We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a s...We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.展开更多
In this paper, we consider the Goldbach's problem for matrix rings, namely, we decompose an n × n (n 〉 1) matrix over a principal ideal domain R into a sum of two matrices in Mn,(R) with given determinants....In this paper, we consider the Goldbach's problem for matrix rings, namely, we decompose an n × n (n 〉 1) matrix over a principal ideal domain R into a sum of two matrices in Mn,(R) with given determinants. We prove the following result: Let n 〉 1 be a natural number and A = (aij) be a matrix in Mn(R). Define d(A) := g.c.d{aij}. Suppose that p and q are two elements in R. Then (1) If n 〉 1 is even, then A can be written as a sum of two matrices X, Y in Mn(R) with det(X) = p and det(Y) = q if and only if d(A) [ p - q; (2) If n 〉 1 is odd, then A can be written as a sum of two matrices X, Y in Mn(R) with det(X) = p and det(Y) = q if and only if d(A) | p + q. We apply the result to the matrices in Mn(Z) and Mn(Q[x]) and prove that if R = 7. or Q[x], then any nonzero matrix A in Mn(R) can be written as a sum of two matrices in Mn(R) with prime determinants.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recogn...BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.展开更多
利用生物信息学数据库分析泛素样含PHD和环指结构域蛋白1(UHRF1)在恶性胸膜间皮瘤(MPM)中的表达水平及临床意义。基于TCGA数据库和GTEx数据库差异表达分析UHRF1 m RNA在MPM组织和正常肺组织中的表达水平;使用R软件分析UHRF1 mRNA表达量...利用生物信息学数据库分析泛素样含PHD和环指结构域蛋白1(UHRF1)在恶性胸膜间皮瘤(MPM)中的表达水平及临床意义。基于TCGA数据库和GTEx数据库差异表达分析UHRF1 m RNA在MPM组织和正常肺组织中的表达水平;使用R软件分析UHRF1 mRNA表达量与临床病理参数的相关性;构建Kaplan-Meier模型和单因素多因素COX回归模型分析UHRF1基因在MPM中的预后;利用TIMER2.0数据库分析UHRF1基因与免疫细胞浸润的关系;GSEA分析UHRF1基因发挥功能的主要富集通路。选取8例MPM组织及4例非MPM胸膜组织,通过RT-q PCR的方法验证UHRF1在MPM与非MPM胸膜组织的表达情况。数据库分析结果表明,与正常肺组织相比,UHRF1 m RNA在MPM组织中高表达;UHRF1高表达患者提示MPM患者预后不良;UHRF1基因表达量与CD4^(+)辅助型T细胞2、CD4^(+)效应记忆性T细胞、巨噬细胞等多种免疫细胞浸润水平具有显著的相关性(P<0.01),且显著影响MPM患者的预后。功能富集分析显示,UHRF1主要在DNA复制、蛋白酶体、同源重组等通路中起作用。在收集到的病例样本中,与非MPM胸膜组织相比,UHRF1 mRNA在MPM组织中的表达显著增高(P<0.001)。UHRF1在MPM组织中高表达,可能通过调节DNA甲基化和免疫细胞浸润来影响MPM患者预后,有望成为MPM治疗和预后评估的潜在靶点。展开更多
RING finger E3 ligases play an important role in regulating plant growth and development by mediating substrate degradation.In this study,we identified TaGW2L,encoding a Grain width and weight2(GW2)-like RING finger E...RING finger E3 ligases play an important role in regulating plant growth and development by mediating substrate degradation.In this study,we identified TaGW2L,encoding a Grain width and weight2(GW2)-like RING finger E3 ligase,as a novel positive regulator of heading date in wheat(Triticum aestivum L.).TaGW2L exhibited high amino acid sequence similarities with TaGW2 homoeologs,particularly in the conserved RING finger domain.Expression analysis indicated that TaGW2L was constitutively expressed in various wheat tissues.TaGW2L showed transactivation activity in yeast and could interact with the ubiquitin-conjugating enzymes E2_(s).An in vitro ubiquitination assay verified that TaGW2L possessed a similar E3 ligase activity to TaGW2.Overexpression of the TaGW2L-7A homoeolog in wheat led to a significantly earlier heading date under both natural conditions and long-day conditions.Transcriptome analysis revealed that multiple known genes positively regulating wheat heading were significantly upregulated in the TaGW2L-7A-overexpression plants compared with the wild-type control.Together,our findings shed light on the role of TaGW2L in wheat heading date and provide potential applications of TaGW2L for the adaptation improvement of crops.展开更多
In this paper, the traditional proof of “square root of 2 is not a rational number” has been reviewed, and then the theory has been generalized to “if <em>n</em> is not a square, square root of <em&g...In this paper, the traditional proof of “square root of 2 is not a rational number” has been reviewed, and then the theory has been generalized to “if <em>n</em> is not a square, square root of <em>n</em> is not a rational number”. And then some conceptions of ring, integral domain, ideal, quotient ring in Advanced algebra, have been introduced. Integers can be regarded as an integral domain, the rational numbers can be regard as a fractional domain. Evens and odds are principal ideals in integral domain. The operations on evens and odds are operations on quotient ring. After introducing “the minimalist form” in fraction ring. The paper proves the main conclusion: in a integral domain, multiplicative subset <em>S</em> produces a fraction ring <em>S</em><sup><span style="white-space:nowrap;">−</span>1</sup><em>R</em>, and <em>n</em> is not a square element in <em>R</em>, then to every element <em>a</em><span style="white-space:nowrap;">∈</span><em>R</em>, <span style="white-space:nowrap;"><em>a</em><sup>2</sup>≠<em>n</em></span>.展开更多
文摘We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.
文摘In this paper, we consider the Goldbach's problem for matrix rings, namely, we decompose an n × n (n 〉 1) matrix over a principal ideal domain R into a sum of two matrices in Mn,(R) with given determinants. We prove the following result: Let n 〉 1 be a natural number and A = (aij) be a matrix in Mn(R). Define d(A) := g.c.d{aij}. Suppose that p and q are two elements in R. Then (1) If n 〉 1 is even, then A can be written as a sum of two matrices X, Y in Mn(R) with det(X) = p and det(Y) = q if and only if d(A) [ p - q; (2) If n 〉 1 is odd, then A can be written as a sum of two matrices X, Y in Mn(R) with det(X) = p and det(Y) = q if and only if d(A) | p + q. We apply the result to the matrices in Mn(Z) and Mn(Q[x]) and prove that if R = 7. or Q[x], then any nonzero matrix A in Mn(R) can be written as a sum of two matrices in Mn(R) with prime determinants.
基金Supported by National Natural Science Foundation of China,No.82172944 and No.81900558Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149the Key Scientific Research Projects of Universities of Henan Province,No.21A320052。
文摘BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.
文摘利用生物信息学数据库分析泛素样含PHD和环指结构域蛋白1(UHRF1)在恶性胸膜间皮瘤(MPM)中的表达水平及临床意义。基于TCGA数据库和GTEx数据库差异表达分析UHRF1 m RNA在MPM组织和正常肺组织中的表达水平;使用R软件分析UHRF1 mRNA表达量与临床病理参数的相关性;构建Kaplan-Meier模型和单因素多因素COX回归模型分析UHRF1基因在MPM中的预后;利用TIMER2.0数据库分析UHRF1基因与免疫细胞浸润的关系;GSEA分析UHRF1基因发挥功能的主要富集通路。选取8例MPM组织及4例非MPM胸膜组织,通过RT-q PCR的方法验证UHRF1在MPM与非MPM胸膜组织的表达情况。数据库分析结果表明,与正常肺组织相比,UHRF1 m RNA在MPM组织中高表达;UHRF1高表达患者提示MPM患者预后不良;UHRF1基因表达量与CD4^(+)辅助型T细胞2、CD4^(+)效应记忆性T细胞、巨噬细胞等多种免疫细胞浸润水平具有显著的相关性(P<0.01),且显著影响MPM患者的预后。功能富集分析显示,UHRF1主要在DNA复制、蛋白酶体、同源重组等通路中起作用。在收集到的病例样本中,与非MPM胸膜组织相比,UHRF1 mRNA在MPM组织中的表达显著增高(P<0.001)。UHRF1在MPM组织中高表达,可能通过调节DNA甲基化和免疫细胞浸润来影响MPM患者预后,有望成为MPM治疗和预后评估的潜在靶点。
基金supported by the National Natural Science Foundation of China (32172045, 31671687)the National Key Research and Development Program of China (2016YFD0100302)the Agricultural Science and Technology Innovation Program of the CAAS
文摘RING finger E3 ligases play an important role in regulating plant growth and development by mediating substrate degradation.In this study,we identified TaGW2L,encoding a Grain width and weight2(GW2)-like RING finger E3 ligase,as a novel positive regulator of heading date in wheat(Triticum aestivum L.).TaGW2L exhibited high amino acid sequence similarities with TaGW2 homoeologs,particularly in the conserved RING finger domain.Expression analysis indicated that TaGW2L was constitutively expressed in various wheat tissues.TaGW2L showed transactivation activity in yeast and could interact with the ubiquitin-conjugating enzymes E2_(s).An in vitro ubiquitination assay verified that TaGW2L possessed a similar E3 ligase activity to TaGW2.Overexpression of the TaGW2L-7A homoeolog in wheat led to a significantly earlier heading date under both natural conditions and long-day conditions.Transcriptome analysis revealed that multiple known genes positively regulating wheat heading were significantly upregulated in the TaGW2L-7A-overexpression plants compared with the wild-type control.Together,our findings shed light on the role of TaGW2L in wheat heading date and provide potential applications of TaGW2L for the adaptation improvement of crops.
文摘In this paper, the traditional proof of “square root of 2 is not a rational number” has been reviewed, and then the theory has been generalized to “if <em>n</em> is not a square, square root of <em>n</em> is not a rational number”. And then some conceptions of ring, integral domain, ideal, quotient ring in Advanced algebra, have been introduced. Integers can be regarded as an integral domain, the rational numbers can be regard as a fractional domain. Evens and odds are principal ideals in integral domain. The operations on evens and odds are operations on quotient ring. After introducing “the minimalist form” in fraction ring. The paper proves the main conclusion: in a integral domain, multiplicative subset <em>S</em> produces a fraction ring <em>S</em><sup><span style="white-space:nowrap;">−</span>1</sup><em>R</em>, and <em>n</em> is not a square element in <em>R</em>, then to every element <em>a</em><span style="white-space:nowrap;">∈</span><em>R</em>, <span style="white-space:nowrap;"><em>a</em><sup>2</sup>≠<em>n</em></span>.