The geometry,stability,binding energy and electronic properties of（SiO2）n and Ge（SiO2）n clusters（n = 7） have been investigated by Density functional theory（DFT）.The results show that the lowest energy structur...The geometry,stability,binding energy and electronic properties of（SiO2）n and Ge（SiO2）n clusters（n = 7） have been investigated by Density functional theory（DFT）.The results show that the lowest energy structures of Ge（SiO2）n are obtained by adding one Ge on the end site of the O atom or the Si near end site of the O atom in（SiO2）n.The chemical activation of Ge-（SiO2）n is improved compared with（SiO2）n.The calculated second-order difference of energies and fragmentation energies show that the Ge（SiO2）n clusters with n = 2 or 5 are stable.展开更多
Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant chall...Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.展开更多
BACKGROUND N6-methyladenosine(m6A)exerts a pro-carcinogenic effect in diverse cancers.The relationship between m6A-reading protein IGF2BP3 and gastric cancer(GC)has not yet been fully elucidated.AIM To investigate the...BACKGROUND N6-methyladenosine(m6A)exerts a pro-carcinogenic effect in diverse cancers.The relationship between m6A-reading protein IGF2BP3 and gastric cancer(GC)has not yet been fully elucidated.AIM To investigate the molecular mechanisms of IGF2BP3 in GC carcinogenesis and progression and thus provide a rationale for novel therapeutic strategies.METHODS Expression levels of IGF2BP3 in GC were determined using quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot(WB),and immunohistochemistry,and their associations with patients’clinicopathological characteristics were analyzed.The role of IGF2BP3 in GC was investigated using cellular functional assays and subcutaneous xenograft models,and its downstream targets and signaling pathways were identified using highthroughput sequencing,bioinformatics analysis,RNA immunoprecipitation qPCR,dual luciferase reporter assay,qRT-PCR,and WB.The mechanism of IGF2BP3 in GC was validated via WB and rescue and inhibition experiments.RESULTS IGF2BP3 was highly expressed in GC and associated with diffuse-type GC,incidence of lymph node metastasis,advanced tumor node metastasis stage,and deeper tumor invasion depth.In vitro experiments demonstrated that IGF2BP3 promoted proliferation,migration,and invasiveness of GC cells,while inhibiting apoptosis and augmenting intracellular levels of glucose metabolism.In vivo experiments revealed that IGF2BP3 contributes to the growth of GC.Mechanistically,IGF2BP3 recognized and bound to the m6A site at position 1427 on FBXO32 messenger RNA,thereby increasing protein expression of FBXO32,and further activated the downstream cyclic guanosine monophosphate-protein kinase G(cGMP-PKG)signaling pathway to modulate various biological functions of GC cells and promote progression of GC.Furthermore,treatment with a selective PKG inhibitor KT5823 significantly suppressed the proliferative capacity of GC cells.CONCLUSION IGF2BP3 increases FBXO32 protein expression in an m6A-dependent manner,activates the cGMP-PKG signaling pathway,and promotes GC progression.Targeting of the IGF2BP3/FBXO32/cGMP-PKG axis could thus represent a promising therapeutic modality for GC.展开更多
目的研究胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)及长链非编码RNA LINC00160(LINC00160)在胃癌中的作用,及其可能调控胃癌细胞增殖、侵袭的潜在作用机制。方法通过实时定量聚合酶链反应(qRT-PCR)检测胃癌组织和细胞中LINC00160表达...目的研究胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)及长链非编码RNA LINC00160(LINC00160)在胃癌中的作用,及其可能调控胃癌细胞增殖、侵袭的潜在作用机制。方法通过实时定量聚合酶链反应(qRT-PCR)检测胃癌组织和细胞中LINC00160表达水平。通过生物信息学预测及RNA结合蛋白免疫沉淀(RIP)和甲基化RNA免疫沉淀(MeRIP)法验证分析LINC00160与IGF2BP1的结合作用;Pearson检验分析胃癌组织中LINC00160与IGF2BP1表达的相关性;CCK-8法和Transwell检测细胞增殖和侵袭能力;检测分析有氧糖酵解指标[葡萄糖摄取量、乳酸生成量和三磷酸腺苷(ATP)及细胞外酸化率(ECAR)和耗氧率(OCR)]水平变化。结果与癌旁正常组织相比,胃癌组织中LINC00160(5.13±0.62 vs 1.02±0.03)表达量显著上调,差异具有统计学意义(t=-36.266,P<0.001);胃癌细胞中LINC00160表达量亦高于人正常胃上皮细胞系GES-1,差异具有统计学意义(F=24.595,P<0.001)。与对照组相比,沉默LINC00160显著抑制AGS细胞的增殖(0.42±0.03 vs 1.03±0.04)和侵袭(22.13%±1.97%vs 42.15%±2.67%),减少葡萄糖摄取(2.11±0.26mmol/L vs 4.22±0.37mmol/L)和乳酸生成量(6.84±1.25mmol/L vs 11.68±1.55mmol/L),降低ECAR,升高ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)水平和OCR,差异具有统计学意义(t=4.188~24.423,均P<0.01)。胃癌组织中IGF2BP1蛋白(4.07±0.36)表达显著高于癌旁组织(1.01±0.03),差异具有统计学意义(t=-46.396,P<0.01),且与LINC00160表达呈正相关(r 2=0.7745,P<0.01)。IGF2BP1通过与LINC00160的m6A修饰位点结合促进LINC00160稳定性。沉默IGF2BP1显著抑制了LINC00160表达及胃癌细胞的增殖、侵袭和有氧糖酵解,差异具有统计学意义(t=4.386~11.989,均P<0.01);过表达LINC00160可逆转沉默IGF2BP1对胃癌细胞生物学行为及有氧糖酵解的影响。结论胃癌中LINC00160显著上调,IGF2BP1可能通过m6A修饰稳定调控LINC00160表达,促进肿瘤细胞的有氧糖酵解,参与胃癌的发生发展。展开更多
An efficient and mild method for the direct conversion of alcohols into N-alkylphthalimides using 2,4,6-trichloro-1,3,5-triazine and dimethylformamide was described.The reaction was preceded via(alcoxymethylene) dimet...An efficient and mild method for the direct conversion of alcohols into N-alkylphthalimides using 2,4,6-trichloro-1,3,5-triazine and dimethylformamide was described.The reaction was preceded via(alcoxymethylene) dimethylammonium chloride intermediate and produced corresponding N-alkylphthalimides in good-to-excellent yields.展开更多
Structural and electronic properties of Pb_(n)Ag_(n)(n=2–12)clusters were investigated by density functional theory with generalized gradient approximation at BLYP level in DMol3 program package.The optimized bimetal...Structural and electronic properties of Pb_(n)Ag_(n)(n=2–12)clusters were investigated by density functional theory with generalized gradient approximation at BLYP level in DMol3 program package.The optimized bimetallic Pb_(n)Ag_(n)(n=2–12)clusters were viewed as the initial structures,then,those were calculated by ab initio molecular dynamics(AIMD)to search possible global minimum energy structures of Pb_(n)Ag_(n)clusters,finally,the ground state structures of Pb_(n)Ag_(n)(n=2–12)clusters were achieved.According to the structural evolution of lowest energy structures,Ag atoms prefer gather in the central sites while Pb atoms prefer external positions in Pb_(n)Ag_(n)(n=2–12)clusters,which is in excellent agreement with experimental results from literature and the application in metallurgy.The average binding energies,HOMO-LUMO gaps,vertical ionization potentials,vertical electron affinities,chemical hardnessη,HOMO orbits,LUMO orbits and density of states of Pb_(n)Ag_(n)(n=2–12)clusters were calculated.The results indicate that the values of HOMO-LUMO gaps,vertical ionization potentials,vertical electron affinities and chemical hardnessηshow obvious odd-even oscillations when n≤5,Pb_(n)Ag_(n)(n=2–12)clusters become less chemically stable and show insulator-to-metal transition with the variation of cluster size n,Pb_(n)Ag_(n)(n≥9)cluster are good candidates to study the properties of PbAg alloys.Those can be well explained by the density of states(DOS)distributions of Pb atoms and Ag atoms between–0.5 Ha and 0.25 Ha in Pb_(n)Ag_(n)(n=2–12)clusters.展开更多
基金Project supported by the foundation start up for high level talents of Shihezi university (No. RCZX200747)
文摘The geometry,stability,binding energy and electronic properties of（SiO2）n and Ge（SiO2）n clusters（n = 7） have been investigated by Density functional theory（DFT）.The results show that the lowest energy structures of Ge（SiO2）n are obtained by adding one Ge on the end site of the O atom or the Si near end site of the O atom in（SiO2）n.The chemical activation of Ge-（SiO2）n is improved compared with（SiO2）n.The calculated second-order difference of energies and fragmentation energies show that the Ge（SiO2）n clusters with n = 2 or 5 are stable.
基金Supported by National Natural Science Foundation of China,No.82405223Yunling Scholars Program,No.XDYC-YLXZ-2022-0027.
文摘Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.
基金Supported by the Hebei Natural Science Foundation,No.H2025206524,No.H2022206292 and No.H2024206140Hebei Provincial Government-funded Provincial Medical Excellent Talent Project,No.ZF2023025,No.ZF2024134 and No.LS202008+3 种基金Key RD Program of Hebei Province,No.223777103D and No.223777113DPrevention and Treatment of Geriatric Diseases by Hebei Provincial Department of Finance,No.LNB202202 and No.LNB201909Spark Scientific Research Project of the First Hospital of Hebei Medical University,No.XH202504,No.XH202312 and No.XH201805Hebei Province Medical Applicable Technology Tracking Project,No.G2019035.
文摘BACKGROUND N6-methyladenosine(m6A)exerts a pro-carcinogenic effect in diverse cancers.The relationship between m6A-reading protein IGF2BP3 and gastric cancer(GC)has not yet been fully elucidated.AIM To investigate the molecular mechanisms of IGF2BP3 in GC carcinogenesis and progression and thus provide a rationale for novel therapeutic strategies.METHODS Expression levels of IGF2BP3 in GC were determined using quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot(WB),and immunohistochemistry,and their associations with patients’clinicopathological characteristics were analyzed.The role of IGF2BP3 in GC was investigated using cellular functional assays and subcutaneous xenograft models,and its downstream targets and signaling pathways were identified using highthroughput sequencing,bioinformatics analysis,RNA immunoprecipitation qPCR,dual luciferase reporter assay,qRT-PCR,and WB.The mechanism of IGF2BP3 in GC was validated via WB and rescue and inhibition experiments.RESULTS IGF2BP3 was highly expressed in GC and associated with diffuse-type GC,incidence of lymph node metastasis,advanced tumor node metastasis stage,and deeper tumor invasion depth.In vitro experiments demonstrated that IGF2BP3 promoted proliferation,migration,and invasiveness of GC cells,while inhibiting apoptosis and augmenting intracellular levels of glucose metabolism.In vivo experiments revealed that IGF2BP3 contributes to the growth of GC.Mechanistically,IGF2BP3 recognized and bound to the m6A site at position 1427 on FBXO32 messenger RNA,thereby increasing protein expression of FBXO32,and further activated the downstream cyclic guanosine monophosphate-protein kinase G(cGMP-PKG)signaling pathway to modulate various biological functions of GC cells and promote progression of GC.Furthermore,treatment with a selective PKG inhibitor KT5823 significantly suppressed the proliferative capacity of GC cells.CONCLUSION IGF2BP3 increases FBXO32 protein expression in an m6A-dependent manner,activates the cGMP-PKG signaling pathway,and promotes GC progression.Targeting of the IGF2BP3/FBXO32/cGMP-PKG axis could thus represent a promising therapeutic modality for GC.
文摘目的研究胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)及长链非编码RNA LINC00160(LINC00160)在胃癌中的作用,及其可能调控胃癌细胞增殖、侵袭的潜在作用机制。方法通过实时定量聚合酶链反应(qRT-PCR)检测胃癌组织和细胞中LINC00160表达水平。通过生物信息学预测及RNA结合蛋白免疫沉淀(RIP)和甲基化RNA免疫沉淀(MeRIP)法验证分析LINC00160与IGF2BP1的结合作用;Pearson检验分析胃癌组织中LINC00160与IGF2BP1表达的相关性;CCK-8法和Transwell检测细胞增殖和侵袭能力;检测分析有氧糖酵解指标[葡萄糖摄取量、乳酸生成量和三磷酸腺苷(ATP)及细胞外酸化率(ECAR)和耗氧率(OCR)]水平变化。结果与癌旁正常组织相比,胃癌组织中LINC00160(5.13±0.62 vs 1.02±0.03)表达量显著上调,差异具有统计学意义(t=-36.266,P<0.001);胃癌细胞中LINC00160表达量亦高于人正常胃上皮细胞系GES-1,差异具有统计学意义(F=24.595,P<0.001)。与对照组相比,沉默LINC00160显著抑制AGS细胞的增殖(0.42±0.03 vs 1.03±0.04)和侵袭(22.13%±1.97%vs 42.15%±2.67%),减少葡萄糖摄取(2.11±0.26mmol/L vs 4.22±0.37mmol/L)和乳酸生成量(6.84±1.25mmol/L vs 11.68±1.55mmol/L),降低ECAR,升高ATP(3.34±0.29mmol/L vs 1.87±0.24mmol/L)水平和OCR,差异具有统计学意义(t=4.188~24.423,均P<0.01)。胃癌组织中IGF2BP1蛋白(4.07±0.36)表达显著高于癌旁组织(1.01±0.03),差异具有统计学意义(t=-46.396,P<0.01),且与LINC00160表达呈正相关(r 2=0.7745,P<0.01)。IGF2BP1通过与LINC00160的m6A修饰位点结合促进LINC00160稳定性。沉默IGF2BP1显著抑制了LINC00160表达及胃癌细胞的增殖、侵袭和有氧糖酵解,差异具有统计学意义(t=4.386~11.989,均P<0.01);过表达LINC00160可逆转沉默IGF2BP1对胃癌细胞生物学行为及有氧糖酵解的影响。结论胃癌中LINC00160显著上调,IGF2BP1可能通过m6A修饰稳定调控LINC00160表达,促进肿瘤细胞的有氧糖酵解,参与胃癌的发生发展。
基金Shahid Chamran University Research Council,Ahvaz,for financial support of this investigation(No.87)
文摘An efficient and mild method for the direct conversion of alcohols into N-alkylphthalimides using 2,4,6-trichloro-1,3,5-triazine and dimethylformamide was described.The reaction was preceded via(alcoxymethylene) dimethylammonium chloride intermediate and produced corresponding N-alkylphthalimides in good-to-excellent yields.
基金Project(51664032)supported by the Regional Foundation of the National Natural Science Foundation of ChinaProject(51474116)supported by the General Program of the National Natural Science Foundation of China+5 种基金Project(U1502271)supported by the Joint Foundation of the NSFC-Yunnan Province,ChinaProject(2014HA003)supported by the Cultivating Plan Program for the Leader in Science and Technology of Yunnan Province,ChinaProject(2014RA4018)supported by the Program for Nonferrous Metals Vacuum Metallurgy Innovation Team of Ministry of Science and Technology,ChinaProject(2016YFC0400404)supported by the National Key Research and Development Program of ChinaProject(51504115)supported by the Youth Program of National Natural Science Foundation of ChinaProject(IRT_17R48)supported by the Program for Innovative Research Team in University of Ministry of Education of China
文摘Structural and electronic properties of Pb_(n)Ag_(n)(n=2–12)clusters were investigated by density functional theory with generalized gradient approximation at BLYP level in DMol3 program package.The optimized bimetallic Pb_(n)Ag_(n)(n=2–12)clusters were viewed as the initial structures,then,those were calculated by ab initio molecular dynamics(AIMD)to search possible global minimum energy structures of Pb_(n)Ag_(n)clusters,finally,the ground state structures of Pb_(n)Ag_(n)(n=2–12)clusters were achieved.According to the structural evolution of lowest energy structures,Ag atoms prefer gather in the central sites while Pb atoms prefer external positions in Pb_(n)Ag_(n)(n=2–12)clusters,which is in excellent agreement with experimental results from literature and the application in metallurgy.The average binding energies,HOMO-LUMO gaps,vertical ionization potentials,vertical electron affinities,chemical hardnessη,HOMO orbits,LUMO orbits and density of states of Pb_(n)Ag_(n)(n=2–12)clusters were calculated.The results indicate that the values of HOMO-LUMO gaps,vertical ionization potentials,vertical electron affinities and chemical hardnessηshow obvious odd-even oscillations when n≤5,Pb_(n)Ag_(n)(n=2–12)clusters become less chemically stable and show insulator-to-metal transition with the variation of cluster size n,Pb_(n)Ag_(n)(n≥9)cluster are good candidates to study the properties of PbAg alloys.Those can be well explained by the density of states(DOS)distributions of Pb atoms and Ag atoms between–0.5 Ha and 0.25 Ha in Pb_(n)Ag_(n)(n=2–12)clusters.
