The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of ant...The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine storm.In response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ARDS.Here,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with DCs.We show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these cells.In addition,we identified DC-SIGN as a possible interaction partner of ORF8 on DCs.Blockade of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by DCs.Therefore,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.展开更多
Objective To explore the correlation between chromosome 8 open reading frame 76(C8orf76)and cyclin-dependent kinase 4(CDK4)and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer(...Objective To explore the correlation between chromosome 8 open reading frame 76(C8orf76)and cyclin-dependent kinase 4(CDK4)and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer(CRC).Methods We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4.Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram.Results C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts(n=83 and n=597).A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines.The nomogram included prognostic genes(C8orf76 and CDK4)and pathological N and M stages.The concordance index(C-index)in our cohort was 0.776,which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong.Conclusion We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines.Therefore,C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.展开更多
Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population.Of these,38 significant SNPs detected wi...Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population.Of these,38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition.By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis,26 genes were found to contain or be near to such SNPs.Among them,the C14H8orf33 gene is merely 87 bp away from the significant SNP,Hapmap30383-BTC-005848.Hence,we report herein genotype-phenotype associations to further validate the genetic effects of the C14H8orf33 gene.By pooled DNA sequencing of 14 unrelated Holstein sires,a total of 18 with seven novel SNPs were identified.Among them,nine SNPs were in the 5′regulatory region,one in exon 6 and the other in the 3′UTR and 3′regulatory region.A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population.The results showed that these SNPs were statistically significant for more than two traits[P<(0.0001–0.0267)].In addition,mRNA expression analyses revealed that C14H8orf33 was ubiquitous in eight different tissues,with a relatively higher expression level in the mammary gland than in other tissues.These findings,therefore,provide strong evidence for association of C14H8orf33 variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.展开更多
基金supported by the German Research Foundation(DFG)research unit FOR2240(www.FOR2240.de)BO4489/1-1,BO4489/1-2,BO4489/3-1(F.B.)Cu 47/9-1 and 12-1,the Center for Molecular Medicine Cologne(CMMC)(F.B.,C.C.,and M.K.)the German Research Foundation(DFG)research unit FOR2722(M.K.and B.B.)J.S.is a Tier-1 Canada Research Chair and received additional support from the Canadian Institute of Health Research(CIHR-PJTÑ52935 and 178097).
文摘The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine storm.In response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ARDS.Here,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with DCs.We show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these cells.In addition,we identified DC-SIGN as a possible interaction partner of ORF8 on DCs.Blockade of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by DCs.Therefore,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.
基金supported by a grant from National Natural Science Foundation of China(No.82203623)2022&2023 Hebei introduction of foreign expert intelligence projects(Nos.YZ202201&YZ202305)+1 种基金Hebei Natural Science Foundation(Nos.H2020206374 and H2021206306)Hebei Clinical Medicine Excellent Talents Project of Province(No.LS202001).
文摘Objective To explore the correlation between chromosome 8 open reading frame 76(C8orf76)and cyclin-dependent kinase 4(CDK4)and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer(CRC).Methods We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4.Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram.Results C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts(n=83 and n=597).A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines.The nomogram included prognostic genes(C8orf76 and CDK4)and pathological N and M stages.The concordance index(C-index)in our cohort was 0.776,which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong.Conclusion We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines.Therefore,C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
基金supported by the National High-tech R&D Program of China(2013AA102504)the National Key Technology R&D Program(2011BAD28B02)+3 种基金the National Transgenic Major Project(2014ZX08009-053B)the Beijing Innovation Team of Technology System in the National Dairy Industry,the Beijing Research and Technology Program(D121100003312001)the earmarked fund for Modern Agro-industry Technology Research System(CARS-37)the Program for Changjiang Scholar and Innovation Research Team in University(IRT1191).
文摘Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population.Of these,38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition.By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis,26 genes were found to contain or be near to such SNPs.Among them,the C14H8orf33 gene is merely 87 bp away from the significant SNP,Hapmap30383-BTC-005848.Hence,we report herein genotype-phenotype associations to further validate the genetic effects of the C14H8orf33 gene.By pooled DNA sequencing of 14 unrelated Holstein sires,a total of 18 with seven novel SNPs were identified.Among them,nine SNPs were in the 5′regulatory region,one in exon 6 and the other in the 3′UTR and 3′regulatory region.A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population.The results showed that these SNPs were statistically significant for more than two traits[P<(0.0001–0.0267)].In addition,mRNA expression analyses revealed that C14H8orf33 was ubiquitous in eight different tissues,with a relatively higher expression level in the mammary gland than in other tissues.These findings,therefore,provide strong evidence for association of C14H8orf33 variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.
