Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.

Antagonistic Activity and Mechanism of Bacillus subtilis XZ16-1 Suppression of Wheat Powdery Mildew and Growth Promotion of Wheat.

Wheat powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is one of the most serious wheat diseases in the world. Biological control is considered an environmentally safe approach to control plant diseases. Here, to develop effective biocontrol agents for controlling wheat powdery mildew, antagonistic strain XZ16-1 was isolated and identified as Bacillus subtilis based on the morphological, biochemical, and physiological characteristics and 16S rDNA sequence. The culture filtrate of B. subtilis XZ16-1 and its extracts had a significant inhibitory effect on the spore germination of Bgt. Moreover, the therapeutic and prevention efficacy of the 100% culture filtrate on wheat powdery mildew reached 81.18 and 83.72%, respectively, which was better than that of chemical fungicide triadimefon. Further antimicrobial mechanism analysis showed that the XZ16-1 culture filtrate could inhibit the development of powdery mildew spores by disrupting the cell membrane integrity, causing reductions in the mitochondrial membrane potential, and inducing the accumulation of reactive oxygen species in the spores. Biochemical detection indicated that XZ16-1 could solubilize phosphate, fix nitrogen, and produce hydrolases, lipopeptides, siderophores, and indole-3-acetic acid. Defense-related enzymes activated in wheat seedlings treated with the culture filtrate indicated that disease resistance was induced in wheat to resist pathogens. Furthermore, a 106 CFU/ml suspension of XZ16-1 increased the height, root length, fresh weight, and dry weight of wheat seedlings by 77.13, 63.46, 76.73, and 19.16%, respectively, and showed good growth-promotion properties. This study investigates the antagonistic activity and reveals the action mechanism of XZ16-1, which can provide an effective microbial agent for controlling wheat powdery mildew.