BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To ex...BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.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
Objective:To survey the prevalence severe diarrhea arising from these bacteria in children under 5 years old in Marvdasht.Methods:In this study faecal sample from 615 children aged <5years old who were hospitalized...Objective:To survey the prevalence severe diarrhea arising from these bacteria in children under 5 years old in Marvdasht.Methods:In this study faecal sample from 615 children aged <5years old who were hospitalized lor gastroenteritis in Fars hospitals in Iran were collected and then enriched in Escherichia coli(E.coli) broth and modified tryplone soy broth with novobiocin media,fermentation of sorbitol,lactose and β— glucoronidase activity of isolated strains was examined by CT—SMAC,VRBA and chromogenic media respectively.Then isolation of E.coli O157:H7 have been confirmed with the use of specific antisera and with multiplex PCR method presence of virulence genes including:xtx_1.stx_2,eae.A.hly has been analyzed.Results:E.coli O157:H7 was detected in 7(1.14%) stool specimens.A significanl difference was seen between detection rale of isolated bacteria from age groups 18-23 months and other age groups(P=0.004).Out of considered virulence genes.only 1 of the isolated strains(0.16%)he stx,and eaeA genes were seen and also all isolated hacleria had resistance to penicillin,ampicillin and erythromycin antibiotics.Conclusions:We found thai children < 2 years of age were at highest risk of infection with E.coli O157:H7.Regarding severity of E.coli O157:H7 pathogenesis,low infectious dose and lack of routine assay for detection ol these bacleria in clinical laboratory,further and completed studies on diagnosis and genolyping of this E.coli O157:H7 strain has been recommended.展开更多
[Objective] This study aimed to analyze the type III effector tccP and tccP2 genes in Escherichia coli O157：H7 from Chinese water-chestnut. [Method] Gene-specific and locus-specific primers were utilized to amplify t...[Objective] This study aimed to analyze the type III effector tccP and tccP2 genes in Escherichia coli O157：H7 from Chinese water-chestnut. [Method] Gene-specific and locus-specific primers were utilized to amplify tccP/tccP2 and their flanking regions for sequence analysis. [Result] E. coli O157：H7 CWN11 harbored intact tccP and tccP2 genes, however, the number of proline-rich repeats in tccP gene was only one that probably resulted in biological incapability, whereas, the tccP2 gene consisted of five and half proline-rich repeats and could encode functional protein. [Conclusion] Here, we reported the first sequence of tccP gene that consisted of only one proline-rich repeat and tccP2 was assumed to play a crucial role in colonization and subsequent signaling cascades.展开更多
Objective: To construct the genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus (AAV). Methods: The plasmids containing pcDNA3-Smad6/Flag and pcDNA3-Smad7/Flag were digested...Objective: To construct the genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus (AAV). Methods: The plasmids containing pcDNA3-Smad6/Flag and pcDNA3-Smad7/Flag were digested with BamHⅠ and XhoⅠ, respectively. Then the Smad6/Flag and Smad7/Flag gene segments obtained were cloned into plasmid pAAV-MCS respectively to construct the recombinant pAAV-Smad6/Flag and pAAV-Smad7/Flag plasmids. The resulting recombinant plasmids (pAAV-Smad6/Flag or pAAV-Smad7/Flag) or pAAV-LacZ plasmid were co-transfected into the HEK 293cells with pHelper and pAAV-RC by calcium-phosphate precipitation method. Recombinant AAV-2 viral particles were prepared from infected HEK293 cells and then were used to infect mouse macrophages. The expressions of Smad6 and Smad7 in macrophages were detected by immunocytochemical staining and expression of b-galactosidase was evaluated by X-gal staining. Results: The recombinant AAV vector containing Smad6 or Smad7 genes was successfully constructed. More than 95% macrophage cells expressed X-gal and Smad6 and Smad7 genes at 72 h after infection. Conclusion: These results indicate that the genetically engineered macrophages can express Smad6 and Smad7 proteins effectively, laying the foundation for the studies of TGF-β-induced diseases in vivo and highlighting the feasibility of macrophage-based gene therapy.展开更多
METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture s...METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture stimulation treatment group(EA),and JI with non-electroacupuncture stimulation group(NEA).Transmission electron microscopy,transcriptome sequencing and analysis,prediction of protein interaction networks,real-time polymerase chain reaction verification,and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs.RESULTS:The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats.A total of 136 genes were differentially expressed in EA rats relative to JI rats,with 55 genes upregulated and 81 genes downregulated.According to results of transcriptome analysis,and prediction of protein mutual interaction by the online STRING database,Heat shock protein beta-7(Hspb7)and myozenin2(Myoz2)genes were targeted.Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats(P<0.05).The expression of Hspb7 protein was upregulated in EA rats relative to that in NC,JI,and NEA rats(P<0.01,<0.05,and<0.05,respectively).The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats(both P<0.01,respectively).CONCLUSIONS:The present results suggest that electroacupuncture stimulation at Zusanli(ST36)could improve muscle healing following jumping-induced muscle injury,owing to the upregulation of Hspb7 and Myoz2 proteins.展开更多
Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activiti...Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.展开更多
Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammal...Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammalian cortical radial glial cells(primary neural stem cells)and introduces the concept that a genetically step wise process,based on a core molecular pathway already in use,is the evolutionary process that has molded cortical neurogenesis.The core mechanism,which has been identified in our recent studies,is the extracellular signal-regulated kinase(ERK)-bone morphogenic protein 7(BMP7)-GLI3 repressor form(GLI3R)-sonic hedgehog(SHH)positive feedback loop.Additionally,I propose that the molecular basis for cortical evolutionary dwarfism,exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor,is an increase in SHH signaling in radial glia,that antagonizes ERK-BMP7 signaling.Finally,I propose that:(1)SHH signaling is not a key regulator of primate cortical expansion and folding;(2)human cortical radial glial cells do not generate neocortical interneurons;(3)human-specific genes may not be essential for most cortical expansion.I hope this review assists colleagues in the field,guiding research to address gaps in our understanding of cortical development and evolution.展开更多
目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA ...目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA 作为对照进行扩增测序。结果2例患者均存在 SERPINB7基因 c.796C 〉 T 纯合突变，导致编码蛋白质第266位氨基酸出现终止改变（p.R266＊），其父母均为 c.796C 〉 T 杂合突变，而无关健康对照未发现上述突变。结论 SERPINB7基因的 c.796C 〉 T 突变可能是引起2例患者长岛型掌跖角化病的原因。展开更多
基金Supported by National Natural Science Foundation of China,No.82300347Natural Science Foundation of Ningbo,No.2021J296Science Foundation of Lihuili Hospital,No.2022ZD004.
文摘BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.
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.
基金the Islamic Azad University, Jahrom branch,for their executive support of this project
文摘Objective:To survey the prevalence severe diarrhea arising from these bacteria in children under 5 years old in Marvdasht.Methods:In this study faecal sample from 615 children aged <5years old who were hospitalized lor gastroenteritis in Fars hospitals in Iran were collected and then enriched in Escherichia coli(E.coli) broth and modified tryplone soy broth with novobiocin media,fermentation of sorbitol,lactose and β— glucoronidase activity of isolated strains was examined by CT—SMAC,VRBA and chromogenic media respectively.Then isolation of E.coli O157:H7 have been confirmed with the use of specific antisera and with multiplex PCR method presence of virulence genes including:xtx_1.stx_2,eae.A.hly has been analyzed.Results:E.coli O157:H7 was detected in 7(1.14%) stool specimens.A significanl difference was seen between detection rale of isolated bacteria from age groups 18-23 months and other age groups(P=0.004).Out of considered virulence genes.only 1 of the isolated strains(0.16%)he stx,and eaeA genes were seen and also all isolated hacleria had resistance to penicillin,ampicillin and erythromycin antibiotics.Conclusions:We found thai children < 2 years of age were at highest risk of infection with E.coli O157:H7.Regarding severity of E.coli O157:H7 pathogenesis,low infectious dose and lack of routine assay for detection ol these bacleria in clinical laboratory,further and completed studies on diagnosis and genolyping of this E.coli O157:H7 strain has been recommended.
基金Supported by the National Key Technology Research and Development Program of China (2012BAK08B07)the National Natural Science Foundation of China (31201919)~~
文摘[Objective] This study aimed to analyze the type III effector tccP and tccP2 genes in Escherichia coli O157：H7 from Chinese water-chestnut. [Method] Gene-specific and locus-specific primers were utilized to amplify tccP/tccP2 and their flanking regions for sequence analysis. [Result] E. coli O157：H7 CWN11 harbored intact tccP and tccP2 genes, however, the number of proline-rich repeats in tccP gene was only one that probably resulted in biological incapability, whereas, the tccP2 gene consisted of five and half proline-rich repeats and could encode functional protein. [Conclusion] Here, we reported the first sequence of tccP gene that consisted of only one proline-rich repeat and tccP2 was assumed to play a crucial role in colonization and subsequent signaling cascades.
文摘Objective: To construct the genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus (AAV). Methods: The plasmids containing pcDNA3-Smad6/Flag and pcDNA3-Smad7/Flag were digested with BamHⅠ and XhoⅠ, respectively. Then the Smad6/Flag and Smad7/Flag gene segments obtained were cloned into plasmid pAAV-MCS respectively to construct the recombinant pAAV-Smad6/Flag and pAAV-Smad7/Flag plasmids. The resulting recombinant plasmids (pAAV-Smad6/Flag or pAAV-Smad7/Flag) or pAAV-LacZ plasmid were co-transfected into the HEK 293cells with pHelper and pAAV-RC by calcium-phosphate precipitation method. Recombinant AAV-2 viral particles were prepared from infected HEK293 cells and then were used to infect mouse macrophages. The expressions of Smad6 and Smad7 in macrophages were detected by immunocytochemical staining and expression of b-galactosidase was evaluated by X-gal staining. Results: The recombinant AAV vector containing Smad6 or Smad7 genes was successfully constructed. More than 95% macrophage cells expressed X-gal and Smad6 and Smad7 genes at 72 h after infection. Conclusion: These results indicate that the genetically engineered macrophages can express Smad6 and Smad7 proteins effectively, laying the foundation for the studies of TGF-β-induced diseases in vivo and highlighting the feasibility of macrophage-based gene therapy.
基金Supported by Science and Technology Department of Henan Province Effect Mechanisms of Acupuncture to Promote the Repair of Injured Skeletal Muscle(No.212102310260)Study on the Relationship between Hspb7 Protein and JAK/STAT Pathway and Electroacupuncture Intervention in Muscle Injury based on mRNA-Seq Analysis(No.222102320072)Science and Technology Bureau o Kaifeng:the Effect of Platelet Plasma Injection on Patellar Tendon Fibrosis(No.2003006)。
文摘METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture stimulation treatment group(EA),and JI with non-electroacupuncture stimulation group(NEA).Transmission electron microscopy,transcriptome sequencing and analysis,prediction of protein interaction networks,real-time polymerase chain reaction verification,and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs.RESULTS:The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats.A total of 136 genes were differentially expressed in EA rats relative to JI rats,with 55 genes upregulated and 81 genes downregulated.According to results of transcriptome analysis,and prediction of protein mutual interaction by the online STRING database,Heat shock protein beta-7(Hspb7)and myozenin2(Myoz2)genes were targeted.Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats(P<0.05).The expression of Hspb7 protein was upregulated in EA rats relative to that in NC,JI,and NEA rats(P<0.01,<0.05,and<0.05,respectively).The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats(both P<0.01,respectively).CONCLUSIONS:The present results suggest that electroacupuncture stimulation at Zusanli(ST36)could improve muscle healing following jumping-induced muscle injury,owing to the upregulation of Hspb7 and Myoz2 proteins.
基金the Wuhan University Medical Faculty Innovation Seed Fund Cultivation Project(No.TFZZ2018025)the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH12000001-2020313)the National Natural Science Foundation of China(No.81670123 and No.81670144).
文摘Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities.Olfactory receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for immunotherapy.The Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation cohorts.Results OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal programs.Compared to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related proteins.The clustering performed well in the internal and 5 external validation cohorts.Based on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment response.In addition,the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients.The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts.Conclusion Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC.ORIGs can be applied to molecularly stratify patients,and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.
基金supported by the Ministry of Science and Technology of China(STI2030-2021ZD0202300)the National Natural Science Foundation of China(32070971,32100768,32200776,and 32200792)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Human’s robust cognitive abilities,including creativity and language,are made possible,at least in large part,by evolutionary changes made to the cerebral cortex.This paper reviews the biology and evolution of mammalian cortical radial glial cells(primary neural stem cells)and introduces the concept that a genetically step wise process,based on a core molecular pathway already in use,is the evolutionary process that has molded cortical neurogenesis.The core mechanism,which has been identified in our recent studies,is the extracellular signal-regulated kinase(ERK)-bone morphogenic protein 7(BMP7)-GLI3 repressor form(GLI3R)-sonic hedgehog(SHH)positive feedback loop.Additionally,I propose that the molecular basis for cortical evolutionary dwarfism,exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor,is an increase in SHH signaling in radial glia,that antagonizes ERK-BMP7 signaling.Finally,I propose that:(1)SHH signaling is not a key regulator of primate cortical expansion and folding;(2)human cortical radial glial cells do not generate neocortical interneurons;(3)human-specific genes may not be essential for most cortical expansion.I hope this review assists colleagues in the field,guiding research to address gaps in our understanding of cortical development and evolution.
文摘目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA 作为对照进行扩增测序。结果2例患者均存在 SERPINB7基因 c.796C 〉 T 纯合突变，导致编码蛋白质第266位氨基酸出现终止改变（p.R266＊），其父母均为 c.796C 〉 T 杂合突变，而无关健康对照未发现上述突变。结论 SERPINB7基因的 c.796C 〉 T 突变可能是引起2例患者长岛型掌跖角化病的原因。
