The MYB34, MYB51, and MYB122 transcription factors are known to regulate indolic glucosinolate （IG） biosynthesis in Arabidopsis thaliana. To determine the distinct regulatory potential of MYB34, MYB51, and MYB122, t...The MYB34, MYB51, and MYB122 transcription factors are known to regulate indolic glucosinolate （IG） biosynthesis in Arabidopsis thaliana. To determine the distinct regulatory potential of MYB34, MYB51, and MYB122, the accumulation of IGs in different parts of plants and upon treatment with plant hormones were analyzed in A. thaliana seedlings. It was shown that MYB34, MYB51, and MYB122 act together to control the biosynthesis of 13M in shoots and roots, with MYB34 controlling biosynthesis of IGs mainly in the roots, MYB51 regulating biosynthesis in shoots, and MYB122 having an accessory role in the biosynthesis of IGs. Analysis of glucosinolate levels in seedlings of myb34, myb51, myb122, myb34 myb51 double, and myb34 myb51 myb122 triple knockout mutants grown in the presence of abscisic acid （ABA）, salicylic acid （SA）, jasmonate （JA）, or ethylene （ET） revealed that： （1） MYB51 is the central regulator of IG synthesis upon SA and ET signaling, （2） MYB34 is the key regulator upon ABA and JA signaling, and （3） MYB122 plays only a minor role in JA/ET-induced glucosinolate biosynthesis. The myb34 myb51 myb122 triple mutant is devoid of IGs, indicating that these three MYB factors are indispensable for IG production under standard growth conditions.展开更多
Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Hers, we investigate the functional role and regulatory characteristics of indolic meta...Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Hers, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance （SAR） triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine （13A）, and indole-3-carboxylic acid （ICA） are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local 13A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates 13A generation at the expense of its precursor indol-3-ylmethylglucosinolate （13M）, and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics 13A, ICA, and indole-3-carbaldehyde （ICC）. Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemi- cally elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR.展开更多
Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products socia...Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.展开更多
Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Ch...Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Chinese cabbage’s defense responses to A.brassicae infection.Notably,we found that the expression of BrERF109 was induced by A.brassicae infection.Silencing of BrERF109 by an optimized virus-induced gene silencing(VIGS)assay in Chinese cabbage diminished disease resistance,while BrERF109-overexpression in Arabidopsis enhanced it.Additionally,BrERF109 silencing in Chinese cabbage suppressed indolic glucosinolates gene expression,substantially reducing indolic glucosinolates levels,whereas BrERF109-overexpression in Arabidopsis promoted their accumulation.BrERF109 directly interacts with the BrIGMT4 promoter,thereby facilitating indolic glucosinolates accumulation and enhancing defense against A.brassicae.This study elucidates the BrERF109-BrIGMT4 regulatory module in Chinese cabbage’s defense against A.brassicae infection,while providing valuable data for further investigation of plant-A.brassicae interactions.展开更多
Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,whic...Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.展开更多
Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from e...multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.展开更多
Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.展开更多
Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and ef...Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.展开更多
As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are try...As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are trying to figure out how gramine gets into cereal plants: is it inherently present or transformed through a special process? The latest study published in Science by Sara Leite Dias and co-authors, provides a detailed explanation. The starting point of the transformation is identified, and the transformation process is confirmed through rigorous experiments.展开更多
Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells spe...Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.展开更多
BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classifica...BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classification of Tumours of Haematolymphoid Tumours.However,the coexistence of iTCL-GI with epithelial malignancies is rare in clinical practice.This study reports a case of iTCL-GI with gastric signet-ring cell carcinoma(SRCC).We aim to increase diagnostic awareness among clinicians and pathologists regarding multiple primary tumors.CASE SUMMARY A 65-year-old female presented with a 5-month history of lower abdominal pain,bloating,and vomiting.An abdominal computed tomography scan revealed irregular thickening of the gastric wall.Endoscopy revealed diffuse mucosal edema and rigid mucosa along the lesser curvature of the gastric body.There was a 1.5 cm mucosal protrusion on the greater curvature.Biopsy revealed that the lamina propria was expanded by a dense,nondestructive infiltrate of small lymphocytes in the greater curvature,which were characterized by a CD3+/CD8+/TIA-1+immunophenotype with a low Ki-67 index.Clonal T-cell receptor rearrangement was detected,but the Epstein-Barr virus encoded RNA's was negative.Lesions on the lesser curvature of the gastric body were confirmed to be SRCCs.After three months of follow-up,the patient completed four cycles of chemotherapy targeting the SRCC.While her abdominal pain improved,she experienced a weight loss of 5 kg.CONCLUSION Clinicians and pathologists must integrate assessment of these rare cases to prevent misdiagnosis and guide clinical practice.展开更多
BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically e...BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.展开更多
Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;...Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;37(3):404-416.doi:10.21147/j.issn.1000-9604.2025.03.09.展开更多
The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficie...The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficient synthetic strategy include the following:(1)(+)-Taberdicatine B and(+)-tabernabovine B were accessed from common advanced intermediates by varying the substituents;(2) A one-pot asymmetric bromocyclization/hydrolysis was explored to assemble HPI skeleton;(3) Dieckmann condensation to form β-keto ester for the assembly of seven-membered ring;(4) An ester reduction/amide semireduction/cyclization sequence was applied to form the cage-like framework.展开更多
Obesity is a common noncommunicable disease characterized by persistent low-grade chronic inflammation and is associated with various metabolic disturbances,including insulin resistance and diabetes.The search for eff...Obesity is a common noncommunicable disease characterized by persistent low-grade chronic inflammation and is associated with various metabolic disturbances,including insulin resistance and diabetes.The search for effective obesity treatments has led to growing interest in the role of amino acids in metabolic regulation.Tryptophan(TRP),an essential amino acid,participates in several biological pathways,including the kynurenine,5-hydroxytryptamine(5-HT,also known as serotonin),and indole pathways.Recent evidence underscores the significance of TRP metabolism in obesity,showing that various metabolites and enzymes in its metabolic pathways are altered in individuals with obesity.These changes influence physiological processes,mood regulation,and overall metabolic health.This review provides a comprehensive overview of TRP metabolism.It highlights the potential of targeting TRP metabolism as a therapeutic strategy for managing obesity and its related metabolic and psychological comorbidities.展开更多
Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileg...Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.展开更多
A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer...A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.展开更多
文摘The MYB34, MYB51, and MYB122 transcription factors are known to regulate indolic glucosinolate （IG） biosynthesis in Arabidopsis thaliana. To determine the distinct regulatory potential of MYB34, MYB51, and MYB122, the accumulation of IGs in different parts of plants and upon treatment with plant hormones were analyzed in A. thaliana seedlings. It was shown that MYB34, MYB51, and MYB122 act together to control the biosynthesis of 13M in shoots and roots, with MYB34 controlling biosynthesis of IGs mainly in the roots, MYB51 regulating biosynthesis in shoots, and MYB122 having an accessory role in the biosynthesis of IGs. Analysis of glucosinolate levels in seedlings of myb34, myb51, myb122, myb34 myb51 double, and myb34 myb51 myb122 triple knockout mutants grown in the presence of abscisic acid （ABA）, salicylic acid （SA）, jasmonate （JA）, or ethylene （ET） revealed that： （1） MYB51 is the central regulator of IG synthesis upon SA and ET signaling, （2） MYB34 is the key regulator upon ABA and JA signaling, and （3） MYB122 plays only a minor role in JA/ET-induced glucosinolate biosynthesis. The myb34 myb51 myb122 triple mutant is devoid of IGs, indicating that these three MYB factors are indispensable for IG production under standard growth conditions.
基金This work was supported by the German Research Foundation （DFG Cluster of Excellence on Plant Sciences and DFG Graduate program IRTG 1525）, and the Swiss National Science Foundation （SNF Grant No, 3100A-125374）.
文摘Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Hers, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance （SAR） triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine （13A）, and indole-3-carboxylic acid （ICA） are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local 13A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates 13A generation at the expense of its precursor indol-3-ylmethylglucosinolate （13M）, and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics 13A, ICA, and indole-3-carbaldehyde （ICC）. Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemi- cally elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR.
基金supported by the National Natural Science Foundation of China(Nos.82273845,82304331,and 82360695)Guangxi Natural Science Foundation project(No.2023GXNSFBA026305).
文摘Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
基金supported by the National Key Research and Development Program of China(2022YFF1003003)the National Natural Science Foundation of China(32070333)the Key Research and Development Program of Yangling Seed Innovative Center(Ylzy-sc-04).
文摘Black spot,a fungal disease caused by Alternaria brassicae infection,inflicts severe damage on Chinese cabbage.Through comparative transcriptomic analysis,this study investigated the molecular mechanisms underlying Chinese cabbage’s defense responses to A.brassicae infection.Notably,we found that the expression of BrERF109 was induced by A.brassicae infection.Silencing of BrERF109 by an optimized virus-induced gene silencing(VIGS)assay in Chinese cabbage diminished disease resistance,while BrERF109-overexpression in Arabidopsis enhanced it.Additionally,BrERF109 silencing in Chinese cabbage suppressed indolic glucosinolates gene expression,substantially reducing indolic glucosinolates levels,whereas BrERF109-overexpression in Arabidopsis promoted their accumulation.BrERF109 directly interacts with the BrIGMT4 promoter,thereby facilitating indolic glucosinolates accumulation and enhancing defense against A.brassicae.This study elucidates the BrERF109-BrIGMT4 regulatory module in Chinese cabbage’s defense against A.brassicae infection,while providing valuable data for further investigation of plant-A.brassicae interactions.
文摘Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
文摘Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.
基金supported by the National Key Research and Development Program of China(2023YFD1700500,2021YFD1700100)the National Natural Science Foundation of China(22177051,32061143045)+2 种基金the Fundamental Research Funds for the Central Universities(KYCYXT2022010)Sichuan Key Research and Development Program(22ZDYF0186,2021YFN0134)the College Student Research Training Program(202110307002T).
文摘As a natural alkaloid found extensively in cereal crops, gramine not only plays a crucial role in protecting barley and other grasses from various pests, but also reduces palatability for ruminants. Scientists are trying to figure out how gramine gets into cereal plants: is it inherently present or transformed through a special process? The latest study published in Science by Sara Leite Dias and co-authors, provides a detailed explanation. The starting point of the transformation is identified, and the transformation process is confirmed through rigorous experiments.
基金Supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(No.LR20C190001)the National Natural Science Foundation of China(No.42376103)+1 种基金the Natural Science Foundation of Ningbo City(No.2021J062)the K.C.Wong Magna Fund in Ningbo University。
文摘Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.
基金Supported by Key Disciplines of The Sixth Cycle of Tongji Hospital,No.ZDTS24-BLShanghai Municipal Science and Technology Commission 2021"Science and Technology Innovation Action Plan"Medical Innovation Research Project,No.21Y11908800Clinical Research Project of Tongji Hospital of Tongji University,No.ITJ(ZD)2206.
文摘BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classification of Tumours of Haematolymphoid Tumours.However,the coexistence of iTCL-GI with epithelial malignancies is rare in clinical practice.This study reports a case of iTCL-GI with gastric signet-ring cell carcinoma(SRCC).We aim to increase diagnostic awareness among clinicians and pathologists regarding multiple primary tumors.CASE SUMMARY A 65-year-old female presented with a 5-month history of lower abdominal pain,bloating,and vomiting.An abdominal computed tomography scan revealed irregular thickening of the gastric wall.Endoscopy revealed diffuse mucosal edema and rigid mucosa along the lesser curvature of the gastric body.There was a 1.5 cm mucosal protrusion on the greater curvature.Biopsy revealed that the lamina propria was expanded by a dense,nondestructive infiltrate of small lymphocytes in the greater curvature,which were characterized by a CD3+/CD8+/TIA-1+immunophenotype with a low Ki-67 index.Clonal T-cell receptor rearrangement was detected,but the Epstein-Barr virus encoded RNA's was negative.Lesions on the lesser curvature of the gastric body were confirmed to be SRCCs.After three months of follow-up,the patient completed four cycles of chemotherapy targeting the SRCC.While her abdominal pain improved,she experienced a weight loss of 5 kg.CONCLUSION Clinicians and pathologists must integrate assessment of these rare cases to prevent misdiagnosis and guide clinical practice.
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-132.
文摘BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.
文摘Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;37(3):404-416.doi:10.21147/j.issn.1000-9604.2025.03.09.
基金the Qingdao Marine Science and Technology Center(No.2022QNLM030003-2)the Fundamental Research Funds for the Central Universities,Taishan Scholar Program of Shandong Province(No.tsqn202103152)National Natural Science Foundation of China(No.22171251) for financial support。
文摘The first total synthesis of(+)-taberdicatine B and(+)-tabernabovine B has been accomplished in 10steps with 26.9% overall yield and 15 steps with 7.3% overall yield,respectively.The prominent features of this efficient synthetic strategy include the following:(1)(+)-Taberdicatine B and(+)-tabernabovine B were accessed from common advanced intermediates by varying the substituents;(2) A one-pot asymmetric bromocyclization/hydrolysis was explored to assemble HPI skeleton;(3) Dieckmann condensation to form β-keto ester for the assembly of seven-membered ring;(4) An ester reduction/amide semireduction/cyclization sequence was applied to form the cage-like framework.
文摘Obesity is a common noncommunicable disease characterized by persistent low-grade chronic inflammation and is associated with various metabolic disturbances,including insulin resistance and diabetes.The search for effective obesity treatments has led to growing interest in the role of amino acids in metabolic regulation.Tryptophan(TRP),an essential amino acid,participates in several biological pathways,including the kynurenine,5-hydroxytryptamine(5-HT,also known as serotonin),and indole pathways.Recent evidence underscores the significance of TRP metabolism in obesity,showing that various metabolites and enzymes in its metabolic pathways are altered in individuals with obesity.These changes influence physiological processes,mood regulation,and overall metabolic health.This review provides a comprehensive overview of TRP metabolism.It highlights the potential of targeting TRP metabolism as a therapeutic strategy for managing obesity and its related metabolic and psychological comorbidities.
文摘Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.
基金New Teacher Foundation from Ministry of Education in China (Grant No.20090071120)Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No.K20100106)STCSM (Grant No.10431903200)
文摘A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.
