[Pollution Properties and Ecological Risk Assessment of Heavy Metals in Farmland Soils and Crops Around a Typical Manganese Mining Area].

In order to assess the ecological risks of heavy metals and explore the pattern of heavy metal migration between farmland and corresponding crops in a typical and closed manganese mining area in Hunan province, farmland soils and crops surrounding the mining area (pollution area) and away from the mining area (control area) were collected, and then the contents of Cr, Mn, Ni, Cu, Zn, As, Cd, and Pb were analyzed. The sources and distribution of heavy metals in farmland soils were analyzed using Kriging spatial interpolation and principal component analysis, and the ecological risk was evaluated using the single factor index, comprehensive pollution index, and potential ecological risk index. The results showed that the surrounding farmland soils in the closed Manganese mining area presented serious pollution of Cd, Zn, As, and Mn, in which the average contents of the above heavy metals in the dry land soil in the polluted area were 6.22, 612.28, 37.72, and 1506.2 mg·kg-1, respectively. Compared with the soil risk screening value of agricultural land, the over-standard rates of Cd, Zn, and As were 88.41%, 94.20%, and 84.06%, respectively, and the average content of Mn in the farmland soil was three times that of the background value in the Hunan soil; however, the heavy metal pollution in the paddy field was relatively light. The principal component analysis showed that the sources of Cd, Mn, and Zn in the farmland soil were related to the manganese ore mining, whereas the source of As in the farmland soil might originate from agricultural activities. The pollution area was at a heavy pollution level, and the main pollution factors were Cd, Mn, and Zn. The Cd in the farmland soil could pose a strong potential ecological risk, but the rest of the heavy metals presented only a slight potential ecological risk. The content of Cr, Pb, and Cd in the crops in the study area exceeded the standard, and the exceeding standard rate was between 1.1% and 37.3%, where the average content of over-standard heavy metals in corn was higher than that in rice, and the average content of heavy metals in leafy vegetables was higher than that in root vegetables. The soil pollution degree of heavy metals could affect the accumulation ability of crops, and different crops had different accumulation abilities. For instance, leafy vegetables and root vegetables easily accumulated Cd and Zn; however, rice and corn separately enriched Cd and Cr, as well as Zn and Cu. The contents of heavy metals in dryland soils had a positive correlation with the content of heavy metals in corresponding crops. The contents of Cd and As in the paddy field and rice presented a positive correlation, but the remaining six heavy metal contents in rice (i.e., Cr, Mn, Ni, Cu, Zn, and Pb) did not correlate with the content of the paddy fields.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1.

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.