A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

Simiao Wan modulates the gut microbiota and bile acid metabolism during improving type 2 diabetes mellitus in mice.

BACKGROUND: Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored. PURPOSE: Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice. METHODS: The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)/streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW. RESULTS: SMW significantly improved insulin resistance and hepatic lipid accumulation in HFD/STZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OH/non-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver. CONCLUSION: Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.

Disordered serum essential element levels are associated with increased risk of kidney tumors.

Essential elements play vital roles in the regulation of carcinogenesis. We aimed to investigate the relationship between essential elements and kidney tumors. This study included 72 healthy individuals and 100 kidney tumor patients. The concentrations of cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), selenium (Se), and zinc (Zn) were determined by inductively coupled plasma mass spectrometry. The random forest model was used to evaluate the importance of each variable by using the randomForest package. The associations between essential elements and clinical tumor characteristics were examined by the Mann-Whitney U-test, and the log-rank test was used to assess the Kaplan-Meier curves. The levels of Co, Cr, Fe, Mn, Ni, and Zn in patients with kidney tumors were significantly lower. In the random forest model, the top two metallic features were Co and Zn. The Kaplan-Meier curve showed that patients with lower Co, Se, and Zn levels exhibited lower progression-free survival. In summary, this study gathered evidence that disordered essential elements are associated with kidney tumors and thus opens a new path to elucidate the etiology of kidney tumors from the perspective of environmental health and safety.