A novel photocatalytic system coupling metal-free Carbon/g-C3N4 catalyst with persulfate for highly efficient degradation of organic pollutants.

A variety of photocatalytic systems have emerged as the effective methods for the degradation of organic pollutants. In this research, a novel photocatalytic system, named CNC-PDS has been proposed, which couples a metal-free carbon/g-C3N4 (CNC) photocatalyst with persulfate (PDS), and applied for efficient degradation of paracetamol (PCM) under simulated sunlight. The CNC-PDS system exhibited excellent photocatalytic capability, where the PCM was completely degraded in 40 min under simulated sunlight. The degradation rate of CNC-PDS system was 9.5 times compared with the g-C3N4 and PDS coupled systems. The CNC-PDS system can efficiently degrade other representative pollutants in neutral solutions, such as pharmaceuticals, endocrine disrupting compounds (EDCs), azo dyes. The excellent catalytic activity of CNC-PDS system should be ascribed to the two aspects: a) the increased light absorption range led to more photo-induced electron-hole pairs generation compared with the original g-C3N4. Meanwhile, the charge separation efficiency of the CNC photocatalyst was drastically enhanced which was proved by the results of PL and EIS analysis. These results represented the carbon/g-C3N4 might offer more e- to promote PDS activation. b) The introduction of CO and the improved specific surface area provided more active sites for PDS activation. In addition, the EPR analysis and quenching experiments indicated that O2.-, h+ and 1O2 were the main active species for PCM in the CNC-PDS system under simulated sunlight, and the contribution order was O2.->1O2>h+. The degradation pathways of PCM in the CNC-PDS system are proposed based on the results of HPLC-MS. The novel CNC-PDS photocatalytic system has provided a viable option for treatment of contaminated water by organic pollutants.

Sotetsuflavone ameliorates Crohn's disease-like colitis by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and MAPK signalling.

OBJECTIVES: Intestinal inflammation and intestinal barrier dysfunction are two important pathological changes in Crohn's disease (CD). Sotetsuflavone (SF) is a natural monomeric herbal compound with anti-inflammatory and cytoprotective effects that is mostly nontoxic. The effect of SF on CD-like spontaneous colitis was investigated in this study. METHODS: Il-10-/- mice were used as a CD model and were administered different doses of SF. Lipopolysaccharide (LPS) plus IFN-γ-induced macrophages (RAW264.7) and a coculture system (RAW264.7 and organoids) were used in vitro. The protective effects of SF against CD-like colitis and macrophage differentiation and the mechanisms were evaluated. RESULTS: SF treatment markedly improved spontaneous colitis in the CD model, as shown by the following evidence: reductions in the DAI, macroscopic scores (3.63 ± 1.30), colonic tissue inflammatory scores (2 ± 0.76) and proinflammatory factor levels and the attenuation of colon shortening (8 ± 0.93 cm) and weight loss (1.75 ± 1.83 g). Decreased intestinal permeability and intestinal bacterial translocation rates provided evidence of the protective effect of SF on intestinal barrier function. We also found that SF suppressed M1 macrophage-induced inflammatory responses. In the coculture system of mouse colonic organoids and RAW264.7 cells, SF significantly ameliorated M1 macrophage-induced intestinal epithelial damage. In addition, SF inhibited JNK and MAPK (p38) signalling in both Il-10-/- mice and LPS plus IFN-γ-induced macrophages (RAW264.7). CONCLUSIONS: The protective effects of SF against CD-like colitis may be achieved partially by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and p38 signalling. SF may have therapeutic potential for treating CD, especially considering its safety.

Microbiota from patients with ulcerative colitis promote colorectal carcinogenesis in mice.

OBJECTIVES: Long-term ulcerative colitis (UC) is associated with both dysbiosis in intestinal microbiota and predisposition to colorectal cancer. In this study, we investigated whether microbiota from patients with UC could increase colorectal carcinogenesis in mice, generated by azoxymethane through intraperitoneal injection. METHODS: Mice were gavaged twice per week with intestinal microbiota from patients with UC or healthy individuals. Intestinal tissues were collected from mice and compared by histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, Western blot, and flow cytometry analyses. Quantification of bacteria in feces was performed using 16 S ribosomal RNA gene selective quantitative polymerase chain reaction. RESULTS: Compared with mice fed microbiota from healthy controls, increased tumorigenesis was observed in mice gavaged with microbiota from patients with UC, including a higher number of colon adenoma and a significantly higher proportion of grade dysplasia. Consistent with tumorigenesis, mice gavaged with microbiota from patients with UC showed an increased expression of Ki67 and proliferating cell nuclear antigen. In addition, an increased expression of cytokines and more abundant presence of T helper cells types 1 and 17 was observed in mice receiving microbiota from patients with UC. Moreover, a decrease in the abundance of short-chain fatty acids was detected in the feces, as well as an altered intestinal microbial composition in mice fed with microbiota from patients with UC. CONCLUSIONS: Fecal microbiota from patients with UC exacerbate tumorigenesis in mice. The disturbance of intestinal microbiota and activation of T helper cells types 1 and 17 cytokines caused by gavaging microbiota from patients with UC both contributed to intestinal carcinogenesis.

gCN-P: a coupled g-C3N4/persulfate system for photocatalytic degradation of organic pollutants under simulated sunlight.

A coupled g-C3N4/PDS system, named gCN-P, has been put forward to degrade refractory organic pollutants under simulated sunlight which integrates photocatalysis and PS-AOPs (advanced oxidation of persulfate based on sulfate radicals). The coupled g-C3N4 and PDS showed superior synergistic effect for MO degradation under simulated sunlight. Results showed that almost all MO was removed in the gCN-P system after irradiation for 80 min under simulated sunlight. The degradation rate of gCN-P system was improved by 12.6 and 4.9 times compared to single PDS and g-C3N4 systems, respectively. And only by adding 0.01 g of persulfate into the gCN-P system. The results of quenching experiments and EPR showed that O2-, 1O2 and h+ were main active species for the degradation of MO in the gCN-P system under simulated sunlight. Application of the gCN-P system in tap water samples demonstrated its excellent performance in real-world water environment, and the gCN-P system was employed for removing other new contaminants such as bisphenol A, ciprofloxacin, and paracetamol. The results demonstrated the gCN-P system can effectively remove organic pollutants under sunlight in practices.

A Two-Stage Hybrid Default Discriminant Model Based on Deep Forest.

Background: the credit scoring model is an effective tool for banks and other financial institutions to distinguish potential default borrowers. The credit scoring model represented by machine learning methods such as deep learning performs well in terms of the accuracy of default discrimination, but the model itself also has many shortcomings such as many hyperparameters and large dependence on big data. There is still a lot of room to improve its interpretability and robustness. Methods: the deep forest or multi-Grained Cascade Forest (gcForest) is a decision tree depth model based on the random forest algorithm. Using multidimensional scanning and cascading processing, gcForest can effectively identify and process high-dimensional feature information. At the same time, gcForest has fewer hyperparameters and has strong robustness. So, this paper constructs a two-stage hybrid default discrimination model based on multiple feature selection methods and gcForest algorithm, and at the same time, it optimizes the parameters for the lowest type II error as the first principle, and the highest AUC and accuracy as the second and third principles. GcForest can not only reflect the advantages of traditional statistical models in terms of interpretability and robustness but also take into account the advantages of deep learning models in terms of accuracy. Results: the validity of the hybrid default discrimination model is verified by three real open credit data sets of Australian, Japanese, and German in the UCI database. Conclusions: the performance of the gcForest is better than the current popular single classifiers such as ANN, and the common ensemble classifiers such as LightGBM, and CNNs in type II error, AUC, and accuracy. Besides, in comparison with other similar research results, the robustness and effectiveness of this model are further verified.

Clematichinenoside AR ameliorated spontaneous colitis in Il-10-/- mice associated with improving the intestinal barrier function and abnormal immune responses.

OBJECTIVES: Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS: Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS: AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS: AR may have therapeutic potential for treating CD in humans.

Bryostatin-1 ameliorated experimental colitis in Il-10-/- Mice by protecting the intestinal barrier and limiting immune dysfunction.

Bryostatin-1 (Bry-1) has been proven to be effective and safe in clinical trials of a variety of immune-related diseases. However, little is known about its effect on Crohn's disease (CD). We aimed to investigate the impact of Bry-1 on CD-like colitis and determine the mechanism underlying this effect. In the present study, 15-week-old male Il-10-/- mice with spontaneous colitis were divided into positive control and Bry-1-treated (Bry-1, 30 µg/kg every other day, injected intraperitoneally for 4 weeks) groups. Age-matched, male wild-type (WT) mice were used as a negative control. The effects of Bry-1 on colitis, intestinal barrier function and T cell responses as well as the potential regulatory mechanisms were evaluated. We found that the systemic delivery of Bry-1 significantly ameliorated colitis in Il-10-/- mice, as demonstrated by decreases in the disease activity index (DAI), inflammatory score and proinflammatory mediator levels. The protective effects of Bry-1 on CD-like colitis included the maintenance of intestinal barrier integrity and the helper T cell (Th)/regulatory T cell (Treg) balance. These effects of Bry-1 may act in part through nuclear factor erythroid 2-related factor 2 (Nrf2) signalling activation and STAT3/4 signalling inhibition. The protective effect of Bry-1 on CD-like colitis suggests Bry-1 has therapeutic potential in human CD, particularly given the established clinical safety of Bry-1.

[IL-12 monoclonal antibody alleviates intestinal inflammation in IL-10-/- mice by regulating intestinal mucosal immunity].

Objective To evaluate the therapeutic effect and possible mechanism of IL-12 monoclonal antibody (IL-12 mAb) on IL-10 knockout(IL-10-/-) mice and its possible mechanism. Methods Sixteen male IL-10-/- mice of 15 weeks old were randomly divided into control group and IL-12 mAb treatment group. The IL-12 mAb treatment group were given intraperitoneal injection of IL-12 mAb (25 mg/kg, once per week), and the control group was given intraperitoneal injection of 0.2 mL of normal saline. After 4 weeks of intervention, the inflammatory bowel disease activity index (DAI) and HE staining were used to evaluate the intestinal inflammation symptoms and histological changes. The intestinal mucosal permeability test was used to evaluate the intestinal mucosal barrier function of the two groups. The expression of claudin-1 in intestinal mucosa was detected by Western blot analysis. The Th1/Th2 cell balance of intestinal mucosa was evaluated by flow cytometry. The ELISA was used to evaluate IL-13 and tumor necrosis factor alpha(TNF-α) of intestinal mucosal of the two groups. The expression of phosphorylated signal transducer and activator of transcription (p-STAT6) in intestinal mucosa was detected by Western blot nanlysis. Results Three and 4 weeks after IL-12 mAb treatment, the DAI and intestinal inflammation scores of IL-12 mAb treatment group were significantly lower than the control group. At the same time, the intestinal mucosal permeability of IL-12 mAb treatment group was significantly lower than that of the control group, and the expression of claudin-1 in intestinal mucosa was significantly higher than that of the control group. At the same time, IL-12 mAb treatment inhibited the proportion of Th1 cells in the intestinal mucosa and up-regulated the proportion of Th2 cells. In the signal pathway analysis, IL-12 mAb treatment increased the levels of p-STAT6 and IL-13 in the intestinal mucosa and inhibited the level of TNF-α. Conclusion IL-12 mAb effectively alleviates intestinal inflammation in the Crohn's disease animal model and protect the intestinal mucosal barrier, which may be through inhibition of Th1 cell immune response in the intestinal mucosa and up-regulation of STAT6 signaling.