Remora Optimization Algorithm with Enhanced Randomness for Large-Scale Measurement Field Deployment Technology.

In the large-scale measurement field, deployment planning usually uses the Monte Carlo method for simulation analysis, which has high algorithm complexity. At the same time, traditional station planning is inefficient and unable to calculate overall accessibility due to the occlusion of tooling. To solve this problem, in this study, we first introduced a Poisson-like randomness strategy and an enhanced randomness strategy to improve the remora optimization algorithm (ROA), i.e., the PROA. Simultaneously, its convergence speed and robustness were verified in different dimensions using the CEC benchmark function. The convergence speed of 67.5-74% of the results is better than the ROA, and the robustness results of 66.67-75% are better than those of the ROA. Second, a deployment model was established for the large-scale measurement field to obtain the maximum visible area of the target to be measured. Finally, the PROA was used as the optimizer to solve optimal deployment planning; the performance of the PROA was verified by simulation analysis. In the case of six stations, the maximum visible area of the PROA reaches 83.02%, which is 18.07% higher than that of the ROA. Compared with the traditional method, this model shortens the deployment time and calculates the overall accessibility, which is of practical significance for improving assembly efficiency in large-size measurement field environments.

Autophagy induction by xanthoangelol exhibits anti-metastatic activities in hepatocellular carcinoma.

Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti-metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3-methyadenine (3-MA) or knockdown of the pro-autophagy Beclin-1 effectively abrogated the XAG-induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p-AMPK while decreasing p-mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy-mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti-metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti-tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti-metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC.

FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis.

AIMS: FL118, a novel camptothecin analogue, has been extensively studied for its superior antitumor potency. The aim of this research study is to explore its potential mechanism of action in anti- colorectal cancer (CRC). MAIN METHODS: The effect of FL118 on CRC cell proliferation was assessed using CCK-8 assay, while apoptosis was detected using Hoechst staining and Flow cytometry assays. The expression levels of CIP2A were analyzed using qRT-PCR. The expression of CIP2A, PP2A-C, Bax, cleaved caspase-3 and PARP were analyzed using western blotting analysis. The expressions of related proteins in CRC tissues were detected using immunohistochemical staining. TUNEL assay was used to detect apoptosis of tissue. Toxicity of FL118 in primary organs were examined using H&E staining. KEY FINDINGS: The results show that FL118 can inhibit the proliferation and clonogenic potential of CRC cells and increase the expression of pro-apoptosis proteins, Bax, cleaved caspase-3 and PARP. Microarray analyses found that FL118 treatment significantly decreases cancerous inhibition of protein phosphatase 2A (CIP2A). Further validation found that CIP2A is aberrantly upregulated in CRC tissues, and is positively correlated with the progression of CRC. In vitro findings confirm that FL118 mediates the downregulation of CIP2A, at both protein and mRNA levels. Co-treatment with Okadaic acid (OA) (a PP2A inhibitor) partially abolishes the anti-proliferative and pro-apoptotic effect of FL118. Consistently, in vivo experiment demonstrates that FL118 can effectively suppress tumorigenesis without any obvious toxic effects. SIGNIFICANCE: Collectively, these findings exhibit the anti-neoplastic effects of FL118 against CRC through the down regulation of CIP2A, which subsequently enhances the activity of PP2A.