Epithelial-mesenchymal transition (EMT) plays a fundamental role in cancer metastasis. The ubiquitin ligase FBXW7, a general tumor suppressor in human cancer, has been implicated in diverse cellular processes, however, its role in cholangiocarcinoma (CCA) metastasis has not been identified. Here, we report a crucial role of FBXW7 in CCA metastasis by regulating EMT. Loss of FBXW7 expression was detected in CCA cells and clinical specimens. Clinicopathological analysis revealed a close correlation between FBXW7 deficiency and metastasis, TNM stage and differentiation in intrahepatic CCA and perihilar CCA. Moreover, FBXW7 silencing in CCA cells dramatically promoted EMT, stem-like capacity and metastasis both in vitro and in vivo. Conversely, FBXW7 overexpression attenuated these processes. Mechanistically, treatment with rapamycin, a mTOR inhibitor, inhibited EMT, stem-like capacity and metastasis induced by FBXW7 silencing both in vitro and in vivo. Furthermore, the expression of EMT regulating transcription factors, snail, slug and ZEB1, were also decreased markedly with rapamycin treatment. In addition, silencing ZEB1 inhibited EMT and metastasis of both CCA cells and FBXW7 deficient CCA cells, which implicated the potential role of ZEB1 in FBXW7/mTOR signaling pathway related CCA metastasis. In conclusion, our findings defined a pivotal function of FBXW7 in CCA metastasis by regulating EMT.
Purpose The present work concerns the distribution of ten heavy metals (Sb, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) in the surrounding agricultural soils of the world largest antimony (Sb) mine in China. The objective is to explore the degree and spatial distribution of heavy metal pollution of the Sb mine-affected agricultural soils. The presented data were compared with metal concentrations in soils from mining and smelting sites in China and other countries. Materials and methods There were 29 environmental samples in all that were collected in the year 2008 for this study. Soil characteristic parameters such as pH, total organic carbon, and cation exchange capacity were determined. Metal contents were determined after digestion in a Teflon bomb with aqua regia. Cd, Cu, Ni, Pb, and Zn concentrations were determined by inductively coupled plasma-mass spectrometry. As, Sb, and Hg concentrations were determined by atomic fluorescence spectrometry (AFS-2202). Fe, Al, Cr, and Mn concentrations were determined by inductively coupled plasma-atomic emission spectrometry.Results and discussion Almost all of the ten heavy metals exhibited much higher concentrations compared with their respective natural background values, especially Sb, and they varied with sampling site. The enriched factor values show that Sb (235.8), Cd (51.8), Hg (13.8), As (3.13), Zn (2.91), Pb (2.46), and Cr (1.67) are significantly accumulated in the study area. All of the integrated pollution indexes (IPI>3) calculated from pollution indexes show that the soils are severely contaminated by investigated heavy metals.Principal component analysis, cluster analysis, and correlation analysis suggest that Cd, Cu, Pb, Zn, and Mn are derived from the sulfide mineralization paragenesis in Xikuangshan area. Cr, As, Hg, Al, and Sb are mainly due to the mining and smelting activities of this area and derived from organic matters, and Ni is mainly generated from agricultural activities. These metal concentrations in Xikuangshan agricultural topsoil are comparable or within the ranges of those in mine areas of other countries. Conclusions The heavy metal concentrations in the topsoil of Xikuangshan area are mostly higher than the background values, especially for Sb and As. Heavy metal pollution has spread in this mine area, both from mining activities and agricultural activities. Analysis of soil samples from 23 sampling locations of the area show significant spatial variation of the ten heavy metals.
To understand the residues and ecological risks of veterinary antibiotics (VAs) in animal faeces from concentrated animal feeding operations in northeastern China, 14 VAs were identified by high performance liquid chromatography, and the preliminary risks of six antibiotics were assessed using the hazard quotient (HQ). The investigated VAs occurred in 7.41 to 57.41 % of the 54 samples, and the levels ranged from 0.08 to 56.81 mg kg(-1). Tetracyclines were predominant with a maximum level of 56.81 mg kg(-1) mostly detected in pig faeces. Sulfonamides were common and detected with the highest concentration of 7.11 mg kg(-1). Fluoroquinolones were more widely detected in chicken faeces rather than in pig or cow faeces, which contained the dominant antibiotic enrofloxacin. In comparison, the residue of tylosin was less frequently found. The risk evaluations of the six antibiotics revealed that tetracyclines, especially oxytetracycline, displayed the greatest ecological risk because of its high HQ value of 15.75. The results of this study imply that multiple kinds of VAs were jointly used in animal feeding processes in the study area. These medicine residues in animal faeces may potentially bring ecological risks if the animal manure is not treated effectively.
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