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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.
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.
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.
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
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-
lines, and discuss their relations with the electron temperature and density.
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
. 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.
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.
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.
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.
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
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
Single-walled carbon nanotube (SWNT) and conductive polymer composite were studied as a potential electrode candidate for plastic electronic devices such as organic light-emitting diodes (OLEDs) and solar cells. A novel conductive polymer, poly(2,7–9,9(di(oxy-2,5,8-trioxadecane))fluorene) (PFO), was synthesized and characterized as a surfactant to disperse SWNTs in solutions. The ethylene oxide (EO) side chain of rigid PFO backbone acts as a template to wrap around SWNTs in solution. Up to 0.02% (by weight) of SWNTs are stabilized and well separated in the solution phase. The carbon nanotube can be dispersed in solutions for over 4 mo. Transmission electron microscopy (TEM) images of solvent cast film suggest highly uniformed SWNT distribution incorporated in the conductive polymer matrix. Transmittance characterization shows the film is as transparent as indium tin oxide conducting glass. Conductivity measurement shows SWNTs can effectively inject charges into the PFO polymer matrix at low voltage. The current versus voltage profile of the SWNT/PFO composite film (2% SWNT in PFO by weight) shows that the majority current conducting is carried by SWNTs.
Routine early integration of palliative care with advanced cancer management is not yet a part of standard practice in many countries, including mainland China. Whether patients in China suffering from advanced cancer are referred to palliative care services in a timely manner remains unclear. We sought to investigate the timing of palliative care referral of Chinese cancer patients at our center and its predictors.
Retrospective medical data including demographic characteristics and referral information were collected for analysis. A total of 759 patients referred to our palliative care unit (PCU) from January of 2007 to December of 2013 were included in the final analysis.
The mean age of the 759 patients included in the study was 62.89 years (range 61.95–63.82). Some 369 patients (48.6%) were male and 559 (73.6%) Shanghainese (indigenous). Lung cancer (17.9%) was the most common diagnosis. The time interval since enrollment into the PCU until a patient's death (length of stay, LOS) was calculated. A longer LOS indicated earlier referral to inpatient PC services. The median LOS was 21 days (CI95% = 19.79–22.21). Multivariate analysis showed that whether or not the patient was indigenous (p = 0.002) and younger than 65 (p = 0.031) were independent factors for a longer LOS. Such other characteristics as gender and primary cancer type bore no relationship to LOS.
Significance of results:
Our findings demonstrate that Chinese cancer patients are referred relatively late in the course of their disease to inpatient palliative care services. To overcome the barriers to early integration of palliative care into a patient's treatment plan, accurate information about palliative care must be provided to both oncologists and patients via comprehensive and systematic educational programs.
Plant-insect interactions are vital for structuring terrestrial ecosystems. It is still unclear how climate change in geological time might have shaped plant-insect interactions leading to modern ecosystems. We investigated the effect of Quaternary climate change on plant-insect interactions by observing insect herbivory on leaves of an evergreen sclerophyllous oak lineage (Quercus section Heterobalanus, HET) from a late Pliocene flora and eight living forests in southwestern China. Among the modern HET populations investigated, the damage diversity tends to be higher in warmer and wetter climates. Even though the climate of the fossil flora was warmer and wetter than modern sample sites, the damage diversity is lower in the fossil flora than in modern HET populations. Eleven out of 18 damage types in modern HET populations are observed in the fossil flora. All damage types in the fossil flora, except for one distinctive gall type, are found in modern HET populations. These results indicate that Quaternary climate change did not cause extensive extinction of insect herbivores in HET forests. The accumulation of a more diverse herbivore fauna over time supports the view of plant species as evolutionary “islands” for colonization and turnover of insect species.
III-V on Si multijunction solar cells represent an alternative to traditional compound III-V multijunction cells as a promising way to achieve high efficiencies. A theoretical study on the energy yield of GaAs/Si tandem solar cells is performed to assess the performance potential and sensitivity to spectral variations. Recorded time-dependent spectral irradiance data in two locations (Singapore and Denver) were used. We found that a 4-terminal contact scheme with thick top cell confers distinctive advantages over a 2-terminal scheme, giving a yield potential 21% higher than the 2-terminal scheme in Singapore and 17% higher in Denver. The theoretical energy yield benefit of a 4-terminal device emphasizes the need for further technology development in this design space.
Climate change during the Quaternary played an important role in the distribution of extant plants. Herein, cone scales of Cedrus (Pinaceae) were uncovered from the Upper Pliocene Sanying Formation, Longmen Village, Yongping County of Yunnan Province in southwestern China. Detailed comparisons show that these fossils all belong to the genus Cedrus (Pinaceae), and a new species is proposed, Cedrus angusta sp. nov. This find expands the known distribution of Cedrus during the Late Pliocene to Yunnan, where the genus no longer exists in natural forests. Based on the analysis of reconstructed Neogene climate data, we suggest that the intensification of the East Asian winter monsoon during the Quaternary may have dramatically increased seasonality and given rise to a much drier winter in Yunnan. Combined with information on Cedrus fossil records and its seed physiology, we conclude that the intensification of a drier climate after the Late Pliocene may have prevented the survival of Cedrus seedlings, leading to the eventual disappearance of Cedrus in western Yunnan. This study indicates that the topography in southwestern China acted as a vital refuge for many plants during the Quaternary, but that other species gradually disappeared due to the intensification of the monsoonal climate.
A study about the achievement of dichromatic white light-emitting diodes (LEDs) was performed. A series of dual wavelength LEDs with different last quantum-well (LQW) structure were fabricated. The bottom seven blue light QWs (close to n-GaN layer) of the four samples were the same. The LQW of sample A was 3 nm, and that of sample B, C and D were 6 nm, a special high In content ultra-thin layer was inserted in the middle of the LQW of sample C and on top of that of sample D. XRD results showed In concentration fluctuation and good interface quality of the four samples. PL measurements showed dual wavelength emitting, the blue light peak position of the four samples were almost the same, sample A with a narrower LQW showed an emission wavelength much shorter than that of sample B, C, D. EL measurement was done at an injection current of 100 mA. Sample A only showed LQW emission due to holes distribution. Because of wider LQW, the emission wavelength of sample B, C and D was longer and peak intensity was weaker. Sample D with insert layer on top of LQW showed strongest yellow light emission with a blue peak. As the injection current increased, sample A showed highest output light power due to narrower LQW. Of the other three samples with wider LQW, sample D showed highest output power. Effective yellow light emission has always been an obstacle to the achievement of dichromatic white LED. Sample D with insert layer close to p-GaN can confine the hole distribution more effectively hence the recombination of holes and electrons was enhanced, the yellow light emission was improved and dichromatic white LED was achieved.