While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluated in vitro and in vivo. Mechanistic studies showed that ailanthone induced G0/G1-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG1 phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer.

Background Challenging working conditions and job characteristics can result in nurses experiencing significant workplace stress and adversity. Aim To examine how and why spiritual leadership may have a positive influence on nurses’ subjective well‐being. Method A total of 339 registered nurses from five public hospitals in Mainland China participated in this study. Hypotheses were tested using the PROCESS macro. Results Spiritual leadership influenced the subjective well‐being indirectly through workplace spirituality. The interaction between spiritual leadership and power distance orientation on workplace spirituality was significant. Power distance orientation moderates the indirect effect of spiritual leadership on the subjective well‐being through workplace spirituality, and this indirect effect is more positive for nurse with lower power distance orientation. Conclusions Spiritual leadership is a significant contextual factor in the workplace that may influence the nurses’ workplace spirituality and subjective well‐being. Based on their power distance orientation, nurses may have different responses to spiritual leadership, resulting in differing levels of workplace spirituality. Implications for Nursing Management Spirituality can satisfy the internal needs of nurses. Spiritual leadership can facilitate a spiritual working context for sustaining the subjective well‐being of nurses. Hospitals should provide training programmes to help existing leaders engage in spiritual leadership.

Arenobufagin, a representative bufadienolide, is the major active component in the traditional Chinese medicine Chan'su. It possesses significant antineoplastic activity in vitro. Although bufadienolide has been found to disrupt the cell cycle, the underlying mechanisms of this disruption are not defined. Here, we reported that arenobufagin blocked the transition from G2 to M phase of cell cycle through inhibiting the activation of CDK1-Cyclin B1 complex; The tumor suppressor p53 contributed to sustaining arrest at the G2 phase of the cell cycle in hepatocellular carcinoma (HCC) cells. Moreover, arenobufagin caused double-strand DNA breaks (DSBs) and triggered the DNA damage response (DDR), partly via the ATM/ATR-Chk1/Chk2-Cdc25C signaling pathway. Importantly, we used a synthetic biotinylated arenobufagin-conjugated chemical probe in live cells to show that arenobufagin accumulated mainly in the nucleus. The microscopic thermodynamic parameters measured using isothermal titration calorimetry (ITC) also demonstrated that arenobufagin directly bound to DNA in vitro. The hypochromicity in the UV-visible absorption spectrum, the significant changes in the circular dichroism (CD) spectrum of DNA, and the distinct quenching in the fluorescence intensity of the ethidium bromide (EB)-DNA system before and after arenobufagin treatment indicated that arenobufagin bound to DNA in vitro by intercalation. Molecular modeling suggested arenobufagin intercalated with DNA via hydrogen bonds between arenobufagin and GT base pairs. Collectively, these data provide novel insights into arenobufagin-induced cell cycle disruption that are valuable for the further discussion and investigation of the use of arenobufagin in clinical anticancer chemotherapy.

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In this article, we analyze the dynamic linkage between crude oil price and the US dollar at multi‐scale frequencies using time‐dependent intrinsic correlation analysis based on the complete ensemble empirical mode decomposition with adaptive noise. After applying a refined method to extract the trend, we reveal that the overall correlation and the long‐term trend correlation exhibit very similar patterns. The correlation coefficients between crude oil and the US dollar are negative at most of the time; however, the coefficients become positive in certain periods, such as 2013–2014 and 2017–2018. Furthermore, the negative correlations in high frequency intrinsic mode functions (IMFs), with a shorter time horizon, are weaker and display time‐varying characteristics, whereas the correlation in low frequency IMFs, with a longer time horizon, are stronger and more static. The findings of this article may have important implications for investors to construct optimal portfolio diversification.

Silver nanowires (AgNWs) are the most promising materials to fabricate flexible transparent electrodes (FTEs) that are used in next-generation electronics. However, there are several bottlenecks for AgNW-based FTEs to achieve large-scale applications, which include the thermal instability and rough surface topography of AgNWs and the poor interfacial adhesion between AgNWs and the used substrate. To simultaneously address these aforementioned issues, a robust and washable FTE is prepared based on a AgNW@TiO 2 core−shell network embedded in polyimide (PI) substrate through a facile and scalable solution-based process. After being treated with TiO 2 sol, an ultrathin, conformal, and continuous TiO 2 shell is coated on the AgNWs, which can effectively suppress the atomic surface diffusion. In comparison with a pristine AgNW network that breaks into nanorods and nanospheres at 250 °C for 10 min, the AgNW@TiO 2 core−shell network is stable at 300 °C, and its resistance just increases by a factor of 11 after being annealed at 400 °C for 1 h. Furthermore, the TiO 2 shell simultaneously increases the electrical and optical properties of the AgNW network. After PI precursors are flowed, dried, and thermally cured, the AgNW@TiO 2 core−shell network is embedded on the surface of the PI substrate with a surface roughness of 1.9 nm. In addition to high thermal stability, the conductivity of the AgNW@ TiO 2 −PI composite FTE remains almost unchanged after repeated peeling off cycles with 3M tape and mechanical bending cycles. It is also demonstrated that the AgNW@TiO 2 −PI composite FTE is washable, and the relative change in resistance (ΔR/R 0 ) is ∼12% after 100 washing cycles, in which a variety of stress situations occur in combination. KEYWORDS: AgNW@TiO 2 core−shell network, TiO 2 sol, flexible transparent electrodes, peeling off and mechanical stabilities, thermal and washing stabilities

BackgroundThis study investigated the effect and the possible mechanism of trimetazidine in atherosclerosis.Material/MethodsWe established an atherosclerotic rat model by high-fat diet and vitamin D injection. Rats were separated into 3 different groups: control, atherosclerosis, and trimetazidine (n=10). The aortic artery was isolated and its morphological features were examined by hematoxylin and eosin (HE) staining. Serum low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and triglycerides (TG) were analyzed using an automatic biochemical analyzer. Human aortic smooth muscle cells (HASMCs) were cultured and divided into 5 groups: no treatment, H2O2 treatment only, trimetazidine preincubation before H2O2 treatment, oxidized low-density lipoprotein (oxLDL) treatment only, and trimetazidine preincubation before oxLDL treatment. HASMCs proliferation was tested using the Cell Counting Kit-8. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity of the aortic artery, and HASMCs were measured using commercially available kits.ResultsHE staining assay showed that trimetazidine suppressed the progression of atherosclerosis and reduced foam cell formation in the aortic artery without affecting serum lipid levels. HASMCs proliferation assay revealed that trimetazidine alleviated the inhibitory effect of H2O2 on HASMCs proliferation and inhibited oxLDL-induced proliferation of HASMCs. Moreover, trimetazidine ameliorated ROS up-regulation elicited by H2O2 or oxLDL in HASMCs. Additionally, trimetazidine restored SOD activity and reduced MDA content of HASMCs.ConclusionsTrimetazidine suppressed the progression of atherosclerosis by enhancing energy value, decreasing ROS level of aortic artery, modulating HASMCs proliferation, and reducing oxidative stress in HASMCs.

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