In a sample of 1252 Chinese adolescents (mean age = 15.00 years), this study examined the direct relations between gratitude and adolescents’ suicidal ideation and suicide attempts. This study also examined indirect relations between gratitude and suicidal ideation and suicide attempts via two self‐system beliefs—coping efficacy and self‐esteem. Finally, this study examined the extent to which stressful life events moderated the direct and indirect relations between gratitude and suicidal ideation and suicide attempts. The odds of suicidal ideation and suicide attempts were lower among adolescents who scored higher on gratitude, after controlling for demographic variables. Self‐esteem mediated the relations between gratitude and suicidal ideation and suicide attempts, while the mediating role of coping efficacy was not significant. Moreover, stressful life events moderated the mediated path through self‐esteem. This indirect effect was stronger for adolescents low on stressful life events than that for those high on stressful life events. This study discusses the theoretical and practical implications of these findings.

Background: Metastasis is the leading cause of death in colorectal cancer (CRC) patients. It is regulated mainly by tumor cell angiogenesis, and angiogenesis is caused by the binding of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor 2 (VEGFR2). Tumor necrosis factor--induced protein 8 (TNFAIP8, hereto after TIPE) plays an important role in tumorigenesis, development, and prognosis. However, the relationship between TIPE and VEGFR2 in CRC angiogenesis and the mechanism of action remain unknown. Method: In this study, we used quantitative real-time PCR, Western blotting and immunohistochemistry to detect TIPE and VEGFR2 expression in 55 specimens from CRC patients. We also used HCT116 CRC cells and human umbilical vein endothelial cells (HUVECs) for in vitro experiments by stably transducing shTIPE and shRNA control lentivirus into HCT116 cells, detecting VEGFR2 expression after TIPE knockdown and repurposing the culture supernatant as conditioned medium to stimulate angiogenesis of HUVECs. In vivo experiments with chicken chorioallantoic membranes (CAMs) and a nude mouse matrix subcutaneous tumor model were performed to validate the effects of TIPE on angiogenesis. Additionally, we analyzed the expression and phosphorylation levels of PDK1 and blocked PDK1 expression using inhibitors to determine whether TIPE-induced changes in VEGFR2-mediated angiogenesis acted via the PI3K-Akt pathway. Results: We found that TIPE and VEGFR2 are highly expressed in CRC and act as oncogenes. TIPE knockdown also downregulated VEGFR2 expression, which resulted in simultaneous inhibition of cell proliferation, cell migration and angiogenesis. Then, in vivo experiments further demonstrated that TIPE promotes angiogenesis in CRC. Finally, we found that TIPE promotes VEGFR2-mediated angiogenesis by upregulating PDK1 expression and phosphorylation and that blocking PDK1 expression can inhibit this process. Conclusion: TIPE promotes angiogenesis in CRC by regulating the expression of VEGFR2, which may be a target for antiangiogenic cancer therapy.

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

In this paper, we constructed a novel core–shell structured nanocarrier used as a drug carrier to investigate the storage and controllable release properties of the cancer chemotherapeutic drug etoposide (VP16). The new composite nanocomposite composed of a mesoporous silica shell with magnetic Fe3O4 core and ZnO interlayer with a core–shell structure was prepared by a simple process. The mesoporous nanocarrier possesses high surface area (643.9 m2/g), provides large accessible pore volume (0.32 cm3/g) for the adsorption of drug molecules, and has a high magnetization saturation value (56.8 emu/g) for drug targeting under foreign magnetic fields, and the ZnO interlayer acts as a good microwave absorber with excellent microwave thermal response property for microwave-triggered drug release (the VP16 release of over 85% under microwave discontinuous irradiation outclasses the 14% within 10 h only stirring release). This multifunctional system shows a good performance for targeting delivery and controllable release of anticancer drugs based on all the properties they possess.