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Background: Autoantibody against M2-muscarinic acetylcholine receptor (anti-M2AChR) has a biological effect similar to a vagus agonist. Digoxin has a function of vagus nervous system stimulation. We hypothesized that anti-M2AChR is highly correlated with digoxin in patients with chronic heart failure (CHF). Methods: Synthetic M2AChR peptides served as the target antigen in an ELISA were used to screen the sera of 80 CHF patients, who were separated into a negative (–) or positive (+) anti-M2AChR group according to their anti-M2AChR reactivity. Echocardiography and serum digoxin concentration (SDC) were performed at baseline and after 1 year of digoxin in combination with the standard treatment regime. The end-point events were compared over 1 year of follow-up. Results: Seventy-two CHF patients completed the final data analysis, including 32 (+)anti-M2AChR and 40 (–)anti-M2AChR patients. The resting heart rate of the positive group was higher than that of the negative group at baseline (p < 0.05; 89.0 ± 1.6 vs. 83.8 ± 1.1 bpm). Both groups showed improvement in the left ventricular end-diastolic and end-systolic dimensions and ejection fraction with digoxin in combination with the standard treatment regime for 1 year (all p < 0.01). However, the 32 patients with (–)anti-M2AChR had greater improvements than the 40 patients with (+)anti-M2AChR, and this was accompanied by a marked decrease of rehospitalization (all p < 0.01) but not of cardiovascular mortality after 1 year. The SDC of patients with (–)anti-M2AChR was significantly lower than that of patients with (+)anti-M2AChR (p< 0.05; 0.63 ± 0.05 vs.1.16 ± 0.06 ng/mL) and had a positive correlation with anti-M2AChR (r = 0.81, p < 0.001). Conclusion: These results suggested that anti-M2AChR could be a useful biomarker of vagus nerve overactivation and is associated with a poor response to digoxin treatment in CHF patients. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we reported a missense mutation (C722G) in the M2-muscarinic acetylcholine receptor (CHRM2) gene associated with familial dilated cardiomyopathy. However, the exact molecular mechanisms by the related protein changes of CHRM2-C722G mutation induced are still unclear. CHRM2 and CHRM2-C722G lentiviral vector was infected to CHO cells. Proteomic analysis by label-free shotgun strategy and the STRING 9.0 software were performed. A total of 102 proteins with at least 2-fold change in the CHRM2-C722G group were identified, 42 proteins were up-regulated, whereas 57 were down-regulated. These altered proteins belong to three broad functional categories: (i) metabolic (e.g. Cytosolic acyl coenzyme A thioester hydrolase, Malate dehydrogenase); (ii) cytoskeletal (e.g. Actin-related protein, Myosin light polypeptide 6 and Alpha-actinin-1) and (iii) stress response (e.g. heat shock protein 70, Ras-related protein Rab-10). Interestingly, the marked differences in the expression of selected eight proteins (change >4.0-fold), were connected with many proteins related to apoptosis and immune/inflammatory response such as: FOS, BAX, MYC, TP53 and IL6. This novel study demonstrated for the first time a full-scale screening of the proteomics research by CHRM2-C722G mutation and profiled 102 changed proteins, of which, eight might be critical in cardiac dysfunction for future mapping. Significance: It was a full-scale screening of the proteomics research by CHRM2-C722G mutation. These proteins might serve as valuable biomarkers that could predict the presence of a precursor field. These proteins might serve to further explore the pathophysiological mechanisms in familial DCM patients with C176W mutation. [Copyright &y& Elsevier]

• We developed a novel iron-based metal organic framework (Fe-MOF) with excellent peroxidase-like activity. • The Fe-MOF was designed for detecting F− based on the strong interaction of F− toward Fe3+ and boronic groups of Fe-MOF. • A portable test kit based on the Fe-MOF was constructed for the visual determination of F− by using smartphone. Fluoride ion (F−) is an essential micronutrient in the human body, however, an abnormal large intake of F− can result in adverse effects, such as skeletal fluorosis or DNA damage. Therefore, it is of great significance to develop convenient assays for the visual detection of F− with high sensitivity. We rationally developed the nanosized iron-based metal organic frameworks (Fe-MOFs) by using 3,5-dicarboxybenzeneboronic acid as organic linkers and Fe3+ as metal ions through the solvothermal method, which can be applied for detecting F− with high sensitivity and selectivity owing to the specific recognition of boronic acid groups towards F− and the strong binding affinity between F− and Fe3+. The Fe-MOFs possess excellent peroxidase-like activity, which can be effectively inhibited by F−. Moreover, a portable test kit for the determination of F− was developed by embedding Fe-MOFs into hydrogel, and the visual measurement of F− was realized based on smartphone by identifying the color signal of the oxidation of 3,3',5,5'-tetramethylbenzidine dihydrochloride. The output signal (R/G) was linear with F− concentration in the range of 10.0–200.0 μM. The Fe-MOFs-based colorimetric strategy is easy-operation, low-cost and equipment-free, which has been further applied to detect F− in the real water samples. [ABSTRACT FROM AUTHOR]

Preparation of porous cement-based materials via freeze casting is a process with great potential. However, freeze-drying and steam curing complicate the preparation process and increase the preparation period. To simplify the process, heat-dry curing was used for replacing freeze-drying and steam curing during operation. The new preparation method combined freeze casting and heat-dry curing possesses characteristics of low-energy, simplicity, and time-saving. Compared with the traditional preparation method of porous cement-based materials, the novel preparation process can shorten preparation time by at least 16 % and retrench energy consumption by at least 18 %. As the improvement condition, temperature of heat-drying curing has great influence on the structure and performance of the samples. Therefore, it is of great significance to discuss the relationship between heat-dry temperatures and structural parameters by SEM, N 2 -adsorption/desorption, TG, and ATR-FTIR. Lamellar pores of membranes can be easier observed at low temperatures than that at 100 °C. The separation performance of oil-water is generally improved with the increase of temperature. Meanwhile, the molecular dynamics simulation was operated to illustrate the reaction mechanism of hydration with three temperatures. This study probably provides more theoretical basis for expanding the application of porous silicate cement membranes. [Display omitted] • Novel coupled method simplifies the fabricating process complexity of cement-based samples. • Influences of heat-dry curing temperatures on porous silicate cement membranes are discussed. • Silicate cement membranes own excellent permeation, oil-water separation and mechanical strengths. • Influences of heat-dry curing temperatures are illustrated by using molecular dynamics. [ABSTRACT FROM AUTHOR]

Preparation of porous cement-based materials via freeze casting is a process with great potential. However, freeze-drying and steam curing complicate the preparation process and increase the preparation period. To simplify the process, heat-dry curing was used for replacing freeze-drying and steam curing during operation. The new preparation method combined freeze casting and heat-dry curing possesses characteristics of low-energy, simplicity, and time-saving. Compared with the traditional preparation method of porous cement-based materials, the novel preparation process can shorten preparation time by at least 16 % and retrench energy consumption by at least 18 %. As the improvement condition, temperature of heat-drying curing has great influence on the structure and performance of the samples. Therefore, it is of great significance to discuss the relationship between heat-dry temperatures and structural parameters by SEM, N 2 -adsorption/desorption, TG, and ATR-FTIR. Lamellar pores of membranes can be easier observed at low temperatures than that at 100 °C. The separation performance of oil-water is generally improved with the increase of temperature. Meanwhile, the molecular dynamics simulation was operated to illustrate the reaction mechanism of hydration with three temperatures. This study probably provides more theoretical basis for expanding the application of porous silicate cement membranes. [Display omitted] • Novel coupled method simplifies the fabricating process complexity of cement-based samples. • Influences of heat-dry curing temperatures on porous silicate cement membranes are discussed. • Silicate cement membranes own excellent permeation, oil-water separation and mechanical strengths. • Influences of heat-dry curing temperatures are illustrated by using molecular dynamics. [ABSTRACT FROM AUTHOR]

Abstract: Two rhodamine-based NO probes were designed and synthesized. Both RB-TP and RB-Py can detect NO by spectroscopic and ‘naked-eye’ methods in HEPES buffer assisted by Cu2+. The detection limits for NO were 5 nM and 20 nM, respectively. Other biologically relevant reactive species, such as , H2O2, 1O2, and ClO− did not give any obvious interferences. RB-TP and RB-Py have been also applied to detect the intracellular NO by fluorescence imaging method. [Copyright &y& Elsevier]

One-stage degradation process was observed for a poly(methyl methacrylate) (PMMA) sample. The fractional conversion αmax at the maximum reaction rate is thus applied to determine reaction order of the thermal degradation. It is found that the PMMA degraded in the first order kinetics with weight loss. This is consistent with the fact that PMMA thermally degrades into its monomer. Activation energy was calculated. Compensation effect of the Arrhenius parameters is also found. [Copyright &y& Elsevier]

A number of studies have suggested that autoantibodies against β1-adrenoreceptors (β1R-AAbs) have an important role in pathophysiological processes of heart failure. The aim of the present study was to determine whether β1R-AAbs are implicated in cardiac dysfunction following acute myocardial infarction (AMI) and their association with prognosis. A total of 33 cases with systolic heart failure (SHF), 49 with diastolic heart failure (DHF) and 44 with normal heart function following AMI were recruited. β1R-AAbs were detected by ELISA and major adverse cardiac events (MACEs) were recorded during the 5-year follow-up. The positive rate of β1R-AAbs in the SHF group (45.5%) was significantly higher compared with that in the DHF (22.4%; P<0.05) and normal (15.9%; P<0.05) groups. The area under the receiver operating characteristics curve for the diagnosis of SHF was 0.630 (95% CI: 0.514–0.747, P=0.026). During a median follow-up period of 51.0±15.4 months, the positive rate of β1R-AAbs in the MACEs group was significantly higher compared with that in the non-MACEs group (P<0.05). Multivariate logistic regression analysis indicated that the left ventricular ejection fraction and diabetes were independent predictors of 5-year MACEs following AMI, whereas β1R-AAbs were not. Kaplan-Meier analysis revealed that the cumulative MACEs-free survival rate was the lowest in the SHF group, followed by the DHF and normal groups (P<0.05). Therefore, β1R-AAbs were indicated to be of value for early diagnosis of SHF after AMI but not as independent predictors for the prognosis of patients with AMI. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is the leading cause of maternal and neonatal morbidity and mortality with incompletely understood etiopathogenesis. The purpose of the current study is to determine whether there is a relationship between the presence of autoantibodies against β1, β2 and α1 adrenoreceptors and severe pre-eclampsia. Methodology/Principal Findings: Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of β1, β2 and α1 adrenoreceptors were synthesized as antigens to test 34 patients with severe pre-eclampsia, 36 normal pregnancy women and 40 non-pregnant controls for the presence of autoantibodies using enzyme-linked immunosorbent assay. The respective frequencies of autoantibodies against β1, β2 and α1 adrenoreceptors were 50.0% (17/34), 52.9% (18/34) and 55.9% (19/34) in patients with severe pre-eclampsia, 19.4% (7/36) (p = 0.011), 19.4% (7/36) (p = 0.006) and 17.6% (6/36) (p = 0.001) in normal pregnancy women and 10% (4/40), 7.5% (3/40) and 10% (4/40) (p<0.001) in non-pregnant controls. Titers of these autoantibodies were also significantly increased in patients with severe pre-eclampsia. By logistic regression analysis, the presence of these three autoantibodies significantly increased the risk of neonatal death (odds ratio, 13.5; 95% confidence interval, 1.3–141.3; p = 0.030) and long-term neonatal hospitalization (odds ratio, 5.0; 95% confidence interval, 1.3–19.1; p = 0.018). The risk of hypertension and fetal distress were also associated with the presence of these three autoantibodies. Conclusions/Significance: This novel pilot study demonstrated for the first time that the presence of autoantibodies against β1, β2 and α1 adrenoreceptors are increased in patients with severe pre-eclampsia. Pregnant women who are positive for the three autoantibodies are at increased risks of neonatal mortality and morbidity. We posit that these autoantibodies may be involved in the pathogenesis of severe pre-eclampsia. [ABSTRACT FROM AUTHOR]

Abstract: The geometrical structures and electronic properties of six fullerene isomers of C100 were studied at the HF/6-31G⁎ and B3LYP/6-31G⁎ levels, respectively. The results of the fully optimized calculations show that three C100 isomers 449:D2, 425:C1 and 442:C2 are near isoenergetic isomers. The energies and properties of C100 hexaanions were calculated. The C100 6− (450:D5) isomer is predicted to be the most stable isomer at the B3LYP/6-31G⁎ level, and the C100 6− (449:D2) isomer is 44.1kcal/mol higher in energy. The heterofullerenes C96X4 (X=N, P, B, Si) formed from the initial C100 (449:D2) have also been investigated at the B3LYP/6-31G⁎ level. The HOMO–LUMO gaps and aromaticities show that the replacement of fullerene carbon atoms with four heteroatoms can enhance the electronic stabilization of C100 (449:D2). [Copyright &y& Elsevier]

Abstract: The structural and electronic properties of hydrogenated armchair and zigzag SWCNTs with carbon ad-dimer (CD) defect were investigated by means of the B3LYP hybrid density functional method using 6-31G∗ basis set. It is found that the chemisorptions of two hydrogen atoms inside and outside the CD defective SWCNTs are exothermic processes. Exohedral nanotube adsorption is energetically more favorable than endohedral adsorption. These results are in agreement with hydrogen on pristine nanotubes. The positional preference for the chemisorption of two hydrogen atoms is the same for the CD defective armchair and zigzag nanotubes. However, the reaction energy of two hydrogen atoms on the exterior sidewalls of CD defective SWCNTs is almost independent of the tube diameter. This is different from the results reported on pristine nanotubes. The calculated energy gaps indicate that the hydrogen-chemisorbed CD defective armchair tubes are always wide energy gap structures, while the hydrogen-chemisorbed CD defective zigzag tubes have significantly lower gaps. The HOMO–LUMO gap and reaction energy for the chemisorption of more hydrogen atoms on the exterior sidewalls of CD defective armchair SWCNTs were also explored. [ABSTRACT FROM AUTHOR]

Abstract: Based on the recently isolated and characterized nanotube-like D 5 h C90 fullerene, the nonclassical hept-C100 fullerene created by inserting symmetrically five C2 around the circumference of D 5 h C90 and its derivatives C100 X 10 (X =H, F, Cl, and Br) have been reported here. The geometrical structures and electronic properties of them are studied using density functional theory (DFT) at the B3LYP/6-31G∗ level of theory. The reaction energies, HOMO–LUMO gaps, and aromaticities all show that the nonclassical fullerene derivatives C100H10, C100F10, C100Cl10, and C100Br10 are molecules with high stability; the stable behavior resembles the well-known C50 X 10 (X =H, F, Cl, and Br). It is quite possible that they can be synthesized experimentally. [Copyright &y& Elsevier]

Abstract: Ab initio and density functional theory (DFT) methods at the HF/6-31G*, B3LYP/6-31G*, MP2/6-31G*, and MP2/TZVP levels of theory were applied to the investigation of the relative stability of six fullerene isomers of C32. Full geometry optimization of the systems was carried out and electrostatic potential distributions were calculated. The effect of electron correlation on the electrostatic potential distribution of C32 isomers was analyzed. [Copyright &y& Elsevier]

Abstract: Pre-column derivatization allowed stacking amino acid enantiomers on C18 reversed-phase micro extraction columns, thus facilitating sample loading in capillary HPLC/tandem mass spectrometry. Two tagging reagents, i.e. 7-fluoro-4-nitrobenzoxadiazole (NBD-F) and 1-fluoro-2,4-dinitrobenzene (DNB-F) were evaluated. Both of them reacted readily with amino acids at an elevated temperature, resulting in derivatives that were effectively stacked and suitable for a sensitive MS/MS detection as well. Separation of the tagged enantiomers on a teicoplanin chiral stationary phase (CSP) with mobile phases compatible with MS detection was investigated. NBD-amino acid enantiomers (12 pairs) tested were all base-line resolved. However, the efforts to separate DNB-F tagged amino acid enantiomers on this CSP were not successful. Separation conditions including pH, organic modifiers, and column dimension were studied. All the NBD-amino acids studied could be sensitively detected by MS/MS detection set in the negative ion mode, but only a few including NBD-Asp, BND-Glu, NBD-Ser, and NBD-Thr were detected in the positive ion mode. Thus, the selectivity for enantiomeric determination of excitatory amino acids (e.g. Asp and Glu) was further improved by choosing MS/MS detection in the positive ion mode. [Copyright &y& Elsevier]

Enantiomers of clenbuterol were directly separated by a new high performance chromatographic method on Chirex 3005 column. Several parameters such as mobile phase composition, column temperature and flow rate were studied. Baseline enantioseparation was achieved, using the optimized mobile phase of n-hexane–1,2-dicholoethane–methanol (54:38:8, v/v/v) at 17 °C and 1.0 ml/min, with the separation factor (α) 1.43 and the resolution factor (RS) 1.81. The mechanism of separation was also discussed. Standard linear calibration cures were established for the R- and S-enantiomers, over the range of 26.1–1045.8 and 5.7–229.6 nmol/ml, with the correlation coefficient of 0.9999 for both. The limits of detection were 0.47 and 1.04 nmol/ml for R- and S-enantiomers, respectively. Recovery and precision of the method were also evaluated, which had been successfully used to monitor and identify quantitatively the profile of the clenbuterol enantiomers in human serum. [Copyright &y& Elsevier]

In this article, a novel fluorescent probe (NRBE) for detecting H 2 O 2 was developed using benzyl boronic ester as the H 2 O 2 -recognized group and Nile red as the matrix. The probe has several advantages, such as good selectivity, high sensitivity (LOD = 75 nM), good water solubility and emission in the near-infrared region (ex/em:585/670 nm). With the NRBE probe, the endogenous H 2 O 2 in human hepatocellular carcinoma cells BEL-7402, was detected, and the H 2 O 2 generated during the ischemia-reperfusion of the cells was imaged. These results show that NRBE can be applied for real-time detection of H 2 O 2 in biological systems. Unlabelled Image • A novel Nile red-based fluorescent probe NRBE was designed and synthesized for H 2 O 2 detection. • The probe has good selectivity, high sensitivity, good water solubility and emission in the near-infrared region. • The probe can be applied for real-time detection of H 2 O 2 in biological systems. [ABSTRACT FROM AUTHOR]

Halogenated pyridin-2(1H)-ones are facile and efficiently synthesized via one-pot Vilsmeier cyclization of readily available ketene-N,S-acetal derivatives (IV). [ABSTRACT FROM AUTHOR]