BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRN...BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.展开更多
The lower Cambrian Qiongzhusi(Є1 q)shale in the Sichuan Basin,formerly considered a source rock,recently achieved high gas production(7.388×105 m^(3)·d^(-1))from well Z201 in the Deyang-Anyue rift trough(DAR...The lower Cambrian Qiongzhusi(Є1 q)shale in the Sichuan Basin,formerly considered a source rock,recently achieved high gas production(7.388×105 m^(3)·d^(-1))from well Z201 in the Deyang-Anyue rift trough(DART),marking an exploration breakthrough of the world’s oldest industrial shale gas reser-voir.However,the shale gas enrichment mechanism within the DART is not fully understood.This study reviews the formation of the Qiongzhusi shale gas reservoirs within the DART by comparing them with cotemporaneous deposits outside the DART,and several findings are presented.The gas production interval was correlated with the main phase of the Cambrian explosion(lower Cambrian stage 3).In the early Cambrian ecosystem,dominant animals likely accelerated the settling rates of organic matter(OM)in the upper 1st member ofЄ_(1) q(Є_(1) q_(12))by feeding on small planktonic organisms and producing larger organic fragments and fecal pellets.High primary productivity and euxinic con-ditions contributed to OM enrichment in the lower 1st member ofЄ1 q(Є_(1) q_(11)).Additionally,shale reservoirs inside the DART demonstrated better properties than those outside in terms of thickness,brittle minerals,gas content,and porosity.In particular,the abundant OM pores inside the DART facil-itated shale gas enrichment,whereas the higher thermal maturity of the shales outside the DART pos-sibly led to the graphitization and collapse of some OM pores.Meanwhile,the overpressure of high-production wells inside the DART generally reflects better shale gas preservation,benefiting from the shale’s self-sealing nature,"upper capping and lower plugging"configuration,and limited faults and microfractures.Considering these insights,we introduced a"ternary enrichment"model for the Qiongzhusi shale gas.Although the current high gas production of Z201 was found at the reservoir 3,two additional reservoirs were identified with significant potential,thus suggesting a"multilayer stereoscopic development"strategy in future shale gas exploration within the DART.展开更多
为了满足海工市场的业务需求并提升海工装备能力,海洋石油工程股份有限公司对“海洋石油201”船的铺管作业线进行了改造建设。其中,在原有400 t A&R绞车的基础上增加了1台300 t A&R绞车,并在布置上进行了整合。通过建立并车控...为了满足海工市场的业务需求并提升海工装备能力,海洋石油工程股份有限公司对“海洋石油201”船的铺管作业线进行了改造建设。其中,在原有400 t A&R绞车的基础上增加了1台300 t A&R绞车,并在布置上进行了整合。通过建立并车控制系统通信和专用并车锁具将2套A&R绞车系统并车,从而使铺管作业线收弃管能力提升至600 t。展开更多
背景与目的:肿瘤的发生、发展过程中会发生代谢重编程,1-酰基甘油-3-磷酸O-酰基转移酶(1-acylglycerol-3-phosphate O-acyltransferase,AGPAT)作为三酰甘油(triacylglycerol,TAG)从头合成的关键酶,与肿瘤的进展密切相关。但目前作为亚...背景与目的:肿瘤的发生、发展过程中会发生代谢重编程,1-酰基甘油-3-磷酸O-酰基转移酶(1-acylglycerol-3-phosphate O-acyltransferase,AGPAT)作为三酰甘油(triacylglycerol,TAG)从头合成的关键酶,与肿瘤的进展密切相关。但目前作为亚型之一的AGPAT5在癌症中的研究还十分有限,本研究深入剖析AGPAT5在肝癌发生、发展中发挥的作用及潜在的分子机制,旨在为肝癌诊断和治疗策略提供新思路。方法:利用慢病毒感染将多种肝癌细胞系中的AGPAT5敲减,并通过锥虫蓝计数、划痕、transwell及平板克隆等实验在体外检测AGPAT5对肝癌细胞增殖、迁移及抗失巢凋亡能力的影响。通过回复野生型或酶活性缺失型的AGPAT5,探究其作为代谢酶是否发挥经典代谢作用调控肝癌细胞迁移。构建BALB/c裸鼠尾静脉注射移植瘤模型,从体内层面验证体外的细胞表型。采用免疫沉淀质谱联用(immunoprecipitation mass spectrum,IP-MS)鉴定出与AGPAT5相互作用的蛋白,并进行免疫共沉淀(co-immunoprecipitation,coIP)验证。蛋白质翻译后通过修饰鉴定分析AGPAT5潜在的修饰位点,通过体外实验探究点突变前后对肝癌细胞迁移的影响。通过coIP探究该位点突变前后AGPAT5与相互作用蛋白结合的情况。通过敲低相互作用蛋白确定其在细胞表型中的作用。通过回复实验验证AGPAT5是否通过相互作用蛋白发挥作用。检测野生型肝癌细胞系中的AGPAT5和相互作用蛋白的表达水平,检验两者之间是否具有相关性。结果:肝癌细胞敲减AGPAT5后会更加耐受无血清饥饿,并促进细胞迁移,但不会影响细胞增殖和失巢凋亡。而酶活性缺失并不影响AGPAT5对肝癌细胞迁移的抑制。敲减AGPAT5可促进肝癌细胞在裸鼠体内的肺转移和肝转移。AGPAT5可以与原纤维蛋白(fibrillarin,FBL)相互作用,并在无血清饥饿刺激下加强两者的结合。遏制FBL的表达会抑制肝癌细胞迁移,且效果与过表达AGPAT5相似。抑制FBL的表达可削弱敲低AGPAT5对肝癌细胞迁移的促进作用。在已检测的肝癌细胞系中,AGPAT5和FBL在蛋白水平上并不存在相关性。K201位点突变使AGPAT5对肝癌细胞迁移的抑制作用减弱,并使AGPAT5与FBL的结合减弱。结论:敲低AGPAT5能够显著提高肝癌细胞迁移能力。AGPAT5可以与FBL相互作用,在无血清饥饿刺激下,AGPAT5或通过K201位点的乙酰化加强与FBL的结合,从而更有效地遏制FBL,进而抑制肝癌细胞迁移。但这种抑制作用并非来自AGPAT5的代谢酶活性,而是由非代谢作用所驱动。展开更多
基金Changzhou Sci and Tech Program,No.CJ20220008Young Talent Development Plan of Changzhou Health Commission,No.CZQM2020118+2 种基金Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105Cultivation Project of Changzhou Medical Center,Nanjing Medical University,No.CMCB202211Development Foundation of Affiliated Hospital of Xuzhou Medical University,No.XYFC202304,and No.XYFM202307。
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.
基金supported by the National Natural Science Foundation of China(U23B20155 and 42303004)China Postdoctoral Science Foundation(2023M730038)+1 种基金the Science and Technology Research Project for the China National Petroleum Corporation(2021DJ1802 and 2021YJCQ03)the National Postdoctoral Researcher Program of China(GZC20233111).
文摘The lower Cambrian Qiongzhusi(Є1 q)shale in the Sichuan Basin,formerly considered a source rock,recently achieved high gas production(7.388×105 m^(3)·d^(-1))from well Z201 in the Deyang-Anyue rift trough(DART),marking an exploration breakthrough of the world’s oldest industrial shale gas reser-voir.However,the shale gas enrichment mechanism within the DART is not fully understood.This study reviews the formation of the Qiongzhusi shale gas reservoirs within the DART by comparing them with cotemporaneous deposits outside the DART,and several findings are presented.The gas production interval was correlated with the main phase of the Cambrian explosion(lower Cambrian stage 3).In the early Cambrian ecosystem,dominant animals likely accelerated the settling rates of organic matter(OM)in the upper 1st member ofЄ_(1) q(Є_(1) q_(12))by feeding on small planktonic organisms and producing larger organic fragments and fecal pellets.High primary productivity and euxinic con-ditions contributed to OM enrichment in the lower 1st member ofЄ1 q(Є_(1) q_(11)).Additionally,shale reservoirs inside the DART demonstrated better properties than those outside in terms of thickness,brittle minerals,gas content,and porosity.In particular,the abundant OM pores inside the DART facil-itated shale gas enrichment,whereas the higher thermal maturity of the shales outside the DART pos-sibly led to the graphitization and collapse of some OM pores.Meanwhile,the overpressure of high-production wells inside the DART generally reflects better shale gas preservation,benefiting from the shale’s self-sealing nature,"upper capping and lower plugging"configuration,and limited faults and microfractures.Considering these insights,we introduced a"ternary enrichment"model for the Qiongzhusi shale gas.Although the current high gas production of Z201 was found at the reservoir 3,two additional reservoirs were identified with significant potential,thus suggesting a"multilayer stereoscopic development"strategy in future shale gas exploration within the DART.
文摘为了满足海工市场的业务需求并提升海工装备能力,海洋石油工程股份有限公司对“海洋石油201”船的铺管作业线进行了改造建设。其中,在原有400 t A&R绞车的基础上增加了1台300 t A&R绞车,并在布置上进行了整合。通过建立并车控制系统通信和专用并车锁具将2套A&R绞车系统并车,从而使铺管作业线收弃管能力提升至600 t。
文摘背景与目的:肿瘤的发生、发展过程中会发生代谢重编程,1-酰基甘油-3-磷酸O-酰基转移酶(1-acylglycerol-3-phosphate O-acyltransferase,AGPAT)作为三酰甘油(triacylglycerol,TAG)从头合成的关键酶,与肿瘤的进展密切相关。但目前作为亚型之一的AGPAT5在癌症中的研究还十分有限,本研究深入剖析AGPAT5在肝癌发生、发展中发挥的作用及潜在的分子机制,旨在为肝癌诊断和治疗策略提供新思路。方法:利用慢病毒感染将多种肝癌细胞系中的AGPAT5敲减,并通过锥虫蓝计数、划痕、transwell及平板克隆等实验在体外检测AGPAT5对肝癌细胞增殖、迁移及抗失巢凋亡能力的影响。通过回复野生型或酶活性缺失型的AGPAT5,探究其作为代谢酶是否发挥经典代谢作用调控肝癌细胞迁移。构建BALB/c裸鼠尾静脉注射移植瘤模型,从体内层面验证体外的细胞表型。采用免疫沉淀质谱联用(immunoprecipitation mass spectrum,IP-MS)鉴定出与AGPAT5相互作用的蛋白,并进行免疫共沉淀(co-immunoprecipitation,coIP)验证。蛋白质翻译后通过修饰鉴定分析AGPAT5潜在的修饰位点,通过体外实验探究点突变前后对肝癌细胞迁移的影响。通过coIP探究该位点突变前后AGPAT5与相互作用蛋白结合的情况。通过敲低相互作用蛋白确定其在细胞表型中的作用。通过回复实验验证AGPAT5是否通过相互作用蛋白发挥作用。检测野生型肝癌细胞系中的AGPAT5和相互作用蛋白的表达水平,检验两者之间是否具有相关性。结果:肝癌细胞敲减AGPAT5后会更加耐受无血清饥饿,并促进细胞迁移,但不会影响细胞增殖和失巢凋亡。而酶活性缺失并不影响AGPAT5对肝癌细胞迁移的抑制。敲减AGPAT5可促进肝癌细胞在裸鼠体内的肺转移和肝转移。AGPAT5可以与原纤维蛋白(fibrillarin,FBL)相互作用,并在无血清饥饿刺激下加强两者的结合。遏制FBL的表达会抑制肝癌细胞迁移,且效果与过表达AGPAT5相似。抑制FBL的表达可削弱敲低AGPAT5对肝癌细胞迁移的促进作用。在已检测的肝癌细胞系中,AGPAT5和FBL在蛋白水平上并不存在相关性。K201位点突变使AGPAT5对肝癌细胞迁移的抑制作用减弱,并使AGPAT5与FBL的结合减弱。结论:敲低AGPAT5能够显著提高肝癌细胞迁移能力。AGPAT5可以与FBL相互作用,在无血清饥饿刺激下,AGPAT5或通过K201位点的乙酰化加强与FBL的结合,从而更有效地遏制FBL,进而抑制肝癌细胞迁移。但这种抑制作用并非来自AGPAT5的代谢酶活性,而是由非代谢作用所驱动。
