Formic acid induces hypertension-related hemorrhage in hSSAOTG in mice and human.

Hypertension is a confirmed risk factor for cerebral hemorrhage in humans. Which endogenous factor directly induces hypertension-related hemorrhage is unclear. In this study, 42 hemorrhagic patients with hypertension and hyperlipidemia and 42 age-matched healthy controls were enrolled. The contents of serum semicarbazide-sensitive amine oxidase (SSAO) and formic acid (FC, FC is a final product of SSAO through the oxidation of endogenous formaldehyde, which results from the enzymatic oxidative deamination of the SSAO substrate, methylamine) were examined in the patients after stroke. Hemorrhagic areas were quantified by computer tomography. In the animal study, hemorrhagic degree was assessed by hemotoxylin & eosin or tissue hemoglobin kits. The relationship between FC and blood pressure/hemorrhagic degree was examined in wild-type mice and hSSAOTG mice fed with high-fat diets or high-fat and -salt diets. The results showed that the levels of serum FC were positively correlated with blood pressure and hemorrhagic areas in hemorrhagic patients. Transfection of microRNA-134 could enhance SSAO expression in human vascular smooth muscle cells. Consistently, after treatment with high-fat and -salt diets, hSSAOTG mice exhibited higher levels of miR134 and FC, higher blood pressure, and more severe hemorrhage than wild-type mice. Interestingly, folic acid reduced hypertension and hemorrhage in hSSAOTG mice fed with high-fat diets. These findings suggest that FC is a crucial endogenous factor for hypertension and hemorrhage.

Dissecting the Genetic Architecture of Melon Chilling Tolerance at the Seedling Stage by Association Mapping and Identification of the Elite Alleles.

Low temperature is an important abiotic stress that negatively affects morphological growth and fruit development in melon (Cucumis melo L.). Chilling stress at the seedling stage causes seedling injury and poor stand establishment, prolonging vegetative growth and delaying fruit harvest. In this study, association mapping was performed for chilling tolerance at the seedling stage on an expanded melon core collection containing 212 diverse accessions by 272 SSRs and 27 CAPSs. Chilling tolerance of the melon seedlings was evaluated by calculating the chilling injury index (CII) in 2016 and 2017. Genetic diversity analysis of the whole accession panel presented two main groups, which corresponded to the two subspecies of C. melo, melo, and agrestis. Both the subspecies were sensitive to chilling but with agrestis being more tolerant. Genome-wide association study (GWAS) was conducted, respectively, on the whole panel and the two subspecies, totally detecting 51 loci that contributed to 74 marker-trait associations. Of these associations, 35 were detected in the whole panel, 21 in melo, and 18 in agrestis. About half of the associations identified in the two subspecies were also observed in the whole panel, and seven associations were shared by both the subspecies. CMCT505_Chr.1 was repeatedly detected in different populations with high phenotypic contribution and could be a key locus controlling chilling tolerance in C. melo. Nine loci were selected for evaluation of the phenotypic effects related to their alleles, which identified 11 elite alleles contributing to seedling chilling tolerance. Four such alleles existed in both the subspecies and six in either of the two subspecies. Analysis of 20 parental combinations for their allelic status and phenotypic values showed that the elite alleles collectively contributed to enhancement of the chilling tolerance. Tagging the loci responsible for chilling tolerance may simultaneously favor dissecting the complex adaptability traits and elevate the efficiency to improve chilling tolerance using marker-assisted selection in melon.

γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the association of the measurement of serum γ-glutamyl transferase (GGT) concentrations at admission with 1-year all-cause or cardiovascular disease (CVD) mortality in patients with acute ischemic stroke. METHODS: This prospective, multicenter cohort study was conducted in 4 stroke centers in China. Baseline GGT measurements were tested. The relationship of GGT to the risk of death from all-cause or CVD was examined among 1-year follow-up patients. RESULTS: We recorded results from 5912 patients with stroke. In those patients, 51.0% were men, and the median age was 61 years. In both men and women, high GGT was significantly associated with total mortality from all-cause or CVD (P<0.001). The elevated GGT revealed adjusted hazard ratios (95% confidence interval) of 3.03 (1.99-4.54) and 3.24 (2.14-4.92) for mortality from all-cause and CVD, respectively. With an area under the curve of 0.69 (95% confidence interval, 0.66-0.73), GGT showed a significantly greater discriminatory ability to predict all-cause mortality as compared with others factors. GGT improved the National Institutes of Health Stroke Scale score (area under the curve of the combined model, 0.75 [95% confidence interval, 0.73-0.78]; P<0.01). CONCLUSIONS: This study demonstrates that GGT is independently associated with all-cause and CVD mortality in patients with ischemic stroke.

One-Step Growth of Iron-Nickel Bimetallic Nanoparticles on FeNi Alloy Foils: Highly Efficient Advanced Electrodes for the Oxygen Evolution Reaction.

Electrochemical water splitting is an important process to produce hydrogen and oxygen for energy storage and conversion devices. However, it is often restricted by the oxygen evolution reaction (OER) due to its sluggish kinetics. To overcome the problem, precious metal oxide-based electrocatalysts, such as RuO2 and IrO2, are widely used. The lack of availability and the high cost of precious metals compel researchers to find other resources for the development of cost-effective, environmentally friendly, earth-abundant, nonprecious electrocatalysts for OER. Such catalysts should have high OER performance and good stability in comparison to those of available commercial precious metal-based electrocatalysts. Herein, we report an inexpensive fabrication of bimetallic iron-nickel nanoparticles on FeNi-foil (FeNi4.34@FeNi-foil) as an integrated OER electrode using a one-step calcination process. FeNi4.34@FeNi-foil obtained at 900 °C shows superior OER activity in alkaline solution with an overpotential as low as 283 mV to achieve a current density of 10 mA cm-2 and a small Tafel slope of 53 mV dec-1. The high performance and durability of the as-prepared nonprecious metal electrode even exceeds those of the available commercial RuO2 and IrO2 catalysts, showing great potential in replacing the expensive noble metal-based electrocatalysts for OER.

Circulating FABP4 (Fatty Acid-Binding Protein 4) Is a Novel Prognostic Biomarker in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: FABP4 (fatty acid-binding protein 4) is an intracellular lipid chaperone involved in coordination of lipid transportation and atherogenesis. This study aimed at observing the effect of FABP4 on the 3-month outcomes in Chinese patients with acute ischemic stroke. METHODS: In a prospective multicenter observational study, serum concentrations of FABP4 were on admission measured in plasma of 737 consecutive patients with acute ischemic stroke. Serum concentrations of FABP4, National Institutes of Health Stroke Scale score, and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 3 months. RESULTS: During follow-up, an unfavorable functional outcome was found in 260 patients (35.3%), and 94 patients (12.8%) died. In multivariate models comparing the third and fourth quartiles to the first quartile of FABP4, the concentrations of FABP4 were associated with poor functional outcome and mortality. Compared with the reference category (Q1-Q3), the concentrations of FABP4 in Q4 had a relative risk of 4.77 (95% confidence interval [CI], 2.02-8.15; P<0.001) for poor functional outcome and mortality (odds ratio, 6.15; 95% CI, 3.43-12.68) after adjusting for other significant outcome predictors in univariate logistic regression analysis. Receiver-operating characteristic curves to predict poor functional outcome and mortality demonstrated areas under the curve of FABP4 of 0.78 (95% CI, 0.75-0.82) and 0.83 (95% CI, 0.79-0.88), which improved the prognostic accuracy of National Institutes of Health Stroke Scale score with combined areas under the curve of 0.83 (95% CI, 0.76-0.89; P<0.01) and 0.86 (95% CI, 0.81-0.92), respectively. CONCLUSIONS: Data show that FABP4 is a novel independent prognostic marker improving the currently used risk stratification of stroke patients.

Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischaemic stroke.

Low vitamin D levels have been reported to contribute to the risk of cardiovascular events and mortality, especially stroke. In the present study we therefore evaluated the short-term prognostic value of serum 25(OH)D (25-hydroxyvitamin D) in Chinese patients with AIS (acute ischaemic stroke). From February 2010 to September 2012, consecutive stroke patients admitted to the emergency department at two hospitals in Beijing, China were identified. Clinical information was collected, and the serum concentration of 25(OH)D and NIHSS (National Institutes of Health Stroke Scale) were measured at the time of admission. Short-term functional outcome was measured using a modified Rankin Scale (mRS) at 90 days after admission. Multivariate analyses were performed using logistic regression models. During the inclusion period, 231 patients were diagnosed as having AIS, and 220 completed follow-up. The median serum 25(OH)D level was significantly lower in patients with AIS compared with normal controls [14.2 (10.2-18.9) ng/ml compared with 17.9 (12.5-22.9) ng/ml; P<0.001; values are medians (interquartile range)]. 25(OH)D was an independent prognostic marker of short-term functional outcome and death {0.79 (0.73-0.85) and 0.70 (0.50-0.98) respectively [values are odds rations (95% confidence intervals)]; P<0.01 for both, adjusted for NHISS, other predictors and vascular risk factors} in patients with AIS. In ROC (receiver operating characteristic) curve analysis, the prognostic accuracy of 25(OH)D was higher compared with all of the other serum predictors and was in the range of NIHSS score. In conclusion, these findings suggest that 25(OH)D is an independent prognostic marker for death and functional outcome within 90 days in Chinese patients with AIS even after adjusting for possible confounding factors.

Combination of high-sensitivity C-reactive protein and homocysteine predicts the short-term outcomes of Chinese patients with acute ischemic stroke.

BACKGROUND: Ischemic stroke is one of the most common causes of death worldwide. Early and accurate prediction of outcome in acute ischemic stroke (AIS) is important and influences risk-optimized therapeutic strategies. We investigated the changes in high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) levels, two of the risk factors, during the acute period of AIS and evaluated the relationship between these levels and short-term prognosis. METHODS: We prospectively studied 189 patients with AIS who were admitted within 24 hours after the onset of symptoms. Serum Hs-CRP, HCY levels, and National Institutes of Health Stroke Scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by the modified Rankin scale (mRS), 90 days after admission. RESULTS: The median serum Hs-CRP and HCY levels were significantly higher in AIS patients as compared to normal controls (P < 0.0001, respectively). High-sensitivity C-reactive protein and HCY were independent prognostic markers of functional outcome and death (adjusted for age and the NIHSS) in patients with AIS. In receiver operating characteristic curve analysis, the prognostic accuracy of the combined model (HCY and Hs-CRP) was higher compared to all measured biomarkers individually and the NIHSS score. CONCLUSION: High-sensitivity C-reactive protein and HCY are independent predictors of short-term outcome and mortality after AIS. The combined model may provide additional general prognostic information.

Inositol-requiring protein 1α signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy.

Accumulating evidence suggests that repeated seizures could induce endoplasmic reticulum (ER) stress. Inositol-requiring protein 1α (IRE1α) is a vital pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling pathway mediated by IRE1α is involved in human temporal lobe epilepsy. In this report, we investigated IRE1α-mediated ER stress pro-apoptotic signaling pathway in resected anterior temporal neocortex from 32 patients with intractable mesial temporal lobe epilepsy by immunofluorescence and western blot analysis. Our results indicate that chronic epilepsy induces ER stress, and IRE1α-mediated ER stress apoptotic signaling pathway is involved in brain damage after repeated seizures, which may provide a new therapeutic target to prevent brain damage caused by epilepsy.

Serum levels of inflammation factors and cognitive performance in amnestic mild cognitive impairment: a Chinese clinical study.

Early diagnosis of Alzheimer's disease (AD) is important for initiating timely therapy to block or slow the rate of disease progression. This study was designed to investigate the potential of inflammation-related biomarkers in peripheral blood to accurately reflect AD onset and progression. Individuals (n=150) with amnestic mild cognitive impairment (aMCI) were divided into two subgroups (low- and high-risk) based on APOEε4 allele carrier status, and administered a battery of neuropsychological tests and tested for serum levels of IL-6, IL-10, TNF-α, and IFN-γ by using specific enzyme-linked immunosorbent assays. Results were compared with those from age-matched healthy controls (n=150). The levels of IL-6 were significantly higher in the aMCI group than in controls (P<0.01). When the aMCI group was stratified by APOEε4 status, significant differences were found between the low- and high-risk groups and controls in the levels of IL-6 and IFN-γ (P<0.01 and P=0.041, respectively). Moreover, the IL-6 level in the low-risk aMCI group was higher than that in the high-risk aMCI group (P=0.028). A weak but significant negative correlation was found between IL-6 and cognitive performance. Taken together, these findings indicate that IL-6, while not useful alone, has potential in combination with other biomarkers to support early diagnosis of aMCI due to its association with the progression of cognitive impairment.