Exposure to social stress and dysregulated serotonergic neurotransmission have both been implicated in the etiology of psychiatric disorders. However, the serotonergic circuit involved in stress vulnerability is still unknown. Here, we explored whether a serotonergic input from the dorsal raphe (DR) to ventral tegmental area (VTA) influences vulnerability to social stress. We identified a distinct, anatomically and functionally defined serotonergic subpopulation in the DR that projects to the VTA (5-HT
DR→VTA
neurons). Moreover, we found that susceptibility to social stress decreased the firing activity of 5-HT
DR→VTA
neurons. Importantly, the bidirectional manipulation of 5-HT
DR→VTA
neurons could modulate susceptibility to social stress. Our findings reveal that the activity of 5-HT
DR→VTA
neurons may be an essential factor in determining individual levels of susceptibility to social stress and suggest that targeting specific serotonergic circuits may aid the development of therapies for the treatment of stress-related disorders.
As interest grows in the use of linguistically annotated corpora in research and teaching of foreign languages and literature, treebanks of various historical texts have been developed. We introduce the first large-scale dependency treebank for Classical Chinese literature. Derived from the Stanford dependency types, it consists of over 32K characters drawn from a collection of poems written in the 8 th century CE. We report on the design of new dependency relations, discuss aspects of the annotation process and evaluation, and illustrate its use in a study of parallelism in Classical Chinese poetry.
Licoricidin, a type of isoflavonoid, is extracted from the root of Glycyrrhiza glabra. It has been widely proven that licoricidin possesses multiple biological activities, including anti-cancer effects and a powerful antimicrobial effect against Helicobacter pylori (H. pylori). However, the exact mechanism of licoricidin against gastric cancer remains unclear. In this study, we comprehensively explored the effects of licoricidin on MGC-803 gastric cancer cells in vitro and in vivo and further elucidated its mechanism of action. Our results revealed that licoricidin exhibited multiple anti-gastric cancer activities, including suppressing proliferation, inducing apoptosis, arresting the cell cycle in G0/G1 phase, and inhibiting the migration and invasion abilities of MGC-803 gastric cancer cells. In addition to this, a total of 5861 proteins were identified by quantitative proteomics research strategy of TMT labeling, of which 19 differential proteins (two upregulated and 17 downregulated) were screened out. Combining bioinformatics analyses and the reported roles in cancer progression of the 19 proteins, we speculated that isoprenyl carboxyl methyltransferase (ICMT) was the most likely target of licoricidin. Western blot assays and IHC assays subsequently proved that licoricidin significantly downregulated the expression of ICMT, both in MGC-803 cells and in xenograft tumors. Moreover, licoricidin effectively reduced the level of active Ras-GTP and blocked the phosphorylation of Raf and Erk, which may be involved in its anti-gastric cancer effects. In summary, we first demonstrated that licoricidin exerted favorable anti-gastric cancer activities via the ICMT/Ras pathway, which suggests that licoricidin, as a natural product, could be a novel candidate for the management of gastric cancer.
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