Sustained inflammation from infiltrated immune cells plays a pivotal role in the pathogenesis of ulcerative colitis （UC）. Previously, we established the role of ribosomal protein L13a in the regulation of an inflamm...Sustained inflammation from infiltrated immune cells plays a pivotal role in the pathogenesis of ulcerative colitis （UC）. Previously, we established the role of ribosomal protein L13a in the regulation of an inflammation-responsive post-transcriptional operon in myeloid cells. However, the role of this protein as a molecular cue to control the severity of colitis is not known. Here, we examined whether L13a-dependent translational control in macrophages could serve as an endogenous defense against colitis. The administration of dextran sodium sulfate induced experimental colitis in myeloid-specific L13a-knockout （KO） and control mice. Pathological scoring and injury to the colon mucosa evaluated the severity of colitis. The steady-state levels of several pro-inflammatory cytokines and chemokines were determined through ELISA and polyribosome profile analysis. Rapid weight loss, severe rectal bleeding, shortening of the colon, and significantly reduced survival rate were observed in the KO mice. Histopathological analysis of the colons of KO mice showed a severe disruption of epithelial crypts with immune cell infiltrates. Elevated levels of several inflammatory cytokines and chemokines and abrogation of their naturally imposed translational silencing were observed in the colons of the KO mice. Higher serum levels of several pro-inflammatory cytokines and the release of gut bacteria and endotoxins into the blood streams of KO mice were detected, suggesting the amplification of the inflammatory response to septicemia. Taken together, these results reveal an essential role for L13a in the endogenous protection against UC and demonstrate the potential for new therapeutic opportunities through the deliberate promotion of this mechanism.展开更多
背景与目的 肺腺癌易发生脑转移,患者预后极差。蛋白磷酸酶1调节亚基13样(protein phosphatase 1 regulatory subunit 13-like, PPP1R13L)基因编码的p53凋亡刺激蛋白家族抑制成员(inhibitor of apoptosis-stimulating protein of p53, i...背景与目的 肺腺癌易发生脑转移,患者预后极差。蛋白磷酸酶1调节亚基13样(protein phosphatase 1 regulatory subunit 13-like, PPP1R13L)基因编码的p53凋亡刺激蛋白家族抑制成员(inhibitor of apoptosis-stimulating protein of p53, iASPP)蛋白是p53通路的关键抑制因子,在多种肿瘤中促癌,但其在肺腺癌脑转移中的作用未知。本研究通过单细胞测序数据整合与临床样本分析,旨在分析肺腺癌脑转移患者的肿瘤微环境特征,并探讨PPP1R13L在脑转移组织中的表达情况及其临床意义。方法 收集2014年1月至2024年12月新疆医科大学附属肿瘤医院就诊的4例肺腺癌脑转移和2例少突胶质细胞瘤患者的脑组织进行单细胞测序,并结合公共数据库中4例肺腺癌样本和4例正常肺组织样本的单细胞测序数据解析肿瘤微环境;另收集此医院50例肺腺癌脑转移患者的临床资料及石蜡切片,采用免疫组化技术检测iASPP蛋白表达,分析其与临床特征及预后的关系。结果 相较于胶质瘤和肺腺癌组,肺腺癌脑转移组特异的上皮细胞主要富集于氧化磷酸化、细胞凋亡、缺氧和p53通路;PPP1R13L作为上调差异基因,在脑转移组特异上皮细胞亚群高表达;PPP1R13L阳性细胞与成纤维细胞交互作用显著,激活细胞-基质黏附相关通路,关键配体-受体对为I型胶原蛋白α1链-白细胞分化抗原44(collagen type I alpha 1 chain-cluster of differentiation 44, COL1A1-CD44)。临床数据分析显示,吸烟史(HR=2.543, 95%CI:1.159-5.583, P=0.020)和iASPP高表达(HR=3.351, 95%CI:1.310-8.575, P=0.012)为肺腺癌脑转移患者预后的独立危险因素。结论 本研究阐明了肺腺癌脑转移微环境中上皮细胞与成纤维细胞的相互作用,提示PPP1R13L可作为潜在预后标志物及治疗靶点,为肺腺癌脑转移的精准治疗提供依据。展开更多
Wheat yield mainly depends on leaf photosynthesis and grain carbohydrate accumulation.The aux/indole-3-acetic acid 13-like(Aux/IAA13L)gene was successfully cloned from Tritipyrum‘Y1805’and transformed into common wh...Wheat yield mainly depends on leaf photosynthesis and grain carbohydrate accumulation.The aux/indole-3-acetic acid 13-like(Aux/IAA13L)gene was successfully cloned from Tritipyrum‘Y1805’and transformed into common wheat.A bioinformatics analysis showed that the TtAux/IAA13L protein,encoding 232 amino acids,was hydrophilic and unstable.TtAux/IAA13L and Tel5E01G609500 were grouped together in a phylogenetic tree.The TtAux/IAA13L expression levels in the overexpression lines were higher than in the wild-type(WT)plants at five developmental stages:tillering,elongation,heading,flowering,and grain-filling.The expression levels in the overexpression lines first increased,peaked at the flowering stage,and then decreased.However,the expression level in WT plants changed little among the five stages.The chlorophyll contents,net photosynthetic rates,stomatal conductances,and transpiration rates of the overexpression lines were higher than in the WT plants.Compared with WT plants,plant height in the overexpression lines decreased,whereas stem diameter,flag leaf area,grain number per spike,1000-grain weight,and grain yield per plant increased.The average grain yield per plant of two overexpression lines increased by 24.56%and 23.46%,compared with those of WT plants,in 2024 and 2025,respectively.In brief,the TtAux/IAA13L gene enhanced the chlorophyll content and flag leaf area,thereby increasing the net photosynthetic rate and grain yield per plant.Consequently,it could be used to breed high-yield wheat cultivars.展开更多
AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was ind...AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histological and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema （E）, polymorphonuclear neutrophU （pIVlN） infiltration, cytoplasmic vacuolization （V）, zymogen granule depletion （ZD） and acinar disorganization （AD） were microscopically evaluated. Accumulation of pancreatitis- associated protein （PAP） and L13A mRNAs were quantified by real-time PCR. RESULTS： The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d. CONCLUSION： From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pan- creas occur and PAP expression is exclusively an acute response of pancreatitis.展开更多
文摘Sustained inflammation from infiltrated immune cells plays a pivotal role in the pathogenesis of ulcerative colitis （UC）. Previously, we established the role of ribosomal protein L13a in the regulation of an inflammation-responsive post-transcriptional operon in myeloid cells. However, the role of this protein as a molecular cue to control the severity of colitis is not known. Here, we examined whether L13a-dependent translational control in macrophages could serve as an endogenous defense against colitis. The administration of dextran sodium sulfate induced experimental colitis in myeloid-specific L13a-knockout （KO） and control mice. Pathological scoring and injury to the colon mucosa evaluated the severity of colitis. The steady-state levels of several pro-inflammatory cytokines and chemokines were determined through ELISA and polyribosome profile analysis. Rapid weight loss, severe rectal bleeding, shortening of the colon, and significantly reduced survival rate were observed in the KO mice. Histopathological analysis of the colons of KO mice showed a severe disruption of epithelial crypts with immune cell infiltrates. Elevated levels of several inflammatory cytokines and chemokines and abrogation of their naturally imposed translational silencing were observed in the colons of the KO mice. Higher serum levels of several pro-inflammatory cytokines and the release of gut bacteria and endotoxins into the blood streams of KO mice were detected, suggesting the amplification of the inflammatory response to septicemia. Taken together, these results reveal an essential role for L13a in the endogenous protection against UC and demonstrate the potential for new therapeutic opportunities through the deliberate promotion of this mechanism.
文摘背景与目的 肺腺癌易发生脑转移,患者预后极差。蛋白磷酸酶1调节亚基13样(protein phosphatase 1 regulatory subunit 13-like, PPP1R13L)基因编码的p53凋亡刺激蛋白家族抑制成员(inhibitor of apoptosis-stimulating protein of p53, iASPP)蛋白是p53通路的关键抑制因子,在多种肿瘤中促癌,但其在肺腺癌脑转移中的作用未知。本研究通过单细胞测序数据整合与临床样本分析,旨在分析肺腺癌脑转移患者的肿瘤微环境特征,并探讨PPP1R13L在脑转移组织中的表达情况及其临床意义。方法 收集2014年1月至2024年12月新疆医科大学附属肿瘤医院就诊的4例肺腺癌脑转移和2例少突胶质细胞瘤患者的脑组织进行单细胞测序,并结合公共数据库中4例肺腺癌样本和4例正常肺组织样本的单细胞测序数据解析肿瘤微环境;另收集此医院50例肺腺癌脑转移患者的临床资料及石蜡切片,采用免疫组化技术检测iASPP蛋白表达,分析其与临床特征及预后的关系。结果 相较于胶质瘤和肺腺癌组,肺腺癌脑转移组特异的上皮细胞主要富集于氧化磷酸化、细胞凋亡、缺氧和p53通路;PPP1R13L作为上调差异基因,在脑转移组特异上皮细胞亚群高表达;PPP1R13L阳性细胞与成纤维细胞交互作用显著,激活细胞-基质黏附相关通路,关键配体-受体对为I型胶原蛋白α1链-白细胞分化抗原44(collagen type I alpha 1 chain-cluster of differentiation 44, COL1A1-CD44)。临床数据分析显示,吸烟史(HR=2.543, 95%CI:1.159-5.583, P=0.020)和iASPP高表达(HR=3.351, 95%CI:1.310-8.575, P=0.012)为肺腺癌脑转移患者预后的独立危险因素。结论 本研究阐明了肺腺癌脑转移微环境中上皮细胞与成纤维细胞的相互作用,提示PPP1R13L可作为潜在预后标志物及治疗靶点,为肺腺癌脑转移的精准治疗提供依据。
基金This work was funded by the National Natural Science Foundation of China(32160442 and 32560458).
文摘Wheat yield mainly depends on leaf photosynthesis and grain carbohydrate accumulation.The aux/indole-3-acetic acid 13-like(Aux/IAA13L)gene was successfully cloned from Tritipyrum‘Y1805’and transformed into common wheat.A bioinformatics analysis showed that the TtAux/IAA13L protein,encoding 232 amino acids,was hydrophilic and unstable.TtAux/IAA13L and Tel5E01G609500 were grouped together in a phylogenetic tree.The TtAux/IAA13L expression levels in the overexpression lines were higher than in the wild-type(WT)plants at five developmental stages:tillering,elongation,heading,flowering,and grain-filling.The expression levels in the overexpression lines first increased,peaked at the flowering stage,and then decreased.However,the expression level in WT plants changed little among the five stages.The chlorophyll contents,net photosynthetic rates,stomatal conductances,and transpiration rates of the overexpression lines were higher than in the WT plants.Compared with WT plants,plant height in the overexpression lines decreased,whereas stem diameter,flag leaf area,grain number per spike,1000-grain weight,and grain yield per plant increased.The average grain yield per plant of two overexpression lines increased by 24.56%and 23.46%,compared with those of WT plants,in 2024 and 2025,respectively.In brief,the TtAux/IAA13L gene enhanced the chlorophyll content and flag leaf area,thereby increasing the net photosynthetic rate and grain yield per plant.Consequently,it could be used to breed high-yield wheat cultivars.
基金Supported by The Mexican Council for Science and Technology,CONACyT, grant 43928
文摘AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histological and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema （E）, polymorphonuclear neutrophU （pIVlN） infiltration, cytoplasmic vacuolization （V）, zymogen granule depletion （ZD） and acinar disorganization （AD） were microscopically evaluated. Accumulation of pancreatitis- associated protein （PAP） and L13A mRNAs were quantified by real-time PCR. RESULTS： The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d. CONCLUSION： From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pan- creas occur and PAP expression is exclusively an acute response of pancreatitis.
