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Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg(−1) · d(−1)) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg(−1) · d(−1)) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.

Retinal explant cultures provide a valuable system to study retinal function in vitro. This study established a new retinal explant culture method to prolong the survival of retinal ganglion cells (RGCs). Explants were prepared in two different ways: with or without optic nerve. Retinas from newborn mice that had received an injection of MitoTracker Red into the contralateral superior colliculus to label axonal mitochondria were cultured as organotypic culture for 7 days in vitro. At several time points during the culture, viability of RGCs was assessed by multi-electrode array recording, and morphology by immunohistochemical methods. During the culture, the thickness of the retinal tissue in both groups gradually decreased, however, the structure of the layers of the retina could be identified. Massive apoptosis in the retinal ganglion cell layer (GCL) appeared on the first day of culture, thereafter the number of apoptotic cells decreased. Glial activation was observed throughout the culture, and there was no difference in morphology between the two groups. RGCs loss was exacerbated on 3

Objectives Anlotinib hydrochloride (AL3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin-induced pulmonary fibrosis in mice and explored the antifibrosis mechanism. Methods We have evaluated the effect of anlotinib on bleomycin-induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL-1β, IL-4, IL-6 and TNF-α were determined by ELISA. Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGFβ/Smad3 and non-Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism. Key findings The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF-β1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF-β1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts. Conclusions In summary, the results suggest that anlotinib-mediated suppression of pulmonary fibrosis is related to the inhibition of TGF-β1 signalling pathway.

In the past three decades, nuclear energy has gained much attention as carbon-free electricity. Due to the supply of cooling water in nuclear power plant, large amount of waste heat will increase the water temperature, promote the microalgae and cyanobacteria propagation and increase the chance of red tide. Excess phytoplankton of cool source will result in abnormal operation of cooling system, even core overheating and nuclear leakage. Consequently, it is very important to remove microalgae and cyanobacteria from cold source of nuclear power plants. This review summarizes the formation mechanism and monitoring methods of red tide, compares the advantages and disadvantages of traditional microalgae removal technology including physical, chemical and biological methods. Furthermore, the improved electrochemical method and micro-nano bubble method are introduced in detail. Their combination is considered to be a low-cost, efficient and environmentally-friendly technology to prevent and control red tides for cold source of nuclear power plant.

BACKGROUND AND PURPOSE Diosmetin exhibits a series of therapeutic efficacy but little is known of its effects on colitis. EXPERIMENTAL APPROACH In this study, two mouse models of DSS (the concentration of 3% and 5%)-induced colitis and Caco2 and IEC-6 cells were employed. The 16S amplicon sequencing was used to assess Gut microbiota changes by diosmetin. Various physical signs of mice (body weight, colon length and DAI score), proinflammatory cytokines and antioxidant enzymes were tested. KEY RESULTS The results showed that diosmetin can markedly decrease the disease activity index and microscopic colon tissue damage, increase the expression of tight junction protein (Occludin, Claudin-1 and Zo-1) and reduce the secretion of proinflammatory cytokines. And diosmetin also significantly inhibited colon oxidative damage through adjusting the levels of intracellular ROS, mitochondrial ROS, GSH-Px, SOD, MDA and GSH in vitro and in vivo. Furthermore, it was found that diosmetin can modulate the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were reported to be the crucial bacteria related to inflammatory bowel disease (IBD). Also, diosmetin significantly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, thereby inhibiting oxidative stress and inflammation. CONCLUSIONS AND IMPLICATIONS Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is regulated by diosmetin. It implies that diosmetin may be a novel candidate to alleviate DSS-induced colitis or a lead compound for future optimization and modification.

Background: Pirfenidone(PFD) and nintedanib(NDN), the only two drugs for IPF, which should be accurately selected in treatment, has no relevant basic research for reference. Objective: Compare the effect of PFD and NDN in bleomycin(BLM)-induced pulmonary fibrosis model of different periods, so as to provide theoretical basis for clinical application. Methods: The BLM model of different periods were performed in Fig1. Results: 1) Anti-inflammatory and antioxidant capacity: The inhibition rate of NDN on inflammatory cell numbers was higher than that of PFD, while PFD has better inhibitory effect on IL-1β and IL-4 and NDN has higher inhibitory rate on IL-6 and IFN-γ. The activity of SOD in PFD group was higher than that of NDN group, while the content of MDA in lung tissues and the concentration of MPO in serum were significantly lower in NDN group than of PFD group. 2) Anti-fibrosis capacity: In prevention model, hydroxyproline content in PFD group was 140.29±3.59μg/right lung and NDN group was 162.87±2.91μg/right lung. In treatment models, HYP content was much less in NDN group than in PFD group. Pathological change was consistent with the HYP results. Conclusion: Both PFD and NDN have anti-inflammatory and antioxidative effects and selectively suppressed different biomarkers. PFD is more effective in the prophylactic model of fibrosis, while NDN has a better effect in early and late treatment models.

Background: Idiopathic pulmonary fibrosis is incurable and has no effective treatment. The marketed drugs are only pirfenidone and nintedanib. By evaluating the inhibition effects of pirfenidone and nintedanib on the proliferation, migration and activation of human lung fibroblasts (HFL1), the anti-fibrotic mechanism of two drugs was tested and compared to provide reference for accurate clinical medication. Methods: HFL1 cells were divided into control group, TGF-β1/ PDGF-stimulate-model group, and drug-add group. The effect of pirfenidone and nintedanib on the proliferation and migration of HFL1 were evaluated by MTT assay and scratch test, respectively. Anti-pulmonary fibrosis effects of pirfenidone and nintedanib were evaluated by detecting the inhibitory activity of each drug on the expression of fibroblasts activation markers. The inhibitory effects of pirfenidone and nintedanib on TGF-β/Smad3 signaling pathway were evaluated by Western Blotting. Results: The results of MTT assays showed that both pirfenidone and nintedanib could inhibit TGF-β-induced proliferation of fibroblasts. In addition, both pirfenidone and nintedanib inhibited the migration of HFL1; Both pirfenidone and nintedanib can inhibit the expression of fibroblast activation markers, and they can inhibit the activation of TGF-β/Smad3 protein signaling pathway by inhibiting the phosphorylation of Smad3. The inhibition rate of Smad3 phosphorylation by nintedanib was 51%, and the inhibition rate of pirfenidone on Smad3 phosphorylation was 13%. Conclusion: Both pirfenidone and nintedanib could inhibit the proliferation, migration and activation of myofibroblasts, And all of them can exert anti-pulmonary fibrosis through TGF-β signaling pathway.

The focusing phenomenon is a difficult point during the electrokinetic remediation (EKR) of contaminated soil. It restricts the extraction and removal of heavy metals. There is still a lack of methods to discern focusing position rapidly and take proper measures. Therefore, a total of seven tests with or without intervening and regulating measures were conducted. Among the four tests without regulating and intervening measures, focusing position often appeared in low-voltage region after three days’ treatment. When using ammonium citrate as electrolyte, the highest removal efficiency of total chromium (Cr) (32.20%) was achieved. The intervening measure that adding citric acid near section 4 decreased the area of high-voltage and made it move towards cathode. Meanwhile, the removal efficiency of Cr(VI) (60.17%) was significantly improved. Using sodium dodecyl sulfate (SDS) as pretreatment agent and electrolyte made the position of high-voltage area move towards anode and removed 35.80% of total Cr and 53.47% of Cr(VI) eventually. Simultaneously, the energy consumption per gram of removed Cr was also the lowest. The focusing degree was reduced with intervening and regulating measures conducted but focusing position still existed in low voltage area, which further indicated that focusing position preferred to appear in low voltage area and we could discern focusing position through voltage distribution across the soil roughly.

Heavy metals chemical speciation significantly effects the electrokinetic removal of heavy metals contaminated soil, but how to regulate and intervene the chemical speciation for improving the removal efficiency in the electrokinetic remediation of the contaminated soil is still an opened problem. In this study, we used increasing citric acid electrolyte concentration and soil pretreatment as regulating measures and the anolyte circulation and reduction wells as intervening act to explore the detailed transformation and migration of Cr speciation over time during electrokinetic remediation, the effect of the transformation and migration of Cr speciation in arid area contaminated soil on the removal efficiency. Based on the results of sequential extraction, the regulating measures can significantly improve the soil pH and the transformation of Cr speciation in arid areas, but the detailed transformation occurs in the early stage of remediation. The material flows showed that the transformation of other speciation to exchangeable (EXC) was higher than its migration to the electrode chamber and the EXC was not completely removed throughout the experiment. By adding HCl to the soil prior to the electrokinetic remediation, more Cr (III) can migrate to the cathode region. Regulating measure for pretreatment of real contaminated soil in arid area based on high concentration of citric acid and intervening act for the anolyte circulation could significantly reduce the bound to Fe/Mn oxides (FM), but the overall removal efficiency of the real contaminated soil (from 44.86% to 44.90%) was not improved, while the removal efficiency of artificially contaminated soil was higher. Furthermore, the multivariate linear regression analysis of the link between the five fractions and removal efficiency of Cr also shows that their correlation was much higher in artificially contaminated soils than in real contaminated soils. The scale effect would affect the transformation of the speciation, and the smaller the scale of the experiment is, the larger the influence on the migration and transformation of Cr speciation will be. The combination of regulating measures and intervening act provide a valuable reference for the specific transformation and migration of heavy metals speciation and the improvement of removal efficiency during EKR of contaminated soil in arid area.