Professor Jia Chunsheng is one of the sixth of old traditional Chinese medicine experts,and often instructs students in ordinary clinics to attach importance to learning and clinical practices of classic works.Now Pro...Professor Jia Chunsheng is one of the sixth of old traditional Chinese medicine experts,and often instructs students in ordinary clinics to attach importance to learning and clinical practices of classic works.Now Professor Jia Chunsheng selects a poet-Song to Elucidate Mysteries in the Guidelines of Acupuncture Classic by Dou Hanqing in the Jin and Yuan Dynasties,and requires the students to read carefully,investigate deeply,and apply at times;Moreover,Professor Jia Chunsheng discusses the"important factors to achieve good clinical therapeutic effects by acupuncture"contained in the Song to Elucidate Mysteries,in many aspects of understanding acupoint characteristics,defining clearly acupoint compatibility,selecting appropriate needling manipulation,how to determine needling depth,how to determine needling direction,how to determine needle retention time,and how to select acupuncture&moxibustion method,etc.Now they are discussed as follows,to discover and spread Dou's acupuncture technique and to increase clinical therapeutic effects.展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despit...Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despite extensive research,no effective treatment exists,highlighting the need to elucidate mechanisms driving ALS pathogenesis.About 90%of ALS cases are sporadic ALS and lack a clear genetic cause;the remaining 10%are familial ALS,associated with mutations in over 25 genes.The most common mutations are in superoxide dismutase 1(SOD1)and C9ORF72,with rarer variants in FUS,TARDBP,TBK1,and VCP.展开更多
Two new glutarimide derivatives,2-hydroxy-3-[2-(2-hydroxy-3-methylphenyl-5-hydroxymethyl)-2-oxoethyl]glutarimide(1)and 2-hydroxy-3-[2-[2-hydroxy-3-hydroxymethyl-5-methylphenyl]-2-oxoethyl]glutarimide(2),along with 8 k...Two new glutarimide derivatives,2-hydroxy-3-[2-(2-hydroxy-3-methylphenyl-5-hydroxymethyl)-2-oxoethyl]glutarimide(1)and 2-hydroxy-3-[2-[2-hydroxy-3-hydroxymethyl-5-methylphenyl]-2-oxoethyl]glutarimide(2),along with 8 known compounds were isolated from the liquid fermentation broth of endophytic Streptomyces sp.YINM00048 obtained from Agrimonia pilosa.Their structures were elucidated through comprehensive spectroscopic analysis,including nuclear magnetic resonance,high-resolution mass spectrometry,and single-crystal X-ray diffraction,supported by time-dependent density functional theory(TDDFT)-electronic circular dichroism(ECD)calculations.Furthermore,compound 2 displayed weak cytotoxic activity against A549 and SMMC-7721 cell lines with IC50 values of 62.69 and 55.07μmol/L,respectively.展开更多
new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The che...new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The chemical structure of compound 1 was determined to be a neopentapyrrole natural product with a 5/5/6 tricyclic skeleton and one amide functional group,by using spectroscopic techniques such as nuclear magnetic resonance(1D/2D NMR)and high-resolution mass spectrometry(HR-ESI-MS).Its structural information indicates that it is probably the shunt product of neopentalenolactone biosynthetic pathway.In antibacterial activity evaluations,compound 1 demonstrated no inhibitory effects against the tested strains including Escherichia coli(DH5a),Staphylococcus aureus,and Bacillus subtilis under the experimental conditions.展开更多
In 1957,Christian Anfinsen postulated his famous dogma based on the study of ribonuclease(Sela et al.,1957),stating that the amino acid sequence of a protein determines its tertiary structure,a unique and kinetically ...In 1957,Christian Anfinsen postulated his famous dogma based on the study of ribonuclease(Sela et al.,1957),stating that the amino acid sequence of a protein determines its tertiary structure,a unique and kinetically accessible energy minimum,in a given environment.As a result,determination of a global energy minimum,or the most populated structure,has been the main focus of structural biology in the ensuing half a century.With more and more structures have been determined,people have gain some insights of why protein functions,but the detailed mechanisms and the function process,or how protein functions,remains elusive.展开更多
Traditional Chinese medicine(TCM)possesses unique advantages in disease prevention and treatment,yet its inherent complexity and diversity pose tremendous challenges for structural elucidation,mechanism research,and b...Traditional Chinese medicine(TCM)possesses unique advantages in disease prevention and treatment,yet its inherent complexity and diversity pose tremendous challenges for structural elucidation,mechanism research,and bioactivity characterization.Highresolution mass spectrometry(HRMS)technology demonstrates immense potential in TCM analysis due to its high sensitivity,high resolution,high throughput,and high efficiency.However,its application in TCM research remains constrained by the lack of intelligent analytical methods and unified standardized databases.Therefore,this paper focuses on the integration of artificial intelligence(AI)and mass spectrometry,providing a systematic review of the applications and potential of AI-driven mass spectrometry analysis in structural elucidation,data resource integration,multi-omics mechanism studies,and chemical biology.Furthermore,this article emphasizes that by leveraging AI models to learn the complex mapping from chemical structures to biological functions,fragmentbased characterization has emerged as the bridge connecting chemical structures with biological activities.Molecular fragments themselves serve as the core“knowledge units”that carry bioactive information.Future research will focus on establishing highquality mass spectrometry databases for the complete chemical profiles of TCM and promoting the standardization and open sharing of mass spectrometry databases,thereby advancing the integration of AI and mass spectrometry in TCM analysis and providing new tools for TCM research.展开更多
Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature....Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.展开更多
The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene divers...The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene diversity across the clade,Aeollanthus species remain underexplored,with only two studies focusing on their diterpene profiles.The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq.reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues.Interestingly,the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra.These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.展开更多
Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin...Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.展开更多
(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectr...(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.展开更多
Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were ch...Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.展开更多
The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mi...The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.展开更多
A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These c...A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures,with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component.The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism(ECD)calculations.Notably,diphenylemestrin C(3)exhibited moderate cytostatic activity against NB4 cells,with a half maximal inhibitory concentration(IC50)value of 21.99μmol·L-1,and induced apoptosis at higher concentrations.展开更多
The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspocha...The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.展开更多
Cervical cancer is a major malignancy that poses a significant threat to women's health[1].In 2020,an estimated 604,000 new cases and 342,000 deaths were reported globally[2].The most common pathological subtype i...Cervical cancer is a major malignancy that poses a significant threat to women's health[1].In 2020,an estimated 604,000 new cases and 342,000 deaths were reported globally[2].The most common pathological subtype is squamous cell carcinoma[3,4].However,treatment options for advanced cervical squamous cell carcinoma(CSCC)are limited.Surgery is often not feasible at this stage,resulting in poor prognosis[5,6].Therefore,identifying novel molecular markers and elucidating the mechanisms that drive CSCC growth and metastasis are crucial for improving treatment outcomes.展开更多
[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereoche...[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereochemistry,presents a significant challenge.Plumerubradins A-C(1-3),three novel iridoid glycoside[2+2]dimers featuring a highly functionalized cyclobutane core and multiple stereogenic centers,were isolated from the flowers of Plumeria rubra.Through biomimetic semisynthesis and chemical degradation of compounds 1-3,synthesis of phenylpropanoid-derived[2+2]dimers 7-10,combined with extensive spectroscopic analysis,single-crystal X-ray crystallography,and microcrystal electron diffraction experiments,the structures with absolute configurations of 1-3 were unequivocally elucidated.Furthermore,quantum mechanics-based^(1)H NMR iterative full spin analysis successfully established the correlations between the signal patterns of cyclobutane protons and the structural information of the cyclobutane ring in phenylpropanoid-derived[2+2]dimers,providing a diagnostic tool for the rapid structural elucidation of[2+2]-type cyclobutane derivatives.展开更多
Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were e...Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were elucidated using comprehensive spectroscopic data,calculated 13C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus(13C NMR-DP4+)probability analysis,and ECD calculations.These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties.Notably,compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane-or rulepidanol-type sesquiterpene,while compound 7 features a hydroxylated monomeric acylphloroglucinol motif.A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus(RSV)with IC50 values ranging from 0.75 to 3.12μmol·L^(-1) compared to the positive control(ribavirin).展开更多
Bipolarpenoids A–J(1–10),ten undescribed ophiobolin-derived sesterterpenoids,were identified from the fungus Bipolaris oryzae.Their structures were elucidated by high resolution electrospray ionization mass spectrom...Bipolarpenoids A–J(1–10),ten undescribed ophiobolin-derived sesterterpenoids,were identified from the fungus Bipolaris oryzae.Their structures were elucidated by high resolution electrospray ionization mass spectrometry(HRESIMS),spectroscopic analyses,quantum chemical ^(13)C nuclear magnetic resonance(NMR),electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analyses.Notably,compounds 1 and 2 were uniquely characterized by a multicyclic caged pentacyclo[8.4.0.0^(1,5).0^(4,9).0^(7,11)]tetradecane-bridged system;compounds 4–6 featured unprecedented5/8/5/6 and 5/8/5/5 fused cores,respectively;compound 7 represented the first example of 3,4-secoophiobolin-alkaloid hybrid with a modified 5/6/8/5/5 fused carbon skeleton.Compound 9 showed potential anti-inflammatory effect in RAW264.7 macrophages and ulcerative colitis mice.展开更多
Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental s...Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner.However,existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes,thereby hindering a comprehensive understanding of their interactions.Here,we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria,respectively.Using a key oral pathobiont,Fusobacterium nucleatum,as the primary test bed,we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes.Compared to conventional models,this system enhanced bacterial invasion,elevated intracellular bacterial loads,and elicited more robust host pro-inflammatory responses,including increased secretion of CXCL10,IL-6,and IL-8.In addition,the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens.Finally,we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont,Porphyromonas gingivalis.These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics,offering a physiologically relevant approach to advance oral and systemic health research.展开更多
基金"No.333 Talent Project"Program of Hebei Province:2016-3-0713Heritage program of the sixth national batch of old traditional Chinese medicine expertsScientific Research Plan Program of Hebei Administration of Traditional Chinese Medicine:Dou Hanqing's Life Story and Research on His Academic Thoughts(No.2021096).
文摘Professor Jia Chunsheng is one of the sixth of old traditional Chinese medicine experts,and often instructs students in ordinary clinics to attach importance to learning and clinical practices of classic works.Now Professor Jia Chunsheng selects a poet-Song to Elucidate Mysteries in the Guidelines of Acupuncture Classic by Dou Hanqing in the Jin and Yuan Dynasties,and requires the students to read carefully,investigate deeply,and apply at times;Moreover,Professor Jia Chunsheng discusses the"important factors to achieve good clinical therapeutic effects by acupuncture"contained in the Song to Elucidate Mysteries,in many aspects of understanding acupoint characteristics,defining clearly acupoint compatibility,selecting appropriate needling manipulation,how to determine needling depth,how to determine needling direction,how to determine needle retention time,and how to select acupuncture&moxibustion method,etc.Now they are discussed as follows,to discover and spread Dou's acupuncture technique and to increase clinical therapeutic effects.
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despite extensive research,no effective treatment exists,highlighting the need to elucidate mechanisms driving ALS pathogenesis.About 90%of ALS cases are sporadic ALS and lack a clear genetic cause;the remaining 10%are familial ALS,associated with mutations in over 25 genes.The most common mutations are in superoxide dismutase 1(SOD1)and C9ORF72,with rarer variants in FUS,TARDBP,TBK1,and VCP.
文摘Two new glutarimide derivatives,2-hydroxy-3-[2-(2-hydroxy-3-methylphenyl-5-hydroxymethyl)-2-oxoethyl]glutarimide(1)and 2-hydroxy-3-[2-[2-hydroxy-3-hydroxymethyl-5-methylphenyl]-2-oxoethyl]glutarimide(2),along with 8 known compounds were isolated from the liquid fermentation broth of endophytic Streptomyces sp.YINM00048 obtained from Agrimonia pilosa.Their structures were elucidated through comprehensive spectroscopic analysis,including nuclear magnetic resonance,high-resolution mass spectrometry,and single-crystal X-ray diffraction,supported by time-dependent density functional theory(TDDFT)-electronic circular dichroism(ECD)calculations.Furthermore,compound 2 displayed weak cytotoxic activity against A549 and SMMC-7721 cell lines with IC50 values of 62.69 and 55.07μmol/L,respectively.
基金supported by the National Natural Science Foundation of China(No.22077134)。
文摘new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The chemical structure of compound 1 was determined to be a neopentapyrrole natural product with a 5/5/6 tricyclic skeleton and one amide functional group,by using spectroscopic techniques such as nuclear magnetic resonance(1D/2D NMR)and high-resolution mass spectrometry(HR-ESI-MS).Its structural information indicates that it is probably the shunt product of neopentalenolactone biosynthetic pathway.In antibacterial activity evaluations,compound 1 demonstrated no inhibitory effects against the tested strains including Escherichia coli(DH5a),Staphylococcus aureus,and Bacillus subtilis under the experimental conditions.
文摘In 1957,Christian Anfinsen postulated his famous dogma based on the study of ribonuclease(Sela et al.,1957),stating that the amino acid sequence of a protein determines its tertiary structure,a unique and kinetically accessible energy minimum,in a given environment.As a result,determination of a global energy minimum,or the most populated structure,has been the main focus of structural biology in the ensuing half a century.With more and more structures have been determined,people have gain some insights of why protein functions,but the detailed mechanisms and the function process,or how protein functions,remains elusive.
基金supported by Zhejiang Provincial Natural Science Foundation of China(LD25H280002,J.L.)the National Natural Science Foundation of China(Grant No.U23A20513,X.F.)+2 种基金the Key Project of Zhejiang Provincial Administration of Traditional Chinese Medicine(Grant No.GZY-KJS-ZJ-2025-071,J.L.)the Starlit South Lake Leading Elite Program(Grant No.2023A303005,X.F.)the Fundamental Research Funds for the Central Universities(226-2025-00009,X.F.).
文摘Traditional Chinese medicine(TCM)possesses unique advantages in disease prevention and treatment,yet its inherent complexity and diversity pose tremendous challenges for structural elucidation,mechanism research,and bioactivity characterization.Highresolution mass spectrometry(HRMS)technology demonstrates immense potential in TCM analysis due to its high sensitivity,high resolution,high throughput,and high efficiency.However,its application in TCM research remains constrained by the lack of intelligent analytical methods and unified standardized databases.Therefore,this paper focuses on the integration of artificial intelligence(AI)and mass spectrometry,providing a systematic review of the applications and potential of AI-driven mass spectrometry analysis in structural elucidation,data resource integration,multi-omics mechanism studies,and chemical biology.Furthermore,this article emphasizes that by leveraging AI models to learn the complex mapping from chemical structures to biological functions,fragmentbased characterization has emerged as the bridge connecting chemical structures with biological activities.Molecular fragments themselves serve as the core“knowledge units”that carry bioactive information.Future research will focus on establishing highquality mass spectrometry databases for the complete chemical profiles of TCM and promoting the standardization and open sharing of mass spectrometry databases,thereby advancing the integration of AI and mass spectrometry in TCM analysis and providing new tools for TCM research.
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2024C03106,X.F.)the National Natural Science Foundation of China(No.82474160,X.S.)+2 种基金the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LBZ24H270001,X.P.)the Major Joint Projects Supported by the National Administration of TCM and Zhejiang Province(No.GZY-ZI-KJ-23037,X.P.)the Ningbo Top Medical and Health Research Program(No.2022030309,X.P.)。
文摘Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.
基金funded by a grant to MSJS from Procter and Gamble.
文摘The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene diversity across the clade,Aeollanthus species remain underexplored,with only two studies focusing on their diterpene profiles.The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq.reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues.Interestingly,the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra.These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.
基金financially supported by the National Natural Science Foundation of China(Nos.32270413,82060631,82160808,and 82360035)the Science and Technology Department of Guizhou Province(Nos.QKHJC 2020–1Z076,QKHJC-ZK[2023]YB156,QKHJC-ZK[2021]YB569,and QKHPTRC[2020]5008)+4 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13thbatch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC–CXTD[2022]007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(Nos.FAMP202102K and QJJ[2023]113)。
文摘Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
基金supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82173706,and 82104028)the Science and Technology Major Project of Hubei Province(No.2021ACA012).
文摘(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.
基金National Natural Science Foundation of China(U22A20380,82173706,82104028)Fundamental Research Funds for the Central Universities(2024BRA018)financially supported this project.
文摘Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.
基金supported by the Basic Research Program of the Natural Science Fund-Frontier Leading Technology Basic Research Special Project(No.SBK2023050003)by the University Science and Technology Innovation Team of Department of Education of Guizhou Province(No.QJ[2023]099).
文摘The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.
基金The National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82104028,82173706,and 82373755)+1 种基金the Science and Technology Major Project of Hubei Province(No.2021ACA012)the Fundamental Research Funds for the Central Universities,HUST(No.2021JYCXJJ058)。
文摘A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures,with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component.The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism(ECD)calculations.Notably,diphenylemestrin C(3)exhibited moderate cytostatic activity against NB4 cells,with a half maximal inhibitory concentration(IC50)value of 21.99μmol·L-1,and induced apoptosis at higher concentrations.
基金supported by the National Natural Science Foundation of China(Nos.31972852,32371496,and 81903527)the Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302)。
文摘The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.
基金supported by the Hebei Provincial Central Guidance Local Science and Technology Development Fund(grant number 236Z7714G).
文摘Cervical cancer is a major malignancy that poses a significant threat to women's health[1].In 2020,an estimated 604,000 new cases and 342,000 deaths were reported globally[2].The most common pathological subtype is squamous cell carcinoma[3,4].However,treatment options for advanced cervical squamous cell carcinoma(CSCC)are limited.Surgery is often not feasible at this stage,resulting in poor prognosis[5,6].Therefore,identifying novel molecular markers and elucidating the mechanisms that drive CSCC growth and metastasis are crucial for improving treatment outcomes.
基金supported by the National Key R&D Program of China(No.2023YFC3503902)the National Natural Science Foundation of China(Nos.82293681(82293680)and 82321004)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120015 and 2021A1515111021)the Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000026)the Science and Technology Projects in Guangzhou(No.202102070001).
文摘[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereochemistry,presents a significant challenge.Plumerubradins A-C(1-3),three novel iridoid glycoside[2+2]dimers featuring a highly functionalized cyclobutane core and multiple stereogenic centers,were isolated from the flowers of Plumeria rubra.Through biomimetic semisynthesis and chemical degradation of compounds 1-3,synthesis of phenylpropanoid-derived[2+2]dimers 7-10,combined with extensive spectroscopic analysis,single-crystal X-ray crystallography,and microcrystal electron diffraction experiments,the structures with absolute configurations of 1-3 were unequivocally elucidated.Furthermore,quantum mechanics-based^(1)H NMR iterative full spin analysis successfully established the correlations between the signal patterns of cyclobutane protons and the structural information of the cyclobutane ring in phenylpropanoid-derived[2+2]dimers,providing a diagnostic tool for the rapid structural elucidation of[2+2]-type cyclobutane derivatives.
基金supported by the National Natural Science Foundation of China(Nos.82173695,82003609 and 82003743)the Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515011896 and 2020A1515110453)+1 种基金the Science and Technology Planning Project of Guangzhou City(No.2023A03J0566)the High-performance Public Computing Service Platform of Jinan University.
文摘Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were elucidated using comprehensive spectroscopic data,calculated 13C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus(13C NMR-DP4+)probability analysis,and ECD calculations.These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties.Notably,compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane-or rulepidanol-type sesquiterpene,while compound 7 features a hydroxylated monomeric acylphloroglucinol motif.A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus(RSV)with IC50 values ranging from 0.75 to 3.12μmol·L^(-1) compared to the positive control(ribavirin).
基金financially supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82173706,and 82104028)+1 种基金the Fundamental Research Funds for the Central Universities(No.2024BRA018)the Science and Technology Major Project of Hubei Province(No.2021ACA012)。
文摘Bipolarpenoids A–J(1–10),ten undescribed ophiobolin-derived sesterterpenoids,were identified from the fungus Bipolaris oryzae.Their structures were elucidated by high resolution electrospray ionization mass spectrometry(HRESIMS),spectroscopic analyses,quantum chemical ^(13)C nuclear magnetic resonance(NMR),electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analyses.Notably,compounds 1 and 2 were uniquely characterized by a multicyclic caged pentacyclo[8.4.0.0^(1,5).0^(4,9).0^(7,11)]tetradecane-bridged system;compounds 4–6 featured unprecedented5/8/5/6 and 5/8/5/5 fused cores,respectively;compound 7 represented the first example of 3,4-secoophiobolin-alkaloid hybrid with a modified 5/6/8/5/5 fused carbon skeleton.Compound 9 showed potential anti-inflammatory effect in RAW264.7 macrophages and ulcerative colitis mice.
基金supported by National Science Foundation CAREER (2238972)National Institute of Dental and Craniofacial Research awards (R03DE031329 and R01DE030943)The Translational Tissue Modeling Laboratory is supported by the University of Michigan (Center for Gastrointestinal Research,Office of the Dean, Comprehensive Cancer Center, and the Departments of Pathology, Pharmacology, and Internal Medicine) with additional funding from the Endowment for Basic Sciences
文摘Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner.However,existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes,thereby hindering a comprehensive understanding of their interactions.Here,we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria,respectively.Using a key oral pathobiont,Fusobacterium nucleatum,as the primary test bed,we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes.Compared to conventional models,this system enhanced bacterial invasion,elevated intracellular bacterial loads,and elicited more robust host pro-inflammatory responses,including increased secretion of CXCL10,IL-6,and IL-8.In addition,the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens.Finally,we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont,Porphyromonas gingivalis.These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics,offering a physiologically relevant approach to advance oral and systemic health research.
