Salt-Sensitive Ileal Microbiota Plays a Role in Atrial Natriuretic Peptide Deficiency-Induced Cardiac Injury.

Atrial natriuretic peptide (ANP) activity deficiency contributes to salt-sensitive hypertension in humans and mice. However, the role of ileal microbiota in salt sensitivity in ANP deficiency-related cardiac injury has not been investigated yet. This study used ANP-/- mice to analyze the role of the salt-sensitive ileal microbiome on cardiac injury. ANP-/- mice showed an increase in blood pressure (BP), the heart weight/body weight (HW/BW) ratio, and cardiac hypertrophy compared with wild-type (WT) mice. ANP deficiency did not impact the histological structure but reduced occludin expression in the ileum. Antibiotics significantly relieved BP and cardiac hypertrophy in ANP-/- mice. A high-salt diet (HSD) increased BP, the HW/BW ratio, and cardiac hypertrophy/fibrosis in WT and ANP-/- mice, and an HSD treatment in ANP-/- mice exacerbated these cardiac parameters. The HSD markedly decreased muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of WT and ANP-/- mice. Furthermore, the HSD increased the level of TLR4 and IL-1ß in ANP-/- mice ileum compared with WT mice. Antibiotics reduced the HW/BW ratio, cardiac hypertrophy/fibrosis, and the level of TLR4 and IL-1ß in the ileum, and rescued the muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of HSD-ANP-/- mice. Importantly, ANP deficiency induced the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum on the NSD diet, which was only observed in HSD-induced WT mice but not in WT mice on the NSD. Besides, the HSD significantly enhanced the sum of the percentage of the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum of ANP-/- mice. Ileal microbiota transfer (IMT) from ANP-/- mice to healthy C57BL/6J mice drove Lactobacillus johnsonii and Lactobacillus reuteri colonization in the ileum, which manifested an increase in BP, the HW/BW ratio, cardiac hypertrophy, and ileal pathology compared with IMT from WT mice. The HSD in C57BL/6J mice with IMT from ANP-/- mice drove the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum and further exacerbated the cardiac and ileal pathology. Our results suggest that salt-sensitive ileal microbiota is probably related to ANP deficiency-induced cardiac injury.

LncRNA Gas5 regulates Fn1 deposition via Creb5 in renal fibrosis.

Aim: Although studies on lncRNAs in renal fibrosis have focused on target genes and functions of lncRNAs, a comprehensive interaction analysis of lncRNAs is lacking. Materials & methods: Differentially expressed genes in renal fibrosis were screened, and the interaction between lncRNAs and miRNAs was searched. Results: We constructed a ceRNA network associated with renal fibrosis, by which we found the transcription factor Creb5, a target gene of lncRNA Gas5 that might regulate extracellular Fn1 deposition. Conclusion: Our study not only provides a theoretical basis for the ceRNA regulation mechanism of Gas5 but also provides experimental evidence supporting the use of Gas5 targeting in the treatment of renal fibrosis.

Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell.

Ulcerative colitis (UC) is a recurrent intestinal inflammatory disease. Slit2, a secreted protein, interacts with its receptor Robo1 to regulate the differentiation of intestinal stem cells and participate in inflammation and tumor development. However, whether Slit2/Robo1involved in the pathogenesis of UC is not known. We investigated Slit2/Robo1-mediated UC using a dextran sodium sulfate (DSS)-induced model. Eight-week-old male Slit2-Tg (Slit2 transgene) mice, Robo1/2+/- (Robo1+/- Robo2+/-) mice, and their WT littermates were allocated into two groups: (I) control group (n=10), of mice fed a normal diet and tap water and (II) DSS group (n=10), of mice fed a normal diet and drinking water with 2% DSS for 7 days. Colon tissues were collected and analyzed by qPCR, immunohistochemistry, western blot, and immunofluorescence. Slit2-Tg DSS mice showed less body weight loss, less blood in the stool, and less viscous stool compared to those of WTSlit DSS mice. Robo1/2+/- DSS mice displayed a heavier degree of blood in the stool and a more apparent viscosity of the stool compared to those of WTRobo1/2 DSS mice. Slit2 overexpression maintained Lgr5+ stem cell proliferation in the crypt after DSS treatment, significantly increased the LC3II/I ratio, and slightly stimulated p62 expression in the crypt compared to those of DSS-induced WTSlit mice. Robo1/2 partial knockout reduced the number of Lgr5+ stem cells, decreased the LC3II/I ratio, and markedly increased p62 expression in the crypt compare to those of DSS-treated WTRobo1/2 mice. Our findings suggest that Slit2/Robo1 mediates DSS-induced UC probably by activating the autophagy of Lgr5+ stem cells.

Shock initiation of multi-component insensitive PBX explosives: Experiments and MC-DZK mesoscopic reaction rate model.

To facilitate the pre-estimation and optimization of the prescription design of a multi-component polymer bonded explosive (PBX), a multicomponent mesoscopic reaction rate model (MC-DZK model) is developed to predicate preferably the influence of both the explosive components and the particle size of on the shock initiation. All the parameters in the model are determined directly by the parameters in the DZK model for each explosive component. Furthermore, for the multicomponent insensitive explosive PBXC10 (70% TATB, 25% HMX, and 5% Kel-F800 by weight) with different explosive particle sizes, both shock initiation experiments and corresponding numerical simulations are performed, and there is satisfactory agreement between the numerical results and the available experimental data. It is found that the pressure histories present as a shape of step increase during the whole shock initiation process, which is resulted mainly from the rapid chemical reaction rate just behind the precursory shock wave front. It is also found that the smaller the size of the explosive particulates, the faster the pressure grows on the precursory shock wave front, the shorter the run distance to detonation, and the higher the chemical reaction rate just behind the precursory shock wave front.

Quantitative determination of Freon gas using an electronic nose.

This paper reports a quantitative electronic nose (enose) for the quantitative determination of Freon gas within the concentration range 0-1000 ppm in the presence of interfering gases such as water, lubricant and petrol vapours. This quantitative enose is a new type of Freon detection system, composed of an array of four sensors. The artificial neural network (ANN) and fuzzy logic type of ANN (FNN), in combination with the relative error concept in analytical chemistry, are integrated for both quantification and discrimination. The predicted results are satisfied with a pass rate of > 80% within the permitted relative errors. The results show that the Freon enose developed in this study is reliable for both the qualitative and quantitative determination of Freon gas and exhibits the merits of high sensitivity, anti-interference and accuracy.

Determination of thiols in urinary sample by capillary-column liquid chromatography with amperometric detection at a carbon electrode.

The fabrication and application of an end-column amperometric detection (AD) system with a carbon electrode for capillary-column liquid chromatography (CLC) were described. This new amperometric detector showed good sensitivity and stability in detecting the thiocompounds and other analytes with CLC. In order to obtain the better separation and detection performance for analytes, several operational parameters had been investigated: the working potentials, pH and flow rate. Under the optimum conditions, the method could effectively separate and determine cysteine (Cys), glutathione (GSH), dopamine (DA) and 6-thiopurine (6-TP). Good repeatability for retention time was obtained with a relative standard deviation (R.S.D.) value of 0.5%. The linear range covered over three orders of magnitude and the limits of detection were 8 fmol for cysteine, 20 fmol for glutathione, 8 fmol for dopamine and 20 fmol for 6-thiopurine. This method was successfully applied in determination of urinary sample with characteristics of simplicity, high sensitivity and good repeatability.