The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as “miRNA sponge”. Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out. The overlapped predicted miRNAs as downstream targets of circRNAs and upstream regulators of mRNAs were verified by qRT-PCR and final circRNA-miRNA-mRNA network was constructed. Gene Ontology (GO) and KEGG pathway analysis were further applied to enrich the huge mRNA microarray data. To sum up, there were 69 up and 63 down regulated circRNAs as well as 2760 up and 2465 down regulated mRNAs in NASH group, comparing with control group. Randomly selected 13 of 14 mRNAs and 2 of 8 circRNAs were successfully verified by qRT-PCR. Through predicted overlapped miRNA verification, four circRNA-miRNA-mRNA pathways were constructed, including circRNA_002581-miR-122-Slc1a5, circRNA_002581- miR-122-Plp2, circRNA_002581-miR-122-Cpeb1 and circRNA_007585-miR-326- UCP2. GO and KEGG pathway analysis also enriched specific mRNAs. Therefore, circRNA profile may serve as candidate for NASH diagnosis and circRNA-miRNA -mRNA pathway may provide novel mechanism for NASH.
Structural materials with excellent mechanical properties are vitally important for architectural application. However, the traditional structural materials with complex manufacturing processes cannot effectively regulate heat flow, causing a large impact on global energy consumption. Here, we processed a high-performance and inexpensive cooling structural material by bottom-up assembling delignified biomass cellulose fiber and inorganic microspheres into a 3D network bulk followed by a hot-pressing process; we constructed a cooling lignocellulosic bulk that exhibits strong mechanical strength more than eight times that of the pure wood fiber bulk and greater specific strength than the majority of structural materials. The cellulose acts as a photonic solar reflector and thermal emitter, enabling a material that can accomplish 24-h continuous cooling with an average dT of 6 and 8 °C during day and night, respectively. Combined with excellent fire-retardant and outdoor antibacterial performance, it will pave the way for the design of high-performance cooling structural materials.
BackgroundThe coexistence of HBV infection and nonalcoholic fatty liver disease (NAFLD) becomes characteristic of liver disease in China, with unknown bilateral influence. We aimed to investigate the effect of hepatic steatosis, a common hepatocyte change in NAFLD, on antiviral therapy in patients with chronic hepatitis B (CHB).Methods and FindingsWe carried out a prospective nested case control study in CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric and clinical data at baseline, 24wk, 48wk and 96wk. Univariate analysis and multivariate logistic regression were applied to find out independent factors of hepatic steatosis and Entecavir treatment failure. The rates of HBV-DNA clearance, HBeAg seroconversion and ALT normalization were compared between CHB patients with and without steatosis by post hoc analysis. A total of 267 Chinese patients with CHB entered final analysis, with overall percentages of hepatic steatosis and HBeAg positive as 30.5% and 62.4%. Multivariate analysis showed waist circumference, serum TG and uric acid levels were independent factors of hepatic steatosis. The response rates to Entecavir were 54.9%, 63.8%, 74.2% at 24wk, 48wk and 96wk. Hepatic steatosis was revealed as an independent factor of Entecavir treatment failure by multivariate logistic regression at 24wk, 48wk and 96wk. In CHB patients with hepatic steatosis, HBV-DNA clearance and HBeAg seroconversion were both lower throughout the follow-up, but only the former reached statistical significance. Besides, ALT normalization was also significantly lower at 24wk and 48wk.ConclusionHepatic steatosis is significantly associated with Entecavir treatment failure and metabolic factors are independent factors of hepatic steatosis in CHB patients, which called for a specified antiviral strategy in CHB patients with NAFLD.
BackgroundNon-alcoholic steatohepatitis (NASH) is a condition that occurs during the progression of non-alcoholic fatty liver disease. Effective therapy for NASH is still lacking. In this study, we investigated the effects of Ursodeoxycholic acid (UDCA) in the treatment of NASH.MethodsWestern and Chinese databases were searched by independent investigators using appropriate MESH headings to identify randomized, controlled Western and Chinese clinical trials, published between January 1990 and October 2012, testing the effects of UDCA in patients with NASH. Patient characteristics and trial endpoints were analyzed, with quality assessment according to widely acknowledged criteria. P < 0.05 was defined as statistically significant in all trials.ResultsTwelve qualified randomized clinical trials, including six from China and involving 1160 subjects, were selected. Seven of these trials assessed the effects of UDCA Monotherapy, with the other five testing combinations of UDCA with vitamin E, polyene phosphatidylcholine, silymarin, glycyrrhizin and tiopronin. The duration of therapy ranged from 3 to 24 months, with two studies using high doses of UDCA (23–35 mg/kg/d). The average quality point was 2.69, and was significantly lower in articles from China than in those from Western countries (2.2 ± 0.4 vs. 3.8 ± 1.1, respectively, p < 0.05). UDCA Monotherapy significantly improved liver function in five studies and improved steatosis and fibrosis in two studies. All five studies assessing UDCA combination therapy showed significant improvements liver function, while two studies also improved steatosis and inflammation. One study of high-dose UDCA showed significant improvements in ALT, γGT and liver fibrosis, whereas the other study showed no significant change in ALT and liver pathology.ConclusionsUDCA therapy is effective in NASH, especially when combined with other drugs. However, the low quality of these studies and the heterogeneity of their results precluded further meta-analysis. Additional carefully designed clinical trials are needed, especially in China.
Natural lignocellulose has been a significant renewable raw material attributable to its high specific mechanical performance, compared to the benefits of traditional reinforcing fibers. However, the unsatisfactory mechanical performance of lignocellulose-based materials has limited applications in many advanced engineering domains. Herein, we demonstrate that layered bulk delignified nanolignocellulose/brushite composites with a multifold increase in strength and toughness. Our procedure contains the partially removable lignin and hemicellulose from the nanolignocellulose and the precipitating process of brushite on the nanolignocellulose surface via the mechanochemical process and flow-directed assembly followed by hot-pressing, resulting in the complete toppling of cell walls and the densification of the nanolignocellulose/brushite composites with highly ordered layered structures. This composite exhibits an ultrastrong specific strength 1.8−4.4 times higher than that of modified lignocellulose-based materials, which surpasses that of most natural structural materials and some metals and alloys, opening a path for production of ultrastrong lignocellulose-based load-bearing materials in practical applications by various farming and forestry surplus operations.
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