Background:Triple-negative breast cancer(TNBC)is a heterogeneous,recurring cancer characterized by a high rate of metastasis,poor prognosis,and lack of efficient therapies.KBU2046,a small molecule inhibitor,can inhibi...Background:Triple-negative breast cancer(TNBC)is a heterogeneous,recurring cancer characterized by a high rate of metastasis,poor prognosis,and lack of efficient therapies.KBU2046,a small molecule inhibitor,can inhibit cell motility in malignant tumors,including breast cancer.However,the specific targets and the corresponding mechanism of its function remain unclear.Methods:In this study,we employed(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium)(MTS)assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro.RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC.Finally,confirmed the predicted important signaling pathways through RT-qPCR and western blotting.Results:In this study,we found that KBU2046 functioned as a novel transforming growth factor-β(TGF-β1)inhibitor,effectively suppressing tumor cell motility in vitro.Mechanistically,it directly down-regulated leucine-rich repeat-containing 8 family,member E(LRRC8E),latent TGFβ-binding protein 3(LTBP3),dynein light chain 1(DNAL1),and MAF family of bZIP transcription factors(MAFF)genes,along with reduced protein expression of the integrin family.Additionally,KBU2046 decreased phosphorylation levels of Raf and ERK.This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis.Conclusions:In summary,these findings advocate for the utilization of TGF-β1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC.Furthermore,our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.展开更多
骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)导致血细胞增加、血液高凝,是非肝硬化门静脉海绵样变性的重要病因。JAK2V617F基因突变可以帮助诊断MPN。我们报道1例JAK2V617F基因突变阳性的MPN患者发生门静脉海绵样变性(cavernous ...骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)导致血细胞增加、血液高凝,是非肝硬化门静脉海绵样变性的重要病因。JAK2V617F基因突变可以帮助诊断MPN。我们报道1例JAK2V617F基因突变阳性的MPN患者发生门静脉海绵样变性(cavernous transformation of the portal vein,CTPV)。该例患者脾脏显著肿大,一方面是由于骨髓增殖性疾病本身的原因,另一方面是由于PVCT、门脉高压和脾脏淤血造成,表现为外周血血细胞计数基本在正常范围,亦是血细胞增殖和脾脏对血细胞的处理增加的共同作用的结果。抗凝治疗效果差,而应以预防食管曲张静脉破裂出血(EVB)为主。展开更多
Correlation between site occupation evolution of alloying elements in L12 phase and growth of DO22 phase in Ni75Al7.5V17.5 was studied using microscopic phase field model. The results demonstrate that the growing proc...Correlation between site occupation evolution of alloying elements in L12 phase and growth of DO22 phase in Ni75Al7.5V17.5 was studied using microscopic phase field model. The results demonstrate that the growing process of DO22 phase can be divided into two stages. At the early stage, composition in the centre part of L12 phase almost remains unchanged, and the nucleation and growth of DO22 phase is controlled by the decrease of interface between L12 phases. At the late stage, part of V for growth of DO22 phase is supplied from the centre part of L12 phase and mainly comes from Al sublattice, the excess Ni spared from the decreasing L12 phase migrates into the centre part of L12 phase and occupies the Ni sublattices exclusively, while the excess Al mainly occupies the Al sublattice. At the late stage, the growth of DO22 phase is controlled by the evolution of antisite atoms and ternary additions in the centre part of L12 phase.展开更多
Based on the microscopic phase-field model, the correlation between site occupation evolution of alloying elements in Ni3V-DO22 phase and growth of Ni3Al-L12 phase was studied during the phase transformation of Ni75Al...Based on the microscopic phase-field model, the correlation between site occupation evolution of alloying elements in Ni3V-DO22 phase and growth of Ni3Al-L12 phase was studied during the phase transformation of Ni75Al4.2V20.8. The results demonstrate that the growth of L12 phase can be divided into two stages： at the early stage, the composition of alloying elements in DO22 phase almost remains unchanged; at the late stage, the compositions of Ni and Al decrease while V increases in DO22 phase. Part of alloying elements for L12 phase growth are supplied from the site occupation evolution of alloying elements on three kinds of sublattices in DO22 phase. Ni is mainly supplied from V sublattice, and part of Al is supplied from NiⅠ and V sites at the centre of DO22 phase. The excessive V from the decreasing DO22 phase migrates into the centre of DO22 phase and mainly occupies V and NiII sites. It is the site occupation evolution of antisite atoms and ternary additions in DO22 phase that controls the growth rate of L12 phase at the late stage.展开更多
KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction...KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction pathway.Nevertheless,the electrochemical behavior of KVPF is limited by the inherent poor electronic conductivity of the phosphate framework and unstable electrode/electrolyte interface.To address the above issues,this work proposes an infiltration-calcination method to confine the in-situ grown KVPF into the mesoporous carbon CMK-3(denoted KVPF@CMK-3).The assembled KVPF@CMK-3 nanocomposite features three-dimensional interconnected carbon channels,which not only offer abundant active sites and significantly accelerate K t/electron transport,but also prevent the growth of KVPF nanoparticle agglomerates,hence stabilizing the structure of the material.Additionally,V–F–C bonds are created at the interface of KVPF and CMK-3,which reduce the loss of F and stabilize the electrode interface.Thus,when tested as a cathode material for PIBs,the KVPF@CMK-3 nanocomposite delivers superior reversible capacitiy(103.2 mAh g^(-1) at 0.2 C),outstanding rate performance(90.1 mAh g^(-1) at 20 C),and steady cycling performance(92.2 mAh g^(-1) at 10 C and with the retention of 88.2%after 500 cycles).Moreover,its potassium storage mechanism is further examined by ex-situ XRD and ex-situ XPS techniques.The above synthetic strategy demonstrates the potential of KVPF@CMK-3 to be applied as the cathode for PIBs.展开更多
基金support from various funding sources,including the National Natural Science Foundation of China(Grant Nos.U21A20415,82002531)Hebei Provincial Key Research Projects(Grant No.223777157D)the Beijing Health Promotion Association,China(2022).
文摘Background:Triple-negative breast cancer(TNBC)is a heterogeneous,recurring cancer characterized by a high rate of metastasis,poor prognosis,and lack of efficient therapies.KBU2046,a small molecule inhibitor,can inhibit cell motility in malignant tumors,including breast cancer.However,the specific targets and the corresponding mechanism of its function remain unclear.Methods:In this study,we employed(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium)(MTS)assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro.RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC.Finally,confirmed the predicted important signaling pathways through RT-qPCR and western blotting.Results:In this study,we found that KBU2046 functioned as a novel transforming growth factor-β(TGF-β1)inhibitor,effectively suppressing tumor cell motility in vitro.Mechanistically,it directly down-regulated leucine-rich repeat-containing 8 family,member E(LRRC8E),latent TGFβ-binding protein 3(LTBP3),dynein light chain 1(DNAL1),and MAF family of bZIP transcription factors(MAFF)genes,along with reduced protein expression of the integrin family.Additionally,KBU2046 decreased phosphorylation levels of Raf and ERK.This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis.Conclusions:In summary,these findings advocate for the utilization of TGF-β1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC.Furthermore,our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.
文摘目的 筛选卵巢癌预后不良的分子生物学标志。方法 从GEO数据库获得卵巢癌GSE14001、GSE14407数据集,用在线分析工具GEO2R、Venn筛选得到卵巢癌和正常卵巢组织差异表达基因(DEGs),对DEGs进行富集分析,构建蛋白互作网络(PPI),以及构建网络模块得到关键基因,利用Kaplan Meier plotter网站分析关键基因与卵巢癌患者总生存期之间关系,应用GEPIA数据库分析DEGs在卵巢和卵巢癌组织中表达,应用The Human Protein Atlas数据库获取筛选基因的免疫组化结果,对比它们在卵巢和卵巢癌组织间的表达差异。结果 得到211个DEGs,92个上调和119个下调。差异基因生物学过程主要涉及侧枝发芽的正向调控、乏氧反应、间充质-上皮细胞信号传导;细胞组分主要集中在质膜顶、细胞表面、细胞外外泌体等部位;分子功能主要涉及丝氨酸型内肽酶活性、金属内肽酶活性、受体活性等;信号通路富集于白细胞跨内皮细胞迁移、细胞黏附通路、癌症通路等信号通路。得到35个候选基因,其中14个基因高表达、8个基因低表达与患者总生存期相关(P<0.05)。其中ATP6V1F、GINS1、GINS4基因在卵巢癌组织中在RNA水平和蛋白质水平表达均高于正常组织(P<0.05)。GNB3在卵巢癌组织中RNA水平表达低于正常组织,而在蛋白质水平恰好相反(P<0.05)。结论 ATP6V1F、GINS1、GINS4有可能是卵巢癌预后不良的新分子标志物。
文摘骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)导致血细胞增加、血液高凝,是非肝硬化门静脉海绵样变性的重要病因。JAK2V617F基因突变可以帮助诊断MPN。我们报道1例JAK2V617F基因突变阳性的MPN患者发生门静脉海绵样变性(cavernous transformation of the portal vein,CTPV)。该例患者脾脏显著肿大,一方面是由于骨髓增殖性疾病本身的原因,另一方面是由于PVCT、门脉高压和脾脏淤血造成,表现为外周血血细胞计数基本在正常范围,亦是血细胞增殖和脾脏对血细胞的处理增加的共同作用的结果。抗凝治疗效果差,而应以预防食管曲张静脉破裂出血(EVB)为主。
基金Projects (50941020, 10902086, 50875217, 20903075) supported by the National Natural Science Foundation of ChinaProjects (SJ08-ZT05, SJ08-B14) supported by the Natural Science Foundation of Shaanxi Province, China
文摘Correlation between site occupation evolution of alloying elements in L12 phase and growth of DO22 phase in Ni75Al7.5V17.5 was studied using microscopic phase field model. The results demonstrate that the growing process of DO22 phase can be divided into two stages. At the early stage, composition in the centre part of L12 phase almost remains unchanged, and the nucleation and growth of DO22 phase is controlled by the decrease of interface between L12 phases. At the late stage, part of V for growth of DO22 phase is supplied from the centre part of L12 phase and mainly comes from Al sublattice, the excess Ni spared from the decreasing L12 phase migrates into the centre part of L12 phase and occupies the Ni sublattices exclusively, while the excess Al mainly occupies the Al sublattice. At the late stage, the growth of DO22 phase is controlled by the evolution of antisite atoms and ternary additions in the centre part of L12 phase.
基金Projects(51174168,51274167)supported by the National Natural Science Foundation of ChinaProject(2013M532082)supported by Postdoctoral Science Foundation of ChinaProjects(13R21421700,13R21421800)supported by the Postdoctoral Science Foundation of Shanghai,China
文摘Based on the microscopic phase-field model, the correlation between site occupation evolution of alloying elements in Ni3V-DO22 phase and growth of Ni3Al-L12 phase was studied during the phase transformation of Ni75Al4.2V20.8. The results demonstrate that the growth of L12 phase can be divided into two stages： at the early stage, the composition of alloying elements in DO22 phase almost remains unchanged; at the late stage, the compositions of Ni and Al decrease while V increases in DO22 phase. Part of alloying elements for L12 phase growth are supplied from the site occupation evolution of alloying elements on three kinds of sublattices in DO22 phase. Ni is mainly supplied from V sublattice, and part of Al is supplied from NiⅠ and V sites at the centre of DO22 phase. The excessive V from the decreasing DO22 phase migrates into the centre of DO22 phase and mainly occupies V and NiII sites. It is the site occupation evolution of antisite atoms and ternary additions in DO22 phase that controls the growth rate of L12 phase at the late stage.
基金This work was supported by the National Natural Science Foundation of China(22179063).
文摘KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction pathway.Nevertheless,the electrochemical behavior of KVPF is limited by the inherent poor electronic conductivity of the phosphate framework and unstable electrode/electrolyte interface.To address the above issues,this work proposes an infiltration-calcination method to confine the in-situ grown KVPF into the mesoporous carbon CMK-3(denoted KVPF@CMK-3).The assembled KVPF@CMK-3 nanocomposite features three-dimensional interconnected carbon channels,which not only offer abundant active sites and significantly accelerate K t/electron transport,but also prevent the growth of KVPF nanoparticle agglomerates,hence stabilizing the structure of the material.Additionally,V–F–C bonds are created at the interface of KVPF and CMK-3,which reduce the loss of F and stabilize the electrode interface.Thus,when tested as a cathode material for PIBs,the KVPF@CMK-3 nanocomposite delivers superior reversible capacitiy(103.2 mAh g^(-1) at 0.2 C),outstanding rate performance(90.1 mAh g^(-1) at 20 C),and steady cycling performance(92.2 mAh g^(-1) at 10 C and with the retention of 88.2%after 500 cycles).Moreover,its potassium storage mechanism is further examined by ex-situ XRD and ex-situ XPS techniques.The above synthetic strategy demonstrates the potential of KVPF@CMK-3 to be applied as the cathode for PIBs.
