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Previous studies showed that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. In the current study, we aimed to investigate whether the compound L6123, a novel non-ATP-competitive FGFR1 inhibitor, could show better antitumor activity than the leading compound, nordihydroguaiaretic acid (NDGA), in FGFR1-overexpressing gastric cancer cells. Using an MTT assay, we investigated the inhibitory effect of L6123 on the viability of three gastric cancer cells (MGC-803, SGC-7901, and BGC-823) overexpressing FGFR1, wild-type mouse embryonic fibroblast (MEF), and MEF expressing FGFR1, FGFR2, and FRS2α gene knockout (MEF). We studied the antitumor mechanism of L6123 against the gastric cancer cell line SGC-7901 by western blot analysis. The antitumor effects of L6123 on the gastric cancer cell line SGC-7901 were detected by flow cytometry, Hoechst staining, western blot analysis, and Transwell invasion assay. L6123 had lower IC50 in all three gastric cancer cells than NDGA and showed better inhibitory activity against MEF cells than against MEF cells. In the SGC-7901 gastric cell, L6123 inhibited the FGF2-induced phosphorylation of FGFR1/FRS2α/ERK1/2 in a dose-dependent manner, induced the activation of the apoptosis-related proteins, cleaved-PARP and cleaved-caspase-3, decreased the expression of pro-caspase-3 and Bcl-2, and induced tumor cell apoptosis. L6123 also dose-dependently reduced cell invasion ability, and showed better activity than NDGA at the same concentration. A novel non-ATP-competitive inhibitor L6123 showed excellent antigastric cancer activity by inhibiting the FGFR1 signaling pathway. Thus, we discovered a potential agent for the treatment of FGFR1-overexpressing gastric cancer.

For the single-phase high-power railway traction system, the inevitable second-order resonating power has become a critical issue to the traction system. In this paper, a power decoupling solution is proposed to replace the conventional passive LC resonance filter by utilizing the buck-type bidirectional DC/DC converter (BBDC) of Hybrid Electric Multiple Units (HEMU), which is designed to power the train in non-electrified routes using the on-board battery. By considering both the current ripples in the battery mode and the power decoupling in the catenary mode, the corresponding parameter design process of the BBDC is presented. Based on the power coupling phenomenon and the spectrum characteristic of the BBDC, a direct resonance control method is proposed to decouple the low-order resonating power. Simulations and experiments are carried out to validate the effectiveness of the new proposal. The results demonstrate that the proposal is almost the same as using the conventional passive LC resonance filter for power decoupling in both steady and dynamic operation scenarios. 1

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