23:T4a3,Various dietary fibers are considered to prevent obesity by modulating the gut microbiota. Cordyceps sinensis polysaccharide (CSP) is a soluble dietary fiber known to have protective effects against obesity and related diseases, but whether these effects induce any side effects remains unknown. The function and safety of CSP were tested in high-fat diet (HFD)-feding C57BL/6J mice. The results revealed that even though CSP supplementation could prevent an increase in body weight, it aggravated liver fibrosis and steatosis as evidenced by increased inflammation, lipid metabolism markers, insulin resistance (IR) and alanine aminotransferase (ALT) in HFD-induced obesity. 16S rDNA gene sequencing was used to analyze the gut microbiota composition, and the relative abundance of the Actinobacteria phylum, including the Olsenella genus, was significantly higher in CSP-treated mice than in HFD-fed mice. CSP supplementation may increase the proportion of Actinobacteria, which can degrade CSP. The high level of Actinobacteria aggravated the disorder of the intestinal flora and contributed to the progression from obesity to nonalcoholic steatohepatitis (NASH) and related diseases.24:T50b,Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIR^GABA+-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIR^GABA+-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIR^GABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABA_AR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIR^GABA+-PVT pathway acts through GABA_AR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

#	Concept	H-Index	Publications	Citations
1	Medicine	2	2	57
2	Engineering	1	1	25
3	Health Sciences	1	1	18
4	Natural Sciences	1	1	39
5	Public Health	1	1	193

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