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3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid (BCAA)-associated mammalian target of rapamycin complex 1 (mTORC1) activation. Previous studies have demonstrated the therapeutic effects of BT2 on arthritis, liver cancer, and kidney injury. However, the effects of BT2 on ulcerative colitis (UC) are unknown.To investigate the anti-UC effects of BT2 and the underlying mechanism.Mouse UC models were created through the administration of 3.5% dextran sodium sulfate (DSS) for 7 d. The mice in the treated groups were administered salazosulfapyridine (300 mg/kg) or BT2 (20 mg/kg) orally from day 1 to day 7. At the end of the study, all of the mice were sacrificed, and colon tissues were removed for hematoxylin and eosin staining, immunoblot analyses, and immunohistochemical assays. Cytokine levels were measured by flow cytometry. The contents of BCAAs including valine, leucine, and isoleucine, in mouse serum were detected by liquid chromatography-tandem mass spectrometry, and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice. BT2 also reduced the production of the proinflammatory cytokines interleukin 6 (IL-6), IL-9, and IL-2 and increased the anti-inflammatory cytokine IL-10 level. In addition, BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice. Furthermore, high-throughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis. Compared with the DSS group, BT2 treatment increased the ratio ofOur results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient’s fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis.

Cette proposition de communication a pour but d’expliquer comment la prosodie émotionnelle, en passant par le principe phonographique, est représentée par la substance graphique dans un texte multimodal doté de moindre de littéralité comme la BD. Les modèles de mesure des variations matérielles de la prosodie des émotions basiques (colère, tristesse, joie, peur et surprisse) permettent de construire un protocole dans le codage d’une émotion selon les changements de paramètres acoustiques et ainsi de comprendre les variations prosodiques à représenter graphiquement. Après avoir cité les exemples concrets des représentations graphiques des émotions basiques dans les BD francobelges, nous pouvons en conclure que le codage idéographique dans la BD se compose de deux phénomènes :diagramme et icône. Cette notation présentant quelque consensus de configurations graphiques, reste néanmoins imparfaite, non-conventionnelle, mais laisse le libre choix aux auteurs.

San Leng powder extract has been used as medicinal compound for the prevention and treatment of cancers. The antitumor activity of SLPE was determined by treating BALB/C mice harboring a human gastric cancer xenograft with SPLE for 17 days. Mice were also treated with fluorouracil (5-Fu, 25 mg/kg) or a combination of SLPE and 5-Fu. Our results indicate that the inhibition of tumor growth by SLPE might be due to a block in the cell cycle and the induction of apoptosis. These results suggest that SLPE might be useful in the treatment of gastric cancer.

Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no significant toxicity below 800 μg/ml sodium caprate and water-soluble chitosan at different concentrations. In pharmacokinetics study, water-soluble chitosan at dosage of 50mg/kg improved the bioavailability of FTA in weeping forsythia extract to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with weeping forsythia extract with water-soluble chitosan at dosage of 50 mg/kg prevented PC12 cell damage upon H₂O₂ stimulation better than that of control. All findings above suggested that water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antioxidant activity in vivo in weeping forsythia extract.

Transformer fluid directly affects the working state of the components and the cooling efficiency of transformer. There are three kinds of transformer fluid used for electric locomotive, EMU and suburban rail vehicles: mineral oil, silicone liquid and synthetic ester based insulating oil. In this paper, the three kinds of oil are compared from the fire safety, environmental protection, reliability and low maintenance. It provides a strong basis for the selection of transformer fluid. By comprehensive analysis, synthetic ester based insulating oil can completely replace mineral oil and silicone liquid. With rail transport safety and environmental protection standards improving, synthetic ester based insulating oil will be the best choice for transformer.

To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus.An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used.In the in vitro Caco-2 cell model, the mean apparent permeability value (P(app)-value) was 4.15×10(-7) cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6-10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport,96% of the apically loaded FTA was retained on the apical side, while97% of the basolaterally loaded FTA was retained on the basolateral side. The P(app)-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the P(app)-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the P(app)-values. In the in situ intestinal perfusion model, both the absorption rate constant (K(a)) and the effective permeability (P(eff)-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the P(eff)-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the P(eff)-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the Peff-values. Mannitol did not cause significant change in the P(app)-values for the duodenum, jejunum or ileum.The results suggest that the intestinal absorption of FTA may occur through passive diffusion, and the predominant absorption site may be in the upper part of small intestine. Paracellular transport route is also involved. P-gp, MRPs and OATP may participate in the absorption of FTA in the intestine. The low permeability of FTA contributes to its low oral bioavailability.

Rice with low glutelin content is suitable as functional food for patients affected with diabetes and kidney failure. The fine mapping of the gene(s) responsible for low glutelin content will provide information regarding the distribution of glutelin related genes in rice genome and will generate markers for the selection of low glutelin rice varieties. Following an SDS-PAGE screen of rice germplasm from Taihu Valley of China, Japonica selection W3660 is identified to be a novel mutant characterized with low glutelin content. For fine mapping the mutant gene for low glutelin content, F2 and F3 populations were derived from a cross between W3660 and Jingrennuo. SDS-PAGE analysis of the total endosperm protein showed that the low glutelin content trait was controlled by a single dominant nuclear gene. Genetic mapping, using SSRs, located this gene to chromosome 2, in the region between SSR2-001/SSR2-004 and RM1358. The distances of the two markers to the target gene were 1.1 cM and 3.8 cM respectively. By semi-quantitative RT-PCR analysis, the transcripts of GluB4/GluB5 genes located within the region do not change. However, GluB5 gene located proximal to SSR2-001/SSR2-004 was specifically reduced. SSR profiles of seven Japonica varieties were compared with that of W3660 for loci in the relevant genetic region. The markers SSR2-004 and RM1358 were used for marker-assisted selection. The selection efficiencies of SSR2-004 and RM1358 were 96.8% and 92.7% respectively. This provides a standard starting point for the breeding of low glutelin content rice varieties in China.