As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of ...As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.展开更多
Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a se...Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.展开更多
The silk gland cells of silkworm are special cells which only replicate DNA in the nucleus without cell division throughout the larval stage. The extrachromosomal circular DNAs (eccDNAs) have not yet been reported in ...The silk gland cells of silkworm are special cells which only replicate DNA in the nucleus without cell division throughout the larval stage. The extrachromosomal circular DNAs (eccDNAs) have not yet been reported in the silk gland of silkworms. Herein, we have explored the characterization of eccDNAs in the posterior silk gland of silkworms. A total of 35 346 eccDNAs were identified with sizes ranging from 30 to 13 569 549 bp. Motif analysis revealed that dual direct repeats are flanking the 5′ and 3′ breaking points of eccDNA. The sequences exceeding 1 kb length in eccDNAs present palindromic sequence characteristics flanking the 5′ and 3′ breaking points of the eccDNA. These motifs might support possible models for eccDNA generation. Genomic annotation of the eccDNA population revealed that most eccDNAs (58.6%) were derived from intergenic regions, whereas full or partial genes were carried by 41.4% of eccDNAs. It was found that silk protein genes fib-H, fib-L, and P25, as well as the transcription factors SGF and sage, which play an important regulatory role in silk protein synthesis, could be carried by eccDNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes carried by eccDNAs were mainly associated with the development and metabolism-related signaling pathways. Moreover, it was found that eccDNAfib-L could promote the transcription of fib-L gene. Overall, the results of the present study not only provide a novel perspective on the mechanism of silk gland development and silk protein synthesis but also complement previously reported genome-scale eccDNA data supporting that eccDNAs are common in eukaryotes.展开更多
Chlorinated paraffins(CPs)are produced in large amounts and used worldwide.Dietary intake is the primary pathway for the exposure of pets to CPs,but limited information is available concerning the potential contaminat...Chlorinated paraffins(CPs)are produced in large amounts and used worldwide.Dietary intake is the primary pathway for the exposure of pets to CPs,but limited information is available concerning the potential contamination of pet food by CPs.In the present study,the concentrations and congener group profiles of short-chain CPs(SCCPs)and medium-chain CPs(MCCPs)were assessed in 35 imported commercial dry cat and dog foods collected in China,and the estimated daily intakes of SCCPs and MCCPs for cats and dogs through the consumption of such foods was calculated.The concentrations of SCCPs and MCCPs in the cat and dog foods were determined to be in the ranges of 108e45,300 ng/g(median:1340 ng/g)and 3.8e52,700 ng/g(median:11 ng/g),respectively.The predominant congener groups were C10Cl6 for SCCPs and C14Cl7-8 for MCCPs.The high levels of CPs found in certain pet foods suggest the potential for adverse health effects.展开更多
基金supported by the grants from the Sichuan Science and Technology Program,China(Grant Nos.:2023NSFSC0614 and 2022YFS0624)Southwest Medical University Science and Technology Program,China(Grant No.:2021ZKZD017)+2 种基金the Luzhou Science and Technology Program,China(Grant Nos.:2022-YJY-127,2022YFS0624-B1,2022YFS0624-C1,and 2022YFS0624-B3)the Open Research Project Program funded by the Science and Technology Development Fund(Grant No.:SKL-QRCM(UM)-2020-2022)the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao,Macao,China)(Grant No.:SKL-QRCMOP21006).
文摘As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production.Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
基金supported by the grants from the Sichuan Science and Technology Program,China(No.2023NSFSC0614,2022YFS0624)grant from Science and Technology Program of Luzhou,China(No.21CGZHPT0001,2022-YJY-127)+1 种基金grant from Southwest Medical University,China(No.2021ZKZD017)grant from The Open Research Project Program of the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao),China(SKL-QRCM-OP21006).
文摘Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.
基金funded by National Key R&D Program of China(2019YFA0905200)the Natural Science Founda-tion of the Jiangsu Higher Education Institutions ofChina(22KJB23003)+2 种基金the National Natural Science Foundation of China(31872424,31972620,and 32072792)China Postdoctoral Science Foundation(2019M661937)Priority Academic Program of Development of Jiangsu Higher Education Institutions.
文摘The silk gland cells of silkworm are special cells which only replicate DNA in the nucleus without cell division throughout the larval stage. The extrachromosomal circular DNAs (eccDNAs) have not yet been reported in the silk gland of silkworms. Herein, we have explored the characterization of eccDNAs in the posterior silk gland of silkworms. A total of 35 346 eccDNAs were identified with sizes ranging from 30 to 13 569 549 bp. Motif analysis revealed that dual direct repeats are flanking the 5′ and 3′ breaking points of eccDNA. The sequences exceeding 1 kb length in eccDNAs present palindromic sequence characteristics flanking the 5′ and 3′ breaking points of the eccDNA. These motifs might support possible models for eccDNA generation. Genomic annotation of the eccDNA population revealed that most eccDNAs (58.6%) were derived from intergenic regions, whereas full or partial genes were carried by 41.4% of eccDNAs. It was found that silk protein genes fib-H, fib-L, and P25, as well as the transcription factors SGF and sage, which play an important regulatory role in silk protein synthesis, could be carried by eccDNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the genes carried by eccDNAs were mainly associated with the development and metabolism-related signaling pathways. Moreover, it was found that eccDNAfib-L could promote the transcription of fib-L gene. Overall, the results of the present study not only provide a novel perspective on the mechanism of silk gland development and silk protein synthesis but also complement previously reported genome-scale eccDNA data supporting that eccDNAs are common in eukaryotes.
基金the National Natural Science Foundation of China(grant nos.21707164 and 3187131629)the Central Public Interest Scientific Institution Basal Research Fund of the Chinese Academy of Agricultural Sciences(grant no.Y2020PT38).
文摘Chlorinated paraffins(CPs)are produced in large amounts and used worldwide.Dietary intake is the primary pathway for the exposure of pets to CPs,but limited information is available concerning the potential contamination of pet food by CPs.In the present study,the concentrations and congener group profiles of short-chain CPs(SCCPs)and medium-chain CPs(MCCPs)were assessed in 35 imported commercial dry cat and dog foods collected in China,and the estimated daily intakes of SCCPs and MCCPs for cats and dogs through the consumption of such foods was calculated.The concentrations of SCCPs and MCCPs in the cat and dog foods were determined to be in the ranges of 108e45,300 ng/g(median:1340 ng/g)and 3.8e52,700 ng/g(median:11 ng/g),respectively.The predominant congener groups were C10Cl6 for SCCPs and C14Cl7-8 for MCCPs.The high levels of CPs found in certain pet foods suggest the potential for adverse health effects.
