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Inflammation plays a key role in the pathogenesis of depression and antidepressant therapies. Astragalin (AST) is a bioactive flavonoid that possesses an anti-inflammatory property. However, the antidepressant action of astragalin has not been addressed. In this study, we explored the antidepressant effects of astragalin and its underlying mechanism. Our results showed that AST significantly improved the behavioral defects in chronic unpredictable mild stress (CUMS) model, promoted SIRT1 expression, and decreased the protein levels of NF-κB p65, NLRP3, cleaved capase-1, cleaved IL-1β and cleaved gasdermin D in the hippocampus. Immunohistochemistry revealed AST mitigated CUMS-induced microglia overactivation. In vitro, AST profoundly increased the cell viability in lipopolysaccharides (LPS) and adenosine triphosphate (ATP) treated BV2 cells, with upregulated SIRT1 expression and downregulated protein levels of nuclear NF-κB p65, NLRP3, cleaved capase-1, and cleaved gasdermin D. Declined cleavage of gasdermin D was observed after AST administration in immunocytochemistry. Nevertheless, the in vivo and in vitro effects of AST were compromised by SIRT1 inhibitor EX-527. These results indicated that AST possessed an antidepressant property, which was dependent on SIRT1 signaling modulated NLRP3 inflammasome deactivation.

Background The NLRP3-mediated pyroptosis, which could be regulated by miRNA-27a, is a key player in the development of depression. Isoliquiritin is a phenolic flavonoid compound that has been demonstrated to suppress NLRP3-mediated pyroptosis. However, it is still unknown whether isoliquiritin could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by stimulating miRNA-27a. Thus, in the current study, we explored the antidepressant activity of isoliquiritin and its underlying mechanism. Methods Expression of miRNA-27a in depressed patients or mice was measured using qRT-PCR. Luciferase reporter assay was performed to illustrate the link between miRNA-27a and SYK. Lipopolysaccharide (LPS) and chronic social defeat stress (CSDS) depression models were established to investigate the antidepressant actions of isoliquiritin. Changes in miRNA-27a/SYK/NF-κB axis and NLRP3-mediated pyroptosis were also examined. The role of miRNA-27a in isoliquiritin-related antidepressant effect was further investigated by using miRNA-27a inhibitors and mimics of miRNA-27a. Results Our results showed the miRNA-27a expression was downregulated in the serum of depressed patients, and decreased serum and hippocampus expression of miRNA-27a were observed in rodent models of depression. SYK gene expression was significantly reduced by miRNA-27a mimic incubation. Isoliquiritin profoundly attenuated LPS or CSDS-induced depressive symptoms, as well as CSDS-induced anxiety behavior. In the hippocampus, LPS and CSDS decreased miRNA-27a mRNA expression; increased the protein levels of SYK, p-NF-κB, and NLRP3: cleaved Caspase-1, IL-1β, and GSDMD-N: and elevated the concentration of IL-1β, IL-6, and TNF-α, which were all restored by isoliquiritin administration. Meanwhile, isoliquiritin upregulated the hippocampal NeuN protein level, improved the survival and morphology of neurons, and decreased pyroptosis-related neuronal cell death. Moreover, isoliquiritin protected primary microglia against LPS and adenosine triphosphate (ATP) elicited NLRP3 inflammasome activation in vitro, evidenced by declined protein levels of p-NF-κB, NLRP3; cleaved Caspase-1, IL-1β, and GSDMD-N; upregulated miRNA-27a mRNA expression; and decreased the mRNA and protein levels of SYK. Nevertheless, miRNA-27a inhibitors significantly reversed isoliquiritin-generated therapeutic efficacy in CSDS mice and in vitro. Furthermore, the cytoprotective effect of isoliquiritin was similar to that of miRNA-27a mimics in LPS and ATP-treated primary microglia. Taken together, these findings suggest that isoliquiritin possesses potent antidepressant property, which requires miRNA-27a/SYK/NF-κB axis controlled decrease of pyroptosis via NLRP3 cascade.

A CFD (computational Fluid Dynamics) simulation model of the porous ceiling radiant air-conditioning system was established to study the influence of the ceiling temperature and envelope temperature (including the temperature of the walls and the floor of a room) on the thermal environment in the room equipped with such a system. The results showed that, for the summer condition, higher ceiling temperatures would result in higher indoor air temperature and higher Predicted Percentage Dissatisfied (PPD), which meant potential discomfort of occupants in the room. For the winter condition, however, a higher ceiling temperature within 28°C would result in a lower PPD, thus improved the thermal comfort. Considering the energy-conservation, the thermal comfort could be assured if the ceiling temperature was not more than 28°C. As for the effect of envelope temperature, the result showed that the increase in the envelope temperature during summer could result in a higher indoor air temperature, but the thermal comfort of occupants could still be ensured under such condition. Considering both the thermal comfort and the energyconservation, a ceiling temperature of 18°C (underside surface temperature of the ceiling) and an envelope temperature between 26°C and 32°C were proved appropriate for the summer. Similarly, based on the simulation results, a ceiling temperature of 26°C, and an envelope temperature between 8°C and 11°C were found appropriate for the winter. The results indicated that for the porous ceiling radiant air-conditioning system, ceiling temperature should be controlled to increase the ratio of radiant heat transfer in the summer, and the envelope temperature should be lowered to improve the energy-conservation of the system. In the winter, the heat transfer by radiation of the porous ceiling would account for a larger ratio, therefore the system showed good heating capacity and energyconservation performance in winter.

Vision-language navigation (VLN) is the task of entailing an agent to carry out navigational instructions inside photo-realistic environments. One of the key challenges in VLN is how to conduct a robust navigation by mitigating the uncertainty caused by ambiguous instructions and insufficient observation of the environment. Agents trained by current approaches typically suffer from this and would consequently struggle to avoid random and inefficient actions at every step. In contrast, when humans face such a challenge, they can still maintain robust navigation by actively exploring the surroundings to gather more information and thus make more confident navigation decisions. This work draws inspiration from human navigation behavior and endows an agent with an active information gathering ability for a more intelligent vision-language navigation policy. To achieve this, we propose an end-to-end framework for learning an exploration policy that decides i) when and where to explore, ii) what information is worth gathering during exploration, and iii) how to adjust the navigation decision after the exploration. The experimental results show promising exploration strategies emerged from training, which leads to significant boost in navigation performance. On the R2R challenge leaderboard, our agent gets promising results all three VLN settings, i.e., single run, pre-exploration, and beam search., Comment: ECCV2020 (changed with improved perfromance on Pre-Explore and Beam Search settings); website: https://github.com/HanqingWangAI/Active_VLN

Introduction Different parts of Sophora alopecuroides L. (Fabaceae) have historically been used in traditional Chinese medicine for the treatment of dysentery and enteritis. This plant is also utilised as an important resource for industrial preparation of quinolizidine alkaloidal pharmaceuticals. Objective Establish a reliable, simple and fast analytical method for the quantitative determination of the quinolizidine-type alkaloids and extend understanding of the metabolism of quinolizidine-type alkaloids in S. alopecuroides. Methods Hydrophilic interaction chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode were used to determine seven quinolizidine-type alkaloids and their biosynthetic precursor, lysine, in S. alopecuroides. Results A good separation was obtained on an ultra high-performance liquid chromatography (UHPLC) amide column within 7 min. The overall limits of detection (LODs) were between 1.13 and 2.81 ng/ml, and limits of quantitation (LOQs) were between 3.80 and 8.48 ng/ml. The developed method was successfully applied to 21 samples of S. alopecuroides. The seeds had the highest concentration of alkaloids among the different plant parts. Oxymatrine and oxysophocarpine were the two most abundant alkaloids in all of the different parts and at different phenological growth stages. The contents of quinolizidine alkaloids showed correlations with lysine. Conclusion A rapid and sensitive analytical method was established for the simultaneous determination of seven quinolizidine-type alkaloids and their biosynthetic precursor, lysine, in S. alopecuroides; the content of lysine may be used as a marker to predict alkaloid production.

Quinolizidine alkaloids are the main bioactive components in Sophora alopecuroides L. This study reports a novel ultrasound-assisted enzymatic hydrolysis method for the extraction of these important alkaloids. Box-Behnken design, a widely used response surface methodology, was used to investigate the effects of process variables on ultrasound bath-assisted enzymatic hydrolysis (UAEH) extraction. Four independent variables, pH, extraction temperature (°C), extraction time (min) and solvent-to-material ratio (mL/g), were studied. For the extraction of sophocarpine, oxysophocarpine, oxymatrine, matrine, sophoramine, sophoridine and cytisine, the optimal UAEH condition was found to be a pH of 5, extraction temperature of 54 °C, extraction time of 60 min and solvent-to-material ratio of 112 mL/g. The experimental values obtained under optimal conditions were fairly consistent with the predicted values. UAEH extraction was then compared with reflux heating, enzymatic extraction and ultrasound-assisted extraction. Of these extraction methods, UAEH extraction under optimal conditions produced the highest yield for seven types of alkaloids. In addition, UAEH extraction resulted in lower ingredient degradation than reflux heating extraction.