DP4+analysis and electronic circular dichroism(ECD)calculations.The plausible biosynthetic path-ways for 1 and 2 were postulated.Biologically,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/L.Moreover,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil.Molecular docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with acetylcholinesterase.The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine(Grant No.CBCM2020104).
文摘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.
基金financially supported by 1226 major project [Grant no.AWS16J018]
文摘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
基金The National Natural Science Foundation of China under contract Nos 22264003,42090041 and 42030502the Guangxi Natural Science Fund Project under contract Nos AD17129063,AA17204074 and 2018GXNSFAA281354the Innovation and Entrepreneurship Training Program of College Students from Guangxi University under contract Nos 202210593888 and202210593890。
文摘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.
基金supported by the National Natural Science Foundation of China(No.81573550)。
文摘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.
基金Supported by Guizhou Provincial Science and Technology(ZK(2022)-362,ZK(2024)-047,[2023]ZK01)The Innovation and Entrepreneurship Training Program for Undergraduates from China[202210660131,202310660082]+2 种基金Science Foundation of Guizhou Education Technology(2022-064)University Engineering Research Center for the Prevention and Treatment of Chronic Diseases by Authentic Medicinal Materials in Guizhou Province([2023]035)Science and Technology Research Project of Guizhou Administration of Traditional Chinese Medicine(QZYY-2024-134).
文摘[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.
基金supported by the Scientific and technological innovation project of Guangdong Provincial Drug Administration(ZA20230069,2024ZDZ04)the Science and Technology Plan Project of Guangdong Provincial(2023A1111120025).
文摘Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient to meet regulatory requirements.Objective:To construct a rapid and effective non-targeted screening method for the identification of risk substances,and to provide a high-throughput method for toxicity assessment.Methods:Molecular networking was utilized for the non-targeted screening of risk substances in facial skincare products,and the toxicity of these risk substances was evaluated through molecular docking and quantitative structure-activity relationship(QSAR)models.Results:Through molecular networking,we identified seven known prohibited ingredients,six of which were confirmed using standard substances.In addition,17 potential risk substances were discovered within molecular clusters containing prohibited ingredients,including antibiotics,antihistamines,and phthalates,etc.Notably,chloramphenicol base and N-desmethyl chlorpheniramine exhibited stronger binding affinity to keratin 5/14 than chloramphenicol and chlorpheniramine through molecular docking,respectively.Additionally,toxicity prediction results indicated that the carcinogenicity of antibiotics presented gender differences in mice and rats,and two chlorpheniramine derivatives also showed carcinogenicity in mice.Moreover,of the 24 compounds,11 showed skin sensitization,while 14 caused skin irritation.Furthermore,half of these compounds demonstrated potential developmental toxicity,and only 4-nitrobenzenethiol was found to be mutagenic.Conclusion:In this study,we developed a visualization strategy for non-targeted screening of risk substances and a high-throughput method for initial toxicity assessment of risk substances.
文摘Pre-metastatic niches(PMNs)are the microenvi-ronments prepared by the interaction of tumor cells and the surrounding microenvironment for the colonization of circulating tumor cells at distant metastatic sites and before metastasis and spreading.The formation of PMNs includes processes such as vascular leakage and permeability changes,coagulation abnor-malities,extracellular matrix remodeling,migration and recruit-ment of bone marrow-derived cells,and immunosuppression,in which tumor-derived exosomes,tumor-derived soluble factors(TDSFs),bone marrow-derived cells(BMDCs),etc.are crucial in this process.This article focuses on the pre-metastasis microen-vironment,in-depth analysis of representative factors such as tumor-derived secretory factors,exosomes,bone marrow-derived cells and myeloid-derived suppressor cells,and other molecular network mechanisms involved in the formation of PMNs,and introduces tumors The characteristics of the metastatic cascade and the selection of organ parts outline the different roles of related molecules in the regulation of metastasis.That provide an effective reference value in order to better understand the mechanisms of tumor metastasis,tumor metastasis look for potential markers and diagnosis and treatment of cancer.
基金the financial support from Sichuan Technology Development Program,China(2020YFN0056,2021ZHCG0051,2020YFN0094,2021YFN0048,2020YFN0151)the Natural Science Foundation of Sichuan Province(2022NSFSC0105)Pidu 100 Innovative Talents Program(2022)。
文摘The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-active metabolites in the sauce.To bridge this gap,our study employed metabolomics and webbased computational tools to investigate the dynamic changes of taste-active metabolites during chili sauce fermentation.By leveraging the advantages of the feature-based molecular network(FBMN),we conducted a rapid annotation of metabolites,successfully identifying 205 metabolites,a considerable portion of which were previously unreported.Through the utilization of the Virtual Taste tool,we identified dihydrosphingosine,lactic acid,isoleucine,phytosphingosine,and gluconic acid as potential taste indicators for quality control.Pathway enrichment analysis further supported their primary involvement in key biochemical pathways,including amino acid t RNA biosynthesis,phenylalanine,tyrosine,tryptophan biosynthesis,and sphingolipid metabolism.This investigation provides valuable insights into the underlying mechanisms contributing to the distinctive flavor profile of chili sauce.
基金supported by the National Natural Science Foundation of China(No.31860023)the Light of West China Program of Chinese Academic of Sciences(No.[2019]90)+1 种基金the Basic Research Fund of Guangxi Academy of Sciences,China(No.CQZ-D-1904)the Fundamental Research Fund of the Guangxi Institute of Botany,China(Guizhiye Nos.24010 and 24012).
文摘Soil nitrogen(N)cycling is one of the most critical biogeochemical cycles,and N cycling-related microorganisms are the primary driving force behind N cycling in natural environments.The large karst sinkholes in China,known as Tiankengs,harbor abundant unique biological resources due to their particular environmental conditions.However,N cycling-related microorganisms in Tiankeng soils and their connection to ecosystem processes remain poorly studied.In this study,we investigated the distribution patterns and genomic diversity of N cycling-related microorganisms both inside and outside the Luohun cave Tiankeng in Guizhou,China,utilizing high-throughput sequencing and other techniques.The results indicated that the diversities and abundances of denitrifying bacteria,ammonia-oxidizing bacteria,and ammonia-oxidizing archaea communities inside the Tiankeng were higher than those outside the Tiankeng;however,the microbial network relationships were more fragile inside the Tiankeng.The most abundant species of denitrifying bacteria,ammonia-oxidizing bacteria,and ammonia-oxidizing archaea inside the Tiankeng were unclassified_p_Proteobacteria(47.8%),unclassified_k_norank(AOB,OTU121,37.3%),and unclassified_g_norank_f_norank_o_norank_c_environmental_samples(55.7%),respectively;outside the Tiankeng,they were unclassified_k_norank_d_bacteria(54.5%),unclassified_k_norank(AOB,OTU121,48.1%),and unclassified_k_norank(AOA,OTU70,49.6%),respectively.Additionally,the N content inside the Tiankeng was significantly lower(P<0.05)under the influence of these N cycling-related microorganisms,whereas the nutrient contents were higher than that outside the Tiankeng.To the best of our knowledge,this is the first report on the crucial microbial distribution patterns driving N cycling in karst Tiankengs and provides new insights into the structure and potential functions of N cycling-related microorganisms in the unique ecological environment of fragile Tiankeng ecosystems.
基金supported by grants from the National multidisciplinary collaborative diagnosis and treatment capacity building project for major diseases(TJZ202104)the Natural Science Foundation of China(82270643,82070644,82170621 and 82370645)+2 种基金the Science and Technology Major Program of Sichuan Province(2022ZDZX0019)the Sichuan Science and Technology Program(2024NSFSC0645)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC18008,ZYGD22006).
文摘Liver repair and regeneration are crucial physiological responses to hepatic injury and are orchestrated through intricate cellular and molecular networks.This review systematically delineates advancements in the field,emphasizing the essential roles played by diverse liver cell types.Their coordinated actions,supported by complex crosstalk within the liver microenvironment,are pivotal to enhancing regenerative outcomes.Recent molecular investigations have elucidated key signaling pathways involved in liver injury and regeneration.Viewed through the lens of metabolic reprogramming,these pathways highlight how shifts in glucose,lipid,and amino acid metabolism support the cellular functions essential for liver repair and regeneration.An analysis of regenerative variability across pathological states reveals how disease conditions influence these dynamics,guiding the development of novel therapeutic strategies and advanced techniques to enhance liver repair and regeneration.Bridging laboratory findings with practical applications,recent clinical trials highlight the potential of optimizing liver regeneration strategies.These trials offer valuable insights into the effectiveness of novel therapies and underscore significant progress in translational research.In conclusion,this review intricately links molecular insights to therapeutic frontiers,systematically charting the trajectory from fundamental physiological mechanisms to innovative clinical applications in liver repair and regeneration.
