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[Display omitted] As the main systemic treatment for triple-negative breast cancer (TNBC), the bleak medical prognosis of chemotherapy resulted in impaired life quality by tumor recurrence and metastasis. The feasible cancer starvation therapy could inhibit tumor progression by blocking energy supplements, however, the mono-therapeutic modality showed limited curing efficacy due to heterogeneity and abnormal energy metabolism of TNBC. Thus, the development of a synergistic nano-therapeutic modality involving different anti-tumor mechanisms to simultaneously transport medicines to the organelle where metabolism took place, might remarkably improve curing efficacy, targeting ability, and bio-safety. Herein, the hybrid BLG@TPGS NPs were prepared by doping multi-path energy inhibitors Berberine (BBR) and Lonidamine (LND) as well as the chemotherapeutic agent Gambogic acid (GA). Our research indicated that Nanobomb-BLG@TPGS NPs inherited the mitochondria targeting ability from BBR to accumulate precisely at the "energy factory" mitochondria, and then induce starvation therapy to efficiently eradicated cancer cells by coordinately powered off tumor cells via a "three-prone strategy" to cut off mitochondrial respiration, glycolysis, and glutamine metabolism. The inhibition of tumor proliferation and migration was enlarged by the synergistic combination with chemotherapy. Besides, apoptosis via mitochondria pathway and mitochondria fragmentation supported the hypothesis that NPs eliminated MDA-MB-231 cells by violently attacking MDA-MB-231 cells and especially the mitochondria. In summary, this synergistic chemo-co-starvation nanomedicine proposed an innovative site-specific targeting strategy for improved tumor treatment and decreased toxicity to normal tissues, which provided an option for clinical TNBC-sensitive treatment. [ABSTRACT FROM AUTHOR]

Oysters are a keystone species in estuaries and intertidal zones and have important economic and ecological significance; however, worldwide, the dominant aquaculture oyster species suffers from mass mortality owing to anthropogenic impacts and rapid climate change. As a possible solution, inter/intraspecies hybridization is a feasible way to breed new germplasms with genetic improvement and high environmental adaptability. Suminoe oysters (Crassostrea ariakensis) are broadly distributed in the estuaries of China and have evolved strong genetic divergence between the northern and southern populations; therefore, they are ideal candidates to explore intraspecies heterosis and the associated molecular mechanisms. In this study, we performed reciprocal hybridization and examined fitness traits in oysters cultured in both northern and southern habitats. Reciprocal hybrids performed better than inbred populations in both environments, indicating heterosis in Suminoe oysters. Hybrids reared in maternal habitats showed faster growth, higher field survival, and greater aerobic metabolism than alternative hybrid oysters under the same conditions. The transcriptional analysis identified modules related to heterosis and maternal effect, while genes responsible for galactose metabolism, glycolysis/gluconeogenesis, and the tricarboxylic acid cycle were enriched and upregulated in hybrids, especially those in maternal environments. Our findings reveal that accelerated aerobic energy metabolism, which may result from mitonuclear coadaptation, underlies the molecular basis of heterosis and maternal effect in the hybridization of Suminoe oysters. Thus, we provide important insights for the aquaculture management of marine species, revealing that selecting appropriate environments (maternal habitats) is critical for heterosis in cross-breeding. • Hybrids from divergent oyster populations showed heterosis in growth and survival. • Hybrids in maternal habitat exhibited better performance indicating maternal effect. • Accelerated aerobic metabolism underlies heterosis and maternal effect in oyster. • Our findings propose better hybridization breeding of hybrids in maternal habitat. [ABSTRACT FROM AUTHOR]