[Analysis of Heavy Metal Sources in Groundwater and Assessment of Health Risks: An Example from the Southwest Sub-basin of the Shiqi River].

In order to explore the sources of pollution and health risk profile of heavy metal elements in groundwater, 41 sets of representative groundwater samples from the southwest sub-basin of the Shiqi River were examined for 10 heavy metal elements (As, Cr, Cd, Al, Cu, Zn, Ni, Co, Mn, and Hg), and correlation analysis and principal component analysis were used to resolve the possible sources of heavy metal contamination in groundwater in the study area. The concentration characteristics and health risk levels of the 10 heavy metals were assessed using the single-factor contamination index (Pi), the Nemerow comprehensive contamination index (PN), and the health risk model. The results showed that:① the average values of heavy metal elements of the groundwater in the study area all met the limit of the class Ⅲ water standard in the quality standard for groundwater (GB/T 14848-2017); only the maximum value of Al was exceeded, followed by a large variation in the concentrations of Al, Mn, and Cr. The heavy metal element with the largest average contribution was Al (65.74%). ② The results of the single-factor contamination index evaluation showed that only the heavy metal element Al exceeded the cleaning level, and the results of the Nemerow comprehensive contamination index evaluation showed that the study area was basically at low pollution levels, and the quality of groundwater was good. ③ The results of the multivariate statistical analysis showed that Zn, Co, and Mn were from mixed sources consisting of geological formation and domestic waste; Al, As, and Cu were from agricultural sources; Cd, Cr, and Ni were from industrial sources; and Hg came from long-range atmospheric transport. ④ The health risk values for all heavy metals in the study area were within acceptable limits, with higher health risk values for children than for adults from the drinking water route, lower health risk values than in adults from the dermal route, and higher health risk values for heavy metals from the drinking water route than those from the dermal route, indicating that the drinking water route was the main route of exposure to heavy metals.

DNMT1-maintained hypermethylation of Krüppel-like factor 5 involves in the progression of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It is a challenge to explore effective therapeutic targets and drugs for this kind of cancer. Transcription factor Krüppel-like factor 5 (KLF5) exerts diverse functions in various tumor types. By analyzing cohorts of the Cancer Genome Atlas (TCGA) data sets, we find that KLF5 expression is suppressed in ccRCC patients and higher level of KLF5 expression is associated with better prognostic outcome. Our further investigations demonstrate that KLF5 genomic loci are hypermethylated at proximal exon 4 and suppression of DNA methyltransferase 1 (DNMT1) expression by ShRNAs or a methylation inhibitor 5-Aza-CdR can recover KLF5 expression. Meanwhile, there is a negative correlation between expressions of KLF5 and DNMT1 in ccRCC tissues. Ectopic KLF5 expression inhibits ccRCC cell proliferation and migration/invasion in vitro and decreases xenograft growth and metastasis in vivo. Moreover, 5-Aza-CdR, a chemotherapy drug as DNMTs' inhibitor that can induce KLF5 expression, suppresses ccRCC cell growth, while knockdown of KLF5 abolishes 5-Aza-CdR-induced growth inhibition. Collectively, our data demonstrate that KLF5 inhibits ccRCC growth as a tumor suppressor and highlight the potential of 5-Aza-CdR to release KLF5 expression as a therapeutic modality for the treatment of ccRCC.

Inhibition of Snail Family Transcriptional Repressor 2 (SNAI2) Enhances Multidrug Resistance of Hepatocellular Carcinoma Cells.

China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells. Suppression of SNAI2 suffices to up-regulate several cancer stem genes. Although unrelated to the metastatic ability, SNAI2 inhibition does increase the efflux of Hoechst 33342 and enhance multidrug resistance in vitro and in vivo. In agreement with this data, we demonstrate for the first time that decreasing SNAI2 level can transcriptionally upregulate several ATP binding cassette (ABC) transporter genes such as ABCB1. Moreover, ABC transporters' inhibitor verapamil can rescue the multidrug resistance induced by SNAI2 inhibition. Our results implicate that SNAI2 behaves as a tumor suppressor by inhibiting multidrug resistance via suppressing ABC transporter genes in HCC cells.