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Computer-aid molecular docking is a simulative process that receptors and ligands recognize each other through energy matching and geometric matching. It is widely used in bioactive compounds simulative screening and preliminary exploring the bioactivity and toxicity of molecular, which plays important guiding role in toxicity and bioactivity study of molecular entities. In our study, we used the computer-aid molecular docking software-discovery studio 3.1 client to test the mechanism of aflatoxins such as aflatoxin B1, B2, M1, M2, G1, G2 and the results of our experiment help to illustrate the pathway of aflatoxin’s toxication. We also used this technology to test the preliminary toxicity of zearalenone (ZEN) and its two degradation products: a- zearalenol (a-ZOL) and ß-zearalenol (ß-ZOL), which indicates that these three products possessed significant estrogenic activity. The order of the estrogenic activity is: a-zearalenol > zearalenone >ß-zearalenol.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC). However, the emergence of EGFR-TKIs resistance poses a big challenge to the treatment. Although several resistant mutations have been identified, our understanding of the mechanisms underlying acquired EGFR-TKIs resistance remains incomplete. This study aimed to identify novel mutations and mechanisms that could contribute to acquired EGFR-TKIs resistance in EGFR mutated NSCLC cells., Methods: Erlotinib resistant cells (HCC827/ER cells) were generated from the EGFR mutated NSCLC cell line HCC827, and whole-exome sequencing was performed to identify gene mutations in HCC827/ER cells. The Spred-3 expression was determined using quantitative real-time PCR (qPCR) and Western blotting assays, and the p-p44/42, p44/42, p-Akt and Akt expression was determined using Western blotting. The half maximal inhibitory concentration (IC 50 value) was measured using the MTS assay, and cell migration was detected with a Transwell migration assay., Results: Whole-exome sequencing identified deletion mutation c.120delG at exon 1 of the Spred-3 gene, resulting in a p.E40fs change in amino acid, in HCC827/ER cells. The Spred-3 expression was much reduced in HCC827/ER cells as compared to the HCC827 cells at both mRNA and protein levels. Knocking out Spred-3 in HCC827 cells using CRISPR/Cas9 increased erlotinib resistance and cell migration, while overexpressing Spred-3 in HCC827/ER cells using a cDNA construct reduced erlotinib resistance and cell migration. We also showed the Ras/Raf/MAPK pathway was activated in HCC827/ER cells, and inhibiting ERK1/2 in HCC827/Spred-3-sgRNA cells resulted in reduced erlotinib resistance and cell migration., Conclusions: The results of this study indicate that a loss-of-function mutation in Spred-3 resulted in activation of the Ras/Raf/MAPK pathway that confers resistance to EGFR-TKIs in NSCLC cells harboring an EGFR mutation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.03.05). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)