Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.

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The center cutter of a hard rock tunnel boring machine (TBM) is installed on the cutterhead at a small radius and thus bears complex side force. Given this fact, the formation mechanism and change law of the side force suffered by the center cutter were studied. Based on the rock shear failure criterion in combination with the lateral rolling width, a model for predicting the average side force was set up. Besides, a numerical analysis model of the rock fragmentation of the center cutter was established, and the instantaneous load changing features were investigated. Results shows that the inner side of the center cutter can form lateral rolling annulus in rock during the rotary cutting process. The smaller the installation radius is, the greater the cutter side force will be. In a working condition, the side force of the innermost center cutter is 11.66 kN, while it decreases sharply when installation radius increases. Variation tends to be gentle when installation radius is larger than 500 mm, and the side force of the outermost center cutter is reduced to 0.74 kN.

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