The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding...The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.展开更多
LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking different...LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.展开更多
AIM:To evaluate the effects of LIN28A(human)on high glucose-induced retinal pigmented epithelium(RPE)cell injury and its possible mechanism.METHODS:Diabetic retinopathy model was generated following 48h of exposure to...AIM:To evaluate the effects of LIN28A(human)on high glucose-induced retinal pigmented epithelium(RPE)cell injury and its possible mechanism.METHODS:Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose(HG)in ARPE-19 cells.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot tested the expression of the corresponding genes and proteins.Cell viability as well as apoptosis was determined through cell counting kit-8(CCK-8)and flow cytometry assays.Immunofluorescence assay was adopted to evaluate autophagy activity.Caspase 3 activity,oxidative stress markers,and cytokines were appraised adopting their commercial kits,respectively.Finally,ARPE-19 cells were preincubated with EX527,a Sirtuin 1(SIRT1)inhibitor,prior to HG stimulation to validate the regulatory mechanism.RESULTS:LIN28A was downregulated in HG-challenged ARPE-19 cells.LIN28A overexpression greatly inhibited HGinduced ARPE-19 cell viability loss,apoptosis,oxidative damage as well as inflammatory response.Meanwhile,the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression.In addition,treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis,oxidative damage as well as inflammation in ARPE-19 cells.CONCLUSION:LIN28A exerts a protective role against HG-elicited RPE oxidative damage,inflammation,as well as apoptosis via regulating SIRT1/autophagy.展开更多
Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by...Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by him is the first extant monography on traumatology and orthopedics in China.According to the preface of the book,he had profound medical knowledge especially about the theory,diagnosis and treatment for wounds and fractures.展开更多
基金supported by the National Natural Science Foundation of China(31790410,32160781)。
文摘The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.
基金This work was supported by the Fritz Thyssen Foundation(10.21.1.026MN)to L.Meder.
文摘LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.
基金Supported by Medical and Health Science and Technology Project of Zhejiang Province(No.2023KY1356).
文摘AIM:To evaluate the effects of LIN28A(human)on high glucose-induced retinal pigmented epithelium(RPE)cell injury and its possible mechanism.METHODS:Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose(HG)in ARPE-19 cells.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot tested the expression of the corresponding genes and proteins.Cell viability as well as apoptosis was determined through cell counting kit-8(CCK-8)and flow cytometry assays.Immunofluorescence assay was adopted to evaluate autophagy activity.Caspase 3 activity,oxidative stress markers,and cytokines were appraised adopting their commercial kits,respectively.Finally,ARPE-19 cells were preincubated with EX527,a Sirtuin 1(SIRT1)inhibitor,prior to HG stimulation to validate the regulatory mechanism.RESULTS:LIN28A was downregulated in HG-challenged ARPE-19 cells.LIN28A overexpression greatly inhibited HGinduced ARPE-19 cell viability loss,apoptosis,oxidative damage as well as inflammatory response.Meanwhile,the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression.In addition,treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis,oxidative damage as well as inflammation in ARPE-19 cells.CONCLUSION:LIN28A exerts a protective role against HG-elicited RPE oxidative damage,inflammation,as well as apoptosis via regulating SIRT1/autophagy.
文摘Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by him is the first extant monography on traumatology and orthopedics in China.According to the preface of the book,he had profound medical knowledge especially about the theory,diagnosis and treatment for wounds and fractures.
