Occurrence, risk assessment, and in vitro and in vivo toxicity of antibiotics in surface water in China.

Antibiotics have been widely detected in the water environment and thus pose a potential threat to human health. Although antibiotics have health-promoting properties, whether and how they affect health at environmental concentrations remains uncharacterised. We detected antibiotics in surface water and groundwater in China. Sulfonamides (851 ng/L) and tetracyclines (1322 ng/L) showed the highest concentrations in surface water, while the highest concentration of sulfonamides detected in groundwater was 250 ng/L. We analysed the distribution of four classes of antibiotics (sulfonamides, tetracyclines, macrolides, and quinolones) and evaluated the associated health risks in the surface water of seven cities. We found that antibiotic pollution caused health risks to the 0-3-months age group, but not to other age groups. We further demonstrated that simulated long-term exposure to environmental concentrations of antibiotics had concentration-dependent toxic effects on L-02 hepatocytes, affected cell proliferation, and induced oxidative damage and DNA damage. Chronic exposure to mixed sulfonamides affected growth, caused liver damage, and reduced the abundance of intestinal flora in mice. Under exposure to antibiotics, the abundance of Helicobacter pylori in the gut flora significantly increased and posed a health risk to humans. These results indicated that exposure to antibiotics at environmental concentrations can cause oxidative damage and inflammation both in vitro and in vivo. These findings add to the body of basic data on the distribution of antibiotics in the water environment, and provide a scientific basis for the evaluation of antibiotic toxicity.

Chimeric RNA RRM2-C2orf48 plays an oncogenic role in the development of NNK-induced lung cancer.

Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we reported that high-expressed chimeric RNA RRM2-C2orf48 was found in malignantly transformed BEAS-2B cells induced by 4-(methyl nitrosamine)-1-(3-pyridinyl)-1-butanone (NNK) in 74 lung cancer patients and several lung cancer cell lines. The expression level of RRM2-C2orf48 was significantly correlated with lymph node metastasis, distant metastasis, tumor-lymph node-metastasis (TNM) stage, and smoking. Overexpressing RRM2-C2orf48 promoted cell growth and accelerated the process of NNK-induced lung cancer. RRM2-C2orf48 knockdown inhibited the growth of RRM2-C2orf48-overexpressing BEAS-2B cells. Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48 in lung cancer. In summary, chimeric RNA RRM2-C2orf48 accelerated the process of NNK-induced lung cancer, and miR-219a-2-3p may be involved in this process.

Involvement of m6A regulatory factor IGF2BP1 in malignant transformation of human bronchial epithelial Beas-2B cells induced by tobacco carcinogen NNK.

Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However, its carcinogenic mechanism has not yet been fully elucidated. In this study, we performed colony formation assays, soft-agar assays, and tumor growth in nude mice to show that 100 mg/L NNK facilitates the malignant transformation of human bronchial epithelial Beas-2B cells. Transcriptome sequencing showed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a post-transcriptional regulator, was differentially expressed in NNK-induced malignant transformed Beas-2B cells (2B-NNK cells). Small interfering RNA (SiRNA) was used to downregulate the expression of the IGF2BP1 gene. The reduction in protein expression, cell proliferation rate, and colony-forming ability and the increase in the apoptosis rate of Beas-2B cells transfected with the SiRNA indicated a role for IGF2BP1 in NNK-induced malignant transformation. IGF2BP1 is an N6-methyladenosine (m6A) regulatory factor, but it is not known whether its association with m6A mediates the malignant transformation of cells. Therefore, we measured the overall levels of m6A in Beas-2B cells. We found that the overall m6A level was lower in 2B-NNK cells, and knocking down IGF2BP1, the overall level of m6A was restored. Hence, we concluded that IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, possibly via m6A modification. This study therefore contributes novel insights into the environmental pathogenesis of lung cancer and the gene regulatory mechanisms of chemical carcinogenesis.

Monte Carlo Simulation of Strain-Enhanced Stereocomplex Polymer Crystallization.

We performed dynamic Monte Carlo simulations to investigate strain-induced polymer crystallization under separate enhancements of the driving forces for homocomponent and stereocomplex crystallization in the half-half symmetric racemic polymer blends. The results showed that the polymer strain significantly enhances the stereocomplex crystallization, in comparison to the parallel cases of template-induced crystal growth without any strain in the previous simulations. We attributed the results to the strain-induced polymer crystallization favoring intermolecular crystal nucleation at high temperatures, which benefits the stereocomplex crystallization. Our observations provided a molecular-level interpretation to the strain- or shear-enhanced stereocomplex crystallization in the racemic polylactide blends.