Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3.

Element contamination, including that from heavy metals, is associated with gastrointestinal tumorigenesis, but the effects and mechanisms of crucial element exposure associated with colorectal cancer remain unclear. We profiled 56 elements by ICP-MS and used logistic regression, LASSO, BKMR, and GAM to identify colorectal cancer-relevant elements. A series of biochemical experiments were performed to demonstrate the cytotoxicity and the mechanisms of malignant transformation after metal exposure. Using an elementomics approach, we first found that the metal thallium (Tl) was positively correlated with many toxic metals and was associated with a significantly increased risk of colorectal cancer. Acute exposure to Tl induced cytotoxicity and cell death by accelerating the generation of reactive oxygen species and DNA damage. Chronic exposure to Tl led to the inhibition of cell death and thereby induced the malignant transformation of normal colon cells and xenograft tumor formation in nude mice. Furthermore, we describe the first identification of a significant metal quantitative trait locus for the novel colorectal cancer susceptibility locus rs1511625 near ATP13A3. Mechanistically, Tl increased the level of aberrant N6-methyladenosine (m6A) modification of ATP13A3 via the METLL3/METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis. This study provides a basis for the development of public health strategies for reducing metal exposure among populations at high risk for colorectal cancer.

Evaluation of Euglena gracilis 815 as a New Candidate for Biodiesel Production.

Euglena comprises over 200 species, of which Euglena gracilis is a model organism with a relatively high fatty acid content, making it an excellent potential source of biodiesel. This study isolated and characterized a new strain named E. gracilis 815. E. gracilis 815 cells were cultivated under light and dark conditions, with either ethanol or glucose as an external carbon source and an autotrophic medium as control. To achieve maximum active substances within a short period i.e., 6 days, the effects of the light condition and carbon source on the accumulation of bioactive ingredients of E. gracilis 815 were explored, especially fatty acids. In comparison with the industrially used E. gracilis Z strain, E. gracilis 815 exhibited high adaptability to different carbon sources and light conditions, with a comparable biomass and lipid yield. The content and composition of fatty acids of E. gracilis 815 were further determined to assess its potential for biodiesel use. Results suggested that E. gracilis 815 has biodiesel potential under glucose addition in dark culture conditions and could be a promising source for producing unsaturated fatty acids. Therefore, E. gracilis 815 is a candidate for short-chain jet fuel, with prospects for a wide variety of applications.

Sex hormones and genetic variants in hormone metabolic pathways associated with the risk of colorectal cancer.

OBJECTIVE: The different incidence of colorectal cancer between the sexes suggests that sex hormones may be involved in the susceptibility to colorectal cancer. The association between sex hormones and genetic variants in hormone metabolic pathways and the colorectal cancer risk remains unclear. METHODS: We detected sex hormone levels in plasma from colorectal cancer patients and controls in males by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We evaluated the clinical significance of sex hormones on colorectal cancer diagnosis with the area under the receiver operating characteristic curve (AUC). The role of genetic variants in hormone metabolic pathways in the colorectal cancer risk was assessed by a logistic regression model. The biological functions were detected by luciferase reporter assays and cell behavior experiments. RESULTS: We found that 2-methoxyestrone (2-MeO-E1) was highly expressed in cases (PFDR = 3.48 × 10-19). The expression of 2-MeO-E1 in plasma showed improved accuracy for predicting colorectal cancer (AUC = 0.88). In the 2-MeO-E1 metabolic pathway, rs165599 in COMT was significantly associated with an increased risk of colorectal cancer (P = 0.009). Mechanistically, we found that the rs165599 G allele could decrease the binding ability of miR-22-3p to the COMT 3'-UTR. Furthermore, knockdown of COMT inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle in the G1 phase. CONCLUSION: This is the first study to show that 2-MeO-E1 and a genetic variant in COMT contribute to the susceptibility to colorectal cancer. These results shed light on the different incidence of colorectal cancer between the sexes.