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This research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA−), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.
OBJECTIVES/SPECIFIC AIMS: MicroRNAs (miRNA) affect transcription of a number of genes involved in the development and progression of diabetic nephropathy (DN), and have become attractive therapeutic targets and biomarkers. Elevated renal gluconeogenesis, fibrosis, and albuminuria are early markers of incipient DN. Recent studies report that renal miRNA-451 may protect against DN and reduce renal gluconeogenesis in rodent models. MiRNA-451 is thought to act by targeting select factors resulting from disrupted insulin and growth factor signaling and the mechanistic-target of rapamycin (mTOR) in early DN. This study aimed to elucidate the role of miRNA-451 in the development and progression of DN. METHODS/STUDY POPULATION: To further elucidate the role of miRNA-451 in DN, we placed male insulin-resistant, TALLYHO/Jng mice on a high-fat diet (60% kCal). The mice were divided into 2 treatment groups and received 8 consecutive weekly intraperitoneal injections of locked nucleic acid (LNA) miR-451-inhibitor or LNA-scrambled compound (2 mg/kg·bw; n=8/treatment). Mice were euthanized after 12 weeks (4 weeks sans injections) and kidneys, liver, pancreas and abdominal adipose tissue were harvested for analysis. RESULTS/ANTICIPATED RESULTS: Renal homogenate expression of miRNA-451 was drastically reduced in inhibitor-treated mice (~6-fold) in comparison with scramble-treated mice. Western blotting of cortex homogenates for indicators of fibrosis and targets of miRNA-451 revealed a significant reduction in collagen IV (marker of epithelial integrity) in inhibitor-treated mice. In addition, metalloproteinase type 9 (MMP9, a known type IV collagenase), YWHAZ (a scaffolding protein and known target of miR-451), mTOR, and fructose bisphosphatase (FBP1, a rate-limiting gene in gluconeogenesis) were significantly increased in this group in comparison to scramble-treated mice. However, no differences were found in protein levels for glucose-6-phosphatase (G-6-Pase) or phosphoenolpyruvate (PEPCK), 2 additional gluconeogenic rate-limiting genes. MiRNA-451 antagonist did not significantly affect final body weight or blood glucose; however, mean blood sodium concentrations were slightly, but significantly higher (2%) in the LNA-inhibitor treated group (when compared with the scramble-treated group). No differences in blood potassium or chloride were found. Anion gap was 90% higher in the LNA-inhibitor treated group when compared with scramble-treated mice. No differences in urinary albumin to creatinine ratio were found between the two treatment groups. However, Masson Trichrome scoring revealed a 59% increase in fibrosis in inhibitor-treated mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these findings support a potentially protective role of miRNA-451 in attenuating signaling via mTOR that may alter both renal gluconeogenic potential (contributing to the diabetic phenotype) and activation and progression of renal fibrosis. Therapies to enhance miRNA-451 signaling may be beneficial to reduce renal pathology associated with DN.
A hypoeutectic CoCrFeNiNbχ system was synthesized to investigate the effect of Nb content on the thermal stability, mechanical properties, and corrosion behaviors. The hypoeutectic CoCrFeNiNbχ alloy, which contained the Laves phase, possessed two-phase eutectic structures. The elevated temperature may have an impact on the stability of the Laves phase. Nanoindentation measurements showed that the Laves phase is much harder than the FCC phase, which could be confirmed by the shallower maximum penetration depth in the typical P–h curve. Furthermore, the plasticity of the Laves phase was characterized by nanoindentation measurements. Compared with the FCC phase, the activation energy of dislocation nucleation in the Laves phase is much higher due to the large atomic size difference and the phase difference. Corrosion and passivation behaviors of CoCrFeNiNbχ were investigated in 3.5% NaCl solution. All the alloys exhibited spontaneous passivity and low current densities in 3.5% NaCl solution. Furthermore, the corrosion potential increased with the increasing Nb content, which indicated that the corrosion resistance enhanced with a higher Nb content.
In this paper, both the proportional derivative feedback control and variable-structure sliding mode control approaches based on dual numbers are presented to design space flyaround and in-orbit inspection missions. Dual-number-based spacecraft kinematics and dynamics models are formulated. The integrated translational and rotational motions can be described in one compact expression, and the mutual coupling effect can be considered. A space flyaround and in-orbit inspection mission model based on dual numbers is derived. Both proportional derivative feedback control and variable-structure sliding mode control laws are designed using dual numbers. Simulation results indicate that both the proposed control system can provide high-precision control for relative position and attitude. Of the two systems, the variable-structure sliding mode control system performs the best.
Obesity and insulin resistance play important roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Mg intake is linked to a reduced risk of metabolic syndrome and insulin resistance; people with NAFLD or alcoholic liver disease are at high risk of Mg deficiency. The present study aimed to investigate whether Mg and Ca intakes were associated with risk of fatty liver disease and prediabetes by alcohol drinking status.
We analysed the association between Ca or Mg intake and fatty liver disease, prediabetes or both prediabetes and fatty liver disease in cross-sectional analyses.
Third National Health and Nutrition Examination Survey (NHANES III) follow-up cohort of US adults.
Nationally representative sample of US adults in NHANES (n 13 489).
After adjusting for potential confounders, Mg intake was associated with approximately 30 % reduced odds of fatty liver disease and prediabetes, comparing the highest intake quartile v. the lowest. Mg intake may only be related to reduced odds of fatty liver disease and prediabetes in those whose Ca intake is less than 1200 mg/d. Mg intake may also only be associated with reduced odds of fatty liver disease among alcohol drinkers.
The study suggests that high intake of Mg may be associated with reduced risks of fatty liver disease and prediabetes. Further large studies, particularly prospective cohort studies, are warranted to confirm the findings.
To improve the antimicrobial properties of ZnO, ZnO-supported 13X zeolite (X-ZnO) was prepared via the facile chemical method. Antimicrobial activities of X-ZnO and ZnO were tested against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. X-ZnO showed noticeable antimicrobial activities against E. coli and S. aureus under visible light conditions, especially against E. coli. The minimum inhibitory concentration (MIC) of X-ZnO against E. coli was 0.12–0.24 mg/mL. However, there were still much bacteria alive in the nano-ZnO suspensions at the same concentration. To elucidate the antimicrobial activities of X-ZnO, the average concentration of the total reactive oxygen species (ROS) and Zn2+ ions released from X-ZnO and nano-ZnO were quantitatively analyzed. The obtained results indicated that the average concentration of ROS produced by supported ZnO was much higher than that of nano-ZnO. And the released Zn2+ ions from X-ZnO and nano-ZnO suspensions were much lower than the MIC of Zn2+. Thus, it is believed that the production of ROS in X-ZnO and nano-ZnO suspensions resulted in the difference of antibacterial activities.
Early life is considered a critical period for determining long-term metabolic health. Postnatal over-nutrition may alter glucocorticoid (GC) metabolism and increase the risk of developing obesity and metabolic disorders in adulthood. Our aim was to assess the effects of the dose and timing of a fish oil diet on obesity and the expression of GC-activated enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD1) in postnatal overfed rats. Litter sizes were adjusted to three (small litter (SL)) or ten (normal litter) rats on postnatal day 3 to induce overfeeding or normal feeding. The SL rats were divided into three groups after weaning: high-dose fish oil (HFO), low-dose fish oil (LFO) and standard-diet groups. After 10 weeks, the HFO diet reduced body weight gain (16 %, P<0·05), improved glucose intolerance and decreased hyperlipaemia levels (P<0·05) in SL rats, but the LFO diet did not have any effect on the same rats. Moreover, we chose postnatal week 3 (W3), 6 (W6) and 8 (W8) as the intervention time points at which to begin the 10-week HFO diet, and found that the HFO diet improved glucose utilisation and lipid metabolism at all time points. However, body weight of SL rats was reversed to normal levels by the post-weaning intervention (461 (sem 9·1) v. 450 (sem 2·0)). 11β-HSD1 mRNA expression in the adipose tissue (49 (sem 7·5) v. 161 (sem 18·3), P<0·05) and hepatic tissue (11 (sem 0·9) v. 16 (sem 1·5), P<0·05) was decreased by the HFO diet at W3, but not at W6 or W8 (P>0·05). In conclusion, the post-weaning HFO diet could reverse adverse outcomes and decrease tissue GC activity in postnatal overfed rats.
The aim of the present work was to determine maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP) in twin pregnancies. All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Data on maternal demographics and obstetric complications together with fetal outcomes were collected. The risk of adverse maternal and fetal outcomes were determined in relation to ICP by crude odds ratios (OR) and adjusted ORs (aOR) with 95% confidence intervals (CI). Subgroup analysis concentrated on the effect of assisted reproductive technology (ART), ICP severity, and onset time. A total of 1,472 twin pregnancies were included, of which 362 were cholestasis patients and 677 were conceived by ART. Higher rates of preeclampsia (aOR 1.96; 95% CI 1.35, 2.85), meconium-stained amniotic fluid (aOR 3.10; 95% CI 2.10, 4.61), and preterm deliveries (aOR 3.20; 95% CI 2.35, 4.37) were observed in ICP patients. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP groups. In conclusion, adverse maternal and fetal outcomes were strongly associated with ICP in twin patients. Active management and close antenatal monitoring are needed, especially in the early onset and severe groups.
I deficiency is a worldwide public health problem. Median urinary I concentration in school-aged children has been used globally as a proxy for all populations. This study aims to determine whether median urinary I concentration of school-aged children is an appropriate indicator of I nutritional status in different adult populations. This is a secondary data analysis of two national I Deficiency Disorder surveys (2011, 2014) and two regional surveys (in coastal areas, 2009, and in high-risk areas, 2009–2014). Population groups included in these surveys were school-aged children (8–10 years), pregnant women, lactating women, women of childbearing age and adults (men and women, 18–45 years). All participants were self-reported healthy without history of thyroid diseases or were not using thyroid medicines. The median urinary I concentration of school-aged children was matched with that of the other population at the county level. The matched populations had similar iodised salt supply, food and water I, food composition and I content in salt. Weak or moderate correlation of median urinary I concentrations was observed between school-aged children and pregnant women and between children and lactating women. However, the agreement was stronger between children and women of childbearing age and between children and adult men and women. The results could be affected by cut-off values, data aggregation level and sample size. Using median urinary I concentration of school-aged children tends to overestimate that of pregnant women and lactating women. Median urinary I concentration of school-aged children can be used for assessing I nutrition in the adult population.
In light of government investment over the past decade, we explored the capacity for disaster response in Heilongjiang Province, identifying the factors that affect response capacity.
We surveyed 1257 medical staff in 65 secondary and tertiary hospitals in Heilongjiang province to explore their perceptions of disaster management capacity using a cross-sectional multistage, stratified cluster sampling method.
All tertiary hospitals (100%) and most secondary hospitals (93%) have documented disaster management plans that are regularly reviewed. In secondary hospitals, drills were less prevalent (76.7%) but the occurrence of simulated training exercises was closer to tertiary hospitals (86.0%). We noted that 95.4% of all hospitals have leadership groups responsible for disaster preparedness capacity building, but only 10.8% have a stockpiled network of reserve supplies.
Although response capacity has improved in Heilongjiang Province, vulnerabilities remain. We recommend that priorities should be targeted at preparedness capacity building, in terms of reliable and relevant operational response plans, the expansion of existing response mechanisms to oversee local education and scenario training, and to ensure there is sufficient access to protective equipment and materials, either held in reserve, or alternatively by activating resilient supply chain mechanisms. (Disaster Med Public Health Preparedness. 2018;12:176–183)
A novel relative spacecraft attitude and position estimation approach based on an Unscented Kalman Filter (UKF) is derived. The integrated sensor suite comprises the gyro sensors on each spacecraft and a vision-based navigation system on the slave spacecraft. In the traditional algorithm, an assumption that the master's body frame coincides with its Local Vertical Local Horizontal (LVLH) frame is made to construct the line-of-sight observations for convenience. To solve this problem, two relative quaternions that map the master's LVLH frame to the slave and master body frames are involved. The general relative equations of motion for eccentric orbits are used to describe the positional dynamics. The implementation equations for the UKF are derived. A modified version of the UKF is presented based on the averaging-quaternion algorithm. Simulation results indicate that the proposed filters provide more accurate estimates of relative attitude and position than the Extended Kalman Filter (EKF).
First principles studies about the influence of electric field and anisotropic oxygen vacancy on the dielectric properties of rutile titanium dioxide (TiO2) are investigated. These results demonstrate that dielectric properties of perfect TiO2 presents dependent on the low electric field that less than 5.2 MV/cm. As a comparison, the dielectric properties of defected TiO2 in (1 1 0) plane and [1 1 0] direction show more sensitive to high electric field. Further more, considering the different positions of oxygen vacancy, the oxygen vacancy locates in (1 1 0) plane of defected TiO2 appears more active to high electric field than it does in [1 1 0] direction. The effect of electric field and oxygen vacancy induce the distorted supercell structure and broken bond between the nearer oxygen atoms and titanium atoms. Moreover, the oxygen vacancy locates in (1 1 0) plane of defected TiO2 can create more potential broken bond. These results account for the difference of dielectric properties in perfect TiO2 and defected TiO2.
The split Hopkinson pressure bar (SHPB) was used to study the compressibility of shear thickening fluid (STF) at high deformation rate. In this study, a steel bulk was introduced into the SHPB system to confine and load the STF. A series of STFs with different particle types (SiO2 and PSt-EA) and volume fractions (63 vol.% and 65 vol.%) were tested and the results were compared. The reliability of the results was proved by repeating the tests and the force balance in suspension. The bulk modulus was used to evaluate the compressibility of STF, which indicated that the SiO2-based STF exhibited a larger compressibility than the PSt-EA-based STF. It was found that the bulk modulus increases with increasing of the strain rate and the volume fraction shows little effect on the bulk modulus. The structure-dependent mechanical property was analyzed and the loading effect of bulk modulus was considered to be originated from the interparticle clustering.
In our recent study, we first reported that mutation in vascular endothelial growth factor-A is associated with bicuspid aortic valve stenosis. However, to date no groups have explored the role of vascular endothelial growth factor-A variations in the aetiology of congenital tricuspid aortic valve stenosis.
We sequenced all eight coding exons and exon–intron boundaries of the vascular endothelial growth factor-A gene in deoxyribonucleic acid samples of a cohort of 32 sporadic patients with tricuspid aortic valve stenosis, 300 normal controls, and 103 disease controls – conotruncal defects – in order to identify sequence variants.
We identified a c.973C > T heterozygous nonsense variation in exon 6 of the vascular endothelial growth factor-A gene in a patient with an isolated tricuspid aortic valve stenosis. The c.973C > T variation, which was absent in all controls, changes a highly conserved arginine at amino acid position 325 to a stop codon (p.Arg325X) and is predicted to produce a truncated protein of 324 amino acid residues. The proband's parents had a normal cardiac phenotype; however, his father was a carrier of the p.Arg325X variation, which indicates that the p.Arg325X variation is inherited and incompletely penetrant.
We report for the first time that the p.Arg325X nonsense variation in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis.
Epidemiological studies of dietary glycaemic index (GI) and glycaemic load (GL) in relation to diabetes risk have yielded inconsistent results. We aimed to examine the associations between dietary GI and GL and the risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies. Relevant studies were identified by a PubMed database search up to February 2011. Reference lists from retrieved articles were also reviewed. We included prospective cohort studies that reported risk estimates with 95 % CI for the associations between dietary GI and GL and the risk of type 2 diabetes. Either a fixed- or random-effects model was used to compute the summary relative risk (RR). We identified thirteen prospective cohort studies of dietary GI or GL related to diabetes risk. The summary RR of type 2 diabetes for the highest category of the GI compared with the lowest was 1·16 (95 % CI 1·06, 1·26; n 12), with moderate evidence of heterogeneity (P = 0·02, I2 = 50·8 %). For the GL, the summary RR was 1·20 (95 % CI 1·11, 1·30; n 12), with little evidence of heterogeneity (P = 0·10, I2 = 34·8 %). No evidence of publication bias was observed. In addition, the associations persisted and remained statistically significant in the sensitivity analyses. In conclusion, the present meta-analysis provides further evidence in support of significantly positive associations between dietary GI and GL and the risk of type 2 diabetes. Reducing the intake of high-GI foods may bring benefits in diabetes prevention.