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Non-alcoholic fatty liver disease (NAFLD) has become the main cause of end-stage liver disease. Probiotics have the potential effect of alleviating NAFLD. The aim of this study was to explore functional probiotics and their underlying mechanisms. The bile salt hydrolase (BSH) activity in thirty-four strains was determined in vitro. Then, C57BL/6 mice were used to explore the effects of probiotics on NAFLD. Body weight and food intake were measured, and serum lipid concentrations, oxidative stress and proinflammatory cytokines levels were determined using commercial kits. The expressions of intestinal bile acid pathway genes were evaluated via real-time PCR. The results showed that Lactobacillus casei YRL577 and L. paracasei X11 had higher BSH activity. L. casei YRL577 significantly reduced liver weight and liver index and could regulate the levels of lipid metabolism, oxidative stress and proinflammatory cytokines as compared with L. paracasei X11. Furthermore, the results indicated that L. casei YRL577 up-regulated the mRNA levels of farnesoid X receptor and fibroblast growth factor 15, whereas down-regulated the mRNA level of apical Na-dependent bile acid transporter. These findings suggested that L. casei YRL577 modified genes in the intestinal bile acid pathway which might contribute to the alleviation of NAFLD.
Probiotics and plant extracts are considered to prevent the development of non-alcoholic fatty liver disease (NAFLD). This study explores the effects of using both probiotics and plant extracts on NAFLD. This study evaluated the effects of plant extracts on lipid droplet accumulation and the growth of probiotics in vitro. A C57BL/6 mouse model was used to examine the effects of probiotics and plant extracts on NAFLD. The body weight and food intake were measured. The levels of serum lipids, oxidative stress, and the liver injury index were determined using commercial kits. HE staining, gas chromatography and Real-Time PCR were also used for analysis. The results revealed that administration of Lactobacillus casei YRL577 and Lactobacilli paracasei X11 with resveratrol (RES) or tea polyphenols (TP) significantly reduced the levels of total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C) and increased the level of the high-density lipoprotein cholesterol (HDL-C). The groups of L. casei YRL577 with RES and TP also regulated the liver structure, oxidative stress, and injury. Furthermore, L. casei YRL577 with TP exhibited a more positive effect toward improving the NAFLD and increased the concentrations of the butyric acid than other three combined groups. L. casei YRL577 with TP up-regulated the mRNA levels of the farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) and decreased the mRNA levels of the apical sodium-dependent bile acid transporter (ASBT). These findings showed that L. casei YRL577 + TP modified genes in the intestinal bile acid pathway improved markers of NAFLD.
Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize–soyabean meal, and the negative control (NC) diet was based on maize–non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.
In this paper, CNTs reinforced foam aluminum matrix composites with small pore diameter were prepared by powder metallurgy method. When the mass fraction of CNTs was 0.75%, the tensile strength, flexural strength and compressive yield strength of the materials were 3.4 times, 2.4 times and 2.4 times of pure foam aluminum, respectively, reaching the maximum value, which obviously improved the mechanical properties of aluminum foam. The tensile property model of foam aluminum matrix composites was built to predict the properties of the composites, and the effects of defects and reinforcement on the mechanical properties of the composites were compared. The results show that the tensile fitting is consistent with the measured results when the mass fraction of CNTs is less than 0.75%, but the weakening effect of defects on the strength of aluminum foam is much greater than the enhancement of CNTs. With the increase of CNTs mass fraction, the damping loss factor of foam aluminum composites increases, dislocation damping and grain boundary damping play a role in advance, and the damping peak moves to the low temperature region.
Fe–6.5 Si–0.05 B alloy was used in the study to investigate the texture evolution and magnetic property of the ferromagnetic crystal under an axial high magnetic field during bulk solidification. Optical microscopy (OM) and X-ray diffraction (XRD) were applied to analyze the microstructures and texture evolution of the alloy solidified under different magnetic field intensities. The result shows that with an increase in the magnetic field intensity from 0 to 2 T, the texture gradually changes from random orientation to {100} 〈120〉, eventually becoming a mixture of cube and Goss texture. The alloys treated at 1 and 2 T showed magnetic anisotropic behavior, while the alloy treated at 0 T showed magnetic isotropic behavior. The change in magnetic property comes from the evolution of α-Fe crystal orientation. Furthermore, a method for controlling the crystallization process and crystallographic orientation by adjusting the magnetic field intensity was proposed.
The uncertainty and information asymmetry that surround initial public offering firms (IPOs) often introduce difficulties for potential investors to discern organizational value, thereby leading to ‘underpricing’. Using the signaling theory, we investigate the role of organizational reputation in the underpricing of IPOs. We analyze 463 initial public offerings in China from the period of 2010 to 2016 and find that being known for quality and generalized favorability dimensions of reputation are negatively related with underpricing on the first day of trading. In addition, we find that the negative effects of organizational reputation on underpricing are mediated by investor attention.
Dairy cows with ketosis display severe oxidative stress as well as high blood concentrations of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). Cytochrome P4502E1 (CYP2E1) plays an important role in the induction of oxidative stress. The aim of this study was to investigate CYP2E1 expression and activity in the liver of clinically ketotic cows (in vivo) and the effects of NEFA and BHB on CYP2E1 expression and activity in hepatocytes (in vitro). Dairy cows with clinical ketosis exhibited a low blood concentration of glucose but high concentrations of NEFA and BHB. Hepatic mRNA, protein expression, and activity of CYP2E1 were significantly higher in cows with clinical ketosis than in control cows. In vitro, both NEFA and BHB treatment markedly up-regulated the mRNA and protein expressions as well as activity of CYP2E1 in cow hepatocytes. Taken together, these results indicate that high levels of NEFA and BHB significantly up-regulate the expression and activity of hepatic CYP2E1, and may be influential in the induction of oxidative stress in cows with clinical ketosis.
Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor and also a negative regulator of insulin signaling and peripheral insulin sensitivity. We investigated the hypothesis that PTEN may affect the insulin pathway-mediated hepatic glucose and lipid metabolism in dairy cows. Adenovirus vectors that over-express and silence PTEN were constructed, and then transfected into hepatocytes isolated from calves to investigate the effect of PTEN on PI3K/AKT signaling pathway. PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3β (GSK-3β) and expression of sterol regulatory element-binding protein-1c (SREBP-1c). Increased GSK-3β phosphorylation further up-regulated expression of the key enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase) involved in gluconeogenesis. Furthermore, the expression of SREBP-1c target gene fatty acid synthase (FAS) also increased significantly. We further showed that PTEN over-expression could reverse the above results. PTEN negatively regulates the enzymes involved in hepatic gluconeogenesis and lipid synthesis, which suggests that PTEN may be a therapeutic target for ketosis and fatty liver in dairy cows.
Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5′UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.
The object of this paper is to prove a version of the Beurling–Helson–Lowdenslager invariant subspace theorem for operators on certain Banach spaces of functions on a multiply connected domain in
$\mathbb{C}$
. The norms for these spaces are either the usual Lebesgue and Hardy space norms or certain continuous gauge norms. In the Hardy space case the expected corollaries include the characterization of the cyclic vectors as the outer functions in this context, a demonstration that the set of analytic multiplication operators is maximal abelian and reflexive, and a determination of the closed operators that commute with all analytic multiplication operators.
Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.
Neuroimaging studies have shown that major depressive disorder is associated with altered activity patterns of the default-mode network (DMN). In this study, we sought to investigate the topological organization of the DMN in patients with remitted geriatric depression (RGD) and whether RGD patients would be more likely to show disrupted topological configuration of the DMN during the resting-state.
Methods:
Thirty-three RGD patients and thirty-one healthy control participants underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans. The functional connectivity (FC) networks were constructed by thresholding Pearson correlation metrics of the DMN regions defined by group independent component analysis, and their topological properties (e.g. small-world and network efficiency) were analyzed using graph theory-based approaches.
Results:
Relative to the healthy controls, the RGD patients showed decreased FC in the posterior regions of the DMN (i.e. the posterior cingulate cortex/precuneus, angular gyrus, and middle temporal gyrus). Furthermore, the RGD patients showed abnormal global topology of the DMN (i.e. increased characteristic path length and reduced global efficiency) when compared with healthy controls. Importantly, significant correlations between these network measures and cognitive performance indicated their potential use as biomarkers of cognitive dysfunction in RGD.
Conclusions:
The present study indicated disrupted FC and topological organization of the DMN in the context of RGD, and further implied their contribution to cognitive deficits in RGD patients.
We present laboratory measurement and theoretical analysis of silicon K-shell lines in plasmas produced by Shenguang II laser facility, and discuss the application of line ratios to diagnose the electron density and temperature of laser plasmas. Two types of shots were carried out to interpret silicon plasma spectra under two conditions, and the spectra from 6.6 Å to 6.85 Å were measured. The radiative-collisional code based on the flexible atomic code (RCF) is used to identify the lines, and it also well simulates the experimental spectra. Satellite lines, which are populated by dielectron capture and large radiative decay rate, influence the spectrum profile significantly. Because of the blending of lines, the traditional
$G$
value and
$R$
value are not applicable in diagnosing electron temperature and density of plasma. We take the contribution of satellite lines into the calculation of line ratios of He-
$\unicode[STIX]{x1D6FC}$
lines, and discuss their relations with the electron temperature and density.
A non-precious metal catalytic system of Fe-doped Ta2O5 is developed by pulsed laser deposition toward efficient oxygen evolution reaction (OER). The optimal Fe concentration is determined to be 5 at.% for optimized OER activity via a series of electrochemical characterizations. The 5 at.% Fe-doped Ta2O5 nanolayer possesses a low onset overpotential of 0.22 V, an overpotential of 0.38 V at 10 mA/cm2 and a Tafel slope of 54 mV/dec. Comprehensive first-principles calculations attribute the enhanced OER activity to the substitutional FeTa dopants, which generate a new active OER site on surface and simultaneously accelerate electron transfer over oxygens.
In this work, temperature-dependent optical properties of a series of AlN thin films with different thickness are studied by spectroscopic ellipsometry (SE) ranging from 300 to 825K. The fitted refractive index at 300K is in good agreement with the reported by others, which confirms the high accuracy of the optical model used in this work. The degradation of the absorption properties and the decrease of the bandgap become more pronounced with temperature increases above 475K. A larger change of bandgap at elevated temperature is observed for the thinner AlN epi-layer (300nm) than the thicker ones (404nm). This can be attributed to the poor surface morphologies and crystal qualities in the thinner AlN epi-layer.
Dairy cows with fatty liver or ketosis exhibit hyperketonemia, oxidative stress, and a low rate of very low density lipoprotein (VLDL) assembly, and there may be a potential link among these characteristics. Therefore, the objective of this study was to determine the effect of acetoacetic acid (AcAc) on the assembly of VLDL in cow hepatocytes. Cultured cow hepatocytes were treated with different concentrations of AcAc with or without N-acetylcysteine (NAC, an antioxidant). AcAc treatment decreased the mRNA expression and activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and significantly increased malondialdehyde (MDA) content, indicative of oxidative stress. Furthermore, AcAc treatment significantly down-regulated the mRNA expression of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), and low density lipoprotein receptor (LDLR), which thus decreased VLDL assembly and increased triglyceride (TG) accumulation in these bovine hepatocytes. Importantly, NAC relieved AcAc-induced oxidative stress and increased VLDL assembly. In summary, these results suggest that AcAc-induced oxidative stress affects the assembly of VLDL, which increases TG accumulation in bovine hepatocytes.
Hot deformation and dynamic recrystallization (DRX) behavior of the Cu–Cr–Zr–Ag alloy were studied by hot compressive tests in the 650–950 °C temperature and 0.001–10 s−1 strain rate ranges using Gleeble-1500D thermomechanical simulator. The activation energy of deformation was determined as Q = 343.23 kJ/mol by the regression analysis. The critical conditions, including the critical strain and stress, for the occurrence of DRX were determined based on the alloy strain hardening rate. The critical strain related to the onset of DRX decreases with temperature. The ratios of the critical to peak stress and critical to peak strain were also identified as 0.91 and 0.49, respectively. The evolution of DRX microstructure strongly depends on the deformation conditions in terms of temperature and strain rate. Dislocation generation and multiplication are the main hot deformation mechanisms for the alloy. The addition of Ag can refine the grain and effectively improve the DRX of the Cu–Cr–Zr alloy. It can also inhibit the growth of the DRX grains at 950 °C deformation temperature, making the microstructure much more stable.
Elevated levels of blood interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor–α (TNF–α) increase insulin resistance and result in inflammation. It is not clear whether elevated blood level of acetoacetate (ACAC) and decreased blood level of glucose, which are the predominant characteristics of clinical biochemistry in ketotic dairy cows, increase proinflammatory cytokines and subsequent inflammation. The objective of this study was to test the hypothesis that ACAC and glucose activate the NF-κB signalling pathway to regulate cytokines expression in bovine hepatocytes. Bovine hepatocytes were cultured with ACAC (0–4·8 mm) and glucose (0–5·55 mm) with or without NF-κB inhibitor PDTC for 24 h. The secretion and mRNA levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The NF-κB signalling pathway activation was evaluated by western blotting. Results showed that the secretion and expression of IL-1β, IL-6 and TNF-α increased in an ACAC dose-dependent manner. Additionally, there was an increase in the secretion and mRNA expression of these three cytokines in glucose treatment group, which increased significantly when the glucose concentrations exceed 3·33 mm. Furthermore, both ACAC and glucose upregulated NF-κB p65 protein expression and IκBα phosphorylation levels. However, these effects were reduced by PDTC. These results demonstrate that elevated levels of ACAC and glucose increase the synthesis and expression of proinflammatory factors by activating NF-κB signalling pathway in hepatocytes, which may contribute to inflammation injury in ketotic dairy cows.
Li et al. [‘On finite self-complementary metacirculants’, J. Algebraic Combin.40 (2014), 1135–1144] proved that the automorphism group of a self-complementary metacirculant is either soluble or has
$\text{A}_{5}$
as the only insoluble composition factor, and gave a construction of such graphs with insoluble automorphism groups (which are the first examples of self-complementary graphs with this property). In this paper, we will prove that each simple group is a subgroup (so is a section) of the automorphism groups of infinitely many self-complementary vertex-transitive graphs. The proof involves a construction of such graphs. We will also determine all simple sections of the automorphism groups of self-complementary vertex-transitive graphs of
$4$
-power-free order.