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Objective. The aims of this study were to investigate the impact of TAK-242 on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signal transduction pathway in rats with hepatic fibrosis (HF) using the liver gut axis and to investigate the molecular mechanism of its intervention on HF. Methods. SPF grade SD male rats were randomly allocated to the control, model, and TAK-242 groups. For 8 weeks, the model and TAK-242 groups received 3 mL·kg-1 (the initial dose 5 mL·kg-1) intraperitoneal injections of 40% CCL4 olive oil solution. TAK-242 (5 mg·kg-1) was administered once a day for 5 days after modeling. The pathological alterations of liver and small intestine tissues in each group were observed using H&E and Masson staining. ELISA was used to measure serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), total bilirubin (TBIL), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RT-qPCR was utilized to identify the mRNA expression level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB in rat liver and small intestine tissues. The protein level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB protein in rat liver and small intestine tissues was determined utilizing Western blot and IHC. Results. TAK-242 significantly reduced AST, ALT, TBIL, and DBIL expression in HF rats' serum (P < 0.01) and alleviated liver tissue injury. Hematoxylin-eosin (H&E) and Masson staining revealed inflammatory cell infiltration and fibrous proliferation in the liver and small intestine tissue in the model group and partial cell swelling in the TAK-242 group, which indicated a considerable improvement compared to the model group. RT-qPCR, Western blot, and IHC data indicated that TAK-242 reduced the IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB expression in the liver and small intestine tissues of HF rats. Conclusion. TAK-242 might downregulate the TLR4/MyD88/NF-κB signal pathway through the liver-gut axis, suppress the inflammatory response, and eventually alleviate HF in rats. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease characterized by a disorder of the dopaminergic system in the midbrain, causing classical PD motor symptoms. The therapeutic effect of cannabidiol (CBD) on PD has been a research frontier in recent years. However, the pathogenesis of PD and the therapeutic mechanism of cannabinoid remain unclear. To further study the causes of PD and the effect of CBD on PD, we exposed the PD transgenic mouse model to CBD and then estimated the motorial and postural coordination through a modified swim test. Afterwards, the mechanism was investigated via the histopathology of substantia nigra and the gut-brain metabolic analysis in the approach of UHPLC-TOF-MS. The results showed that CBD significantly improved motor deficits of PD model and protected the substantia nigra area. The metabolic function of fatty acid biosynthesis, arginine biosynthesis/metabolism, butanoate (ketone body) metabolism, β-alanine metabolism, and pantothenate/CoA biosynthesis was highlighted in the pathological and therapeutic process along the gut-brain axis. In conclusion, CBD could attenuate PD via the neuroprotective effect on the midbrain. The attenuation of the central nervous system in turn improved motor performance of PD, which might be partially induced by the metabolic interaction between the gut-brain. In view of gut-brain metabolomics, the mechanism of PD pathogenesis and the effect of CBD on PD are highly related to the biosynthesis and metabolism of energy and essential substance. [ABSTRACT FROM AUTHOR]

Toxic biogenic amines (BAs), especially histamine, in food is a major safety issue. Two autochthonous Lactobacillus plantarum strains were inoculated as starters to reduce BAs in Yucha, a kind of spontaneously fermented fish in China. Taxonomic analysis demonstrated the proportion of Lactobacillus genus in inoculated Yucha was higher than that in the spontaneously fermented Yucha, suggesting the effective colonization abilities of the starters. Higher abundance of Lactobacillus genus resulted in less BAs contents in the inoculated Yucha as compared to that in the spontaneously ones throughout the fermentation stage. At the end of fermentation, L. plantarum strains reduced total content of the six BAs by 67.5%–97.3%; specifically, they reduced the concentration of histamine by 85.4%–96.4%. The BAs‐degradation ability in the model systems indicated that the two L. plantarum strains could not degrade BAs directly. Instead, starters reduced BAs accumulation by inhibition of the growth or biological activities of BAs‐producing bacterial genera. Practical applications: The presence of biogenic amines (BAs) in fish products poses a health risk for consumers. This work provided two promising starters to reduce BAs accumulation in Yucha and a foundation for better understanding the BAs metabolic features. These findings could contribute to the safe production of Yucha and other similar fermented fish products. [ABSTRACT FROM AUTHOR]

Background. Sleep duration is associated with type 2 diabetes (T2D). However, few T2D risk scores include sleep duration. We aimed to develop T2D scores containing sleep duration and to estimate the additive value of sleep duration. Methods. We used data from 43,404 adults without T2D in the Beijing Health Management Cohort study. The participants were surveyed approximately every 2 years from 2007/2008 to 2014/2015. Sleep duration was calculated from the self-reported usual time of going to bed and waking up at baseline. Logistic regression was employed to construct the risk scores. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to estimate the additional value of sleep duration. Results. After a median follow-up of 6.8 years, we recorded 2623 (6.04%) new cases of T2D. Shorter (both 6-8 h/night and <6 h/night) sleep durations were associated with an increased risk of T2D (odds ratio OR = 1.43 , 95% confidence interval CI = 1.30 -1.59; OR = 1.98 , 95 % CI = 1.63 -2.41, respectively) compared with a sleep duration of >8 h/night in the adjusted model. Seven variables, including age, education, waist-hip ratio, body mass index, parental history of diabetes, fasting plasma glucose, and sleep duration, were selected to form the comprehensive score; the C -index was 0.74 (95% CI: 0.71-0.76) for the test set. The IDI and NRI values for sleep duration were 0.017 (95% CI: 0.012-0.022) and 0.619 (95% CI: 0.518-0.695), respectively, suggesting good improvement in the predictive ability of the comprehensive nomogram. The decision curves showed that women and individuals older than 50 had more net benefit. Conclusions. The performance of T2D risk scores developed in the study could be improved by containing the shorter estimated sleep duration, particularly in women and individuals older than 50. [ABSTRACT FROM AUTHOR]

Liver regeneration is a tissue growth process after loss or injury of liver tissue, which is a compensatory hyperplasia rather than true regeneration, mainly depending on hepatocyte proliferation. Currently, a large number of studies on hepatocyte proliferation have been conducted. However, studies on the regulation of long noncoding RNA (lncRNA) on hepatocyte proliferation are still limited. To identify specially expressed lncRNA during rat liver regeneration, high-throughput sequencing technology was performed, and a total of 2446 lncRNAs and 4091 mRNAs were identified as significantly differentially expressed. Gene ontology (GO) enrichment analysis was performed to analyze the role of differentially expressed mRNAs, and 695 mRNAs were identified to be related to cell proliferation. Then, an lncRNA-mRNA coexpression network based on the differentially expressed lncRNAs and proliferation-related genes was constructed to analyze the potential function of lncRNAs on hepatocyte proliferation, and ten lncRNAs, NONRATT003557.2, NONRATT005357.2, NONRATT003292.2, NONRATT001466.2, NONRATT003289.2, NONRATT001047.2, NONRATT005180.2, NONRATT004419.2, NONRATT005336.2, and NONRATT005335.2, were selected as key regulatory factors, which may play crucial roles in hepatocyte proliferation during rat liver regeneration. Finally, a protein-protein interaction (PPI) network was established to illuminate the interaction between proliferation-related genes, and ten hub genes (Aurkb, Cdk1, Cdc20, Bub1b, Mad2l1, Kif11, Prc1, Ccna2, Top2a, and Ccnb1) were screened with the MCC method in the PPI network, which may be important biomarkers involved in the hepatocyte proliferation during rat liver regeneration. These results may provide clues for a more comprehensive understanding of the molecular mechanism of hepatocyte proliferation during rat liver regeneration. [ABSTRACT FROM AUTHOR]

Global positioning system (GPS) and inertial navigation system (INS) are commonly combined to overcome disadvantages of each and constitute an integrated system that realizes long-term precision. However, the performance of the integrated system deteriorates on which GPS is unavailable. Especially when low-cost inertial sensors based on the microelectromechanical system (MEMS) are used, performance of the integrated system degrades severely over time. In this study, in order to minimize the adverse impact of high-level stochastic noise from low-cost MEMS sensors, denoising technology based on empirical mode decomposition (EMD) is employed to improve signal quality before navigation solution by which significant improvement of removing noise is achieved. Moreover, a random vector functional link (RVFL) network-based fusion algorithm is presented to estimate and compensate position error during GPS outage such that error accumulation is suppressed quickly when INS is working standalone. Performance of the proposed approach is evaluated by experimental results. It is indicated from comparison that the proposed algorithm takes advantages such as better accuracy and lower complexity and is more robust than the commonly reported methods and is more appropriate for real-time and low-cost application. [ABSTRACT FROM AUTHOR]

Background. Hyperuricemia is known to be a risk factor for diabetes. However, information is limited regarding the association between changes in hyperuricemia and the risk of diabetes. Methods. A total of 15,403 participants who were free of diabetes at the time of 2009 and 2011 surveys in the Beijing Health Management Cohort (BHMC) study were recruited and followed up until 2016. Participants were classified into four groups according to 2-year changes in hyperuricemia: no hyperuricemia, remittent hyperuricemia, incident hyperuricemia, and persistent hyperuricemia. Modified Poisson regression models were used to evaluate the effect of 2-year changes in hyperuricemia on the risk of diabetes. Results. During the 5-year follow-up, we identified 841 new cases of diabetes (216 women). Remittent hyperuricemia and incident hyperuricemia had a 35% and 48% higher risk for developing diabetes compared with no hyperuricemia. Especially, persistent hyperuricemia was associated with a 75% higher risk of diabetes (RR = 1.75, 95% CI = 1.47-2.08). Compared with minor serum uric acid (SUA) change, over 10% decline and over 30% increase in SUA levels were subsequently associated with lower (RR = 0.84, 95% CI = 0.72-0.99) and higher (RR = 1.71, 95% CI = 1.27-2.30) diabetes risk, respectively. Conclusions. Changes in hyperuricemia, especially persistent hyperuricemia, are more appropriate to reflect the risk of diabetes than a single measurement of hyperuricemia at baseline. Strategies aiming at preventing hyperuricemia are urgently needed to reduce the increasing burden of diabetes. [ABSTRACT FROM AUTHOR]

In order to provide resilient position, navigation, and time (PNT) information for E-Navigation, the ranging-mode (R-Mode) positioning using automatic identification system (AIS) signals is encouraged. As the accuracy is the key for the positioning system, this paper investigates the position error of the R-Mode positioning based on AIS shore-based station in China. The measurement errors of Gaussian filtered minimum shift keying (GMSK) demodulation based on carrier phase locking loop are investigated in theory. The dilution of precision (DOP) for time of arrival (TOA) and time difference of arrival (TDOA) used in R-Mode positioning of AIS is discussed in two measurement mechanisms. The positioning error distributions in the North, East, and South Sea regions of China based on the existing AIS shore-based stations are evaluated. The positioning accuracy is at the meter level in the most traffic dense areas to meet the requirements for vessel navigation. [ABSTRACT FROM AUTHOR]