Upland cotto n has the highest yield,and accounts for>95%of world cotton production.Deco-ding upland cotton genome s will undoubtedly provide the ultimate reference and resource for structur-al,functional,and evolu...Upland cotto n has the highest yield,and accounts for>95%of world cotton production.Deco-ding upland cotton genome s will undoubtedly provide the ultimate reference and resource for structur-al,functional,and evolutio nary studies of the species.Here,we employed GeneTrek and BAC tag-ging information approaches to predict the general composition and structure of the allotetraploid cot-ton genome.Further,based on our enhanced genetic map between Gossy pium barba dense and G.hir-sutum,we carried out the integration of 26 genetic and physical maps from G.hirsutum by chromo-some-specific BACs and FISH technology and put a foundation for BAC-byBAC sequencing from ho-mologous chr.12 and chr.26.142 BAC sequences from G.展开更多
Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-d...Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-dihydrobenzo[b]cyclopenta[e][1,4]thiazine.Single-crystal X-ray diffraction analysis was conducted on four distinct compounds isolated during the reaction,and electrospray ionization mass spectrometry(ESI-MS)of both solid products and intermediate reaction solutions enabled the identification of 15 consecutive reaction steps,where Fe(Ⅲ)was directly involved in eight steps.These transformations comprise nine intermolecular C─C coupling events and six intramolecular ring expansion processes.The heteroatoms(N,O,and S)play distinct mechanistic roles according to their positions within the heterocyclic framework:(1)nitrogen and oxygen coordinate with Fe(Ⅲ),facilitating activation of the reaction site;(2)homolytic cleavage of the C─O bond promotes C─C coupling reactions;and(3)C─S migration induces intramolecular ring expansion.Notably,theoretical calculations indicate a decrease in Gibbs free energy along the intramolecular reaction pathways,substantiating the proposed mechanism and activation mode,which underscores the essential role of Fe(Ⅲ)in enabling the reaction progression.Furthermore,an investigation of the photophysical properties revealed that the resulting heterocyclic aggregates exhibit strong luminescence within the 535–610 nm wavelength range,approaching the near-infrared region.These findings highlight the significance of this reaction pathway in the controlled synthesis of functional oligomers and polymers from monomeric precursors,particularly through catalysis by cost-effective metal ions.展开更多
We present a protocol that combines the support vector machine(SVM)model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p)level of theory,denoted as SVM-M(i.e.,SVM for magnetic property).We show...We present a protocol that combines the support vector machine(SVM)model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p)level of theory,denoted as SVM-M(i.e.,SVM for magnetic property).We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence.Of particular significance is that,by utilizing the dual role of the decision values in SVM,the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue(i.e.,“is a given structure correct or incorrect?”)and the comparison-based problem(i.e.,“which structure is more likely to be correct or wrong among several candidate structures?”).A significantly high success rate has been reached(i.e.,∼100%on a set of 760 sample molecules with 1592813C chemical shifts),which makes the SVMM protocol a powerful tool for routine applications in structural and stereochemical assignments,as well as in detecting misassignments,for complex organic compounds,including natural products.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
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
Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the ho...Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the hole overdoped Ba_(0.4)K_(0.6)Fe_(2)As_(2) near a Lifshitz transition,where the electron pocket at M point is nearly replaced by four hole pockets.In the normal state,the spin excitations is observed at incommensurate wave vectors with a chimney-like dispersion.By cooling down to the superconducting state,a neutron spin resonance mode emerges with a peak energy of Er=14-15 meV,weakly modulated along the L-direction.The incommensurability notably increases at low energies,giving rise to downward dispersions of the resonance mode.This behavior contrasts sharply with the upward dispersions of resonance observed in optimally doped Ba_(0.67)K_(0.33)Fe_(2)As_(2) contributed by the hole to electron scattering,but resembles those in KFe_(2)As_(2) and KCa_(2)Fe_(4)As_(4)F_(2) where the fermiology is dominated by hole pockets.These results highlight the critical role of electronic structure modifications near the Fermi level,especially in governing interband scattering under imperfect nesting conditions,which fundamentally shape the spin dynamics of FeSCs.展开更多
The quantum geometric tensor(QGT)is a fundamental quantity for characterizing the geometric properties of quantum states and plays an essential role in elucidating various physical phenomena.The traditional QGT,defned...The quantum geometric tensor(QGT)is a fundamental quantity for characterizing the geometric properties of quantum states and plays an essential role in elucidating various physical phenomena.The traditional QGT,defned only for pure states,has limited applicability in realistic scenarios where mixed states are common.To address this limitation,we generalize the defnition of the QGT to mixed states using the purifcation bundle and the covariant derivative.Notably,our proposed defnition reduces to the traditional QGT when mixed states approach pure states.In our framework,the real and imaginary parts of this generalized QGT correspond to the Bures metric and the mean gauge curvature,respectively,endowing it with a broad range of potential applications.Additionally,using our proposed mixed-state QGT,we derive the geodesic equation applicable to mixed states.This work establishes a unifed framework for the geometric analysis of both pure and mixed states,thereby deepening our understanding of the geometric properties of quantum states.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
[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
Background The Registrar Clinical Encounters in Training(ReCEnT)project is an Australian general practice vocational training programme with integrated and interdependent education and research functions.Trainees(regi...Background The Registrar Clinical Encounters in Training(ReCEnT)project is an Australian general practice vocational training programme with integrated and interdependent education and research functions.Trainees(registrars)contemporaneously document in-consultation clinical experience and actions.Objectives Using a realist lens,we elucidate the mechanisms underpinning project outcomes to answer questions around programme effectiveness,impacts,sustainability and the lessons and findings that are translatable to other primary care training programmes.Methods The context,input,process and product framework was used.As a means to understand the interactions between each of the interdependent components,it allows for inferences regarding causal mechanisms for specific outcomes.Results Context:ReCEnT occurs within an apprenticeship-like model of general practice vocational training entailing a central supervisor/apprentice relationship.ReCEnT has demystified the content and characteristics of registrar consultations.Input:multiple stakeholder involvement is both advantageous and a logistical challenge,with the programme’s success dependent on registrars,practices and training providers providing detailed and accurate data,with prompt subsequent processing.Process:contemporaneous consultation data collection in different stages of training constitutes a component of registrars’programmatic assessment.Product:individualised feedback provides educational benefit through reflection.Clinical and educational research questions can be addressed with resulting research translation feeding back into the programme model and government policy.Clinical behaviour change is also evaluated.Conclusion ReCEnT is unique,globally,in its scope and longevity(2010–present).Creation of meaningful,individualised feedback facilitates reflection and provides both immediate educational benefits and the substrate for further research,programme and policy design and targeted formal teaching and learning.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
文摘Upland cotto n has the highest yield,and accounts for>95%of world cotton production.Deco-ding upland cotton genome s will undoubtedly provide the ultimate reference and resource for structur-al,functional,and evolutio nary studies of the species.Here,we employed GeneTrek and BAC tag-ging information approaches to predict the general composition and structure of the allotetraploid cot-ton genome.Further,based on our enhanced genetic map between Gossy pium barba dense and G.hir-sutum,we carried out the integration of 26 genetic and physical maps from G.hirsutum by chromo-some-specific BACs and FISH technology and put a foundation for BAC-byBAC sequencing from ho-mologous chr.12 and chr.26.142 BAC sequences from G.
文摘Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-dihydrobenzo[b]cyclopenta[e][1,4]thiazine.Single-crystal X-ray diffraction analysis was conducted on four distinct compounds isolated during the reaction,and electrospray ionization mass spectrometry(ESI-MS)of both solid products and intermediate reaction solutions enabled the identification of 15 consecutive reaction steps,where Fe(Ⅲ)was directly involved in eight steps.These transformations comprise nine intermolecular C─C coupling events and six intramolecular ring expansion processes.The heteroatoms(N,O,and S)play distinct mechanistic roles according to their positions within the heterocyclic framework:(1)nitrogen and oxygen coordinate with Fe(Ⅲ),facilitating activation of the reaction site;(2)homolytic cleavage of the C─O bond promotes C─C coupling reactions;and(3)C─S migration induces intramolecular ring expansion.Notably,theoretical calculations indicate a decrease in Gibbs free energy along the intramolecular reaction pathways,substantiating the proposed mechanism and activation mode,which underscores the essential role of Fe(Ⅲ)in enabling the reaction progression.Furthermore,an investigation of the photophysical properties revealed that the resulting heterocyclic aggregates exhibit strong luminescence within the 535–610 nm wavelength range,approaching the near-infrared region.These findings highlight the significance of this reaction pathway in the controlled synthesis of functional oligomers and polymers from monomeric precursors,particularly through catalysis by cost-effective metal ions.
基金National Natural Science Foundation of China(NSFC)(22233002,21991130,21773193)Natural Science Foundation of Fujian Province of China(2021J01020)Innovation Program for Quantum Science and Technology(2021ZD0303305).
文摘We present a protocol that combines the support vector machine(SVM)model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p)level of theory,denoted as SVM-M(i.e.,SVM for magnetic property).We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence.Of particular significance is that,by utilizing the dual role of the decision values in SVM,the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue(i.e.,“is a given structure correct or incorrect?”)and the comparison-based problem(i.e.,“which structure is more likely to be correct or wrong among several candidate structures?”).A significantly high success rate has been reached(i.e.,∼100%on a set of 760 sample molecules with 1592813C chemical shifts),which makes the SVMM protocol a powerful tool for routine applications in structural and stereochemical assignments,as well as in detecting misassignments,for complex organic compounds,including natural products.
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 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.
基金supported by the National Key Research and Development Program of China(Grant Nos.2023YFA1406100,2018YFA0704200,2022YFA1403400 and 2021YFA1400400)the National Natural Science Foundation of China(Grant Nos.11822411 and 12274444)+2 种基金the Strategic Priority Research Program(B)of the CAS(Grant Nos.XDB25000000 and XDB33000000)K.C.Wong Education Foundation(GJTD-2020-01)AP by HBNI-RRCAT and MPCST under the FTYS program。
文摘Elucidating the relationship between spin excitations and fermiology is essential for clarifying the pairing mechanism in iron-based superconductors(FeSCs).Here,we report inelastic neutron scattering results on the hole overdoped Ba_(0.4)K_(0.6)Fe_(2)As_(2) near a Lifshitz transition,where the electron pocket at M point is nearly replaced by four hole pockets.In the normal state,the spin excitations is observed at incommensurate wave vectors with a chimney-like dispersion.By cooling down to the superconducting state,a neutron spin resonance mode emerges with a peak energy of Er=14-15 meV,weakly modulated along the L-direction.The incommensurability notably increases at low energies,giving rise to downward dispersions of the resonance mode.This behavior contrasts sharply with the upward dispersions of resonance observed in optimally doped Ba_(0.67)K_(0.33)Fe_(2)As_(2) contributed by the hole to electron scattering,but resembles those in KFe_(2)As_(2) and KCa_(2)Fe_(4)As_(4)F_(2) where the fermiology is dominated by hole pockets.These results highlight the critical role of electronic structure modifications near the Fermi level,especially in governing interband scattering under imperfect nesting conditions,which fundamentally shape the spin dynamics of FeSCs.
基金supported by the National Natural Science Foundation of China(Grant Nos.12347104,U24A2017,12461160276,and 12175075)the National Key Research and Development Program of China(Grant No.2023YFC2205802)+1 种基金the Natural Science Foundation of Jiangsu Province(Grant Nos.BK20243060 and BK20233001)in part by the State Key Laboratory of Advanced Optical Communication Systems and Networks,China。
文摘The quantum geometric tensor(QGT)is a fundamental quantity for characterizing the geometric properties of quantum states and plays an essential role in elucidating various physical phenomena.The traditional QGT,defned only for pure states,has limited applicability in realistic scenarios where mixed states are common.To address this limitation,we generalize the defnition of the QGT to mixed states using the purifcation bundle and the covariant derivative.Notably,our proposed defnition reduces to the traditional QGT when mixed states approach pure states.In our framework,the real and imaginary parts of this generalized QGT correspond to the Bures metric and the mean gauge curvature,respectively,endowing it with a broad range of potential applications.Additionally,using our proposed mixed-state QGT,we derive the geodesic equation applicable to mixed states.This work establishes a unifed framework for the geometric analysis of both pure and mixed states,thereby deepening our understanding of the geometric properties of quantum states.
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 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.
文摘Background The Registrar Clinical Encounters in Training(ReCEnT)project is an Australian general practice vocational training programme with integrated and interdependent education and research functions.Trainees(registrars)contemporaneously document in-consultation clinical experience and actions.Objectives Using a realist lens,we elucidate the mechanisms underpinning project outcomes to answer questions around programme effectiveness,impacts,sustainability and the lessons and findings that are translatable to other primary care training programmes.Methods The context,input,process and product framework was used.As a means to understand the interactions between each of the interdependent components,it allows for inferences regarding causal mechanisms for specific outcomes.Results Context:ReCEnT occurs within an apprenticeship-like model of general practice vocational training entailing a central supervisor/apprentice relationship.ReCEnT has demystified the content and characteristics of registrar consultations.Input:multiple stakeholder involvement is both advantageous and a logistical challenge,with the programme’s success dependent on registrars,practices and training providers providing detailed and accurate data,with prompt subsequent processing.Process:contemporaneous consultation data collection in different stages of training constitutes a component of registrars’programmatic assessment.Product:individualised feedback provides educational benefit through reflection.Clinical and educational research questions can be addressed with resulting research translation feeding back into the programme model and government policy.Clinical behaviour change is also evaluated.Conclusion ReCEnT is unique,globally,in its scope and longevity(2010–present).Creation of meaningful,individualised feedback facilitates reflection and provides both immediate educational benefits and the substrate for further research,programme and policy design and targeted formal teaching and learning.
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.
