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Background: Mitophagy, a prominent cellular homeostasis process, has been implicated in modulating endothelial cell function. Emerging evidence suggests that extracellular vesicles (EVs) participate in intercellular communication, which could modulate tumor angiogenesis, a hallmark of ovarian cancer (OC) progression. However, the underlying mechanisms through how EVs regulate endothelial mitophagy associated with tumor angiogenesis during OC development remain obscure. Methods: The effect of cancer cell-derived EVs on endothelial mitophagy and its correlation with tumor angiogenesis and OC development were explored by in vitro and in vivo experiments. Multi-omics integration analysis was employed to identify potential regulatory mechanisms of cancer cell-derived EVs on endothelial mitophagy, which is involved in tumor angiogenesis associated with OC development. These insights were then further corroborated through additional experiments. An orthotopic OC mouse model was constructed to assess the antiangiogenic and therapeutic potential of the Indoleamine 2,3 dioxygenase-1 (IDO1) inhibitor. Results: Cancer cell-derived EVs promoted tumor angiogenesis via the activation of endothelial mitophagy, contributing to the growth and metastasis of OC. The aberrantly high expression of IDO1 mediated abnormal tryptophan metabolism in cancer cells and promoted the secretion of l-kynurenine (L-kyn)-enriched EVs, with associated high levels of L-kyn in EVs isolated from both the tumor tissues and patient plasma in OC. EVs derived from IDO1high ovarian cancer cells elevated nicotinamide adenine dinucleotide (NAD +) levels in endothelial cells via delivering L-kyn. Besides, IDO1high ovarian cancer cell-derived EVs upregulated sirt3 expression in endothelial cells by increasing acetylation modification. These findings are crucial for promoting endothelial mitophagy correlated with tumor angiogenesis. Notably, both endothelial mitophagy and tumor angiogenesis could be suppressed by the IDO1 inhibitor in the orthotopic OC mouse model. Conclusions: Together, our findings unveil a mechanism of mitophagy in OC angiogenesis and indicate the clinical relevance of EV enriched L-kyn as a potential biomarker for tumorigenesis and progression. Additionally, IDO1 inhibitors might become an alternative option for OC adjuvant therapy. [ABSTRACT FROM AUTHOR]

The cultivated strawberry (Fragaria × ananassa Duch.) is an important horticultural crop. The economic values of strawberry cultivars are decided by their fruit qualities including taste, color and aroma. The important role of MYB transcription factors in fruit quality regulation is recognized increasingly with the identification of MYB genes involved in metabolism. A total of 407 MYB genes of F. × ananassa (FaMYBs) were identified in the genome-wide scale and named according to subgenome locations. The 407 FaMYBs were clustered into 36 groups based on phylogenetic analysis. According to synteny analysis, whole genome duplication and segmental duplication contributed over 90% of the expansion of the FaMYBs family. A total of 101 FaMYB loci with 1–6 alleles were identified by the homologous gene groups on homologous chromosomes. The differentially expressed FaMYB profiles of three cultivars with different fruit quality and fruit ripe processes provided the 8 candidate loci involved in fruit quality regulation. In this experiment, 7, 5, and 4 FaMYBs were screeded as candidate genes involved in the regulation of metabolism/transportation of anthocyanins, sugars or organic acids and 4-hydroxy-2, 5-dimethyl-3(2H)-furanone, respectively. These results pointed out the key FaMYBs for further functional analysis of gene regulation of strawberry fruit quality and would be helpful in the clarification on ofe roles of MYBs in the metabolism of fruit crops. [ABSTRACT FROM AUTHOR]

Purpose: The intent of this paper is to understand the effect of Physical Activity on university students' Subjective Well-being and to explore whether Perceived Health, Social Support, and Self-esteem play roles as mediating variables., Methods: Self-reported data from 404 college students (147 males and 257 females) were analyzed using structural equation modeling (SEM). The relationships between the study variables were tested by mediation models and 5,000 bootstrap samples using AMOS version 24., Results: (1) The six hypotheses were supported in the measurement model in the results ( P  < 0.05). Physical Activity was related to Social Support, Perceived Health, and to Self-esteem; Social Support, Perceived Health, and Self-esteem were all related to Subjective Well-being. However, the direct positive effect of Physical Activity gradually decreased in the order of Self-esteem, Social Support, and Perceived Health. The direct effect of Perceived Health, Social Support, and Self-esteem on Subjective Well-being also decreased sequentially. (2) In the Structural Equation Model ( χ 2  = 825.451, p  < 0.001, df = 455, CMIN/df = 1.814, CFI = 0.942, RMSEA = 0.045), the three hypotheses of mediation were supported ( P  < 0.05), showing positive indirect effects between Physical Activity and Subjective Well-being. Of the three mediating effects, Social Support and Self-esteem were not different, and the mediating effect of Perceived Health showed the largest impact. This indicates that Social Support, Perceived Health, and Self-esteem mediate the effects of Physical Activity, and Subjective Well-being regulation has positive indirect effects., Conclusion: This study demonstrates the importance of meeting the needs of Social Support, Perceived Health, and Self-esteem when designing interventions to promote college students' sports participation to enhance Subjective Well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Liao, Yin, Hu, Tang and Shim.)