Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reductio...Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unkn...BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.展开更多
Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to underst...Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the g...Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.展开更多
Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to t...Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to the survival of seedlings after seeds germination. The basic-helix-loop-helix transcription factors phytochrome-interacting factors (PIFs) are the pivotal direct downstream components of phytochromes. H2A.Z is a highly conserved histone variant regulating gene transcription, and its incorporation into nucleosomes is catalyzed by SWI2/SNF2-related 1 complex, in which SWI2/SNF2-related 1 complex subunit 6 (SWC6) and actin-related protein 6 (ARP6) serve as core subunits. Here, we show that PIFs physically interact with SWC6 in vitro and in vivo, leading to the disassociation of HY5 from SWC6. SWC6 and ARP6 regulate hypocotyl elongation partly through PIFs in red light. PIFs and SWC6 coregulate the expression of auxin-responsive genes such as IAA6, IAA19, IAA20, and IAA29 and repress H2A.Z deposition at IAA6 and IAA19 in red light. Based on previous studies and our findings, we propose that PIFs inhibit photomorphogenesis, at least in part, through repression of H2A.Z deposition at auxin-responsive genes mediated by the interactions of PIFs with SWC6 and promotion of their expression in red light.展开更多
Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including c...Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.展开更多
基金funded by the Science Foundation of China(Grant No.32230097)Earmarked Fund for China Agriculture Research System(Grant No.CARS-28)+2 种基金the Earmarked Fund for Jiangsu Agricultural Industry Technology System(Grant No.JATS[2023]412)Natural Science Foundation of Jiangsu Province for Young Scholar(Grant No.BK20221010)supported by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.
基金Supported by National Natural Science Foundation of China,No.82100594.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.
基金the National Key Research and Development Program of China(2017YFD0800102)the Hubei Provincial Key Research and Development Program,China(2021BCA156)。
文摘Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
文摘Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.
基金This work was supported by the National Natural Science Foundation of China(31900609)the National Key Research and Development Program of China(2017YFA0503802)+1 种基金the National Natural Science Foundation of China(31530085,31900207,and 32000183)the Science and Technology Commission of Shanghai Municipality(18DZ2260500).
文摘Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to the survival of seedlings after seeds germination. The basic-helix-loop-helix transcription factors phytochrome-interacting factors (PIFs) are the pivotal direct downstream components of phytochromes. H2A.Z is a highly conserved histone variant regulating gene transcription, and its incorporation into nucleosomes is catalyzed by SWI2/SNF2-related 1 complex, in which SWI2/SNF2-related 1 complex subunit 6 (SWC6) and actin-related protein 6 (ARP6) serve as core subunits. Here, we show that PIFs physically interact with SWC6 in vitro and in vivo, leading to the disassociation of HY5 from SWC6. SWC6 and ARP6 regulate hypocotyl elongation partly through PIFs in red light. PIFs and SWC6 coregulate the expression of auxin-responsive genes such as IAA6, IAA19, IAA20, and IAA29 and repress H2A.Z deposition at IAA6 and IAA19 in red light. Based on previous studies and our findings, we propose that PIFs inhibit photomorphogenesis, at least in part, through repression of H2A.Z deposition at auxin-responsive genes mediated by the interactions of PIFs with SWC6 and promotion of their expression in red light.
基金Supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Granta Korea University Grant,No.K1512661
文摘Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.
