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Background Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. Methods and results We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. Conclusions Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.

Traditional dielectric electrorheological fluid (ER) is based on the interaction of dielectric particle polarization, and the yield stress is low, which can not meet the application requirements. The giant ER (GER) effect is caused by orientations and interactions of polar molecules adsorbed on the particle surfaces. Despite the high yield stress, these polar molecules are prone to wear and fall off, resulting in a continuous reduction in shear stress of GER liquid, which is also not suitable for application. Here we introduce a new type of ER fluid called induced dipole dominant ER fluid (ID-ER), of which the particles contain oxygen vacancies or conductor microclusters both prepared by high energy ball milling (HEBM) technique. In the electric field E, oxygen vacancies or conductor microclusters form induced dipoles. Because the local electric field E loc in the gaps between particles can be two to three orders of magnitude larger than E, the induced dipole moments must be large. The strong interactions of these induced dipoles make the yield stress of the ID-ER fluid reaching more than 100kPa. Since there are oxygen vacancies or conductor microclusters everywhere in the particles, the particles will not lose the function due to surface wear during use. The experimental results show that the ID-ER fluid possesses the advantages of high shear stress, low current density, short response time, good temperature stability, long service life and anti-settlement, etc. The comprehensive performance is much better than the existing ER materials, and also the preparation method is simple and easy to repeat, thus it should be a new generation of ER fluid suitable for practical application.

Aims The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). Methods and results One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P Conclusions The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

RhoGDIα is an inhibitor of RhoGDP dissociation that involves in Aβ metabolism and NFTs production in Alzheimer's disease (AD) by regulating of RhoGTP enzyme activity. Our previous research revealed that RhoGDIα, as the target of Polygala saponin (Sen), might alleviate apoptosis of the nerve cells caused by hypoxia/reoxygenation (H/R). To further clarify the role of RhoGDIα in the generation of NFTs, we explored the relationship between RhoGDIα and Tau. We found out that RhoGDIα and Tau can bind with each other and interact by using coimmunoprecipitation (Co-IP) and GST pulldown methods in vitro. This RhoGDIα-Tau partnership was further verified by using immunofluorescence colocalization and fluorescence resonance energy transfer (FRET) approaches in PC12 cells. Using the RNA interference (RNAi) technique, we found that the RhoGDIα may be involved in an upstream signaling pathway for Tau. Subsequently, in Aβ

Multidrug resistance (MDR), which is mainly caused by the overexpression of ATP-binding cassette (ABC) transporters, limits the effectiveness of clinical chemotherapy. Although multidrug resistance-associated protein 1 (MRP1) is an important ABC transporter, the relationship between MRP1 expression and drug-resistance has rarely been studied. The results of previous studies either cannot be compared or are contradictory, mainly due to limitations of conventional methods, such as semiquantification and low sensitivity. In addition, few reports have studied low resistance index (RI) levels, which are similar to clinical conditions. In this study, a novel UPLC-MS/MS method was developed and validated using the surrogate peptide (EDAQVDLFR) for the accurate and sensitive quantification of MRP1 expression in drug-resistance at low RI levels. The method was proven to be accurate (±20%, RE%), sensitive (0.09 pM, LLOQ), precise (±15%, RSD%), and stable under different conditions within 0.09-91.56 pM. In addition, the precision and stability of real samples further confirmed that the UPLC-MS/MS method was reliable. Quantification of MRP1 expression showed that there were significant differences (P 0.05) between parental cell lines and drug-resistant cell lines, as well as between various drug-resistance cell lines, which could not be accurately monitored by qRT-PCR and Western blot. Therefore, the UPLC-MS/MS method is more accurate and sensitive when detecting slight changes in MRP1 expression at low RI levels and is an effective choice for related studies. Additionally, MRP1 expression was positively correlated with the RI level based on the Pearson correlation coefficient, which was not discussed in previous studies.

The bottleneck in the application of electrorheological (ER) fluids is the difficulty of simultaneously meeting both the performance and lifetime demands. In this paper, we propose to replace the polar molecules adsorbed on particles with nanoconductors and successfully synthesized a novel giant ER fluid made of TiO2 particles inlaid with nanocarbon clusters (jujube cake structures) by a simple modified hydrolysis-precipitation method to break this bottleneck. Its giant ER effect originates from the polarization of nanocarbon clusters in a local field produced by the polar charges of TiO2 particles and the strong interaction forces between the nanocarbon clusters and between a nanocarbon cluster and the polar charges on the adjacent TiO2 particles. Moreover, the jujube cake structure of the C-TiO2 particles is stable enough to withstand mechanical wear and high temperature, so the material shows a high yield stress, long lifetime, small current leakage and good thermal stability, and is believed to be a promising candidate for practical ER fluids.

Angiotensin II (Ang II) is involved in the pathogenic progress of cardiovascular diseases via the promotion of abnormal proliferation and migration of human vascular smooth muscle cells (HVSMCs). Sulforaphane (SFN) exerts potent anti-inflammatory effects both in vitro and in vivo. In the present study, we aimed to investigate the effects of SFN on Ang II-induced abnormal migration of HVSMCs as well as the underlying mechanisms of those effects. The results showed that Ang II-induced HVSMC proliferation and migration were inhibited by treatment with SFN. SFN also exhibited anti-inflammatory activity, as indicated by its reduction of monocyte adhesion to HVSMCs via the reduction of ICAM1 and VCAM1 levels. Moreover, SFN reduced the Ang II-induced upregulation of HVSMC migration; this effect was inhibited by pretreatment with inhibitors of NADPH oxidase and ROS or transfection with siNOX4. In addition, SFN reversed the Ang II-induced upregulation of HVSMC migration via elevation of Nrf2 activation and expression. Taken together, the results indicate that SFN reverses Ang II-induced HVSMC migration through suppression of the NOX4/ROS/Nrf2 pathway. Thus, SFN is a potential agent to reverse the pathological changes involved in various cardiovascular diseases.

Acute coronary syndrome (ACS) can cause arrhythmia, heart failure, and even sudden death. Our aim in this study was to identify potential metabolic biomarkers in patients with ACS. The serum metabonomics approach based on ultra-performance liquid chromatography (UPLC)/Orbitrap mass spectrometer (MS) was used to analyze the serum samples from 45 patients with ACS and 29 healthy controls. Multivariate statistical analysis was used to screen for ACS biomarkers. In total, 69 biomarkers were identified to be enriched in 19 metabolic pathways; 43 biomarkers were significantly up-regulated, while 26 biomarkers were significantly down-regulated in the ACS group. The main classes were lyso-sphingolipid (SM), cinnamic acids, cholines, and primary amides. Receiver operating characteristic (ROC) curve analysis showed that lysoPC(20:4(8Z,11Z,14Z,17Z)/0:0) (ROC area under the curve, AUC = 0.936), SM(d18:0/16:0) (ROC AUC = 0.932), and SM(d18:1/14:0) (ROC AUC = 0.923) had a high ACS diagnostic ability. The AUC value of the diagnostic model constructed using these combined biomarkers was 0.96. Therefore, these biomarkers may improve the diagnostic efficacy of ACS. The findings of this study also implied that glycerophospholipid metabolism; the biosynthesis of unsaturated fatty acids; linoleic acid metabolism; and valine, leucine, and isoleucine biosynthesis played important roles in ACS. Network analysis by ingenuity pathway analysis (IPA) showed these biomarkers were correlated to the cardiac hypertrophy signaling pathway, ERK/MAPK signaling pathway, NF-kappa B signaling pathway, nitric oxide (NO) signaling pathway in cardiovascular system, and TLR-signaling pathway. These findings will help to improve the ability of accurate diagnosis and intervention of ACS.

Background The circulating levels of Cyr61 (also known as CCN1) may prove to have great clinical value in the diagnosis, monitoring and prognosis of many disorders in humans. However, the reference intervals (RIs) for this analyte in human subjects have not previously been well established. Therefore, establishing RIs and determining the distribution of circulating Cyr61 levels are very important for future clinical studies and could provide an orientation value for exploring its clinical usefulness. Methods The Cyr61 levels in 2,514 healthy Chinese Han subjects (1,250 males and 1,264 females, aged 18 - 88 years, recruited from 4 hospitals in Shanghai and Fujian) were measured with a sandwich ELISA (R&D Systems, USA). The RIs were determined in a manner consistent with the Clinical and Laboratory Standards Institute guidelines. Results The levels of serum Cyr61 showed a non-Gaussian distribution. A statistically significant difference was observed between the males and females such that the median level of Cyr61 in the males was significantly higher than that in the females. Furthermore, the Cyr61 levels significantly increased with age in the female group whereas no difference was observed among the different age groups among the males. The RIs for serum Cyr61 were 3.3 - 184 pg/mL and 5.0 - 182 pg/mL in females aged 18 - 45 and 46 - 88 years, respectively. The RI for serum Cyr61 was 4.0 - 198 pg/mL in the males. Conclusions The RIs for serum Cyr61 were established among Chinese Han individuals. The effects of age and gender on the distribution characteristics of serum Cyr61 were studied, revealing that the RIs were gender and, in females, age-specific, which may suggest that a female hormone, estrogen plays a role in the regulation of Cyr61 expression in vivo.

BackgroundThis paper aimed to explore the average natural menopause age, the span of menopausal age, and the related factors that will probably affect the natural menopause age of Chinese women. MethodsA large-scale random sampling of menopausal women aged 32-75 years in 18 provinces or municipalities throughout China was conducted using paper questionnaire surveys to investigate the menopause age, menarche age, fertility status, illness history, and living habits. The SPSS 24.0 software package was used to carry out t test, chi-square test, logistic regression, and other statistical analyses. ResultsA total of 5852 questionnaires were collected. After excluding questionnaires having no menopause, questionnaires with incomplete or invalid information, and questionnaires that may directly affect the age of menopause, such as hysterectomy, oophorectomy, and other factors that may affect natural menopause, a total of 4426 effective questionnaires have been collected, and the average age of natural menopause was 49.49 ± 3.67 years old. ConclusionFactors that may affect the age of natural menopause are weight, menarche age, marital status, drinking tea or not (often and daily), eating supplements, oral contraceptive contraception, and safe contraception.

BackgroundStatins are the most widely used drugs in elderly patients; the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE–/–) mice, and the possible mechanisms involved in these changes.MethodsTwenty-four 60-week-old apoE–/–mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE–/–mice were differentiated into osteoblasts and treated with atorvastatin and silent information regulator 1 (Sirt1) inhibitor EX-527.ResultsThe results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear obviously changes after the treatment of atorvastatin. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE–/–mice were pretreated with EX527, the higher expression of Runx2, ALP, and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend.ConclusionsAccordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE−/−mice by regulating the Sirt1–Runx2 axis.

Patients with atrial fibrillation (AF) are associated with increased thrombotic events. Our previous case–control study showed low-density lipoprotein cholesterol (LDL-C) was an independent predictor of ischemic stroke in AF patients. To investigate the risks of thrombosis in relation to LDL-C among AF patients at different stroke risks by long-time follow-up. Atrial fibrillation patients without history of thrombosis enrolled from five hospitals were classified into low-risk (LR) and high-risk (HR) group according to CHA2DS2VASc score and followed up with a median period of 26 months. Univariate and multivariate logistic regression analysis were performed in each group. The best cut-off value calculated by receiver operating characteristic (ROC) analysis was used to divide patients into low LDL-C (L-LDL) and high LDL-C (H-LDL) subgroups. Propensity score matching (PSM) and inverse probability of treatment weighted (IPTW) were utilized in both subgroups, after which Kaplan–Meier curves for thrombosis were performed. Univariate and multivariate analysis showed LDL-C was significantly related to thrombosis in LR, but less significantly in HR group. The best cut-off value was 2.155 mmol/L in LR and 2.795 mmol/L in HR group. Lower LDL-C was associated with decreased thrombosis in both groups by PSM and IPTW. Kaplan–Meier curves displayed that H-LDL subgroup was at higher thrombosis risk with significant difference at 24th month in LR patients. LDL-C independently predicts thrombosis with different cut-off values in AF patients at different risks. A stricter control of LDL-C level is necessary for thrombosis reduction in patients with lower score.

Estrogen evidently exerts a protective role against gastric cancer. Accordingly, we evaluated the relationship between the expression of the estrogen receptor ER-α36 and the clinicopathologic features in gastric cancer. ER-α36 expression levels differed among the tumor center, invasion front, and vascular metastases. The effects of E2β (17β-Estradiol, E2β) on invasion ability in SGC7901, High36 (with ER-α36 upregulation), and Low36 (with ER-α36 downregulation) cells were evaluated using Transwell assays. Furthermore, the c-Src signaling pathway was inhibited using PP2 and the effects on E2β-induced increases in E-cadherin, MMP2, and MMP9 were evaluated using western blotting. ER-α36, c-Src, MMP2, and E-cadherin levels were also evaluated in tumor xenografts. We found that 0.1 nM E2β promoted gastric cancer cell invasion by reducing E-cadherin expression and increasing MMP2 and MMP9 levels. The upregulation of ER-α36 promoted gastric cancer cell invasion and the downregulation of ER-α36 reduced the invasive ability of cells. The levels of ER-α36, c-Src, and MMP2 were the highest in tumor xenografts using High36 cells, intermediate in tumor xenografts using SGC7901 cells, and lowest in tumor xenografts using Low36 cells. The opposite results were obtained for E-cadherin expression. ER-α36 enhanced gastric cancer cell invasion by the activation of membrane-initiated c-Src signaling pathways. In particular, treatment with E2β and ER-α36 influenced gastric cancer cell invasion. Furthermore, c-Src was involved in the ER-α36-mediated estrogen signaling pathway and cell invasion.

Background: Allicin, a major component of garlic, is regarded as a cardioprotective agent and is associated with increased endothelial function. Methods: The effects of allicin on lipopolysaccharide (LPS)-induced vascular oxidative stress and inflammation in cultured human umbilical vein endothelial cells (HUVECs) and the mechanisms underlying these effects were studied. The protective effects were measured using cell viability, a lactate dehydrogenase (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was determined by measuring reactive oxygen species (ROS) generation, oxidative products and endogenous antioxidant enzyme activities. HUVEC mitochondrial function was assessed by determining mitochondrial membrane potential (MMP) collapse, cytochrome c production and mitochondrial ATP release. To investigate the potential underlying mechanisms, we also measured the expression of dynamic mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2 antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA). Results: Our results demonstrated that allicin enhanced HUVEC proliferation, which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS-induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and decreased the endogenous antioxidant enzyme activities in HUVECs. These protective effects were associated with the inhibition of mitochondrial dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced inflammatory responses, including endothelial cell adhesion and TNF-α and IL-8 production. Furthermore, allicin increased the expression of LXRα in a dose-dependent manner. Allicin-induced attenuation of inflammation was inhibited by LXRα siRNA treatment. Finally, allicin activated NF-E2-related factor 2 (Nrf2), which controls the defense against oxidative stress and inflammation. Conclusions: Taken together, the present data suggest that allicin attenuated the LPS-induced vascular injury process, which may be closely related to the oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2 activation and protected the cells against LPS-induced vascular injury. Our findings suggest that allicin attenuated the LPS-induced inflammatory response in blood vessels.

Single mineral flotation of chalcopyrite, molybdenite and pyrite with a regular collector (potassium amyl xanthate) and a selective collector (N-isopropoxypropyl-N′-ethoxycarbonyl thiourea) for chalcopyrite in both de-ionized water and synthetic sea water were investigated in this study. The results indicated a wider effective pH range for separation of pyrite from chalcopyrite and molybdenite with N-isopropoxypropyl-N′-ethoxycarbonyl thiourea than with potassium amyl xanthate in de-ionized water flotation. The separation can be achieved in low alkaline conditions only with the selective thiourea collector in synthetic sea water flotation in this study. The results of the mixed minerals flotation in synthetic sea water confirmed the successful separation of pyrite from chalcopyrite and molybdenite by N-isopropoxypropyl-N′-ethoxycarbonyl thiourea at pH 9. In addition, time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis revealed the mechanism of separation.

Endothelial cell (EC) dysfunction induces atherosclerotic coronary heart disease (CHD) development. Recent studies demonstrated that lncRNA NEAT1 mediates multiple biological functions of cells. How NEAT1 regulates EC function is still unclear, so this study explored the role and mechanism of NEAT1 in oxidative stress-induced ECs. The levels of NEAT1 and miR-181d-5p were measured in serum samples from ApoE-/- mice and t-BHP-treated human umbilical vein endothelial cells (HUVECs) by qRT-PCR. The potential role of NEAT1 in viability, migration and apoptosis was analyzed by CCK-8, cell metastasis, flow cytometry, dual-luciferase reporter, RNA immunoprecipitation and Western blot assays using HUVECs overexpressing NEAT1. The expression of NEAT1 was increased, but miR-181d-5p expression was decreased in serum samples from both ApoE-/- mice and t-BHP-treated HUVECs. Overexpression of NEAT1 increased viability, migration and CDKN3 expression but decreased apoptotic rates, caspase-3 activity and miR-181d-5p expression in HUVECs. In addition, NEAT1 acted as a promoter of the proangiogenic capacity of HUVECs by targeting miR-181d-5p/CDKN3. Altogether, these findings indicate that NEAT1 may exert a protective effect on HUVECs by regulating the miR-181d-5p/CDKN3A axis.

Aims Multidrug resistance is a major obstacle in chemotherapy, which is mainly caused by the overexpression of ATP-binding cassette (ABC) transporters. Breast cancer resistance protein (BCRP) is one of the ABC transporters and is strongly associated with multidrug resistance. Results of studies on BCRP and multidrug resistance are always uncomparable and contradictory, which may be stem from the disadvantages of qualitative and semi-quantitative techniques. In addition, there are few literatures studying at low resistance level which is more similar to the clinical situation. Thus, it is imperative to develop a quantitative method to quantitate the expression of BCRP accurately and reveal its relationship with multidrug resistance. Methods SMMC-7721, MCF-7 and HepG-2 were induced by different concentrations of mitoxantrone, doxorubicin and methotrexate respectively to establish resistance cells. An advanced liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) based method with surrogate peptide was developed and validated for determining BCRP at low resistant cells. The amount of BCRP was also evaluated by real-time-polymerase chain reaction (RT-PCR) and Western Blot (WB). Key findings The LC-MS/MS-based method we developed is more sensitive and stable than the similar methods and can monitor the slight variation of BCRP expression accurately and sensitively, while RT-PCR and WB cannot. Significance This study provides a solid foundation for understanding the development of drug resistance in cells and can be used to explain the conflicting results of published studies. Moreover, clinical multidrug resistances are mostly at low levels, which have not been discussed in current quantitative studies of BCRP.

De-ionized water (DI water) and simulated sea water were applied to float molybdenite in this study. Results showed that the flotation recovery of molybdnite was sharply reduced in simulated sea water at pH above 9.5. To find out the exact mechanisms of depression, several advanced apparatuses were applied for surface characterization. Based on the measurements by the scanning electron microscopy (SEM), two kinds of precipitates (colloidal precipitates and crystallized precipitates) were observed on the molybdenite surface which was immersed in the simulated sea water during flotation. It was found that the colloidal precipitates overspread on the surface while the crystallized precipitates randomly scatted on the surface. With the detection by auger electron spectrum (AES), it was found that magnesium and calcium were the main components in the colloidal precipitates and crystallized precipitates, respectively. According to the X-ray photoelectron spectrum (XPS) tests, it was testified that the colloidal precipitates were Mg(OH)2 and the crystallized precipitates were CaCO3, which was confirmed by ToF-SIMS results. These precipitated Mg(OH)2 and CaCO3 particles on the molybdenite surfaces play an important role in inhibiting the flotation of molybdenite in the simulated sea water.

The technology of Zn extraction from sphalerite concentrate by using electro-oxidation in weak alkaline sodium chloride solution has been investigated in this paper. The effects of several parameters on Zn recovery during the electro-oxidation have been investigated, and the optimized conditions are listed as follows : pH in the range of 8.5–8.8, NaCl concentration = 3 mol/L, reaction time = 1 h, solid–liquid ratio ≥ 0.03 g/ml, anodic current density = 1342 A/m 2 , stirring speed = 800 rpm. Under these experimental conditions, sphalerite concentrate can be oxidized efficiently. Furthermore, the electro-oxidation mechanism of sphalerite in weak alkaline NaCl solution has been studied. It was found that the elemental sulfur and the SO 4 2 − were the major existing forms of S from sphalerite and Zn would precipitate in the form of Na 2 Zn 3 (CO 3 ) 4 in the case where Na 2 CO 3 served as electrolyte pH regulator. To prevent SO 4 2 − from accumulating in the electrolyte and precipitate Zn as Zn(OH) 2 instead of Na 2 Zn 3 (CO 3 ) 4 , Na 2 CO 3 was replaced by Ca(OH) 2 to stabilize the pH of electrolyte, and the effect of the addition of Ca(OH) 2 on Zn recovery was investigated.

Multidrug resistance (MDR) of tumors occurs when tumor cells exhibit reduced sensitivity to a large number of unrelated drugs. The molecular mechanism of MDR commonly involves overexpression of the plasma membrane drug efflux pump P-glycoprotein (P-gp). Overexpression of P-gp may be induced by the selection and/or adaptation of cells during exposure to chemotherapeutic drugs, referred to as acquired P-gp-mediated MDR. This study aimed to establish a P-gp quantification method by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry (UPLC-MS/MS) to better understand the regulation of P-gp expression and its relationship with the level of drug resistance. Absolute P-gp expression was determined in the human tumor cells MCF-7, HepG-2, and SMMC-7721 and their corresponding drug-resistant subclones MCF-7/ADMs, MCF-7/MXs, MCF-7/MTXs, HepG-2/ADMs, HepG-2/MXs, HepG-2/MTXs, SMMC-7721/ADMs, SMMC-7721/MXs and SMMC-7721/MTXs. A unique 10-mer tryptic peptide (IATEAIENFR) of P-gp was synthesized for developing the quantitative UPLC-MS/MS method with the stable isotope labeled signature peptide IATEAI (13C6, 15N1) ENFR as the internal standard (IS). The detection signal was linear in the range of 0.1–100 ng mL−1. Quality control (QC) data showed that the within-run and between-run precision (%RSD) and accuracy (%RE) conformed to acceptable criteria of ±15% for the calibration standards and QCs (±20% at the LLOQ). The UPLC-MS/MS method was first applied to quantify P-gp in HepG-2 and SMMC-7721 cells and their drug-resistant subclones. The results confirmed that P-gp expression in most drug-resistant subclones increase significantly compared to parental tumor cells but varied among different types of drugs or tumor cells. This outcome was then compared with published reports and discrepancy was observed in HepG2 cell lines mainly due to different sample types and samples sources. Additionally, P-gp mRNA results ascertained that overexpression of P-gp in subclones was not only regulated by MDR1. The linear correlation between RI and logarithm-transformed P-gp expression was moderate or high and statistically significantly different in subclones, except for SMMC-7721/ADMs. The present study is the first to demonstrate the quantitative relationship between RI and P-gp expression by linear regression modeling and expanded the number of efflux transporters related to MDR quantifiable by LC-MS/MS to better understand the biological significance of effluent transporter expression.

There are controversies about the mechanism of myocardium apoptosis in hypertensive heart disease. The aim of this study was to investigate the relationship among autophagy, Cx43 and apoptosis in aged spontaneously hypertensive rats (SHRs) and establish whether Aliskiren is effective or not for the treatment of myocardium apoptosis. Twenty-one SHRs aged 52 weeks were randomly divided into three groups, the first two receiving Aliskiren at a dose of 10 and 25 mg/kg/day respectively; the third, placebo for comparison with seven Wistar-Kyoto (WKY) as controls. After a 2-month treatment, systolic blood pressure (SBP), heart to bw ratios (HW/BW%) and angiotensin II (AngII) concentration were significantly enhanced in SHRs respectively. Apoptotic cardiomyocytes detected with TUNEL and immunofluorescent labelling for active caspase-3 increased nearly fourfolds in SHRs, with a decline in the expression of survivin and AKT activation, and an increase in caspase-3 activation and the ratio of Bax/Bcl-2. Myocardium autophagy, detected with immunofluorescent labelling for LC3-II, increased nearly threefolds in SHRs, with the up-regulation of Atg5, Atg16L1, Beclin-1 and LC3-II. The expression of Cx43 plaque was found to be down-regulated in SHRs. Aliskiren significantly reduced SBP, HW/BW%, AngII concentration and the expression of AT(1)R. Thus, Aliskiren protects myocardium against apoptosis by decreasing autophagy, up-regulating Cx43. These effects showed a dose-dependent tendency, but no significance. In conclusion, the myocardium apoptosis developed during the hypertensive end-stage of SHRs could be ameliorated by Aliskiren via the regulation of myocardium autophagy and maladaptive remodelling of Cx43.

Background Emerging evidence shows that the chemokine CXCL16 plays an important role in the pathogenesis of myocardial remodeling and development of heart failure following ischemia/reperfusion (I/R) injury. CXCR6, the receptor for CXCL16, is also critically involved. However, the underlying mechanism remained uncertain, and the aim of this research was to investigate this mechanism in CXCR6 knockout (KO) mice. Methods and results CXCR6 KO mice and wild type (WT) mice had no overt phenotype at baseline in the absence of injury, but difference was shown in response to I/R induction. Compared with WT mice, CXCR6 KO mice exhibited a lower infarction size (31.86±1.808% vs. 43.09±1.519%), and better cardiac function (measured by LVEF, LVFS, +dp/dt, LVEDP, and LVSP) following I/R. Moreover, cardiac levels of IFN-γ and IFN-γ-dependent autophagy were found to be significantly attenuated in CXCR6 KO mice. Further data showed that cardiac-enhanced IFN-γ secretion was not induced by cardiomyocytes, but by infiltrated monocytes in the myocardium in response to I/R injury. In vivo injection of IFN-γ and in vitro co-cultured cardiomyocytes with CD11b+ monocytes confirmed IFN-γ activated autophagic response, and induced cardiac dysfunction in a paracrine manner. Conclusions The study suggested that since disruption of the CXCL16/CXCR6 signaling cascade had a cardio-protective effect against I/R injury, the underlying mechanism might be that I/R triggered the infiltration of monocytes into the myocardium, and induced cardiac autophagy through CXCL16/CXCR6-dependent paracrine secretion of IFN-γ.

There are controversies concerning the capacity of Rosuvastatin to attenuate heart failure in end-stage hypertension. The aim of the study was to show whether the Rosuvastatin might be effective or not for the heart failure treatment. Twenty-one spontaneously hypertensive rats (SHRs) aged 52 weeks with heart failure were randomly divided into three groups: two receiving Rosuvastatin at 20 and 40 mg/kg/day, respectively, and the third, placebo for comparison with seven Wistar-Kyoto rats (WKYs) as controls. After an 8-week treatment, the systolic blood pressure (SBP) and echocardiographic features were evaluated; mRNA level of B-type natriuretic peptide (BNP) and plasma NT-proBNP concentration were measured; the heart tissues were observed under electron microscope (EM); myocardial sarcoplasmic reticulum Ca(2+) pump (SERCA-2) activity and mitochondria cytochrome C oxidase (CCO) activity were measured; the expressions of SERCA-2a, phospholamban (PLB), ryanodine receptor2 (RyR2), sodium-calcium exchanger 1 (NCX1), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase inhibitor-1 (PPI-1) were detected by Western blot and RT-qPCR; and the total and phosphorylation of protein kinase Cα/β (PKCα/β) were measured. Aged SHRs with heart failure was characterized by significantly decreased left ventricular ejection fraction and left ventricular fraction shortening, enhanced left ventricular end-diastolic diameter and LV Volume, accompanied by increased plasma NT-proBNP and elevated BNP gene expression. Damaged myofibrils, vacuolated mitochondria and swollen sarcoplasmic reticulum were observed by EM. Myocardium mitochondria CCO and SERCA-2 activity decreased. The expressions of PLB and NCX1 increased significantly with up-regulation of PPI-1 and down-regulation of CaMKII, whereas that of RyR2 decreased. Rosuvastatin was found to ameliorate the heart failure in aged SHRs and to improve changes in SERCA-2a, PLB, RyR2, NCX1, CaMKII and PPI-1; PKCα/β2 signal pathway to be suppressed; the protective effect of Rosuvastatin to be dose dependent. In conclusion, the heart failure of aged SHRs that was developed during the end stage of hypertension could be ameliorated by Rosuvastatin.

End-stage hypertensive heart disease is an increasing cause of cardiac mortality. Therefore, the current study focused on the cardiac remodelling from hypertrophy to fibrosis in old-aged spontaneously hypertensive rats (SHRs), and explored the therapeutic effects of Rosuvastatin and its possible mechanism(s) of action. Spontaneously hypertensive rats at age 52 weeks were randomly divided into three groups, the first two to receive Rosuvastatin at a dose of 20 mg/kg/day and 40 mg/kg/day, respectively, and the third to receive placebo, which was to be compared with Wistar-Kyoto as controls. After 2-month treatment, SBP, heart to body weight ratio (HW/BW%) and echocardiographic features were evaluated, followed by haematoxylin and eosin and Masson trichrome staining in conjunction with qPCR of foetal gene expressions. Transferase-mediated dUTP nick-end labelling assay and immunofluorescent labelling for active caspase-3 were used to detect the apoptotic cardiomyocytes. Signaling pathways involved were examined by using western blot. Old-aged SHR developed end-stage hypertensive heart disease characterized by significant enhancement of HW/BW%, LVAWd and LVPWd, and decreased LVEF and LVFS, accompanied by cardiomyocytes enlargement and fibrosis along with activation of foetal gene programme. Cardiac apoptosis increased significantly during the transition process. Rosuvastatin reduced hypertrophy significantly via AT(1) Receptor-PKCβ2/α-ERK-c-fos pathway; protected myocardium against apoptosis via Akt-FOXO1, Bcl-2 family and survivin pathways and consequently suppressed the caspase-3 activity. The present study revealed that old-aged SHRs developed cardiac remodelling from hypertrophy to fibrosis via cardiac apoptosis during the end stage of hypertensive heart disease. These pathological changes might be the consequence of activation of AT(1) Receptor-PKCβ2/α-ERK-c-fos and AKT-FOXO1/Bcl-2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved.

Hydrophilic, oleophilic and raw TiO2 particles are dispered respectively in silicone oil to form electrorheological suspensions and the effect of surface wettability of TiO2 particles on evaporation enhancement of silicone oil is studied. The results show that the evaporation rate of silicone oil increases with the decrease of surface wettability of the particle and the increase of the depth of suspension which indicates that the evaporation mainly occurs in the bulk. The observed phenomena have been explained mainly on the basis of heterogeneous nucleation theory of bubbles. In the bulk of suspensions, the less wettable surface of nanoparticles, the less critical activation energy needed for bubble nucleation, the easier it is to form bubbles which is the origin of the evaporation.

TiO2 particles prepared by the hydrolysis of titanium butoxide adsorb water molecules with different adsorption energies. The electrorheological (ER) fluid composed of TiO2 particles behaves as the polar-molecule giant electrorheological (GER) fluid at 25°C even after thermal treatment at 75°C. After thermal treatment at 125°C and 175°C, the water molecules with low adsorption energy are removed and the ER fluid behaves as traditional ER fluid at 25°C. However, at 175°C, the ER fluid treated at 175°C behaves as a polar-molecule GER fluid when the external electric field is larger than 2 kV/mm. These results show that the water molecules with low adsorption energy act as polar molecules responsible for the GER effect and, with the help of thermal energy, water molecules with high adsorption energy can work as those with low adsorption energy, resulting in the GER effect.TiO2 particles prepared by the hydrolysis of titanium butoxide adsorb water molecules with different adsorption energies. The electrorheological (ER) fluid composed of TiO2 particles behaves as the polar-molecule giant electrorheological (GER) fluid at 25°C even after thermal treatment at 75°C. After thermal treatment at 125°C and 175°C, the water molecules with low adsorption energy are removed and the ER fluid behaves as traditional ER fluid at 25°C. However, at 175°C, the ER fluid treated at 175°C behaves as a polar-molecule GER fluid when the external electric field is larger than 2 kV/mm. These results show that the water molecules with low adsorption energy act as polar molecules responsible for the GER effect and, with the help of thermal energy, water molecules with high adsorption energy can work as those with low adsorption energy, resulting in the GER effect.

The technology of molybdenum extraction from molybdenite concentrate by using sodium chlorate has been investigated. The results show that leaching time, liquid-to-solid ratio, leaching temperature, agitation speed, sodium chlorate and hydrochloric acid concentration have significant effect; optimum process operating parameters were established as follows: time: 4 h; hydrochloric acid concentration: 20%; liquid-to-solid ratio: 10:1; temperature: 70 °C; agitation speed: 500 rpm; and the molar ratio of NaClO 3 to MoS 2 : 3.21. Under these experimental conditions, the extraction of molybdenum is greater than 98%. The mixture of 30% triotylamine and 20% sec-Caprylic alcohol diluted kerosene oil is an effective extractant of molybdenum; the molybdenum extraction efficiencies in the examined conditions were about 99.6% under conditions of O: a ratio of 1:1, hydrochloric acid 60 g/L for 10 min at room temperature. Stripping of molybdenum to aqueous phase was efficient when 18% ammonia liquor were applied. The molybdenum stripping efficiencies in the examined conditions were about 99.5% under conditions of O: a ratio of 1:1 for 10 min at 40 °C.

In situ scanning electrochemical microscopy (SECM) was used to study N-isopropoxypropyl-N'-ethoxycarbonyl thiourea (iPOPECTU) adsorption on chalcopyrite. The in situ SECM images indicated a preferential adsorption of iPOPECTU on chalcopyrite surfaces, resulting in a decrease in the probing electrochemical current response. The surfaces after iPOPECTU adsorption were analyzed by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). ToF-SIMS results provided a strong evidence of iPOPECTU binding with copper only. XPS analysis showed the reduction of cupric to cuprous on chalcopyrite surfaces as a result of iPOPECTU adsorption. Our results shed light on adsorption mechanism of iPOPECTU on the surface of chalcopyrite samples.

Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging.Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments.The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality.To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.

Target of ablation of peri-mitral flutter: mitral valve isthmus or triggers? {#article-title-2} Introduction Patients with previous ablation for atrial fibrillation (AF) may experience the recurrence of peri-mitral flutter (PMFL). These arrhythmias are usually triggered from sources that may also induce atrial fibrillation. We sought to determine whether ablation of triggers or completing mitral valve isthmus (MVI) block prevents more arrhythmia recurrences. Methods A total of 65 patients with recurrent PMFL after initial ablation of long-standing persistent AF were included in the study. Thirty-two were randomized to MVI ablation only (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV) isolation plus ablation of others non-PV triggers (Group 2). Results MVI bidirectional block was achieved in all but one patient from Group 1. In Group 2, reconnection of 17 PVs was detected in 14 patients (42%, 1.21 veins per patient). With isoproterenol challenge, 44 non-PV trigger sites were identified in 28 patients (85%, 1.57 sites per patient). With a follow-up of 18 months, 27 patients (84%) from Group 1 had recurrent atrial arrhythmias and 15 remained on AAD, while 28 patients from Group 2 (85%, P < 0.0001 vs. Group 1) were free of arrhythmia off AAD. Cox regression model revealed that the ablation strategy used in Group 2 was associated with a significant lower risk of recurrence of atrial tachyarrhythmia (hazard ratio = 0.10, 95% CI = 0.04–0.28, P < 0.001). The Kaplan–Meier curves demonstrated significant better arrhythmia-free survival in Group 2 compared with Group 1 (log rank P < 0.0001). Conclusions In patients presenting with PMFL after ablation for long-standing persistent AF, MVI block had limited impact on arrhythmia recurrence. On the other hand, elimination of all PV and non-PV triggers achieved higher freedom from atrial arrhythmias at follow-up. # Comparison of sensitivity of transthoracic, transoesophageal, and intracardiac echocardiography for guiding transeptal puncture {#article-title-3} Objective Compare the sensitivity of transthoracic (TTE), transoesophageal (TEE), and intracardiac (ICE) echocardiography for guiding interatrial septum (IAS) puncture. Methods The study consisted of 208 patients (48 females, mean age 56.4 ± 11.3 years) who underwent RFA of LA because of atrial fibrillation. Transeptal puncture was performed after IAS visualization using TTE in 32 (15.4%), TEE in 26 (12.5%), ICE in 150 (72.1%) patients. Adequate contact of transeptal needle with IAS was defined as a tension of septum using echocardiographic techniques. Verification of tenting and following transeptal puncture with LA catheterization was defined as a true positive result. Lack of visualization of tenting with successful transeptal puncture under fluoroscopy was defined as a false-negative result. Results Clear visualization of the IAS using TTE technique was demonstrated in 2 (6%) cases, and the sensitivity amounted for 6.7%. Obvious verification of IAS by TEE was revealed in 20 (77%) patients, and sensitivity of this technique was 86.9%. ICE control of septum puncture was performed in 127 patients. ICE allowed visualizing septum and tenting in 125 patients and the tension of septum was unable to be determined in two cases despite of the efforts of specialists. ICE sensitivity for IAS verification was 98.4%. Conclusion ICE is the most sensitive ultrasound technique for verification of optimal location of the transeptal needle in the region of IAS comparing with TTE and TEE. # Pulmonary antrum radial-linear ablation: a new therapy for atrial fibrillation {#article-title-4} The abnormality of substrates in pulmonary vein antrum (PVA) plays a critical role in maintaining atrial fibrillation (AF). PVA radial-linear ablation (PVARA) was performed for an organized modification of substrates in paroxysmal AF. This study consisted of two phases: preclinical phase using 22 canine models with acutely induced AF, and clinical phase in patients with paroxysmal AF ( n = 15) in paired control with PV isolation. Radial-linear lesions were created from PV orifice to left atrium-PV junction in both dogs and patients. Successful creation of chronic radial-linear lesions was confirmed pathologically in dogs. The AF inducibility and duration decreased by 89 and 90%, respectively, after ablation in dogs. All the patients showed inducible AF prior to the procedure. No AF was inducible immediately after PVARA in 14 patients. The procedural time was significantly shorter in patients with PVARA than PV isolation. Within 1 week after ablation, there were six patients with early recurrent AF and seven with atrial tachycardia (AT) in PVARA group, and three patients with AF and six with AT in control. During follow-up of 6–12 months, 11 patients were free of AF and AT with four patients taking propafenone or amiodarone in the PVARA group, and nine patients free of AF and AT with seven patients taking propafenone or amiodarone in control. No complication related to the ablation developed in the two groups. This pilot study demonstrated that PVARA was a simple and safe strategy for paroxysmal AF ablation, and might provide a better long-term outcome than PV isolation. # Pulmonary vein isolation with a multi-electrode ablation catheter using duly-cycled bipolar and unipolar radiofrequency energy {#article-title-5} Background Traditional catheter ablation of atrial fibrillation (AF) requires long procedure times and high level of operator skill. A multielectrode catheter (PVAC, ablation frontier) combining circular mapping and duly-cycled bipolar and unipolar radiofrequency energy delivery has been developed to map and isolate the pulmonary veins. Aim The aim of this study to evaluate the efficacy of PVAC for pulmonary vein isolation in paroxysmal AF ablation. Methods Fifty consecutive patients with paroxysmal AF who had failed at least one anti-arrhythmic drug and eligible for catheter ablation were included in the study. All four pulmonary veins were isolated and confirmed the absence of pulmonary vein potentials with PVAC. At six months, 48 h Holter monitoring was performed to determine freedom of AF. Results All patients had structurally normal hearts with a mean duration of AF of 4.28 + 4.39 years. The mean procedure time was 109.74 + 28.35 min. Mean fluoroscopy time was 36.52 + 12.29 min. Mean number of RF applications were 27.79 + 13.80 min. The mean follow-up duration was 9.39 + 4.90 months. After AF ablation with PVAC, 36 patients completed 6-month follow-up and 25 patients (69.4%) were in sinus rhythm without drugs. No procedure-related complication was observed. Conclusions Pulmonary vein isolation using the PVAC has a success rate of ∼70% with the first ablation. # Autonomic mechanism for complex fractionated atrial electrograms: evidence by pathology {#article-title-6} Background The mechanism(s) underlying complex fractionated atrial electrograms (CFAEs) has not been well elucidated. The present study addressed to observe the histological characteristics at the area with CFAEs in canine atria to investigate the mechanism of CFAEs. Methods Ten adult mongrel dogs were involved in the present study. AF was induced through rapid atrial pacing with vagosympathetic nerve stimulation. CFAEs was recorded by Lasso catheter. Irrigated ablation was performed at sites with CFAEs. After finishing procedures above, all dogs were sacrificed and the whole hearts were taken out and fixed in 4¢Hformalin for more than 48 hours for histological examination. The specimens were divided into CFAEs group and non-CFAEs group. Serial sections were taken and stained with hematoxylin and eosin(HE) and general neural marker protein gene product 9.50(PGP9.50), respectively. Compare the characteristics of myocardial and autonomic nerve distribution between the CFAEs and non-CFAEs groups. Results Sections stained by HE: The myocardium in non-CFAEs group was well-arranged, usually in parallel with little interstitial and epicardial adipose tissue. However, the myocardium in CFAEs group distributed in disorganization with more interstitial tissue and epicardial adipose tissue. Nerve fibers and ganglionated plexi (autonomic nerves) in CFAEs group were more abundant than non-CFAEs group (7±5.4 vs. 1.9±2.7; P