This study identified six novel azaphilones,isochromophilones G-L(1-6),and three novel biosynthetically related congeners(7-9)from Diaporthe sp.SCSIO 41011.The structures and absolute configurations were elucidated th...This study identified six novel azaphilones,isochromophilones G-L(1-6),and three novel biosynthetically related congeners(7-9)from Diaporthe sp.SCSIO 41011.The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism(ECD)spectra.Significantly,three highly oxygenated azaphilones contain an acetyl group at the terminal chain(4)or linear conjugated polyenoid moieties(5 and 6),which occur infrequently in the azaphilone family.Additionally,several compounds demonstrated inhibition of lipopolysaccharide(LPS)-induced nuclear factor kappa-B(NF-κB)activation in RAW 264.7 macrophages at 20μmol·L^(-1).The novel compound(1)effectively inhibited receptor activator of NF-κB ligand(RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW264.7 macrophages,indicating its potential as a promising lead compound for osteolytic disease treatment.This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.展开更多
Marine microorganisms,especially marine fungi,have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites(Deshmukh et al.,2018;Carroll et al.,202...Marine microorganisms,especially marine fungi,have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites(Deshmukh et al.,2018;Carroll et al.,2022).The corals constitute a dominant part of reefs with the highest biodiversity,and harbor highly diverse and abundant microbial symbionts in their tissue,skeleton,and mucus layer,with species-specific core members that are spatially partitioned across coral microhabitats(Wang WQ et al.,2022).The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds,terpenes,alkaloids,peptides,aromatics,lactones,and steroids.展开更多
Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma(ESCC)in China.However,the joint impact of prevention and treatment on the long-term overall survival(OS)of ESCC pati...Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma(ESCC)in China.However,the joint impact of prevention and treatment on the long-term overall survival(OS)of ESCC patients remains largely unknown.We consecutively recruited 13,255 ESCC patients from two Chinese centers:the Northern center,located in a high-risk area with abundant screening programs;and the Southern center,situated in a non-high-risk area with improved clinical practices.Inter-center comparison,longitudinal intra-center comparison,and a simulation analysis were conducted to investi-gate the influence of tumor downstaging and high-quality clinical treatment on OS.During a follow-up period of 12.52 years,the Northern center exhibited higher median survival than the Southern center(6.22 vs.3.15 years;H_(Radjusted)=0.73,95%CI:0.69-0.77).Mediation analysis demonstrated that its OS advantage was largely(77.7%)attributed to earlier TNM stage(stage 0-II:51.3%vs.24.6%).In temporal analyses,patient survival in the Southern center gradually improved(median survival during 2015-2018 vs.2009-2014:3.58 vs.2.93 years;H_(Radjusted)=0.86,95%CI:0.79-0.94),coinciding with the progress of treatment-related indices(completeness of TNM staging in discharge diagnosis[from 53.7%to 99.6%],adoption of minimally invasive esophagectomy[from 0.0%to 51.1%]and right thoracic esophagectomy[from 12.4%to 86.4%],etc.).Simulation analysis further demonstrated that integrating both downstaging and high-quality treatment would lead to the best survival.Tumor downstaging and high-quality clinical treatment have a joint impact on ESCC patient survival.Establishing a comprehensive strategy that inte-grates cancer prevention with optimal clinical treatment is crucial for alleviating the ESCC burden.展开更多
基金supported by the National Natural Science Foundation of China(No.82260692)Guangxi Natural Science Foundation(No.2024GXNSFFA010004)+2 种基金Bagui Youth Talent Development ProgramHigh-Level Talent Training Project Foundation of Guangxi University of Chinese Medicine(Nos.202407 and 2022C038)the Innovation Project of Guangxi Graduate Education(No.YCSW2025457)。
文摘This study identified six novel azaphilones,isochromophilones G-L(1-6),and three novel biosynthetically related congeners(7-9)from Diaporthe sp.SCSIO 41011.The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism(ECD)spectra.Significantly,three highly oxygenated azaphilones contain an acetyl group at the terminal chain(4)or linear conjugated polyenoid moieties(5 and 6),which occur infrequently in the azaphilone family.Additionally,several compounds demonstrated inhibition of lipopolysaccharide(LPS)-induced nuclear factor kappa-B(NF-κB)activation in RAW 264.7 macrophages at 20μmol·L^(-1).The novel compound(1)effectively inhibited receptor activator of NF-κB ligand(RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW264.7 macrophages,indicating its potential as a promising lead compound for osteolytic disease treatment.This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
基金supported by the Guangxi Natural Science Foundation(Nos.2020GXNSFBA159001,2020GXNSF GA297002,and 2021GXNSFAA220052)the National Natural Science Foundation of China(Nos.U20A20101 and 22007019)+1 种基金the Special Fund for Bagui Scholars of Guangxi(Yonghong LIU)the Scientific Research Foundation of Guangxi University of Chinese Medicine(No.2022C038),China.
文摘Marine microorganisms,especially marine fungi,have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites(Deshmukh et al.,2018;Carroll et al.,2022).The corals constitute a dominant part of reefs with the highest biodiversity,and harbor highly diverse and abundant microbial symbionts in their tissue,skeleton,and mucus layer,with species-specific core members that are spatially partitioned across coral microhabitats(Wang WQ et al.,2022).The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds,terpenes,alkaloids,peptides,aromatics,lactones,and steroids.
基金supported by the National Key R&D Program of China(2021YFC2500405)the Natural Science Foundation of Beijing Municipality(7182033).
文摘Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma(ESCC)in China.However,the joint impact of prevention and treatment on the long-term overall survival(OS)of ESCC patients remains largely unknown.We consecutively recruited 13,255 ESCC patients from two Chinese centers:the Northern center,located in a high-risk area with abundant screening programs;and the Southern center,situated in a non-high-risk area with improved clinical practices.Inter-center comparison,longitudinal intra-center comparison,and a simulation analysis were conducted to investi-gate the influence of tumor downstaging and high-quality clinical treatment on OS.During a follow-up period of 12.52 years,the Northern center exhibited higher median survival than the Southern center(6.22 vs.3.15 years;H_(Radjusted)=0.73,95%CI:0.69-0.77).Mediation analysis demonstrated that its OS advantage was largely(77.7%)attributed to earlier TNM stage(stage 0-II:51.3%vs.24.6%).In temporal analyses,patient survival in the Southern center gradually improved(median survival during 2015-2018 vs.2009-2014:3.58 vs.2.93 years;H_(Radjusted)=0.86,95%CI:0.79-0.94),coinciding with the progress of treatment-related indices(completeness of TNM staging in discharge diagnosis[from 53.7%to 99.6%],adoption of minimally invasive esophagectomy[from 0.0%to 51.1%]and right thoracic esophagectomy[from 12.4%to 86.4%],etc.).Simulation analysis further demonstrated that integrating both downstaging and high-quality treatment would lead to the best survival.Tumor downstaging and high-quality clinical treatment have a joint impact on ESCC patient survival.Establishing a comprehensive strategy that inte-grates cancer prevention with optimal clinical treatment is crucial for alleviating the ESCC burden.
