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A three-dimensional gas–liquid two-phase transient numerical model for a twin-screw multiphase pump based on dynamic grid technology was established and validated with experiments. The pump's simulated pressure distributions, velocity fields, and pressure pulsations were analyzed to reveal the mechanisms of pressure transmission and pressure pulsation characteristics. The results indicated that the flow rate of the pump fluctuated twice due to the discharge of the male and female rotors in one cycle. As the inlet gas volume fractions increased, the flow rate decreased, but the pressure pulsations increased. At the engaging positions of the two rotor tips, a sudden pressure drop happened due to the combined effect of both tooth-tip and tooth-flank leakage. When the discharge port opened, the backflow happened; the flow rate and the pressure in the discharge chamber decreased, but the pressure in the working and suction chambers increased. When the suction port closed, a slight compression of the fluid in the low-pressure working chamber occurred, causing a pressure increase in the working chamber. The working chambers inhaled and discharged once in one cycle, so the first harmonic of pressure pulsations at the suction and discharge chamber was two times the running speed. The transient flow due to the simultaneous closing and opening of the suction and discharge ports at both sides of the male and female rotors generated a harmonic of four times the running speed. This study would help to improve the operational stability of twin-screw multiphase pumps. [ABSTRACT FROM AUTHOR]

Background & aimsThere is evidence from clinical studies that compromised intestinal epithelial permeability contributes to the development of nonalcoholic steatohepatitis (NASH), but the exact mechanisms are not clear. Mice with disruption of the gene (F11r) encoding junctional adhesion molecule A (JAM-A) have defects in intestinal epithelial permeability. We used these mice to study how disruption of the intestinal epithelial barrier contributes to NASH.MethodsMale C57BL/6 (control) or F11r(-/-) mice were fed a normal diet or a diet high in saturated fat, fructose, and cholesterol (HFCD) for 8 weeks. Liver and intestinal tissues were collected and analyzed by histology, quantitative reverse-transcription polymerase chain reaction, and flow cytometry. Intestinal epithelial permeability was assessed in mice by measuring permeability to fluorescently labeled dextran. The intestinal microbiota were analyzed using 16S ribosomal RNA sequencing. We also analyzed biopsy specimens from proximal colons of 30 patients with nonalcoholic fatty liver disease (NAFLD) and 19 subjects without NAFLD (controls) undergoing surveillance colonoscopy.ResultsF11r(-/-) mice fed a HFCD, but not a normal diet, developed histologic and pathologic features of severe NASH including steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis, whereas control mice fed a HFCD developed only modest steatosis. Interestingly, there were no differences in body weight, ratio of liver weight:body weight, or glucose homeostasis between control and F11r(-/-) mice fed a HFCD. In these mice, liver injury was associated with significant increases in mucosal inflammation, tight junction disruption, and intestinal epithelial permeability to bacterial endotoxins, compared with control mice or F11r(-/-) mice fed a normal diet. The HFCD led to a significant increase in inflammatory microbial taxa in F11r(-/-) mice, compared with control mice. Administration of oral antibiotics or sequestration of bacterial endotoxins with sevelamer hydrochloride reduced mucosal inflammation and restored normal liver histology in F11r(-/-) mice fed a HFCD. Protein and transcript levels of JAM-A were significantly lower in the intestinal mucosa of patients with NAFLD than without NAFLD; decreased expression of JAM-A correlated with increased mucosal inflammation.ConclusionsMice with defects in intestinal epithelial permeability develop more severe steatohepatitis after a HFCD than control mice, and colon tissues from patients with NAFLD have lower levels of JAM-A and higher levels of inflammation than subjects without NAFLD. These findings indicate that intestinal epithelial barrier function and microbial dysbiosis contribute to the development of NASH. Restoration of intestinal barrier integrity and manipulation of gut microbiota might be developed as therapeutic strategies for patients with NASH.

BACKGROUND: Autophagy, oxidative stress and inflammatory reactions play an important role in non-alcoholic fatty liver disease. Curcumin has biological activities such as regulating autophagy, oxidative stress and inflammatory reaction. OBJECTIVE: To explore the effect and underlying mechanism of curcumin on experimental non-alcoholic fatty liver disease rats. METHODS: Non-alcoholic fatty liver model was established in rats fed 8-week high-fat diets. Forty healthy SPF male Sprague-Dawley rats were randomly divided into control group, model group, curcumin treatment group, and curcumin and 3-methyladenine (3-MA, an autophagic flux blocker) treatment group. AI the end of 8 weeks of high-fat diet, control and model groups were given PBS intragaslrically, curcumin treatment group given curcumin 500 mg/kg per day intragastrically, and curcumin+3-MA given curcumin 500 mg/kg per day intragastrically and 3-MA 2 mg/kg per day intraperitoneally. The interventions in each group were given for 8 continuous weeks. The biochemical parameters including serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, total cholesterol, fasting blood glucose level were measured in rats. Oil red 0 staining was used to characterize the change of hepatic pathology. The ultrastructure of mitochondria was examined by transmission electron microscopy. The hepatic malondialdehyde level and superoxide dismutase activity were measured by thiobarbituric acid method and xanthine oxidase method, respectively. Western blot assay was performed to detect the expression level of autophagic molecular signals including P62, Beclin, LC3B and nuclear factor-κB. The experimental protocol was approved by the Animal Ethic Committee of Renmin Hospital of Wuhan University (approval No. 2018-541). RESULTS AND CONCLUSION: The serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and total cholesterol levels were significantly higher in the model group than the control group (P < 0.05). Compared with the model group, curcumin significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and total cholesterol (P < 0.05), but this effect was partly inhibited by 3-MA (P < 0.05). There was more cellular lipid deposition in the model group than the control group. Compared with the model group, curcumin significantly decreased cellular lipid deposition, but the decrease was partly inhibited by 3-MA. Compared with the control group, mitochondrial edema and cristae rupture (or even completely disappearing) were easily found in the model group. Curcumin significantly attenuated mitochondrial injury, which was partly inhibited by 3-MA. Hepatic superoxide dismutase activity in the model group was significantly lower than that in control group, and it significantly increased after curcumin treatment. The hepatic superoxide dismutase activity in the curcumin+3-MA group was higher than that in model group but lower than that in the curcumin group. Hepatic malondialdehyde level in the model group was higher than that in the control group, and it significantly decreased after curcumin treatment. Whereas the hepatic malondialdehydelevel in the curcumin+3-MA group was lower than that in model group but higher than that in the curcumin group. Compared with the control group, the model group showed significantly increased expressions of P62, nuclear factor-κB but decreased expressions of Beclin-1 and LC311/LC31 (all P < 0.05). Curcumin significantly decreased the expressions of P62 and nuclear factor-κB and increased the expressions of Beclin-1 and LC311/LC31; however, these changes were partly inhibited by 3-MA (all P < 0.05). Therefore, curcumin can effectively prevent hepatic steatosis in experimental non-alcoholic fatty liver disease rats by regulating inflammatory reaction and oxidative stress via activation of autophagy. [ABSTRACT FROM AUTHOR]

Objective: To study whether matrix metalloproteinases-9 (MMP) -1562C/T (rs3918242) and MMP-2-1306C/T (rs243865) were associated with the susceptibility on nonalcoholic fatty liver disease (NAFLD) and the interactions between the two factors and central obesity., Methods: Genotypes of 545 patients and 636 subjects with NAFLD under control were examined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Unconditional logistic regression (ULR) was performed to assess the NAFLD risk. The gene-environment interactions on the risk of NAFLD were explored by generalized multifactor dimensionality reduction (GMDR) and ULR methods., Results: Results from the case-control analysis indicated that there was an increased risk of developing NAFLD for MMP-9 rs3918242 (TT/CT) genotype carriers, when compared with the non-carriers (CC) , with OR=1.67, 95%CI: 1.32-2.12, P=0.001; Adjusted OR=1.65, 95% CI: 1.31-2.01 (P=0.008). However, risk reduction of NAFLD was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with the non-carriers (CC) , with OR=0.68, 95% CI: 0.53-0.86, P=0.001; with adjusted OR=0.66, 95% CI: 0.49-0.90 (P=0.007). Data from the GMDR showed that gene-environment interaction among rs3918242 and central obesity on the risk of NAFLD might be significant (P=0.001). By using the ULR method, subjects as central obesity-positive but with genotype CT/TT, appeared having 4.50 (95% CI: 2.78-7.17, P= 0.007) times risk of NAFLD, when compared to the central obesity-negative subjects with genotype CC after adjusting for the covariates., Conclusion: MMP-9 rs3918242, MMP-2 rs243865 were associated with risk of NAFLD while both rs3918242 and central obesity showing synergistic effects on the risk of the NAFLD.