Prolonged administration of total glucosides of paeony improves intestinal immune imbalance and epithelial barrier damage in collagen-induced arthritis rats based on metabolomics-network pharmacology integrated analysis

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3+, CD4+ and CD8+ in different lymphocyte synthesis sites of the small intestine, including Peyer’s patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysis revealed that TGP reversed the intestinal metabolic profile disturbance in CIA rats, and identified 32 biomarkers and 163 corresponding targets; network pharmacology analysis identified 111 potential targets for TGP to treat RA. By intersecting the results of the two, three key targets such as ADA, PNP and TYR were determined. Pharmacological verification experiments showed that the levels of ADA and PNP in the small intestine of CIA rats were significantly increased, while TGP significantly decreased their ADA and PNP levels. In conclusion, purine metabolism may play an important role in the process of TGP improving RA-induced intestinal immune imbalance and impaired epithelial barrier

Discontinuous moving shot technique for conformal thermal ablation in an ex vivo porcine liver model

PURPOSEWe aimed to determine the ablation characteristics of discontinuous moving shot technique (DMST) in microwave ablation (MWA), radiofrequency ablation (RFA) and laser ablation (LA), and analyze the differences compared with fixed electrode technique (FET) in an ex vivo porcine liver model.METHODSFET was defined as the ablation needle remaining fixed during ablation. In DMST, ablation needle moved backward for a fixed distance twice along the long axis during ablation. Four moving distances (0.5 cm, 0.75 cm, 1 cm and 2 cm) were used in DMST. Long-axis diameter (LAD) and short-axis diameter (SAD) of ablation zones were measured. The ratio of LAD/SAD was calculated.RESULTSThe shape and size of ablation zones were different between DMST and FET. Compared with FET, DMST could achieve greater LAD when the moving distance became long enough. In MWA with DMST, SAD decreased with the extension of moving distance and finally became smaller than the SAD in FET. While in LA and RFA, the change of moving distance did not affect SAD significantly.CONCLUSIONIn MWA, RFA and LA, the characteristics of ablation zone of DMST were different from that of FET. This unique ablation technique may be suitable for conformal thermal ablation

Fluoride-resistant Streptococcus mutans within cross-kingdom biofilms support Candida albicans growth under fluoride and attenuate the in vitro anti-caries effect of fluorine

Fluoride-resistant Streptococcus mutans (S. mutans) might affect the ecological balance of biofilms in the presence of fluoride. We used a S. mutans and Candida albicans (C. albicans) cross-kingdom biofilm model to investigate whether fluoride-resistant S. mutans in biofilms would support C. albicans growth under fluoride stress and attenuate the in vitro anti-caries effect of fluorine. The impact of fluoride-resistant S. mutans on formation of cross-kingdom biofilms by S. mutans and C. albicans in the presence of fluoride was investigated in vitro using the crystal violet staining assay. Biofilm constitution was determined using colony-forming unit (CFU) counts and fluorescent in situ hybridization (FISH). Extracellular polysaccharide (EPS) generation in biofilms was determined by EPS/bacterial dying and water-insoluble polysaccharide detection. Acid production and demineralization were monitored using pH, lactic acid content, and transversal microradiography (TMR). The gene expression of microorganisms in the cross-kingdom biofilm was measured using qRT-PCR. Our results showed that both C. albicans and fluoride-resistant S. mutans grew vigorously, forming robust cross-kingdom biofilms, even in the presence of sodium fluoride (NaF). Moreover, fluoride-resistant S. mutans-containing cross-kingdom biofilms had considerable cariogenic potential for EPS synthesis, acid production, and demineralization ability in the presence of NaF than fluoride-sensitive S. mutans-containing biofilms. Furthermore, the gene expression of microorganisms in the two cross-kingdom biofilms changed dissimilarly in the presence of NaF. In summary, fluoride-resistant S. mutans in cross-kingdom biofilms supported C. albicans growth under fluoride and might attenuate the anti-caries potential of fluorine by maintaining robust cross-kingdom biofilm formation and cariogenic virulence expression in vitro in the presence of NaF

Is green finance fostering high-quality energy development in China? A spatial spillover perspective

As the world's largest energy consumer, it is worth exploring how China can achieve high-quality energy development. This paper aims to assess the role of green finance development in China's high-quality energy development (HED). We develop two indicator systems to measure the level of provincial green finance and HED in China and find a significant contribution of green finance to both local and neighboring HED based on a spatial model. These findings still hold after considering endogeneity and performing a series of robustness tests. In addition, we find that the effect of green finance is more pronounced after exceeding the threshold value, and the spatial spillover boundary of green finance is 1750 km. These findings provide a reference for the government to develop further green finance policies to achieve high-quality energy development

Recognition and Optimization of Ingredients Treating Nitroglycerin-Induced Migraine Rats from Wuzhuyu Decoction

Wuzhuyu decoction (WZYD) has been clinically used to treat migraine effectively since Eastern Han Dynasty of ancient China. However, its antimigrainic ingredients remain unclear. In present study, the antimigrainic ingredients of WZYD were explored and optimized in nitroglycerin-induced migraine rats through correlation analysis of decoction spectra-pharmacological effects and absorption spectra-pharmacological using entropy-weighted partial least squares regression method. The decoction spectra and absorption spectra were obtained through the determination of nine main ingredients in ten kinds of WZYDs and WZYDs’ single-pass intestinal perfusion samples using high performance liquid chromatography-diode array detector. The pharmacodynamics indexes related to migraine model rats were detected using high performance liquid chromatography method and kits after oral administration of WZYDs. Then, the key ingredients influencing indexes were achieved through the correlation analysis. And the optimization of key ingredients was acquired through uniform design experiment. The pharmacodynamic verification test was used to clarify the advantages of the optimized sample. The results showed that the final optimized sample, in which the concentrations of rutaecarpine, evodiamine, ginsendside Rb1, 6-gingerol, ginsendside Rg1, rutaevine, and limonin were 0.081, 0.565, 1.455, 0.159, 0.871, 0.178, and 0.009 mg·mL−1, respectively, provided the best comprehensive effect than another optimized sample and the best uniform design sample. Therefore, a new reliable method for rapidly recognizing and optimizing the effective constituents of WZYD treating migraine was established

Fine-grained Self-supervision for Generalizable Semantic Segmentation

Unsupervised domain adaptative semantic segmentation is a powerful solution for the distribution shift problem between the source and target domains. However, such methods need specified target domain data that may be unavailable in actual applications due to excess expensive collection. Generalizable semantic segmentation as a new paradigm appears in recent research, which aims to generalize well on distinct unseen domains only using source domain data. The existing methods focus on learning domain-invariant features by using global distribution alignment strategies, which may lead to a decreased discriminability of the model. To cope with this challenge, we propose a fine-grained self-supervision (FGSS) framework for generalizable semantic segmentation that takes into account both discriminability and generalizability from the perspective of the intra-class relationship. The FGSS framework contains single-view and multi-view versions. In the single-view version, we propose a fine-grained self-supervision strategy to distinguish the sub-parts of the semantic class for better class discriminability. In the multi-view version, we propose a class prototype feature enhancement strategy to generate another view (i.e. another representation of the original representation). Then, we propose a multi-view mutual supervision loss to enforce consistency between different views and further enhance the generalizability of the model. Experimental results on five widely-used datasets, i.e., GTAV, SYNTHIA, BDD100K, Cityscapes, and Mapillary, demonstrate that our FGSS framework achieves superior performance compared to state-of-the-art methods

Cooperative Multi-RIS Communications for Wideband mmWave MISO-OFDM Systems

International audienceReconfigurable intelligent surfaces (RISs) can shape the wireless environment for enhancing the communication performance. In this letter, we propose a cooperative multi-RIS assisted transmission scheme for a millimeter-wave multi-antenna orthogonal frequency division multiplexing system. We first put forward a delay matching based scheme for simultaneously estimating the multipath channels and the transmission delays of distributed RISs, which requires limited training overhead and feedback. Based on this scheme, we obtain a closed-form solution for the RIS phase shift. Then, we derive an analytical expression of the downlink rate, which is proved to increase logarithmically with the square number of RIS reflecting elements. Simulations are conducted to verify these observations