Intestinal activating transcription factor 4 regulates stress-related behavioral alterations via paraventricular thalamus in male mice.

Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression of ATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut-brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders.

Novel nitrogen-doped carbon dots for "turn-on" sensing of ATP based on aggregation induced emission enhancement effect.

In this work, a nitrogen-doped carbon dots (CDs) was successfully synthesized by hydrothermal synthesis of polyethylenimine (PEI) and citric acid. The as-prepared CDs suffered from aggregation-caused quenching (ACQ) with a high concentration, but after adding adenosine triphosphate (ATP), the CDs aggregated. The generation of aggregates caused the rotation of the surface groups on CDs and reduced the non-radiation decay. The QY of CDs in water was 9.25 %, and increased to 16.60 % and 63.38% in the addition of 100 and 1000 µM ATP. And then, the enhancement of the radiation rate led to the aggregation induced enhancement effect (AIEE). Moreover, we also found that the proportion of precursors for CDs synthesis was a key factor in the occurrence of AIEE. Therefore, such CDs would be excellent candidates as fluorescent probes for the label-free detection of ATP. Our proposed method exhibited simple and easy preparation of nanoprobe, quick response (3 min), wide range of linear rage (1-2000 µM) and eco-friendly. In addition, the method performed successfully as a "turn-on" sensor for detection of ATP in the tablet with a recovery of 100.1~106.9% and RSD below 3.5%.