The demethylase ALKBH5 mediates ZKSCAN3 expression through the m6A modification to activate VEGFA transcription and thus participates in MNNG-induced gastric cancer progression.

N-Nitroso compounds (NOCs) are recognized as important factors that promote gastric cancer development, but the specific effects and potential mechanisms by which NOC exposure promotes gastric cancer are still poorly understood. In this study, we explored the effects and potential molecular mechanisms of NOCs on the promotion of gastric cancer using methylnitronitrosoguanidine (MNNG), a classical direct carcinogen of NOC. The results of in vivo and in vitro experiments showed that chronic and low-concentration MNNG exposure significantly promoted the malignant progression of tumors, including cell migration, cell invasion, vasculogenic mimicry (VM) formation, cell spheroid formation, stem cell-like marker expression, and gastric cancer growth and metastasis. Mechanistically, we revealed that demethylase ALKBH5 regulated the level of the N6­methyladenosine (m6A) modification in the 3'UTR and CDS region of the ZKSCAN3 mRNA to promote ZKSCAN3 expression, mediated the binding of ZKSCAN3 to the VEGFA promoter region to regulate VEGFA transcription, and participated in MNNG-induced gastric cancer cell migration, invasion, VM formation, cell spheroid formation, stem cell-like marker expression and ultimately gastric cancer progression. In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.

Spatial variation, sources identification and risk assessment of soil heavy metals in a typical Torreya grandis cv. Merrillii plantation region of southeastern China.

Torreya grandis (Torreya grandis cv. Merrillii) is a unique nut tree species in China. Currently, researches on Torreya grandis focus on nuts quality and yield, while few works are related to the soil quality of Torreya grandis plantation. In this study, the typical Torreya grandis production areas of Zhuji, Shengzhou, Keqiao and Dongyang cities along the Kuaiji Mountain were selected. A total of 121 topsoil samples (0-20 cm) were collected based on a grid of 1 km × 1 km. The results indicated that the average concentrations of Cd, Cr, Cu, As, Ni and Pb in soils were 0.12, 49.01, 27.95, 14.28, 26.97 and 40.28 mg kg-1, respectively. The concentrations of six heavy metals all exceeded the background values, and there were different degrees of pollution levels. The results of Moran's I indicated that the spatial high-high clusters of soil heavy metals were mainly distributed in Zhuji and the junction of Shengzhou and Keqiao. The partial least squares path analysis of structural equation modeling (PLS-SEM) showed that OM and soil nutrients had extremely significant effects on soil heavy metals. Sources identification of principle component analysis (PCA) and positive matrix factorization model (PMF) revealed that agricultural activities, natural factors and mining were the main sources of soil heavy metals. The human health risks caused by soil heavy metals pollution were generally acceptable based on Monte Carlo simulation method. For the heavy-metal polluted area, management measures should be considered in order to protect human health.