WWC1/2 regulate spinogenesis and cognition in mice by stabilizing AMOT.

WWC1 regulates episodic learning and memory, and genetic nucleotide polymorphism of WWC1 is associated with neurodegenerative diseases such as Alzheimer's disease. However, the molecular mechanism through which WWC1 regulates neuronal function has not been fully elucidated. Here, we show that WWC1 and its paralogs (WWC2/3) bind directly to angiomotin (AMOT) family proteins (Motins), and recruit USP9X to deubiquitinate and stabilize Motins. Deletion of WWC genes in different cell types leads to reduced protein levels of Motins. In mice, neuron-specific deletion of Wwc1 and Wwc2 results in reduced expression of Motins and lower density of dendritic spines in the cortex and hippocampus, in association with impaired cognitive functions such as memory and learning. Interestingly, ectopic expression of AMOT partially rescues the neuronal phenotypes associated with Wwc1/2 deletion. Thus, WWC proteins modulate spinogenesis and cognition, at least in part, by regulating the protein stability of Motins.

The Positive Role and Mechanism of Herbal Medicine in Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease, manifested by the progressive functional impairment of the midbrain nigral dopaminergic neurons. Due to the unclear underlying pathogenesis, disease-modifying drugs for PD remain elusive. In Asia, such as in China and India, herbal medicines have been used in the treatment of neurodegenerative disease for thousands of years, which recently attracted considerable attention because of the development of curative drugs for PD. In this review, we first summarized the pathogenic factors of PD including protein aggregation, mitochondrial dysfunction, ion accumulation, neuroinflammation, and oxidative stress, and the related recent advances. Secondly, we summarized 32 Chinese herbal medicines (belonging to 24 genera, such as Acanthopanax, Alpinia, and Astragalus), 22 Chinese traditional herbal formulations, and 3 Indian herbal medicines, of which the ethanol/water extraction or main bioactive compounds have been extensively investigated on PD models both in vitro and in vivo. We elaborately provided pictures of the representative herbs and the structural formula of the bioactive components (such as leutheroside B and astragaloside IV) of the herbal medicines. Also, we specified the potential targets of the bioactive compounds or extractions of herbs in view of the signaling pathways such as PI3K, NF-κB, and AMPK which are implicated in oxidative and inflammatory stress in neurons. We consider that this knowledge of herbal medicines or their bioactive components can be favorable for the development of disease-modifying drugs for PD.

RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting.

Herein, we reported a RuCo alloy with nitrogen-doped porous carbon (RuCo/NPC) as efficient trifunctional electrocatalysts for Zn-air batteries and water splitting. The versatility and catalytic activity of this catalyst is achieved by adjusting the Ru/Co ratio. The as-assembled Zn-air battery and overall water splitting with RuCo/NPC present outstanding catalytic performances.

N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner.

BACKGROUND: Maternal obesity induces adverse cardiac programming in offspring, and effective interventions are needed to prevent cardiovascular ill-health. Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity in mice results in left ventricular remodelling and hypertrophy in early childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these effects in a sex-dependent manner. METHODS AND RESULTS: The maternal obesity was induced in mice by the consumption of a Western diet accompanied by a 20 % sucrose solution. To determine the effect of NAC on the cardiac outcomes induced by maternal obesity, obese dams were continuously exposed to the obesogenic diet, with or without the oral NAC treatment during pregnancy. Left ventricular remodelling and hypertrophy occurred as early as 7 days after birth in the male offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression of key genes and markers related to cardiac fibrosis accompanied by more disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. When we next evaluated the level of oxidative stress in the hearts of neonatal mice, the activity of enzymatic antioxidants declined and expression of NOX enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate increased heart weight, interventricular septal thickness, and collagen content in male O-OB/NAC pups. CONCLUSIONS: Collectively, our results indicated that NAC blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal offspring in the setting of maternal obesity, potentially acting by reducing oxidative stress. The present study provides a basis for investigating the role of NAC in nutrition-related cardiac programming.