Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated ...Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.展开更多
目的 探讨分离酶(ESPL1)基因在卵巢癌中的表达及意义。方法 利用GEPIA数据库,对比相应正常组织,分析ESPL1在泛癌及卵巢癌中的表达。运用The Human Protein Atlas数据库,分析ESPL1蛋白在卵巢及卵巢癌组织中表达及定位;应用String数据库绘...目的 探讨分离酶(ESPL1)基因在卵巢癌中的表达及意义。方法 利用GEPIA数据库,对比相应正常组织,分析ESPL1在泛癌及卵巢癌中的表达。运用The Human Protein Atlas数据库,分析ESPL1蛋白在卵巢及卵巢癌组织中表达及定位;应用String数据库绘制ESPL1基因的相关蛋白网络图,并进行基因功能富集分析。使用Kaplan-Meier Plotter网站,对ESPL1表达影响不同临床特征患者预后指标及化疗药物疗效进行分析。结果 ESPL1在14种恶性肿瘤中表达明显上调,而在食管癌中表达量下调;与正常卵巢组织相比,在卵巢癌中ESPL1基因在mRNA及蛋白质水平的表达显著升高,在卵巢癌中表达定位于细胞膜或浆及核中。与ESPL1基因相互作用蛋白有SMC3、KIF11、PTTG1等10个,主要富集在细胞周期、卵母细胞减数分裂等信号通路。Kaplan-Meier生存分析显示,ESPL1高表达的卵巢癌患者总生存时间明显短于ESPL1低表达者,且临床I+II期患者总生存期较短(P<0.05),其它期别及病理分级的患者预后无差异;应用多西他赛单药组中,ESPL1高表达组较低表达组总生存期下降,有显著差异(P<0.05),而在铂类、紫杉醇、泰素、吉西他滨、拓扑替康单药治疗的患者中,两组间无显著性差异。结论 ESPL1基因在多种肿瘤组织及卵巢癌组织中高表达;其相互作用的网络蛋白主要富集在细胞周期信号通路;高表达ESPL1基因的卵巢癌患者预后差,特别是早期卵巢癌患者,化疗药物不宜选择多西他赛。该基因也许可作为卵巢癌预后及一线化疗药物选择潜在参考指标。展开更多
The interaction between m^(6)A-methylated RNA and chromatin modification remains largely unknown.We found that targeted inhibition of bromodomain-containing protein 4(BRD4)by siRNA or its inhibitor(JQ1)significantly d...The interaction between m^(6)A-methylated RNA and chromatin modification remains largely unknown.We found that targeted inhibition of bromodomain-containing protein 4(BRD4)by siRNA or its inhibitor(JQ1)significantly decreases mRNA m^(6)A levels and suppresses the malignancy of breast cancer(BC)cells via increased expression of demethylase AlkB homolog 5(ALKBH5).Mechanistically,inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3′untranslated regions(3′UTRs)with RNA-binding protein RALY.Further,BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21(TRIM21)and ALKBH5,resulting in the ubiquitination and degradation of ALKBH5 protein.JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1(ESPL1)and reduces binding between ESPL1 mRNA and m^(6)A reader insulin like growth factor 2 mRNA binding protein 3(IGF2BP3),leading to decay of ESPL1 mRNA.Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression.Further,our study sheds light on the crosstalks between histone modification and RNA methylation.展开更多
本文应用 Vintens ESPI、全息干涉及新发展的 Video 的全息干涉技术,研究了水平热管的自然对流现象。介绍了这三种技术的光学系统,和关于气体温度场的测量原理和测量结果。与热电偶所测温度值比较,结果相当一致。文中还就可能的测量误...本文应用 Vintens ESPI、全息干涉及新发展的 Video 的全息干涉技术,研究了水平热管的自然对流现象。介绍了这三种技术的光学系统,和关于气体温度场的测量原理和测量结果。与热电偶所测温度值比较,结果相当一致。文中还就可能的测量误差作了定性分析。展开更多
A mutant was isolated from the M2 of 60Co-T ray mutagenized male-fertility restorer line Zao-R974 in rice. The mutant showed pleiotropic phenotypes including dwarfism, delayed heading time, short and partially enclose...A mutant was isolated from the M2 of 60Co-T ray mutagenized male-fertility restorer line Zao-R974 in rice. The mutant showed pleiotropic phenotypes including dwarfism, delayed heading time, short and partially enclosed panicles, short uppermost internode, decreased grain and secondary branch numbers per panicle, and partially degenerated spikelets. The mutant was named as espl （enclosed shorter panicle 1）. Genetic analysis indicated that the mutant phenotype was controlled by a recessive locus. Spraying exogenous GA~ did not rescue the panicle enclosure. Using an F2 and a BC, population of the cross between espl and a japonica cultivar Nipponbare, we mapped the ESP1 locus to a region of-260 kb on chromosome 11. This result provides a basis for further map-based cloning of the ESP1 locus.展开更多
基金supported by the National Natural Science Foundation of China under grant number U21A20259the National Key Research and Development Program of China under grant number 2021YFD1800401.
文摘Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.
文摘目的 探讨分离酶(ESPL1)基因在卵巢癌中的表达及意义。方法 利用GEPIA数据库,对比相应正常组织,分析ESPL1在泛癌及卵巢癌中的表达。运用The Human Protein Atlas数据库,分析ESPL1蛋白在卵巢及卵巢癌组织中表达及定位;应用String数据库绘制ESPL1基因的相关蛋白网络图,并进行基因功能富集分析。使用Kaplan-Meier Plotter网站,对ESPL1表达影响不同临床特征患者预后指标及化疗药物疗效进行分析。结果 ESPL1在14种恶性肿瘤中表达明显上调,而在食管癌中表达量下调;与正常卵巢组织相比,在卵巢癌中ESPL1基因在mRNA及蛋白质水平的表达显著升高,在卵巢癌中表达定位于细胞膜或浆及核中。与ESPL1基因相互作用蛋白有SMC3、KIF11、PTTG1等10个,主要富集在细胞周期、卵母细胞减数分裂等信号通路。Kaplan-Meier生存分析显示,ESPL1高表达的卵巢癌患者总生存时间明显短于ESPL1低表达者,且临床I+II期患者总生存期较短(P<0.05),其它期别及病理分级的患者预后无差异;应用多西他赛单药组中,ESPL1高表达组较低表达组总生存期下降,有显著差异(P<0.05),而在铂类、紫杉醇、泰素、吉西他滨、拓扑替康单药治疗的患者中,两组间无显著性差异。结论 ESPL1基因在多种肿瘤组织及卵巢癌组织中高表达;其相互作用的网络蛋白主要富集在细胞周期信号通路;高表达ESPL1基因的卵巢癌患者预后差,特别是早期卵巢癌患者,化疗药物不宜选择多西他赛。该基因也许可作为卵巢癌预后及一线化疗药物选择潜在参考指标。
基金supported by the National Key Research and Development Program of China(No.2022YFC2601800)the National Natural Science Foundation of China(Nos.82472761,32161143017,82173833,82372743,82173126,82373893,82341053,and 32100584)+10 种基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2023B1515040006,China)the Key-Area Research and Development Program of Guangdong Province(No.2023B1111020007,China)the Guangzhou Science and Technology Program(No.2024A04J6480,China)the Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022,China)the Shenzhen Bay Scholars Program,the Natural Science Foundation of Shandong Province(No.ZR2021QC061,China)the Natural Science Foundation of Hunan Province of China(No.2022JJ40413)the Outstanding Youth Project of Hunan Provincial Department of Education(No.22B0814,China)the Young Teachers Cultivation Program of Basic Research Operating Expenses of Universities at Sun Yat-sen University(No.23qnpy117,China)the Research Project of TCM Bureau of Guangdong Province(No.20231324,China)the Special Fund of Foshan Climbing Peak Plan(No.2020B018,China)the Basic and Applied Basic Research Foundation of Guangdong Province(No.2022A1515140091,China).
文摘The interaction between m^(6)A-methylated RNA and chromatin modification remains largely unknown.We found that targeted inhibition of bromodomain-containing protein 4(BRD4)by siRNA or its inhibitor(JQ1)significantly decreases mRNA m^(6)A levels and suppresses the malignancy of breast cancer(BC)cells via increased expression of demethylase AlkB homolog 5(ALKBH5).Mechanistically,inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3′untranslated regions(3′UTRs)with RNA-binding protein RALY.Further,BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21(TRIM21)and ALKBH5,resulting in the ubiquitination and degradation of ALKBH5 protein.JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1(ESPL1)and reduces binding between ESPL1 mRNA and m^(6)A reader insulin like growth factor 2 mRNA binding protein 3(IGF2BP3),leading to decay of ESPL1 mRNA.Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression.Further,our study sheds light on the crosstalks between histone modification and RNA methylation.
基金supported by the National Transgenic Projects of China(2009ZX-08009-109B)the Natural Science Foundation of Fujian Province, China(2012J01091)the New Century Excellent Talents in University of Fujian Province, China(KY0010057)
文摘A mutant was isolated from the M2 of 60Co-T ray mutagenized male-fertility restorer line Zao-R974 in rice. The mutant showed pleiotropic phenotypes including dwarfism, delayed heading time, short and partially enclosed panicles, short uppermost internode, decreased grain and secondary branch numbers per panicle, and partially degenerated spikelets. The mutant was named as espl （enclosed shorter panicle 1）. Genetic analysis indicated that the mutant phenotype was controlled by a recessive locus. Spraying exogenous GA~ did not rescue the panicle enclosure. Using an F2 and a BC, population of the cross between espl and a japonica cultivar Nipponbare, we mapped the ESP1 locus to a region of-260 kb on chromosome 11. This result provides a basis for further map-based cloning of the ESP1 locus.
