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Sexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers “male-like” diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.

Realizing combination drugs at a molecular level via drug−drug cocrystallization opens a new pathway for effective therapeutic hybrids. A "drug-bridge-drug" strategy is developed to cocrystallize two first-line antitubercular drugs isoniazid and pyrazinamide using fumaric acid as the bridge, overcoming the issue of hardly cocrystallizing two different drugs. The first example of ternary cocrystal with combination drugs exhibits optimized formulation capacity and in vitro/vivo synergistic effects, which provides a new insight into antituberculosis combination drugs.

Amyloid-beta peptide (Abeta) is known to induce the redox imbalance, mitochondrial dysfunction and caspase activation, resulting in neuronal cell death. Treatment with antioxidants provided a new therapeutic strategy for Alzheimer's disease (AD) patients. Here we investigate the effects of purple sweet potato anthocyanins (PSPA), the known strong free radical scavengers, on Abeta toxicity in PC12 cells. The results showed that pretreatment of PC12 cells with PSPA reduced Abeta-induced toxicity, intracellular reactive oxygen species (ROS) generation and lipid peroxidation dose-dependently. In parallel, cell apoptosis triggered by Abeta characterized with the DNA fragmentation and caspase-3 activity were also inhibited by PSPA. The concentration of intracellular Ca(2+) and membrane potential loss associated with cell apoptosis were attenuated by PSPA. These results suggested that PSPA could protect the PC-12 cell from Abeta-induced injury through the inhibition of oxidative damage, intracellular calcium influx, mitochondria dysfunction and ultimately inhibition of cell apoptosis. The present study indicates that PSPA may be a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases.