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The magnetic properties of monoclinic VO 2 (M1) nanobelts synthesized by the hydrothermal method are investigated. The VO 2 (M1) nanobelts exhibit ferromagnetism at room temperature, which disagrees with previous literatures. The excessive oxygen vacancies induce the ferromagnetic nature of VO 2 (B) nanobelts, which is attributed to the fact that the Bader charge of V atom changes from +2.34 to +1.84 (V +4 to V +3 ) based on the calculations by using density functional theory (DFT). The calculations indicate that oxygen vacancy may induce the presence of V 3+ atom, in agreement with experimental observations. The observed ferromagnetism should be a result of oxygen vacancies in VO 2 (M1) nanobelts.

The near-surface freeze/thaw cycle in cold regions plays a major role in the surface energy budget, hydrological activity, and terrestrial ecosystems. In this study, the Community Land Model, Version 4 and a suite of high-resolution atmospheric data were used to investigate the changes in the near-surface soil freeze/thaw cycle in response to the warming on the Tibetan Plateau from 1981 to 2010. The in situ observations-based validation showed that, considering the cause of scale mismatch in the comparison, the simulated soil temperature, freeze start and end dates, and freeze duration at the near-surface were reasonable. In response to the warming of the Tibetan Plateau at a rate of approximately 0.44 °C decade−1, the freeze start-date became delayed at an area-mean rate of 1.7 days decade−1, while the freeze end-date became advanced at an area-mean rate of 4.7 days decade−1. The delaying of the freeze start-date, which was combined with the advancing of the freeze end-date, resulted in a statistically significant shortening trend with respect to the freeze duration, at an area-mean rate of 6.4 days decade−1. Such changes would strongly affect the surface energy flux, hydrological processes, and vegetation dynamics. We also found that the rate of freeze-duration shortening at the near-surface soil layer was approximately 3.0 days decade−1 lower than that at a depth of 1 m. This implied that the changes in soil freeze/thaw cycles at the near surface cannot be assumed to reflect the situation in deeper soil layers. The significant correlations between freeze duration and air temperature indicated that the shortening of the near-surface freeze duration was caused by the rise in air temperature, which occurred especially in spring, followed by autumn. These results can be used to reveal the laws governing the response of the near-surface freeze/thaw cycle to climate change and indicate related changes in permafrost.

Nitrobenzene is an important organic intermediate widely used in industry that can be hazardous to the environment. In our previous study, nitrobenzene showed genotoxic effect on soybean and tobacco plants at concentrations in the culture medium higher than 10 mg/L. The genotoxicity of nitrobenzene has been hypothesized to be multifactorial and reflective of the generation of free radicals; however, the mechanism has not been fully elucidated. The aim of this study was to investigate the relationship between the induction of genotoxicity and the production of free radicals in young seedlings of V. faba exposed to nitrobenzene, nitrobenzene + Vitamin C, and the controls (distilled water or Vitamin C). Micronucleus and chromosome aberration assays performed on root and leaf tissue of V. faba seedlings exposed to nitrobenzene (25 mg/L) demonstrated genotoxic effects which were partly reduced by Vitamin C at 25 mg/L. Increases in lipid peroxidase, O2•-, H2O2, superoxide dismutase and catalase activities were also observed in these tissues along with an attenuation of their induction by Vitamin C. Concomitant occurrence of genotoxicity and the generation of free radicals that are attenuated in the presence of Vitamin C, a scavenger of cellular free radicals, indicate that reactive oxygen species may contributes to genotoxicity of nitrobenzene in V. faba. These results are valuable for further understanding the genotoxicity mechanism of nitrobenzene.

It has been reported that bitter tastants decrease blood pressure and relax precontracted vascular smooth muscle. However, the underlying mechanisms remain unclear. The aim of the present study was to determine the mechanism underlying the vasorelaxant effect of the bitter tastants. Thoracic aortic rings were isolated from Wistar rats and contractions were measured using an isometric myograph. Intracellular Ca(2+) ([Ca(2+)]i) in single rat thoracic aortic smooth muscle cells was recorded by calcium imaging. Calcium currents in single cells were recorded using patch-clamp techniques. High K(+) (140 mmol/L) induced contractions in rat thoracic aortic rings that were inhibited by 3 mmol/L chloroquine, 3 mmol/L denatonium and 10 μmol/L nifedipine. In single rat thoracic aortic smooth muscle cells, high K(+) increased [Ca(2+)]i and this effect was also blocked by 3 mmol/L chloroquine and 10 μmol/L nifedipine. Under Ca(2+) -free conditions, high K(+) failed to induce contractions in rat thoracic aortic rings. On its own, chloroquine had no effect on the muscle tension of rat aortic rings and [Ca(2+) ]i. The vasorelaxant effects of chloroquine on precontracted rat thoracic aortic rings were not altered by either 1 μg/mL pertussis toxin (PTX), an inhibitor of Gαo/i-protein, or 1 mmol/L gallein, an inhibitor of Gβγ-protein. The results of patch-clamp analysis in single cells indicate that 1 mmol/L chloroquine blocks voltage-dependent L-type Ca(2+) channel (VDLCC) currents from both extracellular and intracellular sides. Together, the results indicate that chloroquine can block VDLCC, independent of PTX- and gallein-sensitive G-proteins, resulting in relaxation of high K(+)-precontracted thoracic aortic smooth muscle.

The electronic structure and thermoelectric property of GeTe are calculated by the First-principles calculations and Boltzmann transport theory. The deformation potential approximation and single parabolic band model are employed to compute the relaxation time. Owing to the accurate electronic structure calculated by Tran-Blaha modified Becke-Johnson (TB-mBJ) potential, the theoretical data (Seebeck coefficient, electrical conductivity and ZT) are in good agreement with experimental data. The thermoelectric property of n type is found to be significantly better than that of p type for temperature between 300 K and 800 K and carrier concentration between 1020cm−3 and 1022cm−3. For n type, the largest ZT value of 5.05 could be obtained at 2.5 × 1021cm−3 and 800 K, while for p type, the largest ZT value of 3.32 could be obtained at 7.0 × 1020cm−3 and 800 K. Our results give a valuable theoretical guidance for the high performance of GeTe through n doping.

In this study, a Nd(FeMo)12 alloy was prepared using a magnetic levitation melting furnace and subsequent heat treatment. The nitrides of this alloy, which exhibit uniaxial anisotropy, were then synthesized by gas-solid reaction. The melting process of the Nd(FeMo)12 alloy, as well as the microstructure and magnetic properties of the nitrides, was investigated by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and magnetometer measurements. A homogeneous Nd(FeMo)12 phase was obtained by magnetic levitation melting using a MoFe alloy as a raw material, followed by heat treatment for 72 h. The nitrogenation of the Nd(FeMo)12 alloy was investigated. The magnetic properties of Nd(FeMo)12N1.52 powders obtained at a nitriding temperature of 550 °C were enhanced after grinding. No phase decomposition occurred during grinding. The nitriding powders exhibited a fine polycrystalline structure after grinding, as determined by transmission electron microscopy. The coercivity of the powders increased with a decrease in particle size, and Nd(FeMo)12N1.52 nano-powders with a coercivity of 3800 Oe was prepared by 70 h of surfactant-assisted high energy ball milling. Nd(FeMo)12N1.52 powders obtained exhibit an HA of 11 T and TC of 598 K.

Introduction High throughput in vitro profiling of the cardiac Nav1.5 peak sodium current (INa) is widely used in cardiac safety screening. However, there is no standardized high throughput method to measure late INa. This study assessed the pharmacological and biophysical properties of veratridine and ATX-II, as well as the channel mutation (Nav1.5-∆KPQ) on the late INa. We describe a method for simultaneous measurement of both peak and late INa. Methods The planar patch clamp technique (QPatch) was applied to record the peak and late INa. Results The Nav1.5-∆KPQ mutant produced a small late INa (41.9 ± 5.4 pA) not large enough to enable compound profiling. In contrast in wild type Nav1.5 expressing cells veratridine (100 μM) and ATX-II (100 nM) enhanced concentration-dependent increases in the late INa (maximum responses of 1162.2 ± 258.5 pA and 392.4 ± 71.3 pA, respectively). Veratridine inhibited, whereas, ATX-II had a minimal effect, on the peak INa and preserved the current-voltage curve. Peak and late INa inhibition was characterized for 25 clinical INa blockers in the presence of ATX-II. Compound IC50 values for peak INa generated in the absence or presence of ATX-II correlated. The potency of the late INa block was found to be dependent on whether it was measured at the end of the depolarizing pulse or during the ramp. Discussion In the presence of ATX-II, both peak and late INa could be assessed simultaneously. Late INa may be best assessed using the maximum response obtained during the ramp of the voltage protocol.

Electronic and transport properties of Bi2O2Se under strain are calculated using Tran–Blaha modified Becke–Johnson (TB-mBJGGA) potential and semiclassical Boltzmann transport theories. The electronic band gap decreases with tensile and compressive in-plane strain. We predict that the n-type Seebeck coefficient can be increased under compressive in-plane strain, while the p-type Seebeck coefficient can be increased under tensile in-plane strain. Further, the power factor of n-type doping Bi2O2Se can be increased under compressive in-plane strain, while that of p-type doping Bi2O2Se can be increased under tensile in-plane strain. For p-type doping Bi2O2Se, large thermoelectric figure of merit (ZT ≈ 1.42) could be obtained under tensile strain (2.3%) at 800 K. Moreover, a higher ZT ≈ 1.76 could be achieved along the ZZ direction. This study demonstrates that the electronic and thermoelectric properties can be controlled by strain engineering in thermoelectric material.

Optical and magnetic properties of the perovskite barium niobate (BaNbO3) nanocubes are investigated before and after UV irradiation. The energy gap changes from 3.94 to 3.88 eV, and light absorpti...

[1] Permafrost and seasonally frozen ground conditions on the Tibetan Plateau were investigated using the Community Land Model, version 4 (CLM4), forced by a suite of new, high-resolution data. This new data set was highly accurate and had an advantage in the frozen ground simulations for its fine temporal and spatial resolution. The simulated current (1981–2000) near-surface permafrost area was 151.50 × 104 km2, which is close to, but slightly larger than, the range from previous studies (111.80 ~ 150.0 × 104 km2). The simulated current active layer thicknesses ranged from 0 to 4.74 m, with an average of 2.01 m. The other frozen ground parameters, such as the maximum freezing depths for seasonally frozen ground, the date of freeze start, the date of freeze end, and the freeze duration at 1 m depth, were also examined. Considering the issue of scale mismatch, the simulated soil temperature and other frozen ground parameters were reasonable compared to our observations. In response to the Plateau warming of approximately 0.44°C/decade from 1981 to 2010, the near-surface permafrost area decreased at a rate of 9.20 × 104 km2/decade, and the area-mean active layer thickness increased by 0.15 m/decade. The area-mean maximum freezing depth of the seasonally frozen ground decreased by 0.34 m/decade. At a depth of 1 m, the dates of freeze start for permafrost and seasonally frozen ground delayed linearly by 3.8 and 4.0 days/decade, respectively, while the dates of freeze end for them advanced linearly by 5.9 and 4.6 days/decade, respectively. These trends in the dates of freeze start and freeze end resulted in freeze durations that were shortened by 9.7 and 8.6 days/decade for permafrost and seasonally frozen ground, respectively. These results give detailed permafrost and seasonally frozen ground states as well as their changes, which will be useful for studying frozen ground's response to climate change and frozen ground engineering stabilization.

The electronic structure and thermoelectric property of Bi2S3 are investigated. The electron and hole effective mass of Bi2S3 is analyzed in detail, from which we find that the thermoelectric transportation varies in different directions in Bi2S3 crystal. Along ac plane the higher figure of merit (ZT) could be achieved. For n-type doped Bi2S3, the optimal doping concentration is found in the range of (1.0–5.0) × 1019 cm−3, in which the maximal ZT reaches 0.21 at 900 K, but along ZZ direction, the maximal ZT reaches 0.36. These findings provide a new understanding of thermoelectricity-dependent structure factors and improving ZT ways. The donor concentration N increases as T increases at one bar of pressure under a suitable chemical potential μ, but above this chemical potential μ, the donor concentration N keeps a constant.

The level of reactive oxygen species (ROS) and the activity of spontaneous, transient, localized Ca(2+) increases (known as Ca(2+) sparks) in tracheal smooth muscle cells (TSMCs) in an experimental allergic asthma mouse model has not yet been investigated. We used laser confocal microscopy and fluorescent dyes to measure ROS levels and Ca(2+) sparks, and we found that both events were significantly increased in TSMCs obtained from ovalbumin (OVA)-sensitized/-challenged mice compared with control mice. ROS levels began to increase in TSMCs after the first OVA challenge, and this increase was sustained. However, this elevation and Ca(2+)-spark increase was abolished after the administration of the ROS scavenger N-acetylcysteine amide (NACA) for 5days. Furthermore, a similar inhibition was also observed following the direct perfusion of NACA into cells isolated from the (OVA)-sensitized mice that were not treated with NACA. Moreover, we used 0.1-mM caffeine treatment to increase the Ca(2+) sparks in single TSMCs and observed cell shortening. In addition, we did not find increases in the mRNA levels of ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors in the tracheal smooth muscle cells of (OVA)-sensitized mice compared with controls. We concluded that ROS and Ca(2+) sparks increased in (OVA)-sensitized TSMCs. We found that ROS induces Ca(2+) sparks, and increased Ca(2+) sparks resulted in the contraction of (OVA)-sensitized TSMCs, resulting in the generation of airway hyperresponsiveness (AHR). This effect may represent a novel mechanism for AHR pathogenesis and might provide insight into new methods for the clinical prevention and treatment of asthma and asthmatic AHR.

Nitrobenzene (NB) is an important organic compound intermediate that is used widely in industry. In the present study, to evaluate the phytotoxicity and genotoxicity of NB on plants, Vicia faba was exposed to increasing concentrations of NB (5 mg L−1, 10 mg L−1, 25 mg L−1, 50 mg L−1, and 100 mg L−1). The data revealed that germination rate and radicle length of V. faba seedlings were promoted by low NB concentrations and short exposure periods, whereas these parameters were inhibited at greater NB concentrations and longer exposures. When assessed by mitotic index, micronucleus, and chromosomal aberration assays, NB showed dose-dependent genotoxicity at 0 mg L−1 to 50 mg L−1. Environ Toxicol Chem 2013;32:1426–1432. © 2013 SETAC

Therapeutic monoclonal antibodies (mAb) are often produced in Chinese hamster ovary (CHO) cells. Three commonly used CHO host cells for generating stable cell lines to produce therapeutic proteins are dihydrofolate reductase (DHFR) positive CHOK1, DHFR-deficient DG44, and DUXB11-based DHFR deficient CHO. Current Genentech commercial full-length antibody products have all been produced in the DUXB11-derived DHFR-deficient CHO host. However, it has been challenging to develop stable cell lines producing an appreciable amount of antibody proteins in the DUXB11-derived DHFR-deficient CHO host for some antibody molecules and the CHOK1 host has been explored as an alternative approach. In this work, stable cell lines were developed for three antibody molecules in both DUXB11-based and CHOK1 hosts. Results have shown that the best CHOK1 clones produce about 1 g/l for an antibody mAb1 and about 4 g/l for an antibody mAb2 in 14-day fed batch cultures in shake flasks. In contrast, the DUXB11-based host produced ∼0.1 g/l for both antibodies in the same 14-day fed batch shake flask production experiments. For an antibody mAb3, both CHOK1 and DUXB11 host cells can generate stable cell lines with the best clone in each host producing ∼2.5 g/l. Additionally, studies have shown that the CHOK1 host cell has a larger endoplasmic reticulum and higher mitochondrial mass.

MADS-box genes encode important transcription factors in plants that are involved in many processes during plant growth and development. An investigation of the soybean genome revealed 106 putative MADS-box genes. These genes were classified into two classes, type I and type II, based on phylogenetic analysis. The soybean type II group has 72 members, which is higher than that of Arabidopsis, indicating that soybean type II genes have undergone a higher rate of duplication and/or a lower rate of gene loss after duplication. Soybean MADS-box genes are present on all chromosomes. Like Arabidopsis and rice MADS-box genes, soybean MADS-box genes expanded through tandem gene duplication and segmental duplication events. There are many duplicate genes distributed across the soybean genome, with two genomic regions, i.e., MADS-box gene hotspots, where MADS-box genes with high degrees of similarity are clustered. Analysis of high-throughput sequencing data from soybean at different developmental stages and in different tissues revealed that MADS-box genes are expressed in embryos of various stages and in floral buds. This expression pattern suggests that soybean MADS-box genes play an important role in soybean growth and floral development.

Background Wenxin Keli is a popular Chinese herb extract that approximately five million Asians are currently taking for the treatment of a variety of ventricular arrhythmias. However, its electrophysiological mechanisms remain poorly understood. Methods and results The concentration-dependent electrophysiological effects of Wenxin Keli were evaluated in the isolated rabbit left ventricular myocytes and wedge preparation. Wenxin Keli selectively inhibited late sodium current (INa) with an IC50 of 3.8 ± 0.4 mg/mL, which was significantly lower than the IC50 of 10.6 ± 0.9 mg/mL (n = 6, P < 0.05) for the fast INa. Wenxin Keli produced a small but statistically significant QT prolongation at 0.3 mg/mL, but shortened the QT and Tp–e interval at concentrations ≥1 mg/mL. Wenxin Keli increased QRS duration by 10.1% from 34.8 ± 1.0 ms to 38.3 ± 1.1 ms (n = 6, P < 0.01) at 3 mg/mL at a basic cycle length of 2,000 ms. However, its effect on the QRS duration exhibited weak use-dependency, that is, QRS remained less changed at increased pacing rates than other classic sodium channel blockers, such as flecainide, quinidine, and lidocaine. On the other hand, Wenxin Keli at 1–3 mg/mL markedly reduced dofetilide-induced QT and Tp–e prolongation by attenuation of its reverse use-dependence and abolished dofetilide-induced early afterdepolarization (EAD) in four of four left ventricular wedge preparations. It also suppressed digoxin-induced delayed afterdepolarization (DAD) and ventricular tachycardias without changing the positive staircase pattern in contractility at 1–3 mg/mL in a separate experimental series (four of four). Conclusions Wenxin Keli suppressed EADs, DADs, and triggered ventricular arrhythmias via selective inhibition of late INa.

Both enhanced saturation magnetization and coercivity of the flower-shaped hexagonal Ba3V2O8 with a small amount of Ba3VO4.8 in coexistence have been investigated after UV irradiation. The barium vanadate flower is composed of nanosheets with thickness of ∼20 nm. The optical absorption edge changes from 3.85 eV to 3.67 eV after UV irradiation and absorption intensity becomes stronger. The mechanism of magnetic property change is discussed via density functional theory. The result shows that oxygen vacancy produces impurity level within the forbidden energy gap, leading to red shift of optical absorption edge and reduction of V atom from +5 to +4. This study gives a good understanding of the magnetic property induced by the valence state change in Ba3V2O8 nanostructure under the UV irradiation and provides a new route to obtain diluted magnetic semiconductors.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

The currently available treatments for severe asthma are insufficient. Infiltration of neutrophils rather than eosinophils into the airways is an important inflammatory characteristic of severe asthma. However, the mechanism of the phenotypic change from eosinophilic to neutrophilic inflammation has not yet been fully elucidated.In the current study, we examined the effect of lipopolysaccharides (LPS) on eosinophilic asthmatic mice sensitized with ovalbumin (OVA), as well as the roles of interleukin (IL)-17A/T helper (Th) 17 cells on the change in the airway inflammatory phenotype from eosinophilic to neutrophilic inflammation in asthmatic lungs of IL-17A-deficient mice.Following exposure of OVA-induced asthmatic mice to LPS, neutrophil-predominant airway inflammation rather than eosinophil-predominant inflammation was observed, with increases in airway hyperresponsiveness (AHR), the IL-17A level in bronchoalveolar lavage fluid (BALF) and Th17 cells in the spleen and in the pulmonary hilar lymph nodes. Moreover, the neutrophilic asthmatic mice showed decreased mucus production and Th2 cytokine levels (IL-4 and IL-5). In contrast, IL-17A knockout (KO) mice exhibited eosinophil-predominant lung inflammation, decreased AHR, mucus overproduction and increased Th2 cytokine levels and Th2 cells.These findings suggest that the eosinophilic inflammatory phenotype of asthmatic lungs switches to the neutrophilic phenotype following exposure to LPS. The change in the inflammatory phenotype is strongly correlated with the increases in IL-17A and Th17 cells.

Perovskite-type structure BaNbO3 and Fe/Co-doped BaNbO3 nanocubes with a pure cubic phase have been synthesized by a composite-hydroxide-mediated method. X-ray diffraction and X-ray photoelectron s...

Background The ventricular components (QRS and QT) on the electrocardiogram (ECG) depend on the properties of ventricular action potentials that can be modulated by drugs via specific ion channels. However, the correlation of ECG ventricular waveforms with underlying ion actions is not well established and has been extensively debated. Objective To conduct a blinded in vitro assessment of the ionic mechanisms for drug-induced ECG changes. Methods and Results Fourteen cardiac and noncardiac drugs with known effects on cardiac ion channels were selected by the study sponsor, and were tested in the rabbit left ventricular wedge preparation with recording of the ECG and contractility. The investigators who performed the experiments and analyzed the data were blinded to names, concentrations, and molecular weights of the drugs. The compounds were prepared by the sponsor and sent to the investigators as 56 stock solutions. The effects of I Kr , I Ks , I Ca,L , I Na blocker, and I KATP opener on QRS, QT, and T p-e , were evaluated. Disclosure of the names and concentrations after completion of the study revealed that there were highly correlated ECG changes with underlying ionic mechanisms and proarrhythmic potential of drugs that, respectively, target I Kr , I Ks , I Ca,L , I Na , and I KATP . Among ECG parameters, T p-e was more useful in differentiating drugs' actions. Conclusions Specific electrophysiological action and the consequent proarrhythmic potential of a drug can be accurately determined by analysis of drug-induced changes in ECG in the rabbit left ventricular wedge preparation. Change in T p-e provides the most relevant information.

The electronic structure and optical properties of SnO 2 with consideration of oxygen vacancy are computed using the first-principles plane-wave pseudopotential method based on the density functional theory. The results show that SnO 2 with oxygen vacancy has a band gap of 1.03 eV, and the Fermi level shift upward to the conduction band, showing a typical n-type character; besides oxygen vacancy would introduce a new electronic state within the band gap compared with that of pure SnO 2 . Moreover, certain impurity levels are located near the top of the valence band, which narrows the band gap of the compound. Optical properties, including the dielectric function, reflectivity, absorption coefficient and the energy-loss spectrum are calculated and the results are in good agreement with the experiments. The calculated absorption coefficient shows that SnO 2 with oxygen vacancy exhibits an absorption band in the visible region, centered at 2.10 eV (588 nm). It is demonstrated that oxygen vacancy causes the visible light absorption band.

PbMoO 4 dendrites have been synthesized by the composite molten salt method at 180 °C. The dendritic plane is exposed on (0 0 1) facet. PbMoO 4 dendritic crystals exhibited high photocatalytic activity through the degradation of rhodamine B under the irradiation of the simulated sunlight, mainly due to the exposed facet (0 0 1). The (0 0 1) facet is assumed to provide more multi-atomic centers (PbMo 4 ), which are the origin of the active sites for hydrophilicity and adsorption of O 2 and the cause of the high photocatalytic activity. The photocatalytic activity of the PbMoO 4 dendrites was also compared with those of the conventional catalysts, P25 (21 nm) and TiO 2 nanoparticles (50–200 nm).

Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells. Proliferation and migration of SW620 cells were induced by the protease-activated receptor 2-agonist peptide (PAR2-AP, 100 μmol/L) or factor VIIa (10 nmol/L), and analyzed using MTT and Transwell assays, respectively. The cellular cytoskeleton was stained with rhodamine-conjugated phalloidin and examined with a laser scanning confocal fluorescence microscope. The expression of caspase-7, tissue factor (TF) and matrix metalloproteinase (MMP)-9 in the cells was examined using QT-PCR, ELISA and Western blot assays. The activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor-kappa B (NF-κB) signaling pathways was analyzed with Western blot. Both PAR2-AP and factor VIIa promoted SW620 cell proliferation and migration, and caused cytoskeleton reorganization (increased filopodia and pseudopodia). Pretreatment with EGCG (25, 50, 75, and 100 μg/mL) dose-dependently blocked the cell proliferation and migration induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) prevented the cytoskeleton changes induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) counteracted the down-regulation of caspase-7 expression and up-regulation of TF and MMP-9 expression in the cells treated with PAR2-AP or factor VIIa. Furthermore, it blocked the activation of ERK1/2 and NF-κB (p65/RelA) induced by PAR2-AP or factor VIIa. EGCG blocks the proliferation and migration of SW620 cells induced by PAR2-AP and factor VIIa via inhibition of the ERK1/2 and NF-κB pathways. The compound may serve as a preventive and therapeutic agent for colon cancers.

BACKGROUND AND PURPOSE Drug-induced torsades de pointes (TdP) often occurs during bradycardia due to reverse use-dependence. We tested the hypothesis that inhibition or enhancement of late sodium current (INa,L) could modulate the drug-induced reverse use-dependence in QT and Tp-e (an index of dispersion of repolarization), and therefore the liability for TdP.

Abnormal rate adaptation of ventricular repolarization is arrhythmogenic. There is controversy on the underlying ionic mechanisms for rate-dependent change in repolarization.The purpose of this study was to examine the role of the late sodium current (I(Na-L)) in normal rate-dependence of ventricular repolarization and reverse use-dependence of QT-prolonging agents.The effects of I(Na-L) blockade, I(Na-L) enhancement, I(Kr) blockade, and changes in extracellular potassium concentration ([K(+)](o)) on rate adaptation of the QT interval and action potential duration (APD) were examined in isolated rabbit ventricular wedges and single myocytes. Rate dependence of I(Na-L), delayed rectifier potassium current (I(K)), and L-type calcium current (I(Ca)) was determined using a whole-cell, voltage clamp technique.At control, APD exhibited rate-dependent changes in the multicellular preparations as well as in the isolated single ventricular myocytes when [K(+)](o) remained constant. The rate dependence of APD was significantly enhanced by reduction of [K(+)](o) from 4 to 1 mM or by I(Na-L) enhancement but was markedly blunted by the selective sodium channel blocker tetrodotoxin. The I(Kr) blocker dofetilide (3 nM) amplified the QT to basic cycle length slope (71.2 ± 13.1 ms/s vs 35.1 ± 8.8 ms/s in control, n = 4, P.05). This reverse use-dependence was abolished by tetrodotoxin at 5 μM (11.4 ± 4.3 ms/s, n = 4, P.01). There were no significant differences in I(Ca) or I(K) over the range of basic cycle lengths from 2,000 to 500 ms. However, I(Na-L) exhibited a significant rate-dependent reduction.I(Na-L) is sensitive to rate change due to its slow inactivation and recovery kinetics and plays a central role in the rate dependence of APD/QT and in the reverse use-dependence of select APD/QT-prolonging agents.

Freezing and thawing processes at the soil surface play an important role in determining the nature of Tibetan land and atmosphere interactions. In this study, land surface water and heat exchanges under different freezing and thawing conditions over the central Tibetan Plateau were investigated using observations from the Coordinated Enhanced Observing Period/Asia-Australia Monsoon Project on the Tibetan Plateau, and the Simultaneous Heat and Water Model. During the freezing and thawing stages, significant diurnal variation of soil temperature resulted in a diurnal cycle of unfrozen water content at the surface. Radiation and energy components and evapotranspiration averaged over four freeze/thaw stages also changed diurnally. On average, the surface albedo (0·68) during the completely frozen stage was sharply higher than those during the freezing, thawing, and completely thawed stages due to the snow cover. The Bowen ratios were 3·1 and 2·5 in the freezing and thawing stages, respectively, but the ratio was only 0·5 in the completely thawed stage. Latent heat flux displayed distinctly better correlation with unfrozen soil water content during the freezing and thawing stages than during the completely frozen and thawed stages. This implies that the diurnal cycle of unfrozen soil water, resulting from diurnal freeze/thaw cycles at the surface, has a significant impact on latent heat flux. A surface energy imbalance problem was encountered, and the possible sources of error were analysed. Copyright © 2011 John Wiley & Sons, Ltd.

HBI-3000 (sulcardine sulfate) has been shown to suppress various ventricular arrhythmias in animal models. The electrophysiological properties of HBI-3000 were investigated using standard microelectrode and patch-clamp techniques in single human ventricular myocytes. HBI-3000 led to concentration-dependent suppression of dofetilide-induced early afterdepolarizations in single nonfailing human ventricular myocytes and early afterdepolarizations seen in failing ventricular myocytes. The concentration-dependent prolongation of action potential duration (APD) by HBI-3000 was bell shaped with maximum response occurring around 10 μM. Interestingly, HBI-3000 at the concentration of 10 μM modestly prolonged the APD at all 3 basic cycle lengths. The slope of APD-cycle length curve of HBI-3000 was only slightly steeper than that of control (88.8 ± 7.7 ms/s vs. 78.9 ± 5.2 ms/s in control, n = 8, P0.05). HBI-3000 only showed a minimal use-dependent prolongation of the APD in human ventricular myocytes. HBI-3000 inhibited fast sodium current (INa-F), late sodium channel (INa-L), L-type calcium current (ICa-L), and rapidly activating delayed rectifier K current (IKr) in single human ventricular myocytes. The estimated half-maximal inhibitory concentration values of INa-F, INa-L, ICa-L, and IKr were 48.3 ± 3.8, 16.5 ± 1.4, 32.2 ± 2.9, and 22.7 ± 2.5 μM, respectively. The ion channel profile and electrophysiological properties of HBI-3000 are similar to those of ranolazine and chronic amiodarone (reduced INa-F, INa-L, ICa-L, and IKr). HBI-3000 may be a promising antiarrhythmic agent with low proarrhythmic risk.

SummaryOur previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β2-glycoprotein I/β2-glycoprotein I (anti-β2GPI/β2GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its downstream molecules have not been well explored. In this study, we have established that interleukin-1 receptor-associated kinases (IRAKs) and tumour necrosis factor receptor-associated factors (TRAFs) are crucial downstream molecules of anti-β2GPI/β2GPI-induced TLR4 signaling pathway in THP-1 cells and explored the potential mechanisms of their self-regulation. Treatment of THP-1 cells with anti-β2GPI/β2GPI complex induced IRAKs and TRAFs expression and activation. Anti-β2GPI/β2GPI complex firstly induced expression of IRAK4 and IRAK1, then IRAK1 phosphorylation and last IRAK3 upregulation. In addition, anti-β2GPI/β2GPI complex simultaneously and acutely enhanced mRNA levels of TRAF6, TRAF4 and zinc finger protein A20 (A20), while chronically increased A20 protein level. Moreover, anti-β2GPI/β2GPI complex-induced IRAKs and TRAFs expression and activation were attenuated by knockdown of ANX2 by infection with ANX2-specific RNA interference lentiviruses (LV-RNAi-ANX2) or by treatment with paclitaxel, which inhibits TLR4 as an antagonist of myeloid differentiation protein 2 (MD-2) ligand. Furthermore, both IRAK1/4 inhibitor and a specific proteasome inhibitor MG-132 could attenuate TRAFs expression as well as TF expression induced by anti-β2GPI/β2GPI complex. In conclusion, our results indicate that IRAKs and TRAFs play important roles in anti-β2GPI/β2GPI-stimulated TLR4/TF signaling pathway in THP-1 cells and contribute to the pathological processes of antiphospholipid syndrome (APS).

A significant portion of the Tibetan Plateau is underlain by permafrost, and is highly sensitive to climate change. Observational data from recent Chinese investigations on permafrost degradation and its environmental effects in the Tibetan region indicate that a large portion of the Tibetan Plateau has experienced significant warming since the mid-1950s. The air temperature increase is most significant in the central, eastern, and northwestern parts of the Plateau. The warming trend in the cold season was greater than that in the warm season. The duration of seasonal ground freezing has shortened due to the air temperature increase in winter. Numerical simulations indicate that air temperature on the Plateau will continue to increase in the 21st century. Significant warming has resulted in extensive degradation of permafrost. Over the last 30 years, a 25 m increase in the lower altitudinal occurrences of permafrost has taken place in the north. In the south the increase is 50–80 m over the past 20 years. Active-layer thickness and mean annual ground temperature have increased by 0.15–0.50 m during 1996–2001 and by 0.1–0.5 °C during the last 30 years on the Tibetan Plateau, respectively. Widespread permafrost degradation has already caused environmental deterioration. Extensive desertification processes are apparent in the eastern and western portions of the Tibetan Plateau, with the area occupied by desert increasing annually by about 1.8%. With rapid retreat and thinning of permafrost, large carbon pools sequestered in permafrost could be released to increase net sources of atmospheric carbon, creating a positive feedback and accelerated warming. Damage to human infrastructure is also caused by frost heave, thaw settlement, and thaw slumping in the permafrost-affected region. The impact of permafrost degradation on energy and water exchange processes between the ground and atmosphere require further examination. Large-scale intensive monitoring networks, remote sensing investigations, and models for frozen soil are needed to clarify regional details of climate change, permafrost degradation, and their environmental effects.

The relationship between sensible and latent heat flux and diurnal variation in soil surface temperature and moisture under four freeze/thaw soil conditions was investigated using observed soil temperature and moisture and simulated sensible and latent heat flux. The diurnal range of latent heat flux had a similar temporal change pattern as that of unfrozen soil water at depths of 0–3 cm during the freezing stage. Also, there was a better relationship with the diurnal range of unfrozen soil water at depths of 3–6 cm during the thawing stage. Diurnal variation in latent heat flux was significant and depended mostly on solar radiation during the completely thawed stage. However, while diurnal variation in solar radiation during the completely frozen stage was significant, for latent heat flux it was quite weak due to low unfrozen soil water content. Thus, diurnal variation in latent heat flux depended mostly on unfrozen soil water content during this stage. During the freezing and thawing stages, diurnal variation in latent heat flux was also significant and depended mostly on diurnal variation in unfrozen soil water content. However, the impacts of air temperature change from solar radiation on latent heat flux could not be ignored.

Left ventricular hypertrophy (LVH) is frequently associated with clinical atrial arrhythmias, but little is known about how it causes those arrhythmias. Our previous studies have shown that LVH increases the late sodium current ( INa-L) that plays an important role in the genesis of ventricular arrhythmias. We hypothesize that LVH may also induce an upregulation of the INa-L in atrial myocytes, leading to atrial electrical abnormalities. The renovascular hypertension model was used to induce LVH in rabbits. Action potential and membrane current recordings were performed in single myocytes. At a pacing cycle length of 2,000 ms, spontaneous phase-2 early afterdepolarizations (EADs) could be recorded from the left atrial myocytes in 10 of 12 LVH rabbits, whereas no EADs could be elicited in right atrial myocytes of LVH rabbits or atrial myocytes from any of the 12 control rabbits. Spontaneous automaticity (SA) from left atrial myocytes was observed in 9 out of 12 LVH rabbits, but none in right atrial myocytes of LVH rabbits or control rabbits, at a pacing rate of 8,000 ms. The left atrial myocytes of LVH rabbits had a significantly higher density of the INa-L compared with those of control rabbits (0.90 ± 0.12 in LVH vs. 0.50 ± 0.08 pA/pF in control, n = 8, P < 0.01). Tetrodotoxin, an INa-L blocker, abolished all atrial EADs and SA at 10 μM. Our results demonstrate that LVH induction results in a significant increase of INa-L in the left atrial myocytes that may render these cells susceptible to the genesis of EADs and SA. The INa-L may serve as a potentially useful ionic target for antiarrhythmic drugs for the treatment of atrial arrhythmias in the setting of LVH.

An amino acid sequence variant is defined as an unintended amino acid sequence change and contributes to product heterogeneity. Recombinant monoclonal antibodies (MAbs) are primarily expressed from Chinese Hamster Ovary (CHO) cells using stably transfected production cell lines. Selections and amplifications with reagents such as methotrexate (MTX) are often required to achieve high producing stable cell lines. Since MTX is often used to generate high producing cell lines, we investigated the genomic mutation rates of the hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT) gene using a 6-thioguanine (6-TG) assay under various concentrations of MTX selection in CHO cells. Our results show that the 6-TG resistance increased as the MTX concentration increased during stable cell line development. We also investigated low levels of sequence variants observed in two stable cell lines expressing different MAbs. Our data show that the replacement of serine at position 167 by arginine (S167R) in the light chain of antibody A (MAb-A) was due to a genomic nucleotide sequence change whereas the replacement of serine at position 63 by asparagine (S63N) in the heavy chain of antibody B (MAb-B) was likely due to translational misincorporation. This mistranslation is codon specific since S63N mistranslation is not detectable when the S63 AGC codon is changed to a TCC or TCT codon. Our results demonstrate that both a genomic nucleotide change and translational misincorporation can lead to low levels of sequence variants and mistranslation of serine to asparagine can be eliminated by substituting the TCC or TCT codon for the S63 AGC codon without impacting antibody productivity.

Background Quinidine is used to treat atrial fibrillation and ventricular arrhythmias. However, at low concentrations, it can induce torsade de pointes (TdP). Objective The purpose of this study was to examine the role of late sodium current (I Na ) as a modulator of the arrhythmogenicity of quinidine in female rabbit isolated hearts and cardiomyocytes. Methods Epicardial and endocardial monophasic action potentials (MAPs), ECG signals, and ion channel currents were measured. The sea anemone toxin ATX-II was used to increase late I Na . Results Quinidine had concentration-dependent and often biphasic effects on measures of arrhythmogenicity. Quinidine increased the duration of epicardial MAP (MAPD 90 ), QT interval, transmural dispersion of repolarization (TDR), and ventricular effective refractory period. Beat-to-beat variability of MAPD 90 (BVR), the interval from peak to end of the T wave (Tpeak-Tend) and index of Tpeak-Tend/QT interval were greater at 0.1 to 3 μmol/L than at 10–30 μmol/L quinidine. In the presence of 1 nmol/L ATX-II, quinidine caused significantly greater concentration-dependent and biphasic changes of Tpeak-Tend, TDR, BVR, and index of Tpeak-Tend/QT interval. Quinidine (1 μmol/L) induced TdP in 2 and 13 of 14 hearts in the absence and presence of ATX-II, respectively. Increases of BVR, index of Tpeak-Tend/QT interval, and Tpeak-Tend were associated with quinidine-induced TdP. Quinidine inhibited I Kr , peak I Na , and late I Na with IC 50 s of 4.5 ± 0.3 μmol/L, 11.0 ± 0.7 μmol/L, and 12.0 ± 0.7 μmol/L. Conclusion Quinidine had biphasic proarrhythmic effects in the presence of ATX-II, suggesting that late I Na is a modulator of the arrhythmogenicity of quinidine. Enhancement of late I Na increased proarrhythmia caused by low but not high concentrations of quinidine.

T-wave alternans, characterized by a beat-to-beat change in T-wave morphology, amplitude, and/or polarity on the ECG, often heralds the development of lethal ventricular arrhythmias in patients with left ventricular hypertrophy (LVH). The aim of our study was to examine the ionic basis for a beat-to-beat change in ventricular repolarization in the setting of LVH. Transmembrane action potentials (APs) from epicardium and endocardium were recorded simultaneously, together with transmural ECG and contraction force, in arterially perfused rabbit left ventricular wedge preparation. APs and Ca2+-activated chloride current ( ICl,Ca) were recorded from left ventricular myocytes isolated from normal rabbits and those with renovascular LVH using the standard microelectrode and whole cell patch-clamping techniques, respectively. In the LVH rabbits, a significant beat-to-beat change in endocardial AP duration (APD) created beat-to-beat alteration in transmural voltage gradient that manifested as T-wave alternans on the ECG. Interestingly, contraction force alternated in an opposite phase (“out of phase”) with APD. In the single myocytes of LVH rabbits, a significant beat-to-beat change in APD was also observed in both left ventricular endocardial and epicardial myocytes at various pacing rates. APD alternans was suppressed by adding 1 μM ryanodine, 100 μM 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), and 100 μM 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS). The density of the Ca2+-activated chloride currents ( ICl,Ca) in left ventricular myocytes was significantly greater in the LVH rabbits than in the normal group. Our data indicate that abnormal intracellular Ca2+ fluctuation may exert a strong feedback on the membrane ICl,Ca, leading to a beat-to-beat change in the net repolarizing current that manifests as T-wave alternans on the ECG.

An increase in snow cover on the Tibetan Plateau has been observed over the past 50 years. The frequency of snow disasters on the Plateau has also increased. Much of the Qinghai-Xizang (Tibetan) Plateau is underlain by permafrost. Some observation sites of the GEWEX Asian Monsoon Experiment (GAME)-Tibet are located in the Naqu-Anduo

The participation of large-conductance Ca2+ activated K+ channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked spontaneous transient outward currents (STOCs) in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca2+ sparks and caffeine-induced global Ca2+ increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs). We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH). Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax), BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro.

In this paper, we propose an overall framework about Bohai sea ice comprehensive service and expert aid decision-making system, among which six subsystems consists of sea ice multi-source information acquisition subsystem, sea ice comprehensive information database, sea ice comprehensive information integra- tion subsystem, sea ice expert aid decision-making subsystem, sea ice products release subsystem, and sea ice disaster loss evaluation subsystem. The proposing system has such features as functional integration, busi- ness-oriented product services, visual display and decision making, and so on. This paper can provide reference for the construction of sea ice comprehensive service and expert aid decision-making system in China.

The traditional herbPlumula Nelumbinisis widely used in the world because it has many biological activities, such as anti-inflammation, antioxidant, antihypertension, and butyrylcholinesterase inhibition. However, the action ofPlumula Nelumbinison airway smooth muscle (ASM) relaxation has not been investigated. A chloroform extract ofPlumula Nelumbinis(CEPN) was prepared, which completely inhibited precontraction induced by high K+in a concentration-dependent manner in mouse tracheal rings, but it had no effect on resting tension. CEPN also blocked voltage-dependent L-type Ca2+channel- (VDCC-) mediated currents. In addition, ACh-induced precontraction was also completely blocked by CEPN and partially inhibited by nifedipine or pyrazole 3. Besides, CEPN partially reduced ACh-activated nonselective cation channel (NSCC) currents. Taken together, our data demonstrate that CEPN blocked VDCC and NSCC to inhibit Ca2+influx, resulting in relaxation of precontracted ASM. This finding indicates that CEPN would be a candidate of new potent bronchodilators.

Action potential duration in the right ventricle is normally shorter than that in the left. We tested the hypothesis that there may be intrinsic differences in the QT and Tp-e (an interval from the peak to the end of the T wave) intervals between the left and right chest leads that can be exaggerated by systemic hypertension but attenuated by pulmonary hypertension in humans.Electrocardiograms in the left (V4L-V6L) and right (V4R-V6R) chest leads were obtained in 40 healthy individuals, 29 patients with systemic hypertension and left ventricular hypertrophy, and 15 patients with pulmonary hypertension.In healthy individuals, the corrected QT (QTc) and corrected Tp-e [T(p-e)c] intervals were 421+/-5 and 86+/-3 milliseconds in V4L through V6L, respectively, significantly longer than those recorded from V4R through V6R (383+/-5 and 62+/-4 milliseconds, respectively; P.01). Left ventricular hypertrophy prolonged the QTc interval in V4L through V6L (456+/-5 milliseconds), exaggerating the difference in the QTc interval between the left and right chest leads (61+/-4 vs 40+/-3 milliseconds in healthy control subjects; P.01). Left ventricular hypertrophy also resulted in a small but significant increase in the T(p-e)c interval in V4L through V6L (97+/-3 vs 86+/-3 milliseconds in control subjects; P.05) but exerted no significant effect on the T(p-e)c interval in the right. In contrast, pulmonary hypertension lengthened the QTc interval in the right chest leads, reducing the difference in the QTc interval between the left and right chest leads (3+/-8 vs 40+/-3 milliseconds in control subjects; P.01).There are intrinsic differences in the QT and Tp-e intervals between V4L-V6L and V4R-V6R that are significantly amplified by systemic hypertension but markedly attenuated by pulmonary hypertension.

Background— Phase 2 reentry caused by heterogeneous loss of the transient outward potassium current ( I to )–mediated epicardial action potential (AP) dome can produce a closely coupled R-on-T extrasystole leading to ventricular fibrillation (VF) under conditions of ST-segment elevation unrelated to ischemia. The present study examined the role of phase 2 reentry in the initiation of VF during early myocardial ischemia. Methods and Results— Regional myocardial ischemia was produced in an isolated, arterially perfused canine right ventricular wedge preparation. Transmembrane APs from 2 epicardial sites at each side of the ischemic border were simultaneously recorded together with measurements of extracellular potassium concentration ([K + ] o ) and a transmural ECG. Loss of the I to -mediated epicardial AP dome in the ischemic zone but not in the perfused tissue resulted in phase 2 reentry and associated R-on-T extrasystoles capable of initiating VF in 7 of 15 preparations during the first 3 to 9 minutes of myocardial ischemia, with marked ST-segment elevation and [K + ] o accumulation. The I to and phase 1 magnitude of epicardium contributed importantly to the onset of VF. Phase 1 magnitude and I to density at +30 mV in the group with phase 2 reentry–related R-on-T extrasystoles were 32.2±1.3 mV and 30.3±0.5 pA/pF (n=7), respectively, significantly greater than those (24.0±1.8 mV and 23.2±1.0 pA/pF) in the group without the extrasystoles (n=8, P Conclusions— Acute regional myocardial ischemia results in markedly heterogeneous loss of I to -mediated epicardial AP domes across the ischemic border, leading to phase 2 reentry. Phase 2 reentry can in turn produce an R-on-T extrasystole capable of initiating VF.