Fatalism and Suicidal Behaviors Among Chinese College Students: The Mediating Role of Depressive Symptoms and the Moderating Role of Coping Strategies.

The aim of this study was to investigate the relationship between fatalism and suicidal behaviors, the mediating role of depressive symptoms, and the moderating effect of coping strategies on the mediating process. A total of 519 participants completed the Multidimensional Fatalism Scale for General Life Events, the Center for Epidemiologic Studies-Depression scale, the Simplified Coping Style Questionnaire, and the Suicidal Behaviors Questionnaire-Revised. Results suggest that depressive symptoms partially mediated the relationship between fatalism and suicidal behaviors. Active coping moderated the mediating effect of depressive symptoms. The higher the active coping level, the weaker the mediating effect. The findings revealed that the mechanism of fatalism affecting suicidal behaviors, and had theoretical and empirical value for the prevention and intervention of suicide among college students.

Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.

Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.

Ginsenoside (20S)-protopanaxatriol induces non-protective autophagy and apoptosis by inhibiting Akt/mTOR signaling pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) lacks a recognized therapeutic molecular target and has an unfavorable prognosis. (20S)-Protopanaxatriol (g-PPT, PPT) is an active metabolite extracted from ginseng. Accumulating evidence suggests that it has good anti-cancer activity in vivo and in vitro. In this study, we aimed to elucidate the anti-tumor effects of PPT in TNBC cells and tumor-bearing mice, as well as the relevant molecular mechanisms of autophagy and apoptosis. In vitro, we have found that PPT is capable of inducing non-protective autophagy and apoptosis, thus exerting some anti-proliferative and anti-migration activity in TNBC cells. And in vivo, the therapeutic effects of PPT were evaluated by xenograft mouse models. The potential binding mode of PPT and Akt was predicted by molecular docking. Our findings indicated that PPT treatment induced non-protective autophagy in TNBC cells by inhibiting the Akt/mTOR signaling pathway. Therefore, PPT may be a potential treatment for TNBC in the future.

DNA Nanostructure-Programmed Cell Entry via Corner Angle-Mediated Molecular Interaction with Membrane Receptors.

Despite its polyanionic nature, DNA can cross the negatively charged membrane to enter living cells by assembling into specific nanostructures, establishing various opportunities for biomedical applications. Mechanistic studies to explain how the geometrical parameters of DNA nanostructures impact the cell entry are critical but elusive. Here, we use experimentation and simulation to study the interaction between cells and three typical framework nucleic acids (FNAs), including tetrahedron, triangular prism, and cube. Different cellular uptake efficiency was observed among these FNAs, and similar distinction consistently existed in multiple cell lines. Scavenger receptors (SRs) were demonstrated to be essential in mediating the uptake process. Molecular docking simulations revealed that the SR binding predominantly depended on the corner angle of FNAs, determining cellular internalization frequency. This study clearly explains how FNAs interact with the membrane to initiate cell entry, offering new clues for the design of theranostic nanocarriers and the study of virus invasion.

Engineering G-quadruplex aptamer to modulate its binding specificity.

The use of aptamers in bioanalytical and biomedical applications exploits their ability to recognize cell surface protein receptors. Targeted therapeutics and theranostics come to mind in this regard. However, protein receptors occur on both cancer and normal cells; as such, aptamers are now taxed with identifying high vs. low levels of protein expression. Inspired by the flexible template mechanism and elegant control of natural nucleic acid-based structures, we report an allosteric regulation strategy for constructing a structure-switching aptamer for enhanced target cell recognition by engineering aptamers with DNA intercalated motifs (i-motifs) responsive to the microenvironment, such as pH. Structure-switching sensitivity can be readily tuned by manipulating i-motif sequences. However, structure-switching sensitivity is difficult to estimate, making it equally difficult to effectively screen modified aptamers with the desired sensitivity. To address this problem, we selected a fluorescent probe capable of detecting G-quadruplex in complicated biological media.

DNA-Based Dynamic Mimicry of Membrane Proteins for Programming Adaptive Cellular Interactions.

Cells sense and respond to the external environment, mainly through proteins presented on the membrane where their expression and conformation are dynamically regulated via intracellular programs. Here, we engineer a cell-surface nanoarchitecture that realizes molecular-recognition-initiated DNA assembly to mimic the dynamic behavior of membrane proteins, enabling the manipulation of cellular interaction in response to environmental changes. Our results show that this membrane-anchored DNA nanoarchitecture can be specifically activated by cell-responsive signals to external stimulation. Accordingly, multiple functional modules can be assembled onto the membrane to equip the cell with cell-type-specific binding and killing. This system is expected to offer a new paradigm for engineering therapeutic cells with customized sensing/response pathways.

Cell-Membrane-Anchored DNA Nanoplatform for Programming Cellular Interactions.

Cell-cell interactions are mediated through compositions expressed on the membrane. Engineering the cell surface to display functional modules with high biocompatibility, high controllability, and high stability would offer great opportunities for studying and manipulating these intercellular reactions. However, it remains a technical challenge because of the complex and dynamic nature of the cell membrane. Herein, by using three-dimensional (3D) amphiphilic pyramidal DNA as the scaffold, we develop a biocompatible, effective, and versatile strategy for engineering the cell surface with DNA probes. Compared with linear DNA constructs, these pyramidal probes show higher (nearly 100-fold) membrane-anchoring stability and higher (about 2.5-fold) target accessibility. They enable specific, effective, and tunable connections between cells. Meanwhile, our results indicate that connecting cells in close proximity are critical to initiate intercellular communication. By combining high programmability and high diversity of DNA probes, this strategy is expected to provide a powerful and designable membrane-anchored nanoplatform for studying multicellular communication networks.