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Context The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. Objective Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. Materials and methods CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. Results For SMMC7721 (IC50 = 22.5 μM) and PLC8024 (IC50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). Discussion and conclusions TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

Additional file 1: Table S1. Intra- and interobserver variability of cardiac and abdominal MR measures.

A novel wall treatment method, termed as the Slat Cove Wavy Wall (SCWW), is proposed to improve both the aero-acoustic and the aerodynamic performances of high-lift devices. By this treatment, a wavy pattern is imposed on the wall in the slat cove. In the present work, slats with three different SCWWs are designed and applied to a straight wing composed by 30P30N airfoil. Numerical simulations and analyses are conducted to unveil the underlying mechanisms of noise reduction. The unsteady flow field and the far-field noise are predicted by a hybrid SA-IDDES method followed by the integration of the Ffowcs Williams and Hawkings equation. The modified high-lift device is proved to be able to improve the aero-acoustic performance by reducing the low-frequency components of the radiated noise. Meanwhile, the aerodynamic performance is maintained or improved under proper design parameters. The boundary layer separation in the slat cove is accelerated by the SCWW, which transforms low-frequency periodic vortex shedding to high-frequency turbulent flow. This results in the sound energy shift from low-frequency noise to high-frequency broadband noise. The SCWW method is proved to be effective in redistribution of boundary vorticity flux on the slat lower surface. To reveal the mechanism of the SCWW's drag and noise reduction, the vortex dynamic processes near the slat lower surface in terms of the Lamb vector divergence are further investigated. It is found that the Lamb vector divergence is directly related to both the noise source and the drag. The interaction area of positive and negative Lamb vector divergence can be balanced and decreased by SCWW, resulting in the drag and noise reduction. As expressed by the vortex dynamic processes, this feature implies the SCWW method is of great potential in noise attenuation.