Serotonergic multilocus genetic variation moderates the association between interpersonal relationship and adolescent depressive symptoms.

BACKGROUND: Research suggests that genetic variants linked to serotonin functioning moderate the association between environmental stressors and depressive symptoms, but examining gene-environment interactions with single polymorphisms limits power. METHODS: A multilocus genetic profile score (MGPS) approach to measuring serotonergic multilocus genetic variation and examined interactions with interpersonal relationship, insomnia with depressive symptoms as outcomes in an adolescent sample (average age = 14.15 ± 0.63 years since first measurement; range: 13 to 15). RESULTS: (1) interpersonal relationship predicted adolescent depressive symptoms; (2) insomnia mediated the effect of interpersonal relationships on adolescent depressive symptoms; (3) the THP2 gene rs4570625 polymorphism G allele was a key risk factor for depressive symptom, and the MGPS moderated the effects of teacher-student relationship and insomnia on adolescent depressive symptom. Specifically, as the MGPS increased, the effects of insomnia on adolescent depressive symptom were enhanced; further, when the MGPS score increased, the effect of teacher-student relationship on depression showed a similar phenomenon with an increased slope and enhanced prediction; and (4) the results of sensitivity analysis showed that multilocus genetic interaction with the environment had a better explanatory power and stability for depression than single polymorphism studies. CONCLUSION: MGPS provides substantial power to examine gene-environmental interactions linked to affective outcomes among adolescents.

Stress Relaxation-Induced Colon Tumor Multicellular Spheroid Culture Based on Biomimetic Hydrogel for Nanoenzyme Ferroptosis Sensitization Evaluation.

Ferroptosis has recently become a research hotspot, and the induction of tumor cell ferroptosis has emerged as a powerful method for tumor therapy. However, the efficiency of tumor cell ferroptosis induction remains unmet for clinical use, which may be attributed to the large discrepancies between in vitro and in vivo models. To address this issue, in this study, a hydrogel platform with stress relaxation is utilized to develop a multicellular spheroid model of the DLD1 colon cancer cell line through cancer cell self-organization. The spheroids are highly similar to real tumor tissue, and ferroptosis resistance at the transcriptional, protein, and cellular levels. Collaboration of the ferroptosis induction reagent erastin and the nanoenzyme MnZnFe2 O4 @PEG-COOH to overcome the ferroptosis resistance of the spheroids is also demonstrated. Taken together, this study demonstrates the effectiveness of the model developed using this hydrogel platform for further mechanistic studies, and for the assessment of novel cancer treatment strategies based on ferroptosis.