pparß regulates lipid catabolism by mediating acox and cpt-1 genes in Scophthalmus maximus under heat stress.

Peroxisome proliferator-activated receptor ß (pparß) is a key gene-regulating lipid metabolism pathway, but its function in turbot remains unclear. In this study, the CDS of pparß was cloned from kidney for the first time. The CDS sequence length was 1533 bp encoding 510 amino acids. Structural analysis showed that the pparß protein contained a C4 zinc finger and HOLI domain, suggesting that the pparß gene of turbot has high homology with the PPAR gene of other species. The high expression patterns of pparß, acox, and cpt-1 at high temperatures, as shown through qPCR, indicated that high temperatures activated the transcriptional activity of pparß and increased the activity of the acox and cpt-1 genes. The expression of acox and cpt-1 was significantly inhibited when pparß was downregulated using RNAi technology and inhibitor treatments, suggesting that pparß positively regulated acox and cpt-1 expression at high temperatures and, thus, modulates lipid catabolism activity. These results demonstrate that pparß is involved in the regulation of lipid metabolism at high temperatures and expand a new perspective for studying the regulation of lipid metabolism in stress environments of teleost.

[Research advances in influencing factors for immune tolerance to food allergens in children].

Food allergen-specific immune tolerance is defined as nonresponsiveness of the adaptive immune system to food antigens. Failed development or inhibition of such tolerance may cause food allergy. With the increasing incidence rate of food allergy year by year, more and more studies have found the association between food allergy and various diseases. The development of food allergen-specific immune tolerance in childhood has been taken more and more seriously. In recent years, many studies have shown that the development of food allergen-specific immune tolerance is influenced by various factors, which can be roughly divided into antigens, organisms, and environment. This article reviews the influencing factors for the development of immune tolerance to food allergens in children, in order to provide help for reducing the incidence of food allergy and improving the prognosis of food allergy.

Changes of serum angiogenic factors concentrations in patients with diabetes and unstable angina pectoris.

BACKGROUND: Diabetic microvascular changes are considered to be influenced by angiogenic factors. As a compensatory mechanism, the expression of some angiogenic factors are elevated in ischemic myocardium. The aim of this study was to investigate the changes of serum angiogenic factors, and the association among these angiogenic factors, the severity of coronary artery stenosis and collateral vessels form in patients with diabetes and unstable angina pectoris (UAP). METHODS: 42 patients with diabetes (diabetes group), 57 patients with UAP (UAP group), and 36 age-matched healthy people (control group) were selected. Serum concentrations of angiogenic factors were measured using cytokine array technology. The severity of coronary artery stenosis was scored using the angiographic Gensini score. Coronary collateral vessels were scored according to Rentrop's classification. RESULTS: No significant differences in the serum concentrations of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), angiogenin, angiostatin, basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) were detected between control group and diabetes group. But in patients with diabetes complicated with UAP and in patients with UAP without diabetes, serum concentrations of VEGF and Ang-2 were elevated (p < 0.01, p < 0.01). Only serum Ang-2 concentrations were significantly correlated with Gensini score (r=0.585, p < 0.001), left ventricular end diastolic diameter (r=0.501, p < 0.001), left ventricular end systolic diameter (r=0.563, p < 0.001) and left ventricular ejection fraction (r=-0.523, p < 0.001). CONCLUSION: Serum concentrations of VEGF and Ang-2 were increased, and diabetes didn't affect this increases in patients with UAP. Serum Ang-2 concentrations were correlated with the severity of coronary artery stenosis.

Texture and Magnetic Property of Fe-6.5 wt % Si Steel Strip with Cu-Rich Particles Modification.

Based on the ordered phase effectively suppressed by rapid solidification technology, the grain refinement concept using Cu is incorporated into the soft magnetic materials. Cu dosage not only could refine the grain size with an average grain size of 8.7 µm but also improve the continuity and consistency of Fe-6.5 wt % Si steel strip. It mainly attributes to the Cu-rich particles precipitating at the grain boundary, nailing the grain boundaries movement and inhibiting the grain growth, and then improving the magnetic properties and mechanical properties. The 1.5 wt % Cu sample exhibits an excellent magnetic property with the saturation magnetization of 236.54 emu/g, which mainly attributes to the strong η, λ, Goss texture formation and the band structure optimization of Si-Cu comodification. Furthermore, the mechanical properties of the steel strip are effectively improved, and the failure plastic deformation of 1.5 wt % Cu steel strip is about 11%. The rapid solidification with Cu-dosage refinement technology also has a remarkable reference on the mechanical properties and magnetic properties modification of other metal materials.

Altered serum levels of IL-33 in patients with advanced systolic chronic heart failure: correlation with oxidative stress.

BACKGROUND: Interleukin-33 (IL-33) has been linked to chronic heart failure (CHF) in animal studies, but data on serum IL-33 levels in human CHF are not available. We analyzed levels of IL-33 in serum, and investigated the possible role of IL-33 in oxidative stress. METHODS: A total of 191 subjects with advanced systolic CHF (CHF group), 175 patients with pre-existing cardiac diseases but no CHF (non-CHF group), and 177 healthy controls (HC group) were enrolled. Serum levels of IL-33, soluble ST2 (sST2) and N-terminal-pro-brain natriuretic peptide (NT-proBNP), malondialdehyde (MDA) content, erythrocyte superoxide dismutase (eSOD) activity, as well as left ventricular ejection fraction (LVEF), were determined. The exact form of IL-33 in serum was identified. Effects of IL-33 and sST2 on MDA content and SOD activity in angiotensin (Ang II)-stimulated AC16 cells were assessed. RESULTS: Serum levels of IL-33 and sST2 were elevated in CHF patients, whereas IL-33/sST2 ratios were decreased. In CHF patients, pre-existing cardiac diseases and medications used upon hospital admission did not affect IL-33 concentrations or the IL-33/sST2 ratio. Full-length IL-33, which could not be detected in serum from HC and barely detected in non-CHF patients, was significantly up-regulated in CHF patients. IL-33 levels were positively correlated with markers of CHF severity. IL-33/sST2 ratios were slightly and negatively related to MDA concentrations. IL-33 directly reduced MDA and enhanced SOD activity in Ang II-stimulated AC16 cells, which were greatly attenuated by sST2. CONCLUSIONS: Serum levels of IL-33, especially the full-length form, were elevated in CHF patients whereas IL-33 bioactivity was reduced. In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2.

Complement factor H Y402H gene polymorphism and coronary heart disease susceptibility: a meta-analysis.

The complement factor H (CFH) Y402H (T1277C) gene polymorphism has been reported to be associated with coronary heart disease (CHD), but results were conflicting. To evaluate the role of the variant in CHD, we performed meta-analyses of all available data. Both electronic and manual searches were performed, all relevant studies were identified. ORs with 95% confidential intervals (CI) under codominant (CC versus TT, TC versus TT), dominant (CC + TC versus TT) and recessive (CC versus TT + TC) models were calculated. Publication bias was addressed. Ten studies including 11 cohorts comprising of 29,764 participants were included. No association between the CFH T1227C polymorphism and CHD could be found. (For overall analysis: dominant model, OR = 1.04, 95%CI: 0.97-1.11; recessive model, OR = 1.04, 95%CI: 0.97-1.11; for Caucasian subgroup: OR = 1.08 95%CI: 0.92-1.27; recessive model, OR = 1.03, 95%CI: 0.96-1.11). Two studies reported positive results in separate population (Caucasian study: recessive model, OR = 0.51, 95%CI: 0.30-0.86; Asians study: dominant model, OR = 2.37, 95%CI: 1.13-4.96). Current evidence do not support the association between the CFH T1277C polymorphism and CHD risk among common population. The association, which could be influenced by CHD onset age, CHD risk factors status and genetics backgrounds, might be significant in some population. More studies on different CHD onset ages and risk factor status should be encouraged.

Effect of Molybdenum on the Impact Toughness of Heat-Affected Zone in High-Strength Low-Alloy Steel.

The microstructure, precipitates, and austenite grain in high-strength low-alloy steel were characterized by optical microscope, transmission electron microscope, and laser scanning confocal microscopy to investigate the effect of Mo on the toughness of steel. The microstructure was refined and the toughness was enhanced after the addition of 0.07% Mo in steel. The addition of Mo can suppress the Widmanstätten ferrite (WF) formation and promote the transformation of acicular ferrite (AF), leading to the fine transformed products in the heat-affected zone (HAZ). The chemical composition of precipitates changed from Nb(C, N) to (Nb, Mo)(C, N) because of the addition of Mo. The calculated lattice misfit between Nb(C, N) and ferrite was approximately 11.39%, while it was reduced to 5.40% for (Nb, Mo)(C, N), which significantly affected the size and number density of precipitates. A detailed analysis of the precipitates focusing on the chemical composition, size, and number density has been undertaken to understand the contribution of Mo on the improvement of steel toughness.

ATG16L1 T300A polymorphism and Crohn's disease susceptibility: evidence from 13,022 cases and 17,532 controls.

Many studies have reported the association between the autophagy-related 16-like 1 gene (ATG16L1) T300A polymorphism (rs2241880) and Crohn's disease (CD) susceptibility, but the results were inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 24 studies including 13,022 cases and 17,532 controls were included in this meta-analysis. Logistic regression analysis indicated that the ATG16L1 T300A polymorphism was associated with CD risk in Caucasians (P < 0.01). The pooled estimations of OR(1) (GG vs. AA) and OR(2) (GA vs. AA) in Caucasian studies by Bayesian meta-analysis method was [1.87, 95% confidence interval (CI) 1.69-2.05] and (1.39, 95% CI 1.27-1.51), respectively. The mode of heritance of the G allele was most likely to be co-dominant in Caucasians. However, no significant association was found in Asians. This meta-analysis suggests that the G allele of ATG16L1 T300A is a low-penetrant gene for developing CD in Caucasians.

CD14 C-260T gene polymorphism and ischemic heart disease susceptibility: a HuGE review and meta-analysis.

The CD14 gene C-260T polymorphism has been reported to be associated with ischemic heart disease, but results were conflicting. To evaluate the role of the CD14 C-260T polymorphism in ischemic heart disease, we performed meta-analyses of all available data. Comprehensive searches for studies on the association between the genotypes (CC, CT, TT) distributions and ischemic heart disease risk were performed. Patients with acute coronary syndrome, prior myocardial infarction, stable angina pectoris, or angiographic coronary artery stenosis were included. Potential sources of heterogeneity were explored by meta-regression. Analyses were performed under European, East Asian, and Indian studies, respectively. Data were available for 19 studies involving 11,813 cases and 6,196 controls. The summary odds ratio under the recessive model was 1.53 (95% confidence interval: 1.20-1.96) for East Asian studies published in English language journals on overall ischemic heart disease. Pooled odds ratios under the codominant model were about 1.81 (95% confidence interval: 1.36-2.40) and 1.70 (95% confidence interval: 1.26-2.29) for Chinese studies on overall ischemic heart disease and other ischemic heart disease (angina pectoris and angiographic coronary artery stenosis), respectively. No significant association was found in a European population, an Indian population, or the vulnerable plaque ischemic heart disease (acute coronary syndrome and prior myocardial infarction) subgroup of an East Asian population. It is probable that T allele and TT genotype are associated with ischemic heart disease in the East Asian population but not in the European or Indian populations. Further studies are warranted to assess these associations in greater details, especially in East Asian and Indian populations.

Mineral Transition and Chemical Reactivity Evolution of a Low-Lime Calcium Aluminate Clinker with MgO and Na2SO4 Codopants.

The mineral formation-transition mechanism, microstructure evolution, crystal structure, pulverization property, and chemical reactivity of the CaO-Al2O3-SiO2 clinker with MgO and Na2SO4 dopants during the sintering process at 1300 °C for 2.0 h were systematically studied using CaO, Al2O3, SiO2, MgO, and Na2SO4 as raw materials when the molar ratio of CaO to Al2O3 is 1.4, the mass ratio of Al2O3 to SiO2 is 3.0, and the mass percentage of MgO and Na2SO4 is 2%. The MgO dopant could result in 12CaO·7Al2O3 and γ-2CaO·SiO2, transform into 20CaO·13Al2O3·3MgO·3SiO2, restrain the crystal transformation of 2CaO·SiO2 from ß to γ, and then deteriorate the pulverization and alumina leaching property corresponding to parts of Al, Si, and Mg atoms occupying the same lattice positions of the crystal structure. MgO and Na2SO4 codoped could promote transformation of 20CaO·13Al2O3·3MgO·3SiO2 into 3CaO·3Al2O3·CaSO4 as well as some 2CaO·Al2O3·SiO2, while 3CaO·3Al2O3·CaSO4 has good alumina leaching property in the Na2CO3-NaOH solution. The ultrasonic assistant mainly could promote the diffusion of reactive samples, enhance the separation of agglomeration, and then accelerate the chemical reaction of the sintered clinker with Na2CO3-NaOH.

Evaluation of the therapeutic effects of QuickOpt optimization in Chinese patients with chronic heart failure treated by cardiac resynchronization.

In this trial, long-term therapeutic effects and clinical improvements in Chinese chronic heart failure patients optimized by QuickOpt or echocardiography were compared for atrioventricular (AV) and interventricular (VV) delay optimizations after cardiac resynchronization therapy (CRT) with pacing (CRT-P) or with pacing and defibrillator (CRT-D) therapy. One hundred and ninety-six subjects (50%) had dilated cardiomyopathy, 108 (27.6%) had ischemic heart disease and 112 (28.6%) were hypertensive and were randomized into QuickOpt (198) or echocardiographic optimization (control) (194) groups at ≤2-weeks post-implantation. Programmed AV/VV delay was optimized at baseline and at 3 and 6 months. Left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) class, specific activity scale (SAS), and the six-minute walk tests (6MWT) were evaluated by blinded researchers at 12 months. Of the QuickOpt group, LVESV decreased significantly by 24.7% ± 33.9% compared with baseline, while LVESV of Controls decreased by 25.1% ± 36.1% (P = 0.924). NYHA class, SAS and 6MWT also improved similarly in both groups at 12 months. Mortality in both groups was not significantly different (11.0% vs 7.6%, P = 0.289). However, there was a significant difference in the time required for optimization by QuickOpt compared with echocardiography (3.33 ± 3.11 vs 58.79 ± 27.03 minutes, P < 0.000).

Smoothing a rugged protein folding landscape by sequence-based redesign.

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.

Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain.

Consensus protein design is a rapid and reliable technique for the improvement of protein stability, which relies on the use of homologous protein sequences. To enhance the stability of a fibronectin type III (FN3) domain, consensus design was employed using an alignment of 2123 sequences. The resulting FN3 domain, FN3con, has unprecedented stability, with a melting temperature >100°C, a ΔG(D-N) of 15.5 kcal mol(-1) and a greatly reduced unfolding rate compared with wild-type. To determine the underlying molecular basis for stability, an X-ray crystal structure of FN3con was determined to 2.0 Å and compared with other FN3 domains of varying stabilities. The structure of FN3con reveals significantly increased salt bridge interactions that are cooperatively networked, and a highly optimized hydrophobic core. Molecular dynamics simulations of FN3con and comparison structures show the cooperative power of electrostatic and hydrophobic networks in improving FN3con stability. Taken together, our data reveal that FN3con stability does not result from a single mechanism, but rather the combination of several features and the removal of non-conserved, unfavorable interactions. The large number of sequences employed in this study has most likely enhanced the robustness of the consensus design, which is now possible due to the increased sequence availability in the post-genomic era. These studies increase our knowledge of the molecular mechanisms that govern stability and demonstrate the rising potential for enhancing stability via the consensus method.

Neuregulin-1/ErbB signaling is impaired in the rat model of diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCP) is one of the leading causes of increased morbidity and mortality in the diabetic population. The neuregulin-1(NRG1)/ErbB signal system plays a critical role in maintenance of adult heart function. But little is known about the changes of NRG1/ErbB signal system in DCP. The aim of this study was to investigate the changes of the NRG1/ErbB signal system in DCP. METHODS: A rat model of DCP was established using a single intraperitoneal injection of streptozotocin (STZ). Cardiac function was assessed using echocardiography. The left ventricle fibrosis was evaluated using Masson's trichrome staining. The mRNA expression profiles of ErbB2 and ErbB4 receptors were evaluated using real-time polymerase chain reaction. The protein expression of NRG1 and the phosphorylation of ErbB2 and ErbB4 receptors were assessed using Western blot analysis. RESULTS: The results showed dramatic left ventricle fibrosis and impaired left ventricle systolic function at 12 weeks after STZ-induced diabetes. This study also showed that ErbB2 and ErbB4 mRNA expression and NRG1 protein expression in the left ventricular myocardium were significantly decreased. In addition, we observed decreased phosphorylation of the ErbB2 and ErbB4 receptors at 12 weeks after the induction of diabetes. CONCLUSIONS: These findings suggest that NRG1/ErbB signaling is impaired in DCP, which may play some roles in the pathogenesis of DCP.

Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study.

Animal studies indicate that monosodium glutamate (MSG) can induce hypothalamic lesions and leptin resistance, possibly influencing energy balance, leading to overweight. This study examines the association between MSG intake and overweight in humans. We conducted a cross-sectional study involving 752 healthy Chinese (48.7% women), aged 40-59 years, randomly sampled from three rural villages in north and south China. The great majority of participants prepared their foods at home, without use of commercially processed foods. Diet was assessed with four in-depth multipass 24-h recalls. Participants were asked to demonstrate MSG amounts added in food preparation. Amounts shaken out were weighed by trained interviewers. Overweight was defined as BMI > or =25.0 or > or =23.0 kg/m(2)(based on World Health Organization recommendations for Asian populations). Eighty-two percent of participants were MSG users. Average intake was 0.33 g/day (s.d. = 0.40). With adjustment for potential confounders including physical activity and total energy intake, MSG intake was positively related to BMI. Prevalence of overweight was significantly higher in MSG users than nonusers. For users in the highest tertile of MSG intake compared to nonusers, the multivariable-adjusted odds ratios of overweight (BMI > or =23.0 and > or =25.0) were 2.10 (95% confidence interval, 1.13-3.90, P for trend across four MSG categories = 0.03) and 2.75 (95% confidence interval, 1.28-5.95, P = 0.04). This research provides data that MSG intake may be associated with increased risk of overweight independent of physical activity and total energy intake in humans.

[Cox regression analysis on influencing factors of coronary heart disease among people over 40 years of age].

OBJECTIVE: To explore the affecting factors on coronary heart disease among people over 40 years of age in Guangxi area, China. METHODS: Baseline data was gathered through the Third National Blood Pressure Survey in 1991 in China. A total number of 11 818 adults over 40 years old had been studied in Guangxi province. Data of morbidity and mortality of coronary heart disease was obtained. RESULTS: Cardiovascular events were related to systolic blood pressure, diastolic blood pressure, pulse pressure, smoking, BMI regardless of their myocardial infarct (MI) history. Cox regression analysis showed that the relative risk for cardiovascular events increased by 21 [95% confidence interval (CI): 9.06-48.44] times for those people having MI history. When pulse pressure, systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardiovascular events increased by 1.29 (95% CI: 1.11-1.49), 1.18 (95% CI: 1.02-1.22), 1.13 (95% CI: 1.05-1.28) respectively. There was 1.23 (95% Cl: 1.05-1.45) times higher in smoker than non-smoker on relative risk for cardiovascular events. When BMI increasing 1, the relative risk for cardiovascular events would increase 1.03 (95% CI: 1.01-1 .05) times. CONCLUSION: Hypertension, smoking, increase of BMI were the risk factors of coronary heart disease among people who were over 40 years of age.

Blood pressure differences between northern and southern Chinese: role of dietary factors: the International Study on Macronutrients and Blood Pressure.

Blood pressure and prevalence of high blood pressure are greater for northern than southern Chinese. Reasons for these differences are unclear. Relationships of north-south blood pressure differences with multiple dietary factors were investigated in 839 Chinese participants, International Study on Macronutrients and Blood Pressure (INTERMAP), 561 northern, 278 southern, aged 40 to 59 years. Daily nutrient intakes were determined from four 24-hour dietary recalls and 2 timed 24-hour urine collections. Average systolic/diastolic pressure levels were 7.4/6.9 mm Hg higher for northern than southern participants. Southern participants had lower body mass index, sodium intake, sodium/potassium ratio, and higher intake of calcium, magnesium, phosphorus, and vitamins A and C. Considered singly, with control for age and gender, several dietary variables (eg, body mass index, urinary sodium/potassium ratio, urinary sodium, dietary phosphorus, and magnesium) reduced north-south blood pressure differences by > or =10%. Controlled for age and gender, nondietary variables had little effect on north-south blood pressure differences. With inclusion in regression models of multiple dietary variables (sodium, potassium, magnesium or phosphorus, body mass index), north-south blood pressure differences became much smaller (systolic -1.1, diastolic 1.6 mm Hg) and statistically nonsignificant. In conclusion, multiple dietary factors accounted importantly for north-south blood pressure differences. Efforts are needed to improve nutrition in China, especially in the north, as well as in other populations including those in the United States, for prevention and control of adverse blood pressure levels and major adult cardiovascular disease.