•A hybrid magnetic polymer-porous agarose (MNs@SiO2M@DNV-A) was fabricated.•The cationic polymer was functionalized on the magnetic nanospheres.•The porous agarose was coated to exclude interfering ...proteins in the plasma matrix.•The MNs@SiO2M@DNV-A combined with HPLC improved the selectivity for AAs detection.
Aristolochic acids (AAs) naturally occurring in the herbal genus Aristolochia are associated with a high risk of kidney failure, multiple tumors and cancers. However, approaches with high selectivity and rapidity for measuring AAs in biological samples are still inadequate. Inspired by the mechanism of AAs-induced nephrotoxicity, we designed a hybrid magnetic polymer-porous agarose (denoted as MNs@SiO2M@DNV-A), mimicking the effect of basic and aromatic residues of organic anion transporter 1 (OAT1) for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in the plasma. The monomers of vinylbenzyl trimethylammonium chloride (VBTAC), N-vinyl-2-pyrrolidinone (NVP) and divinylbenzene (DVB) were employed to construct the polymer layer, which provided a selective adsorption for AAs by multiple interactions. The porous agarose shell contributed to remove interfering proteins in the plasma samples. A magnetic solid-phase extraction (MSPE) based on the proposed composite enhanced the selectivity toward AA I and AA II in the plasma samples. In combination of HPLC analysis, the proposed method was proved to be applicable to fast and specific quantification of AAs in blood samples, which was characterized by a good linearity, high sensitivity, acceptable recovery, excellent repeatability and satisfactory reusability.
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To explore the association of serum retinol-binding protein 4 (RBP4) levels and risk for the development of type 2 diabetes in individuals with prediabetes.
A population-based prospective study was ...conducted among 1,011 Chinese participants with prediabetes (average age 55.6 ± 7.2 years). Incident type 2 diabetes was diagnosed according to the American Diabetes Association 2010 criteria. Serum RBP4 levels were measured using a commercially available ELISA. We analyzed the association of serum RBP4 levels with the risk of incident type 2 diabetes using the Cox proportional hazards model.
During a median follow-up period of 3.1 years, 153 participants developed incident type 2 diabetes. A U-shaped association was observed between serum RBP4 levels and the risk of incident type 2 diabetes, with the lowest risk in the RBP4 range of 31-55 μg/mL. Multivariate Cox regression model analysis showed that serum RBP4 levels <31 μg/mL and RBP4 levels >55 μg/mL were associated with an increased risk of incident type 2 diabetes. The adjusted hazard ratios (95% CI) were 2.01 (1.31-3.09) and 1.97 (1.32-2.93), respectively, after adjusting for age, sex, BMI, waist circumference, γ-glutamyltransferase, HOMA of insulin resistance index, fasting plasma glucose, 2-h plasma glucose, and glycated hemoglobin (HbA
) levels.
A U-shaped relationship exists between serum RBP4 levels and the risk of incident type 2 diabetes in subjects with prediabetes.
With a view of optimization of a waste treatment system, activated polystyrene was employed for effluents laboratory purification tests, by adsorption of Cs, Ce and Co. The effluent contains the ...elements of interest in the case of treatment of radioactive effluents. For this purpose, polystyrene from industrial packaging was sulfonated using a solution containing H2SO4, ethylenediamine tetraacetic acid and benzene. The sulfonation conditions were optimized: solid/liquid ratio: S/L, temperature and sulfonation time. Adsorption tests were carried out under different conditions of temperature (25°C, 40°C and 50°C), contact time (4, 6 and 8 h) and S/L ratios (1:5, 2:5 and 1:2). Sulfonation was followed by Fourier-transform infrared spectroscopy. The characterization showed the main peaks of: O=S=O at 1,030–1,050 cm–1. The examination of the polymeric microstructure was carried out by scanning electron microscopy analysis. Adsorption tests were followed by plasma induction spectrometry quantitative analysis inductively coupled plasma-atomic emission spectroscopy. Cs was the best adsorbed of the three elements, with more than 98% for 50°C and 6 h, followed by Co, and Sr. The best values were 14.91% for Co and 4.70% for Sr. The best adsorption conditions were to the advantage of the average conditions of temperature and time.
Teicoplanin (TEIC) is a glycopeptide antimicrobial medication for management of several bacterial infectious diseases caused by gram-positive bacteria including methicillin-resistant Staphylococcus ...aureus and Enterococcus faecalis. Novel, very simple, fast and cost-effective two spectrofluorimetric methods were developed for the ultra-trace determination of TEIC in pharmaceutical vials and human plasma. The investigated methods based on measuring the fluorescence of TEIC in methanol (method A) and enhancing its fluorescence by 10 folds using silver nanoparticles (AgNPs) without any solvent extraction (method B). The fluorescence of TEIC was investigated at 385nm (excitation at 335 nm) with calibration ranged from 1 to 25 ng mL−1 and from 0.6 to 30 ng mL−1 with Limit of detection (LOD) of 280 and 160 pg mL−1 for method A and B respectively. The established methods were optimized, validated and bio-analytically validated via ICH and US-FDA guidelines. The performed methods were used to determine TEIC in human plasma with high percentage recovery of 98.8 ± 1.75. Further, the proposed methods were applied to study the stability of TEIC after exposure to various degradation stress conditions and kinetic degradations.
•Ultra-sensitive spectrofluorimetric methods for determination of Teicoplanin (TEIC) at nanogram level were developed.•The developed methods based on measuring of the fluorescence in methanol and enhancement of TEIC fluorescence using AgNPs•The proposed method was validated according to ICH guidelines and bio-analytical validated using FDA recommendations.•The proposed methods were applied in dosage form, human plasma and stability kinetic degradation studies were established.
•Cbi(AT)2 is a potent antidote for cyanide, hydrogen sulfide and methanethiol.•The developed method is the first to analyze Cbi(AT)2 in any biological matrix.•The method is sensitive (LOD = 0.3 μM) ...and has a wide dynamic range (2 – 500 μM).•Cbi(AT)2 was easily detected in the plasma of Cbi(AT)2-treated swine.•Day-to-day carryover, a major problem for Cbi analysis, was eliminated in < 1 h.
Cyanide, hydrogen sulfide, and methanethiol are common toxic inhalation agents that inhibit mitochondrial cytochrome c oxidase and result in cellular hypoxia, cytotoxic anoxia, apnea, respiratory failure, cardiovascular collapse, seizure and potentially death. While all are occupational gas exposure hazards that have the potential to cause mass casualties from industrial accidents or acts of terrorism, only cyanide has approved antidotes, and each of these has major limitations, including difficult administration in mass-casualty settings. While bisaminotetrazole cobinamide (Cbi(AT)2) has recently gained attention because of its efficacy in treating these metabolic poisons, there is no method available for the analysis of Cbi(AT)2 in any biological matrix. Hence, in this study, a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of Cbi(AT)2 in swine plasma. The method is extremely simple, consisting of protein precipitation, separation and drying of the supernatant, reconstitution in an aqueous solvent, and LC-MS/MS analysis. The method produced an LOD of 0.3 μM with a wide dynamic range (2 – 500 μM). Inter- and intraassay accuracies (100 ± 12 % and 100 ± 19 %, respectively) were acceptable and the precision (<12 % and < 9 % relative standard deviation, respectively) was good. The developed method was used to analyze Cbi(AT)2 from treated swine and the preliminary pharmacokinetic parameters showed impressive antidotal behavior, most notably a long estimated elimination half-life (t1/2 = 37.5 h). This simple and rapid method can be used to facilitate the development of Cbi(AT)2 as a therapeutic against toxic cyanide, hydrogen sulfide and methanethiol exposure.
•A water-cooled tungsten monoblock divertor concept has been considered in the K-DEMO.•The detached divertor study has been carried out by the impurity seeding for N, Ne, and Ar to reduce the peak ...heat flux and particle flux.•The optimum designs were derived by the response surfaces optimization method for CuCrZr and RAFM steel, the major candidates for the heat sink in the K-DEMO.•The alternative divertor concepts were studied for the super X-divertor and snowflake divertor.
The preliminary conceptual design of the Korean fusion demonstration reactor (K-DEMO) with a major radius of 6.8 m and the fusion power of 2200 MW has been studied since 2012. The overall configuration of the K-DEMO divetor system based on the ITER-like water-cooled tungsten technology is a double-null type symmetric divertor subdivided into 32 toroidal modules for the vertical maintenance. A detached divertor scenario with impurity seeding was considered as the primary approach for the power exhaust to reduce the peak heat flux lower than the engineering limit of 10 MW/m2. The power exhaust performance at the scrap off layer was estimated by using UEDGE-2D code, a two-dimensional fluid transport code for collisional edge plasma and neutral species like N, Ne, and Ar. Particle and heat flux on inboard and outboard divertor targets were calculated for the detached cased depending on parameters such as the impurity seeding rate, pumping rate, and the pedestal density. On the other hand, a magnetic solution like X-divertor, snowflake divertor, and super X-divertor to expand the plasma wet area was considered for K-DEMO since the detached divertor increasing a radiation fraction by impurity seeding might be able to be unstable. However, the extremely high current of poloidal coils was required more than the engineering limit, 20 MA, to form magnetic field lines for the alternative divertors.
Based on the physical calculation of the edge plasma, engineering analyses were carried out to find out the thermal and structural reliability. The thermo-hydraulic analysis confirmed thermal stability, whether all comprising materials are operating within their allowable temperature windows when the case of the peak heat flux is set to 10 MW/m2 on the outboard divertor target. The response surface optimization method derived two optimal design candidates employing two kinds of heat sink materials, respectively: the reduced activation ferritic martensitic (RAFM) steel and CuCrZr alloy. The drawbacks and merits of the two materials were definite. The optimal design with applying RAFM steel was vulnerable to withstand thermal and mechanical loads since low thermal conductivity caused too thin thickness of the heat sink. On the other hand, the CuCrZr alloy has critical drawbacks in terms of activation and radioactive waste despite its high thermal conductivity. Meanwhile, preliminary electromagnetic (EM) analysis was carried out to estimate the EM loads caused by the abnormal behaviors of plasma since EM loads are one of the most critical external loads for designing a DEMO divertor.
OBJECTIVE—To examine select adipokines, including fatty acid–binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) ...mortality among patients with type 2 diabetes mellitus.
APPROACH AND RESULTS—Plasma levels of fatty acid–binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993–2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid–binding protein 4 were significantly associated with a higher CVD mortalitycomparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22–2.59; P trend=0.001). A positive association was also observed for HMW adiponectinthe hazard ratio (95% confidence interval) was 2.07 (1.42–3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50–1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance.
CONCLUSIONS—These data suggest that higher levels of fatty acid–binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus.
Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is ...limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI.
We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography.
Guangzhou, China.
Guangzhou Nutrition and Health Study participants, aged 40-75 years at baseline (n 3051).
After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2-5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD.
Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.
Glycine analysis is important in research fields such as physiology and healthcare because the concentration of glycine in human plasma has been reported to change with various disorders. Glycine ...oxidase from Bacillus subtilis (GlyOX) is useful for quantitative analysis of glycine. However, GlyOX is not sufficiently stable for use in physiology-based research or clinical settings. In this report, site-directed mutagenesis was used to engineer a GlyOX mutant suitable for glycine analysis. The GlyOX triple-mutant (T42 A/C245 S/L301V) retained most of its enzymatic activity during storage for over a year at 4 °C. A colorimetric enzyme analysis protocol was established using the GlyOX triple-mutant to determine glycine concentrations in human plasma. The analysis showed high accuracy (−5.4 to 3.5% relative errors when compared with the results from an amino acid analyzer, and 96.0–98.7% recoveries) and high precision (<4% between-run variation). Sample pretreatments of deproteinization and derivatization were not required. Therefore, this novel enzymatic analysis offers an effective and useful method for determining glycine concentrations in physiology related research and the healthcare field.
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•A glycine oxidase triple-mutant was engineered by site-directed mutagenesis.•The mutant enzyme remained active when stored for over a year at 4 °C.•The mutant enzyme was used to accurately and precisely quantify glycine in human plasma.•Pretreatment of human plasma is not required for this glycine analysis.
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