Evaluation the role of insulin signaling pathway in reproductive toxicity of dispersed diesel particulate extract under environmental conditions.

Diesel particulate extract (DPE), which is a significant constituent of airborne particle pollution, has a strong association with the development of cancer and respiratory diseases. Fulvic acid (FA), a plentiful organic macromolecule found in water, has the capability to modify particle surface charge and adsorption capacity when combined with minerals. Nevertheless, there is a scarcity of data regarding the influence of their interaction on DPE toxicity. To examine the impact of environmental factor on the toxic effects of DPE, we used the Caenorhabditis elegans (C. elegans) model to investigate the reproductive toxicity of DPE and FA on insulin signaling pathway. C. elegans were subjected to a semi-fluid medium (NGG) containing different concentrations of DPE or DPE + FA in order to assess germline apoptosis and the expression of important genes in the insulin signaling pathway. Through several mutant strains, we found that daf-2, age-1, pdk-1, akt-1 and daf-16 were involved in DPE-induced apoptosis. Furthermore, and the expression levels of these genes significantly altered. The ratio of daf-16 translocation to nucleation, as well as the amount of reactive oxygen species (ROS), exhibited a dose-response relationship, however, the presence of FA could altered these effects. The results revealed that the insulin signaling pathway plays a vital role in mediating the harmful effects caused by DPE, whereas environmental factors have a substantial impact on its toxicity. Moreover, it was noted that semi-fluid medium could effectively replicate three-dimensional exposure circumstances closely resembling those observed in actual situations.

Comparison of 2D-QCA, 3D-QCA and coronary angiography derived FFR in predicting myocardial ischemia assessed by CZT-SPECT MPI.

BACKGROUND: Angiography derived fractional flow reserve (angio-FFR) has been proposed. This study aimed to assess its diagnostic performance with cadmium-zinc-telluride single emission computed tomography (CZT-SPECT) as reference. METHODS AND RESULTS: Patients underwent CZT-SPECT within 3 months of coronary angiography were included. Angio-FFR computation was performed using computational fluid dynamics. Percent diameter (%DS) and area stenosis (%AS) were measured by quantitative coronary angiography. Myocardial ischemia was defined as a summed difference score ≥ 2 in a vascular territory. Angio-FFR ≤ 0.80 was considered abnormal. 282 coronary arteries in 131 patients were analyzed. Overall accuracy of angio-FFR to detect ischemia on CZT-SPECT was 90.43%, with a sensitivity of 62.50% and a specificity of 98.62%. The diagnostic performance (= area under ROC = AUC) of angio-FFR [AUC = 0.91, 95% confidence intervals (CI) 0.86-0.95] was similar as those of %DS (AUC = 0.88, 95% CI 0.84-0.93, p = 0.326) and %AS (AUC = 0.88, 95% CI 0.84-0.93 p = 0.241) by 3D-QCA, but significantly higher than those of %DS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) and %AS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) by 2D-QCA. However, in vessels with 50-70% stenoses, AUC of angio-FFR was significantly higher than those of %DS (0.80 vs. 0.47, p < 0.001) and %AS (0.80 vs. 0.46, p < 0.001) by 3D-QCA and %DS (0.80 vs. 0.66, p = 0.036) and %AS (0.80 vs. 0.66, p = 0.034) by 2D-QCA. CONCLUSION: Angio-FFR had a high accuracy in predicting myocardial ischemia assessed by CZT-SPECT, which is similar as 3D-QCA but significantly higher than 2D-QCA. While in intermediate lesions, angio-FFR is better than 3D-QCA and 2D-QCA in assessing myocardial ischemia.

Artificial Intelligence-Based Echocardiographic Left Atrial Volume Measurement with Pulmonary Vein Comparison.

This paper combines echocardiographic signal processing and artificial intelligence technology to propose a deep neural network model adapted to echocardiographic signals to achieve left atrial volume measurement and automatic assessment of pulmonary veins efficiently and quickly. Based on the echocardiographic signal generation mechanism and detection method, an experimental scheme for the echocardiographic signal acquisition was designed. The echocardiographic signal data of healthy subjects were measured in four different experimental states, and a database of left atrial volume measurements and pulmonary veins was constructed. Combining the correspondence between ECG signals and echocardiographic signals in the time domain, a series of preprocessing such as denoising, feature point localization, and segmentation of the cardiac cycle was realized by wavelet transform and threshold method to complete the data collection. This paper proposes a comparative model based on artificial intelligence, adapts to the characteristics of one-dimensional time-series echocardiographic signals, automatically extracts the deep features of echocardiographic signals, effectively reduces the subjective influence of manual feature selection, and realizes the automatic classification and evaluation of human left atrial volume measurement and pulmonary veins under different states. The experimental results show that the proposed BP neural network model has good adaptability and classification performance in the tasks of LV volume measurement and pulmonary vein automatic classification evaluation and achieves an average test accuracy of over 96.58%. The average root-mean-square error percentage of signal compression is only 0.65% by extracting the coding features of the original echocardiographic signal through the convolutional autoencoder, which completes the signal compression with low loss. Comparing the training time and classification accuracy of the LSTM network with the original signal and encoded features, the experimental results show that the AI model can greatly reduce the model training time cost and achieve an average accuracy of 97.97% in the test set and increase the real-time performance of the left atrial volume measurement and pulmonary vein evaluation as well as the security of the data transmission process, which is very important for the comparison of left atrial volume measurement and pulmonary vein. It is of great practical importance to compare left atrial volume measurements with pulmonary veins.

Recurrent atrial fibrillation after initial cryoballoon ablation: New perspectives for intensive ablation in right superior pulmonary vein ostium for atrial fibrillation.

A significant proportion of patients with recurrent atrial fibrillation (AF) require repeat radiofrequency (RF) ablation after cryoballoon (CB) ablation. However, little is known about the pulmonary vein (PV) potential reconnection to left atrium and localization of gaps in the initial lesion sets following cryoablation in patients with recurrent AF. The data of 29 consecutive patients with repeat RF ablation for recurrent AF were analyzed. During the second ablation procedures, PV foci of AF were explored in 116 PVs by the CARTO system. All patients had complete PV isolation from initial cryoablation procedure. The fluoroscopy duration, mean cryoablation time and mean cryoablation frequency were lowest for the right superior pulmonary vein (RSPV) (58.69 ± 9.18 s, 185.10 ± 49.25 s and 1.07 ± 0.26; p = 0.024, p = 0.042 and p = 0.032). A significantly higher incidence of conduction gaps per patient was found for the RSPVs compared to the other PVs (p < 0.05 or p < 0.01). For RSPVs, it seemed that gaps were predominantly located at the anterior segment (22 gaps) and inferior segment (22 gaps). RSPV reconnection was independently related to a lower risk of major adverse events after the second ablation during follow up in the study patients (HR 0.275, 95%CI 0.078-0.967, p = 0.044). AF recurrence in patients after cryoablation is significantly associated with conduction gaps in the anterior and inferior segments of RSPVs. Various ablation strategies of close touch of CB on anterior and inferior segments of RSPV ostium, more freezing time and frequency for RSPV may help achieving durable PV isolation during follow up.

Renal functional impairment in the elderly, the importance of fasting plasma glucose: the Northern Shanghai Study.

BACKGROUND: Chronic kidney disease is a global health problem that is closely related to the aging population. Although plasma glucose levels have been shown to be related to renal dysfunction, risk factors for renal functional impairment in the geriatric population are unknown. The authors therefore aimed to investigate the determinants of renal functional impairment in an elderly population. METHODS: From June 2014 to August 2015, 912 participants (aged > 65 years) were recruited. Renal function was assessed at baseline; follow-up was conducted in 2016. Within the framework of comprehensive cardiovascular examinations, all conventional cardiovascular risk factors, fasting plasma glucose (FPG), and renal function were assessed. Renal function was evaluated by the estimated glomerular filtration rate (e-GFR) using a modified Modification of Diet in Renal Disease formula. Rapid decline in e-GFR was defined as an e-GFR slope > 5 mL/min per 1.73 m2 per year. RESULTS: We observed that FPG levels were significantly higher in participants with (6.15 ± 2.76 mmol/L) than in those without (5.56 ± 1.61 mmol/L) a rapid decline in e-GFR (p = 0.02). The average decline in e-GFR was 0.149 mL/min/1.73m2 per year in this elderly population, and the increasing risk of having rapid decline in e-GFR was 0.44-fold each year. In the full adjustment model, decline in e-GFR (p = 0.02) and rapid decline in e-GFR (OR1.33, 95% CI 1.03-1.72) were significantly associated with FPG, independent of other conventional cardiovascular risk factors. Using the same models, decline in e-GFR (p = 0.04) and rapid decline in e-GFR (OR 1.57, 95% CI 1.05-2.35) were also significantly associated with FPG in diabetic population, but they were not in non-diabetic population. CONCLUSIONS: In community-dwelling elderly Chinese, the average decline in e-GFR was 0.149 mL/min/1.73m2 per year. FPG control is important for delaying renal functional impairment in elderly population. Trial registration NSS, NCT02368938.

Cryoablation Combined with Left Atrial Appendage Closure: A Safe and Effective Procedure for Paroxysmal Atrial Fibrillation Patients.

BACKGROUND: Catheter ablation combined with left atrial appendage closure (LAAC) was reported as a feasible strategy for atrial fibrillation (AF) patients with high risk of stroke or contraindications of oral anticoagulants. We aimed to observe the short-term safety and efficacy of combining cryoballoon ablation (CBA) with LAAC in paroxysmal (PAF) patients. Method and Results. From Jan 2016 to Dec 2017, 304 patients diagnosed with nonvalvular, drug-refractory PAF were included, who underwent either CBA alone (n = 262) or combined procedure (n = 42). Instant pulmonary vein isolation (PVI) with CBA was achieved in all patients, while successful LAAC achieved in 41 (97.6%) of combined procedure patients. 1-year freedom of AF rate was lower in combined procedure group (84.7% vs 70.7%, p = 0.04), with unadjusted hazard ratio (HR = 1.97) and 95% confidence interval (CI) 1.03-3.77. However, the multivariate COX model revealed left atrial diameter (p = 0.002, HR = 1.10, and 95% CI 1.04, 1.17), rather than procedure type (p = 0.51, HR = 1.34, and 95% CI 0.57, 3.17), was the predictor for freedom of AF. Only 2 patients in the CBA group had stroke, contributing to the nonsignificant higher stroke incidence (p = 1.00). Transoesophageal echochardiography (TEE) achieved in 35 patients (83.3%) showed complete occlusion with no obvious residual flow (>3 mm), Device-related thrombosis, or pericardial perfusion. All-cause mortality, rehospitalization, and complication rates were similar. CONCLUSION: Combining CBA with LAAC in a single procedure is a feasible strategy for PAF patients, with comparable short-term safety and efficacy to CBA alone.

Early detection of ST-segment elevated myocardial infarction by artificial intelligence with 12-lead electrocardiogram.

Patient delay is a worldwide unsolved problem in ST-segment elevated myocardial infarction (STEMI). An accurate warning system based on electrocardiogram (ECG) may be a solution for this problem, and artificial intelligence (AI) may offer a path to improve its accuracy and efficiency. In the present study, an AI-based STEMI autodiagnosis algorithm was developed using a dataset of 667 STEMI ECGs and 7571 control ECGs. The algorithm for detecting STEMI proposed in the present study achieved an area under the receiver operating curve (AUC) of 0.9954 (95% CI, 0.9885 to 1) with sensitivity (recall), specificity, accuracy, precision and F1 scores of 96.75%, 99.20%, 99.01%, 90.86% and 0.9372 respectively, in the external evaluation. In a comparative test with cardiologists, the algorithm had an AUC of 0.9740 (95% CI, 0.9419 to 1), and its sensitivity (recall), specificity, accuracy, precision, and F1 score were 90%, 98% and 94%, 97.82% and 0.9375 respectively, while the medical doctors had sensitivity (recall), specificity, accuracy, precision and F1 score of 71.73%, 89.33%, 80.53%, 87.05% and 0.8817 respectively. This study developed an AI-based, cardiologist-level algorithm for identifying STEMI.

Predictive value of left atrial appendage lobes on left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation.

BACKGROUND: Left atrial appendage morphology has been proved to be an important predictor of left atrial thrombus (LAT) and left atrial spontaneous echo contrast (LASEC) and stroke in patients with non-valvular atrial fibrillation (NVAF). However, the relation between left atrial appendage (LAA) lobes and LAT or LASEC is still unknown. The aim of this study is to investigate the correlation between the number of left atrial appendage lobes and LAT/LASEC in patients with NVAF. METHODS: This monocentric cross-sectional study enrolled 472 consecutive patients with non-valvular atrial fibrillation, who had transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) prior to cardioversion or left atrial appendage closure (LAAC) from July 2009 to August 2015 in department of cardiology of Shanghai Tenth People's Hospital. Patients who had significant mitral or aortic valve disease, previous cardiac valvular surgery and other complicated cardiac diseases were excluded. Individuals were divided into two groups:the LAT/LASEC group (16.95%), which comprised patients with LAT or LASEC, as confirmed by TEE; and a negative control group (83.05%).Baseline overall group characterization with demographic, clinical, laboratory data and echocardiographic parameters, alongside with information on medication was obtained for all patients. Subgroup analysis with line chart was applied for exploring the association between LAA lobes and LAT/LAESC. Receptor-operating curves (ROC) were used to test the value of LA anteroposterior diameter detected by different echocardiography methods predicting LAT or LASEC. Multivariable logistic regression analysis was used to investigate independent predictors of LAT/LASEC. RESULTS: Among 472 patients, 23 (4.87%) had LA/LAA thrombus and 57 (12.1%) had LA spontaneous echo contrast. Compared to the negative group, patients in LAT/LASEC group had higher CHA2DS2-VASc score (3.79 ± 1.75 vs 2.65 ± 1.76, p < 0.001), larger LAD (measured by TTE, 48.1 ± 7.7 vs 44.6 ± 6.5, P < 0.001; measured by TEE, 52.2 ± 6.2 vs 46.7 ± 7.1, P < 0.001), lower left upper pulmonary venous flow velocity (LUPVFV) (0.54 ± 0.17 m/s vs 0.67 ± 0.26 m/s, CI 95% 0.05-0.22, P = 0.003), more left atrial appendage lobes (1.67 ± 0.77 vs 1.25 ± 0.50, p < 0.001). There was a good discriminative capacity for LAD detected by TTE (area under the curve (AUC), 0.67, CI 95% 0.61-0.73, p < 0.001) and LAD detected by TEE (AUC, 0.73, CI 95% 0.67-0.79, p < 0.001). The subgroup analysis based on gender and different LAA lobes yielded similar results (male group: p < 0.001;female group: p = 0.004) that the number of LAA lobes were significantly associated with LA thrombus or SEC. In multivariable logistic regression analysis, both the number of LAA lobes (odds ratio: 2.37; CI 95% 1.37-4.09; p = 0.002) and the persistent AF (odds ratio: 3.57; CI 95% 1.68-7.57; p = 0.001) provided independent and incremental predictive value beyond CHA2DS2-VASc score. CONCLUSION: The number of LAA lobes is an independent risk factor and has a moderate predictive value for LAT/LASEC among NVAF patients in China.

Comparison of circulating dendritic cell and monocyte subsets at different stages of atherosclerosis: insights from optical coherence tomography.

BACKGROUND: While specific patterns of circulating dendritic cells (DCs) and monocytes are associated with the incidence of coronary artery disease, the characterization of circulating DC and monocyte subsets in patients with different stages of atherosclerosis remains unclear. METHODS: Forty-eight patients with unstable angina pectoris (UAP) diagnosed by angiography were enrolled. Likewise, 31 patients with ST-segment elevation myocardial infarction (STEMI) were enrolled and confirmed with the presence of thrombosis by angiography. Plaque features of 48 UAP patients were evaluated at the culprit lesions by OCT. Circulating myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte subsets were analyzed using flow cytometry. RESULTS: The proportions and absolute counts of mDC2s, which specifically express CD141 and possess the ability to activate CD8+ T lymphocytes, significantly decreased in patients with UAP and STEMI when compared with controls (0.08 × 104 ± 0.05 × 104/ml and 0.08 × 104 ± 0.06 × 104/ml vs. 0.11 × 104 ± 0.06 × 104/ml, p = 0.027). On the other hand, patients with UAP and STEMI had significantly higher proportions and counts of Mon2 subsets. In the OCT subgroup, patients with thin-cap fibroatheroma (TCFA) had higher proportions and absolute number of Mon2 (11.96% ± 4.27% vs. 9.42% ± 4.05%, p = 0.034; 5.17 × 104/ml ± 1.92 × 104/ml vs. 3.53 × 104/ml ± 2.65 × 104/ml, p = 0.045) than those without TCFA. However, there was no remarkable difference in mDC2s between patients with and without TCFA. CONCLUSIONS: Circulating Mon2 appears to be a promising marker for the severity of atherosclerotic plaque.

Association of arteriosclerosis and/or atherosclerosis with hypertensive target organ damage in the community-dwelling elderly Chinese: the Northern Shanghai Study.

OBJECTIVE: Vascular abnormality includes two forms, arteriosclerosis (ARS) and atherosclerosis (ATS), which coexist in patients with cardiovascular (CV) diseases. However, whether their combination may lead to a worsening status in those patients remains unclear. We therefore aimed to investigate the association of ARS and/or ATS with hypertensive target organ damage (TOD). METHODS: From June 2014 to August 2015, a total of 1,599 community-dwelling elderly subjects (aged >65 years) from northern Shanghai were recruited. Vascular measurements, such as carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial index (ABI) and carotid plaque, were conducted on each participant, and ARS was defined as cf-PWV >12 m/s, while ATS was defined as participants who have carotid plaque or ABI <0.9. Within the framework of comprehensive CV examinations, CV risk factors were assessed, and asymptomatic TOD was evaluated by measuring participants' left ventricular mass index (LVMI), peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), urinary albumin-creatinine rate (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Although LVMI, E/Ea and eGFR were significantly different among subjects with or without ARS and/or ATS (P<0.02), in full adjustment model, only E/Ea showed the independent and significant difference (P=0.023). Moreover, E/Ea was significantly different between participants with ARS or ATS and those without ARS or ATS (P=0.045), while there was no significant difference between participants with ARS and ATS and those without ARS or ATS (P=0.28). Similar results were obtained in the multivariate logistic regression of left ventricular diastolic dysfunction (LVDD). With similar adjustment, LVDD was significantly associated with ATS (P=0.01) but not with ARS (P=0.99). CONCLUSION: In the community-dwelling elderly Chinese, among hypertensive TOD, LVDD was significantly associated with ATS but not with ARS. The proportion of patients with LVDD was not significantly different despite the presence of both ATS and ARS, when compared to patients with ATS alone.

Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy.

BACKGROUND: Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown. METHODS AND RESULTS: In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates. Moreover, we generated cardiomyocyte-specific TIM50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by TIM50. Meanwhile, expression of the ASK1-JNK/P38 axis was increased in TIM50-deficient mice, and TIM50 overexpression decreased the activity of the ASK1-JNK/P38 axis. Finally, we treated mice with the antioxidant N-acetyl cysteine to reduce oxidative stress. After N-acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency were all remarkably reversed. CONCLUSIONS: These data indicated that TIM50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress. TIM50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure.

Comparison of Carotid-Femoral and Brachial-Ankle Pulse-Wave Velocity in Association With Target Organ Damage in the Community-Dwelling Elderly Chinese: The Northern Shanghai Study.

BACKGROUND: Carotid-femoral pulse-wave velocity (cf-PWV) and brachial-ankle PWV (ba-PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf-PWV and ba-PWV. METHODS AND RESULTS: A total of 1599 community-dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf-PWV and ba-PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima-media thickness, arterial plaque, creatinine clearance rate, and urinary albumin-creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba-PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf-PWV and ba-PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf-PWV, but not ba-PWV, was significantly associated with carotid intima-media thickness and creatinine clearance rate (P<0.05). When cf-PWV and ba-PWV were both or separately put into the same full-mode model after adjustment for confounders, only cf-PWV, but not ba-PWV, showed significant association with carotid intima-media thickness and creatinine clearance rate (P<0.05). Similar results were observed in logistic regression analysis. CONCLUSIONS: Taken together, in the community-dwelling elderly Chinese, cf-PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba-PWV. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938.

Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload.

Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.

Smad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload-Induced Pathological Cardiac Hypertrophy.

BACKGROUND: Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear. METHODS AND RESULTS: Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes. Accordingly, SNIP1 deficiency significantly exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac-specific overexpression of SNIP1 markedly recovered pressure overload-induced cardiac hypertrophy and fibrosis. Besides that, SNIP1 protected neonatal rat cardiomyocytes against angiotensin II-induced hypertrophy in vitro. Moreover, we identified that SNIP1 suppressed nuclear factor-κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor-κB signaling by a cardiac-specific conditional inhibitor of κBS32A/S36A transgene blocked these adverse effects of SNIP1 deficiency on hearts. CONCLUSIONS: Together, our findings demonstrated that SNIP1 had protective effects in pressure overload-induced pathological cardiac hypertrophy via inhibition of nuclear factor-κB signaling. Thus, SNIP1 may be a novel approach for the treatment of heart failure.

Growth Arrest-Specific 6 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy.

Growth arrest-specific 6 (GAS6) is a member of the vitamin K-dependent protein family that is involved in the regulation of the cardiovascular system, including vascular remodeling, homeostasis, and atherosclerosis. However, there is still no study that systemically elucidates the role of GAS6 in cardiac hypertrophy. Here, we found that GAS6 was upregulated in human dilated cardiomyopathic hearts, hypertrophic murine hearts, and angiotensin II-treated cardiomyocytes. Next, we examined the influence of GAS6 expression in response to a cardiac stress by inducing chronic pressure overload with aortic banding in wild-type and GAS6-knockout mice or cardiac-specific GAS6 overexpressing mice. Under basal conditions, the GAS6-knockout mice had normal left ventricular structure and function but after aortic banding, the mice demonstrated less hypertrophy, fibrosis, and contractile dysfunction when compared with wild-type mice. Conversely, cardiac-specific overexpression of GAS6 exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and dysfunction. Furthermore, we demonstrated that GAS6 activated the mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 pathway during pressure overload-induced cardiac hypertrophy, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed GAS6 overexpression-induced cardiac hypertrophy and fibrosis, resulting in improved cardiac function. Collectively, our data support the notion that GAS6 impairs ventricular adaptation to chronic pressure overload by activating mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 signaling. Our findings suggest that strategies to reduce GAS6 activity in cardiac tissue may be a novel approach to attenuate the development of congestive heart failure.

Overlay Technique for Transcatheter Left Atrial Appendage Closure.

The Overlay technique is popular in peripheral artery interventions, but not in coronary or cardiac structural procedures. We present an initial experience using three-episode overlays during a transcatheter left atrial appendage closure. The first overlay was applied to facilitate advancement of the delivery sheath into left atrium. The second overlay was used to navigate the advancement of prepped delivery system containing the compressed occluder into its optimal position in the left atrium. The third overlay facilitated the real-time deployment of the closure device. This case report demonstrates the effectiveness of the overlay technique in facilitating each step of the transcatheter left atrial appendage closure.

Optical logic gates based on electro-optic modulation with Sagnac interferometer.

In this work, we present a new structure to realize optical logic operation in a Sagnac interferometer with electro-optical modulation. In the scheme, we divide two counterpropagation signals in a Sagnac loop to two different arms with the electro-optical crystal by using two circulators. Lithium niobate materials whose electro-optical coefficient can be as large as 32.2×10(-12) m/V make up the arms of the waveguides. Using the transfer matrix of the fiber coupler, we analyze the propagation of signals in this system and obtain the transmission characteristic curves and the extinction ratio. The results indicate that this optical switching has a high extinction ratio of about 60 dB and an ultrafast response time of 2.036 ns. In addition, the results reveal that the change of the dephasing between the two input signals and the modification of the modulation voltage added to the electro-optical crystal leads to the change of the extinction ratio. We also conclude that, in cases of the dephasing of two initial input signals Δφ=0, we can obtain the various logical operations, such as the logical operations D=A¯·B, D=A·B¯, C=A+B, and D=A⊕B in ports C and D of the system by adjusting the modulation voltage. When Δφ≠0, we obtain the arithmetic operations D=A+B, C=A⊕B, D=A·B¯, and C=A¯·B in ports C and D. This study is significant for the design of all optical networks by adjusting the modulation voltage.

AlCl3-promoted formal [2 + 3]-cycloaddition of 1,1-cyclopropane diesters with N-benzylic sulfonamides to construct highly stereoselective indane derivatives.

An unprecedented AlCl3-promoted formal [2 + 3]-cycloaddition of 1,1-cyclopropanes with readily available N-benzylic sulfonamides has been developed. Experimental evidence supports an unusual mechanism wherein the donor-acceptor cyclopropane serves as a source of 2-styrylmalonate rather than the "classical" 1,3-dipole. A broad range of 1,1-cyclopropanediesters undergo a carbocation-initiated cyclization reaction with N-benzylic sulfonamides to afford highly functionalized Indane derivatives in a fast and high-yielding procedure.

All-optical logical gates based on pump-induced resonant nonlinearity in an erbium-doped fiber coupler.

In this paper, we theoretically investigate all-optical logical gates based on the pump-induced resonant nonlinearity in an erbium-doped fiber coupler. The resonant nonlinearity yielded by the optical transitions between the (4)I(15/2) states and (4)I(13/2) states in Er(3+) induces the refractive index to change, which leads to switching between two output ports. First, we do a study on the switching performance, and calculate the extinction ratio (Xratio) of the device. Second, using the Xratio, we obtain the truth tables of the device. The results reveal that compared with other undoped nonlinear couplers, the erbium-doped fiber coupler can drop the switching threshold power. We also obtain different logic gates and logic operations in the cases of the same phase and different phase of two initial signals by changing the pump power.

Association of TCF7L2 gene polymorphisms with type 2 diabetes mellitus in Han Chinese population: a meta-analysis.

Variants of transcription factor 7-like 2 (TCF7L2) gene have been reported to be associated with type 2 diabetes mellitus (T2DM), but the available data on this relationship are inconsistent in Han Chinese populations. A meta-analysis was performed to quantitatively analyze the association of TCF7L2 gene polymorphisms with T2DM using previous case-control studies in Chinese Han populations. Several electronic databases were searched for relevant articles up to May 2012. After data collection and gene loci selection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Publication bias was examined by the Egger's linear regression test. Hardy-Weinberg equilibrium (HWE) test and by omitting one study at a time were employed for the sensitivity analysis. Eighteen studies from sixteen eligible papers were included in the meta-analysis. Ten eligible studies were analyzed for rs7903146, and eight were analyzed for rs290487. We found that the rs7903146 T allele was associated with an increased risk for T2DM under a dominant model, a co-dominant model and an allele contrast model, with an OR of 1.54 (1.32, 1.79), an OR of 1.53 (1.31, 1.79) and an OR of 1.52 (1.31, 1.76), respectively. The rs290487 C allele showed no significant overall association with T2DM, yielding ORs of 1.08 (0.88, 1.32) under a dominant model, with strong evidence of heterogeneity. Similar results were also obtained in other genetic models. Sensitivity analysis confirmed the reliability and stability of this meta-analysis. The accumulated evidence suggested that the rs7903146 T allele was associated with an increased risk for T2DM, but the rs290487 C allele is not associated with T2DM in the Chinese Han population. More well-designed large studies are required for the validation of this association.