Xylooligosaccharides ameliorate insulin resistance by increasing Akkermansia muciniphila and improving intestinal barrier dysfunction in gestational diabetes mellitus mice.

Little is known regarding the effects of xylooligosaccharides (XOS) on insulin resistance (IR) in gestational diabetes mellitus (GDM). We aimed to investigate this issue and its mechanism. Sixty female mice were randomly allotted to 4 groups (n = 15): control, high fat diet (HFD), GDM, and GDM + XOS. The control mice were fed an AIN-93 diet, while the mice in the other groups were fed 45% HFD. After pregnancy, mice in GDM and GDM + XOS groups were intraperitoneally injected with 30 mg kg-1 streptozocin for 3 days from the first day of pregnancy. Mice in the GDM + XOS group were then fed an HFD containing 2% XOS. Fasting glucose and insulin levels were monitored. The fecal Akkermansia muciniphila (Akk. muciniphila) and Bifidobacterium were measured by qPCR. The Chiu scores were calculated from hematoxylin-eosin (HE)-stained ileal tissues. Phosphorylated Akt in the liver and occludin and ZO-1 in the intestinal tissues were determined by western blotting. XOS reduced (p < 0.05) fasting blood glucose and insulin and HOMA-IR, and increased (p < 0.05) Akt phosphorylation in the livers of GDM mice. Moreover, XOS decreased (p < 0.05) TNFα, IL-1ß, IL-15 and LPS in the serum, increased (p < 0.05) fecal Akk. muciniphila abundance, lowered (p < 0.05) Chiu's scores, and enhanced (p < 0.05) occludin and ZO-1 expression. XOS ameliorate IR by increasing Akk. muciniphila and improving intestinal barrier dysfunction in GDM mice.

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet-Induced Non-Alcoholic Steatohepatitis (NASH) Mice.

SCOPE: Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A1 and SS-Bb) against NASH and explores the mechanisms by targeting GM. METHODS AND RESULTS: Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A1 , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A1 , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A1 and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A1 and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A1 and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A1 and SS-Bb against NASH. CONCLUSION: GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice.

Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation.

SCOPE: Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity. METHODS AND RESULTS: This study extracted HM exosomes from GDM (GDM-EXO) and healthy (NOR-EXO) parturient by ultracentrifugation, high-throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR-EXO, GDM-EXO has similar morphology, size, concentration, and exosome-specific markers (CD9 and TSG101) expression. GDM-EXO and NOR-EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM-EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR-EXO. Both GDM-EXO and NOR-EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM-EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR-101-3p delivery. CONCLUSION: HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation.

Single-Frequency Precise Point Positioning Using Regional Dual-Frequency Observations.

High-precision and low-cost single-frequency precise point positioning (SF-PPP) has been attracting more and more attention in numerous global navigation satellite system (GNSS) applications. To provide the precise ionosphere delay and improve the positioning accuracy of the SF-PPP, the dual-frequency receiver, which receives dual-frequency observations, is used. Based on the serviced precise ionosphere delay, which is generated from the dual-frequency observations, the high-precision SF-PPP is realized. To further improve the accuracy of the SF-PPP and shorten its convergence time, the double-differenced (DD) ambiguity resolutions, which are generated from the DD algorithm, are introduced. This method avoids the estimation of fractional cycle bias (FCB) for the SF-PPP ambiguity. Here, we collected data from six stations of Shanghai China which was processed, and the corresponding results were analyzed. The results of the dual-frequency observations enhanced SF-PPP realize centimeter-level positioning. The difference between the results of two stations estimated with dual-frequency observations enhanced SF-PPP were compared with the relative positioning results computed with the DD algorithm. Experimental results showed that the relative positioning accuracy of the DD algorithm is slightly better than that of the dual-frequency observations enhanced SF-PPP. This could be explained by the effect of the float ambiguity resolutions on the positioning accuracy. The data was processed with the proposed method for the introduction of the DD ambiguity into SF-PPP and the results indicated that this method could improve the positioning accuracy and shorten the convergence time of the SF-PPP. The results could further improve the deformation monitoring ability of SF-PPP.

Experimental study on the precise orbit determination of the BeiDou navigation satellite system.

The regional service of the Chinese BeiDou satellite navigation system is now in operation with a constellation including five Geostationary Earth Orbit satellites (GEO), five Inclined Geosynchronous Orbit (IGSO) satellites and four Medium Earth Orbit (MEO) satellites. Besides the standard positioning service with positioning accuracy of about 10 m, both precise relative positioning and precise point positioning are already demonstrated. As is well known, precise orbit and clock determination is essential in enhancing precise positioning services. To improve the satellite orbits of the BeiDou regional system, we concentrate on the impact of the tracking geometry and the involvement of MEOs, and on the effect of integer ambiguity resolution as well. About seven weeks of data collected at the BeiDou Experimental Test Service (BETS) network is employed in this experimental study. Several tracking scenarios are defined, various processing schemata are designed and carried out; and then, the estimates are compared and analyzed in detail. The results show that GEO orbits, especially the along-track component, can be significantly improved by extending the tracking network in China along longitude direction, whereas IGSOs gain more improvement if the tracking network extends in latitude. The involvement of MEOs and ambiguity-fixing also make the orbits better.

Satellite- and epoch differenced precise point positioning based on a regional augmentation network.

Precise Point Positioning (PPP) has been demonstrated as a simple and effective approach for user positioning. The key issue in PPP is how to shorten convergence time and improve positioning efficiency. Recent researches mainly focus on the ambiguity resolution by correcting residual phase errors at a single station. The success of this approach (referred to hereafter as NORM-PPP) is subject to how rapidly one can fix wide-lane and narrow-lane ambiguities to achieve the first ambiguity-fixed solution. The convergence time of NORM-PPP is receiver type dependent, and normally takes 15-20 min. Different from the general algorithm and theory by which the float ambiguities are estimated and the integer ambiguities are fixed, we concentrate on a differential PPP approach: the satellite- and epoch differenced (SDED) approach. In general, the SDED approach eliminates receiver clocks and ambiguity parameters and thus avoids the complicated residual phase modeling procedure. As a further development of the SDED approach, we use a regional augmentation network to derive tropospheric delay and remaining un-modeled errors at user sites. By adding these corrections and applying the Robust estimation, the weak mathematic properties due to the ED operation is much improved. Implementing this new approach, we need only two epochs of data to achieve PPP positioning converging to centimeter-positioning accuracy. Using seven days of GPS data at six CORS stations in Shanghai, we demonstrate the success rate, defined as the case when three directions converging to desired positioning accuracy of 10 cm, reaches 100% when the interval between the two epochs is longer than 15 min. Comparing the results of 15 min' interval to that of 10 min', it is observed that the position RMS improves from 2.47, 3.95, 5.78 cm to 2.21, 3.93, 4.90 cm in the North, East and Up directions, respectively. Combining the SDED coordinates at the starting point and the ED relative coordinates thereafter, we demonstrate the performance of RTK PPP with standard deviation of 0.80, 1.34, 0.97 cm in the North, East and Up directions.