Unveiling the Nature and Strength of Selenium-Centered Chalcogen Bonds in Binary Complexes of SeO2 with Oxygen-/Sulfur-Containing Lewis Bases: Insights from Theoretical Calculations.

Among various non-covalent interactions, selenium-centered chalcogen bonds (SeChBs) have garnered considerable attention in recent years as a result of their important contributions to crystal engineering, organocatalysis, molecular recognition, materials science, and biological systems. Herein, we systematically investigated π-hole-type Se∙∙∙O/S ChBs in the binary complexes of SeO2 with a series of O-/S-containing Lewis bases by means of high-level ab initio computations. The results demonstrate that there exists an attractive interaction between the Se atom of SeO2 and the O/S atom of Lewis bases. The interaction energies computed at the MP2/aug-cc-pVTZ level range from -4.68 kcal/mol to -10.83 kcal/mol for the Se∙∙∙O chalcogen-bonded complexes and vary between -3.53 kcal/mol and -13.77 kcal/mol for the Se∙∙∙S chalcogen-bonded complexes. The Se∙∙∙O/S ChBs exhibit a relatively short binding distance in comparison to the sum of the van der Waals radii of two chalcogen atoms. The Se∙∙∙O/S ChBs in all of the studied complexes show significant strength and a closed-shell nature, with a partially covalent character in most cases. Furthermore, the strength of these Se∙∙∙O/S ChBs generally surpasses that of the C/O-H∙∙∙O hydrogen bonds within the same complex. It should be noted that additional C/O-H∙∙∙O interactions have a large effect on the geometric structures and strength of Se∙∙∙O/S ChBs. Two subunits are connected together mainly via the orbital interaction between the lone pair of O/S atoms in the Lewis bases and the BD*(OSe) anti-bonding orbital of SeO2, except for the SeO2∙∙∙HCSOH complex. The electrostatic component emerges as the largest attractive contributor for stabilizing the examined complexes, with significant contributions from induction and dispersion components as well.

Inhibition of Wdr5 Attenuates Ang-II-Induced Fibroblast-to-Myofibroblast Transition in Cardiac Fibrosis by Regulating Mdm2/P53/P21 Pathway.

Cardiac fibrosis is an important pathological process in many diseases. Wdr5 catalyzes the trimethylation of lysine K4 on histone H3. The effects of Wdr5 on the cardiac fibrosis phenotype and the activation or transformation of cardiac fibroblasts were investigated by Ang-II-infused mice by osmotic mini-pump and isolated primary neonatal rat cardiac fibroblasts. We found that the Wdr5 expression and histone H3K4me3 modification were significantly increased in Ang-II-infused mice. By stimulating primary neonatal rat cardiac fibroblasts with Ang II, we detected that the expression of Wdr5 and H3K4me3 modification were also significantly increased. Two Wdr5-specific inhibitors, and the lentivirus that transfected Sh-Wdr5, were used to treat primary mouse cardiac fibroblasts, which not only inhibited the histone methylation by Wdr5 but also significantly reduced the activation and migration ability of Ang-II-treated fibroblasts. To explore its mechanism, we found that the inhibition of Wdr5 increased the expression of P53, P21. Cut&Tag-qPCR showed that the inhibition of Wdr5 significantly reduced the enrichment of H3K4me3 in the Mdm2 promoter region. For in vivo experiments, we finally proved that the Wdr5 inhibitor OICR9429 significantly reduced Ang-II-induced cardiac fibrosis and increased the expression of P21 in cardiac fibroblasts. Inhibition of Wdr5 may mediate cardiac fibroblast cycle arrest through the Mdm2/P53/P21 pathway and alleviate cardiac fibrosis.

Insight into the Effect of Counterions on the Chromatic Properties of Cr-Doped Rutile TiO2-Based Pigments.

Rutile TiO2 pigments codoped with chromophore ion Cr3+ and various charge-balancing ions (i.e., counterions species of Sb, Nb, W and Mo) were prepared by a solid-phase reaction method. The effects of the counterions and calcination temperatures on the phase structure, color-rendering and spectroscopic properties, microstructure, and stability of the synthesized pigments were investigated in detail. The results showed that the introduction of 5-10% counterions improved the solubility of Cr3+ in the TiO2 lattice to form the single-phase rutile pigments calcined at 1100 °C for 2 h. The 10% Cr-doped pigment showed a dark brown color. Depending on the content and type of counterions, the color of the codoped pigments was tailored from yellow to reddish or yellowish-orange to black with different brightness and hue. The influence mechanism of counterions was ascribed to the lattice distortion and variation in the charge balance condition. It was found that the addition of Sb, Nb, or Mo resulted in a remarkable improvement in the NIR reflectance of pigments. The grain growth was inhibited with the codoping of Cr/Sb and Cr/Nb to achieve the nano-sized pigments. In addition, the prepared pigments exhibited good acid and alkali corrosion resistance as well as excellent stability and coloring performance in transparent ceramic glazes.

Reverse transcription recombinase-aided amplification assay for rapid detection of the influenza A(H1N1)pdm09 H275Y mutation that confers oseltamivir resistance.

The emergence of the influenza A(H1N1)pdm09 virus with the NA-H275Y mutation, which confers oseltamivir resistance, must be monitored, especially in patients undergoing neuraminidase inhibitor treatment. In this study, we developed a reverse transcription recombinase-aided amplification assay that has high sensitivity (detection limit: 1.0 × 101 copies/µL) and specificity for detecting the oseltamivir-resistant H275Y mutation; the assay is performed within 30 min at a constant temperature of 39° Celsius using an isothermal device. This method is suitable for the clinical application of targeted testing, thereby providing technical support for precision medicine in individual drug applications for patients with severe infection or immunosuppression.

Interleukin-18 Enhances Vascular Calcification and Osteogenic Differentiation of Vascular Smooth Muscle Cells Through TRPM7 Activation.

OBJECTIVE: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear. We questioned whether IL-18 enhances VC and osteogenic differentiation of VSMCs through TRPM7 channel activation. APPROACH AND RESULTS: Coronary artery calcification and serum IL-18 were measured in patients by computed tomographic scanning and enzyme-linked immunosorbent assay, respectively. Primary rat VSMCs calcification were induced by high inorganic phosphate and exposed to IL-18. VSMCs were also treated with TRPM7 antagonist 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA to block TRPM7 channel activity and expression. TRPM7 currents were recorded by patch-clamp. Human studies showed that serum IL-18 levels were positively associated with coronary artery calcium scores (r=0.91; P<0.001). In VSMCs, IL-18 significantly decreased expression of contractile markers α-smooth muscle actin, smooth muscle 22 α, and increased calcium deposition, alkaline phosphatase activity, and expression of osteogenic differentiation markers bone morphogenetic protein-2, Runx2 (runt-related transcription factor 2), and osteocalcin (P<0.05). IL-18 increased TRPM7 expression through ERK1/2 (extracellular signal-regulated kinase 1/2) signaling activation, and TRPM7 currents were augmented by IL-18 treatment. Inhibition of TRPM7 channel by 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA prevented IL-18-enhanced osteogenic differentiation and VSMCs calcification. CONCLUSIONS: These findings suggest that coronary artery calcification is associated with increased IL-18 levels. IL-18 enhances VSMCs osteogenic differentiation and subsequent VC induced by ß-glycerophosphate via TRPM7 channel activation. Accordingly, IL-18 may contribute to VC in proinflammatory conditions.

Semaphorin 3a transfection into the left stellate ganglion reduces susceptibility to ventricular arrhythmias after myocardial infarction in rats.

AIMS: Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. METHODS AND RESULTS: Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. CONCLUSION: Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.

Combination of high ankle-brachial index and hard coronary heart disease Framingham Risk Score in predicting the risk of ischemic stroke in general population.

Our previous study showed that the patients with more metabolic risk factors had higher risk of high ankle-brachial index (ABI), but the relationship between high ABI and the risk of severe cardiovascular and cerebrovascular diseases is still under debate. This study aims to evaluate this association in the general population. 1486 subjects of South China were recruited in the study. 61 subjects were defined as high ABI group (ABI≥1.3) and 65 subjects were randomly selected as normal ABI group (0.9

Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload.

AIM: To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. METHODS: Hydrogen peroxide (H2O2, 200 µmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. RESULTS: H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 µmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 µmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. CONCLUSION: Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

The diagnostic threshold of HbA1c and impact of its use on diabetes prevalence-a population-based survey of 6898 Han participants from southern China.

OBJECTIVE: The objective of this study is to determine the diagnostic threshold of HbA1c for diabetes and the impact of using it on diabetes prevalence. METHODS: A population-based stratified study was conducted in 2010 among community-dwelling adults aged ≥35years in southern China. Participants without previously-diagnosed diabetes (PDD) took oral glucose tolerance test (OGTT) and HbA1c assay. HbA1c diagnostic threshold was determined by receiver operating characteristic curve. RESULTS: A total of 6989 participants with mean age of 52years were recruited. The area under curve of HbA1c was 0.903 (95% CI: 0.883-0.922), with optimal cut-off value at 6.25% (sensitivity 75.6% and specificity 91.9%). There were 449 (6.42%) patients with PDD and 422 (6.04%), 815 (11.66%) and 918 (13.13%) new cases diagnosed by OGTT, HbA1c ≥6.25% or either, respectively. When either HbA1c or OGTT was used, newly-diagnosed diabetes prevalence increased by 117.4%. CONCLUSIONS: Diabetes is prevalent in southern China. Near half of the patients go undetected with current diagnostic criteria. HbA1c ≥6.25% may be the diagnostic threshold value but needs further verification. The introduction of HbA1c threshold into diabetes diagnosis in China will cause a substantial increase in diabetes prevalence and great challenge on the public healthcare system.

Overexpression of Sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post-myocardial infarction in rats.

The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper-innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus-mediated overexpression of Sema3a (SLV, n = 13) groups. Sham-operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth-associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 µg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper-reinnervation after infarction.

Inflammation and oxidative stress are associated with the prevalence of high aankle-brachial index in metabolic syndrome patients without chronic renal failure.

AIMS: High ankle-brachial index (ABI) is marker of increased cardiovascular morbidity and mortality, while the relationship and mechanism between high ABI and metabolic syndrome (MetS) are unclear. The objectives of this study were to determine the relationship and possible mechanism of MetS with high ABI. METHODS: 341 participants without CRF were recruited. Among these participants, 58 participants (ABI ≥ 1.3) were include in high ABI group and the other 283 participants (0.9 < ABI < 1.3) were include in normal ABI group. Furthermore, these 341 participants were also divided into MetS group (n = 54) and non-MetS group (n = 287). All participants received examinations including body mass index (BMI), ABI and related biochemical parameters. RESULTS: Compared with non-MetS group, the prevalence of high ABI was higher in MetS group (27.8% vs. 15%, p < 0.05). Participants with 3-4 metabolic risk factors had higher prevalence of high ABI than those with 0-1 metabolic risk factors (27.8% vs. 12.7%, p < 0.05). The prevalence of high ABI in overweight participants was higher than those with normal body weight. And the participants with hypertension also had higher prevalence of high ABI than normotensive participants. BMI, high-sensitivity C-reactive protein (hsCRP) and superoxide dismutase (SOD) were all higher in high ABI group than normal ABI group (p < 0.05). CONCLUSIONS: More metabolic risk factors have increased the risk of high ABI. Inflammation and oxidative stress are associated with prevalence of high ABI in metabolic syndrome patients without chronic renal failure.

Effects of valsartan on ventricular arrhythmia induced by programmed electrical stimulation in rats with myocardial infarction.

The impact of angiotensin II receptor blockers (ARBs) on electrical remodelling after myocardial infarction (MI) remains unclear. The purpose of the present study was to evaluate the effect of valsartan on incidence of ventricular arrhythmia induced by programmed electrical stimulation (PES) and potential link to changes of myocardial connexins (Cx) 43 expression and distribution in MI rats. Fifty-nine rats were randomly divided into three groups: Sham (n = 20), MI (n = 20) and MI + Val (20 mg/kg/day per gavage, n = 19). After eight weeks, the incidence of PES-induced ventricular tachycardia (VT) and fibrillation (VF) was compared among groups. mRNA and protein expressions of Cx43, angiotensin II type 1 receptor (AT1R) in the LV border zone (BZ) and non-infarct zone (NIZ) were determined by real-time PCR and Western blot, respectively. Connexins 43 protein and collagen distribution were examined by immunohistochemistry in BZ and NIZ sections from MI hearts. Valsartan effectively improved the cardiac function, reduced the prolonged QTc (163.7 ± 3.7 msec. versus 177.8 ± 4.5 msec., P < 0.05) after MI and the incidence of VT or VF evoked by PES (21.1% versus 55%, P < 0.05). Angiotensin II type 1 receptor expression was significantly increased in BZ and NIZ sections after MI, which was down-regulated by valsartan. The mRNA and protein expressions of Cx43 in BZ were significantly reduced after MI and up-regulated by valsartan. Increased collagen deposition and reduced Cx43 expression in BZ after MI could be partly attenuated by Valsartan. Valsartan reduced the incidence of PES-induced ventricular arrhythmia, this effect was possibly through modulating the myocardial AT1R and Cx43 expression.

[A case-crossover study on air pollutants and the mortality of stroke].

OBJECTIVE: To investigate the short-term effect of particulate matter in air on the mortality of stroke. METHODS: Using time-stratified case-crossover study design, an association was examined between stroke mortality and particulate matter with aerodynamic diameter of < 10 microm (PM10) of 2002 - 2004 in Hangzhou city. Meanwhile, the acute health effect of other gaseous pollutants (sulfur dioxide, SO2 and nitrogen dioxide, NO2) was also analyzed. RESULTS: A total of 9906 deaths of stroke were included. The crude stroke mortality was 83.54 per 100 000. After being adjusted for meteorological factors, when an increase of 10 microg/m3 in PM10, SO2 and NO2 in three days was noticed, it appeared that the increases of mortality of stroke were 0.56% (95% CI: 0.14%-0.99%), 1.62% (95% CI: 0.26% - 3.01%) and 2.07% (95% CI: 0.54% - 3.62%) respectively. There was no distinct association in multi-pollutant models. In sensitivity analysis, the associations were found in all single-pollutant models but not statistically significant in multi-pollutant models after replacing the missing values. CONCLUSION: It is suggested that the short-term elevation in PM10 as well as SO2 and NO2 daily concentrations were related to the increase of stroke mortality in Hangzhou city.