Search

Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays a crucial role in the initiation and progression of CVD, serving as a pivotal factor in the pathogenesis of cardiovascular, metabolic, and other related diseases. The regulation of endothelial dysfunction is influenced by various risk factors and intricate signaling pathways, which vary depending on the specific disease context. Despite numerous research efforts aimed at elucidating the mechanisms underlying endothelial dysfunction, the precise molecular pathways involved remain incompletely understood. This review elucidates recent research findings on the pathophysiological mechanisms involved in endothelial dysfunction, including nitric oxide availability, oxidative stress, and inflammation‐mediated pathways. We also discuss the impact of endothelial dysfunction on various pathological conditions, including atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Furthermore, we summarize the traditional and novel potential biomarkers of endothelial dysfunction as well as pharmacological and nonpharmacological therapeutic strategies for endothelial protection and treatment for CVD and related complications. Consequently, this review is to improve understanding of emerging biomarkers and therapeutic approaches aimed at reducing the risk of developing CVD and associated complications, as well as mitigating endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz–Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal‐specific Lkb1 is sufficient for the development of PJS‐like polyps in mice. However, the cellular origin and components of these Lkb1‐associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen‐inducible Lkb1flox/flox;Myh11‐Cre/ERT2 and Lkb1flox/flox;PDGFRα‐Cre/ERT2 mice, performed single‐cell RNA sequencing (scRNA‐seq) and imaging‐based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11‐Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA‐seq revealed aberrant stem cell‐like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11‐Cre/ERT2 mice. The Lkb1‐associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1–Cd44 or Spp1–Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1‐associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen‐inducible Lkb1flox/flox;PDGFRα‐Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2–3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1‐associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin‐like modifier (SUMO)‐mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO‐specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA‐binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co‐activator yes‐associated protein 1 in the Hippo pathway. Finally, adeno‐associated virus serotype 9 is used to construct TEAD1 wild‐type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy‐related heart failure. [ABSTRACT FROM AUTHOR]

Aims: Insulin resistance (IR) is associated with cardiometabolic multimorbidity (CMM). We aimed to explore the predictive value of six surrogate IR indexes—Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), triglyceride‐glucose (TyG), atherogenic index of plasma (AIP), TyG‐body mass index (TyGBMI), and TyG‐waist circumference (TyGwaist)—to establish the CMM incidence in Chinese middle‐aged and older populations. Material and Methods: To estimate the odds ratio (OR) with a 95% confidence interval (95% CI) for incident CMM using six surrogates, we analysed data from the China Health and Retirement Longitudinal Study using multivariate logistic regression models. The nonlinear dose‐response correlation was evaluated using restricted cubic spline analysis; predictive performance was assessed using receiver operator characteristic curves. Results: Among 6451 eligible participants, 268 (4.2%) developed CMM during the 4‐year follow‐up period. The ORs (95% CI) for incident CMM increased with increasing CVAI quartiles (Q) [Q2: 1.71, 1.03–2.90; Q3: 2.72, 1.70–4.52; Q4: 5.16, 3.29–8.45; all p < 0.05] after full adjustment, with Q1 as the reference. Other indexes yielded similar results. These associations remained significant in individuals with a normal body mass index. Notably, CVAI, AIP, and TyG exhibited a linear dose‐response relationship with CMM (Pnonlinear ≥0.05), whereas LAP, TyGBMI, and TyGwaist displayed significant nonlinear correlations (Pnonlinear <0.05). The area under the curve for the CVAI (0.691) was significantly superior to that of other indexes (all p < 0.05). Conclusions: The six IR surrogates were independently associated with CMM incidence. CVAI may be the most appropriate indicator for predicting CMM in middle‐aged and older Chinese populations. [ABSTRACT FROM AUTHOR]

Background: Differentiating hypertrophic cardiomyopathy (HCM) from hypertensive heart disease (HHD) is challenging. Purpose: To identify differences between HCM and HHD on a patient basis using MRI. Study Type: Retrospective. Population: A total of 219 subjects, 148 in phase I (baseline data and algorithm development: 75 HCM, 33 HHD, and 40 controls) and 71 in phase II (algorithm validation: 56 HCM and 15 HHD). Field Strength/Sequence: Contrast‐enhanced inversion‐prepared gradient echo and cine‐balanced steady‐state free precession sequences at 3.0 T. Assessment: MRI parameters assessed included left ventricular (LV) ejection fraction (LVEF), LV end systolic and end diastolic volumes (LVESV and LVEDV), mean maximum LV wall thickness (MLVWT), LV global longitudinal and circumferential strain (GRS, GLS, and GCS), and native T1. Parameters, which were significantly different between HCM and HHD in univariable analysis, were entered into a principal component analysis (PCA). The selected components were then introduced into a multivariable regression analysis to model an integrated algorithm (IntA) for screening the two disorders. IntA performance was assessed for patients with and without LGE in phase I (development) and phase II (validation). Statistical Tests: Univariable regression, PCA, receiver operating curve (ROC) analysis. A P value <0.05 was considered statistically significant. Results: Derived IntA formulation included LVEF, LVESV, LVEDV, MLVWT, and GCS. In LGE‐positive subjects in phase l, the cutoff point of IntA ≥81 indicated HCM (83% sensitivity and 91% specificity), with the area under the ROC curve (AUC) of 0.900. In LGE‐negative subjects, a higher possibility of HCM was indicated by a cutoff point of IntA ≥84 (100% sensitivity and 82% specificity), with an AUC of 0.947. Validation of IntA in phase II resulted in an AUC of 0.846 in LGE‐negative subjects and 0.857 in LGE‐positive subjects. Data Conclusion: A per‐patient‐based IntA algorithm for differentiating HCM and HHD was generated from MRI data and incorporated FT, LGE and morphologic parameters. Evidence Level: 3. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

The current hypertension guideline emphasizes combination therapy, especially single‐pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age < 55; (2) middle‐aged, 55≤age < 65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular‐related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older‐aged (≥65) patients with low‐risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use. [ABSTRACT FROM AUTHOR]

In situ high‐pressure Raman spectroscopy experiments have been performed to investigate the structural changes of parabanic acid (PA) up to ~12.0 GPa. The analysis of Raman spectroscopy reveals that PA undergoes two phase transitions. The collapse of spacing between molecular layers and the distortion of hydrogen‐bonding networks almost in ac‐plane are the main causes of the first phase transition above 2.1 GPa. The changes of Fermi resonance parameters also provide evidence for the first phase transitions. The second phase transition around 4.0 GPa can attribute to the further reduction of the molecular interlayer spacing and the resulting distortion of hydrogen‐bonding network. First‐principle calculations and Hirshfeld surfaces further confirm the analysis of the experimental results. The analysis of high‐pressure phase transition contributes a better explanation for the high‐pressure phase transition process of layered supramolecular materials with hydrogen‐bond self‐assembly. This study provides the possibility of two new polymorphs for PA under high pressure and is helpful for broadening its potential application of this material, especially in the field of supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Large-diameter monopiles have been widely used for constructing offshore wind turbines. The bearing capacity of a monopile foundation is a significant research problem. In this study, a new type of foundation, known as the pile–bucket foundation, was investigated to improve the bearing capacity of monopiles. A finite element software was used for establishing several numerical models of monopile and pile–bucket foundations to analyze the reinforcement afforded by the bucket attached to the monopile foundation. Furthermore, considering that offshore wind turbines are prone to resonance under the excitation of wind and wave loads, the natural frequencies of the monopile and pile–bucket foundations were determined and compared using both analytical and numerical methods. The results show that compared to the monopile foundation, the pile–bucket foundation has a significantly higher bearing capacity, mainly for large bucket diameters. The natural frequencies of the pile–bucket foundations are slightly higher than those of the monopile foundations. The addition of the bucket can effectively improve the natural frequency without changing the diameter of the monopile and thus saving the foundation cost. [ABSTRACT FROM AUTHOR]

In recent years, reversible data hiding technology has been widely used in JPEG images for special purposes such as file management and image authentication. Histogram shifting is one of the most popular techniques for achieving reversible data hiding technology. However, invalid shifting in histogram shifting limits the performance of existing reversible data hiding schemes. Therefore, we propose a two-dimensional histogram shifting-based reversible data hiding scheme in this article to improve the performance of marked JPEG images in terms of visual quality and file size. In the proposed histogram shifting method, only the coefficient pairs containing two non-zero quantized discrete cosine transform coefficients are changed for embedding data. Specifically, the coefficient pairs with at least one quantized discrete cosine transform coefficient valued −1 or +1 are shifted and the rests leave room for embedding data. With our proposed reversible data hiding scheme, the number of invalid shifting pixels is reduced so that it improves the performance of marked JPEG images. The experimental results show that the proposed method achieves a higher peak signal-to-noise ratio and has a lower increase in file size than state-of-art methods. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Left atrial appendage closure (LAAC) has been proved to be noninferior to traditional Vitamin K antagonists (VKAs) as well as novel oral anticoagulants (NOACs), which is becoming an important alternative to prevent stroke in non‐valvular AF. Catheter‐based AF ablation (CA) is recommended to be a standard of care in patients with AF refractory to drug therapy due to a better rhythm control and improvement of life quality than antiarrhythmic drugs. Theoretically, the one‐stop combination with LAAC and CA tends to bring more benefits in patients with AF, as it not only relieves symptoms, but also reduces the risk of stroke significantly. However, several important questions still need to be considered in the combination procedure although quite a few attempts have already been made in clinical practice. This review provides a comprehensive update on the concept, technique, perioperative management, benefits and other critical issues of the "one‐stop" procedure. [ABSTRACT FROM AUTHOR]

When trench construction of the diaphragm wall passes through an ultradeep and weak interlayer, local instability of the trench wall occurs easily. To study the mechanism of the local instability in the trench and by considering the effect of soil arching based on the length of the trench and the angle of internal friction in the weak interlayer, the disturbed area of the trench is defined to be a semiellipse and the local failure stability model of the semiellipse is established. The local stability safety factor of the trench wall is obtained by the limit equilibrium analysis of the model. By conducting parameter sensitivity studies, the results show that the thickness of the overlying strata, the unit weight of the slurry, the angle of internal friction, and the cohesion of the weak interlayer have a great influence on the stability of the trench wall. The semiellipsoid model is used to analyze the stability of the trench wall of the diaphragm wall of a subway station. The calculated results are basically consistent with the field monitoring results. All the work of the paper shows that the model is practical to some extent. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation (CA) is a promising option in most patients with refractory atrial fibrillation (AF). However, data on over 5 years' outcomes with larger numbers in hypertrophic cardiomyopathy (HCM) patients with AF have not been reported. We assessed the outcome of 120 HCM patients following CA compared with a non‐CA group and general patients without AF matched by HCM type with a 61.9 ± 31.6‐month follow‐up. Methods and Results: A total of 120 patients (age 61 ± 9.8 years, female n = 43, 35.8%) with paroxysmal AF (n = 60, 50%) and persistent AF (n = 60, 50%) were enrolled. Of the 120 patients, 48 (40%) required redo procedures, and 82 (68.3%) were in sinus rhythm at the last evaluation. The composite clinical events rate following the initial CA was lower than that in the non‐CA group (P =.023) and was also comparable to that in general patients without AF matched by HCM type (P =.729). Female (HR 2.358, 95% CI, 1.151‐4.831; P =.019), NYHA functional class III‐IV (HR 2.422, 95% CI, 1.032‐5.685; P =.042) and left atrial diameter ≥50 mm (HR 3.319, 95% CI, 1.469‐7.499; P =.004) were predictors of AF recurrence after multiple procedures. Conclusions: CA was successful in restoring long‐term sinus rhythm and improving symptomatic status in most HCM patients with refractory AF especially for those patients with small atrial size and mild symptoms. In addition, CA may contribute to the prevention of major clinical adverse events in the long‐term clinical course. [ABSTRACT FROM AUTHOR]

Background and Purpose: Atherosclerosis is a chronic inflammatory disease, and retinoid X receptor-α (RXRα) is an intriguing anti-atherosclerosis target. This study investigated whether and how an RXRα modulator, K-80003, derived from a non-steroidal anti-inflammatory drug attenuates atherosclerotic plaque progression and destabilization.Experimental Approach: Our previously established ApoE-/- mouse model of carotid vulnerable plaque progression was treated with K-80003 or vehicle for 4 or 8 weeks. Samples of carotid arteries and serum were collected to determine atherosclerotic lesion size, histological features, expression of related proteins, and lipid profiles. In vitro studies were carried out in 7-ketocholesterol (7-KC)-stimulated macrophages treated with or without K-80003.Key Results: K-80003 significantly reduced lesion size, plaque rupture, macrophage infiltration, and inflammatory cytokine levels. Plaque macrophages positive for nuclear p65 (RelA) NF-κB subunit were markedly reduced after K-80003 treatment. Also, K-80003 treatment inhibited 7-KC-induced p65 nuclear translocation, IκBα degradation, and transcription of NF-κB target genes. In addition, K-80003 inhibited NF-κB pathway mainly through the reduction of p62/sequestosome 1 (SQSTM1), probably due to promotion of autophagic flux by K-80003. Mechanistically, cytoplasmic localization of RXRα was associated with decreased autophagic flux. Increasing cytoplasmic RXRα expression by overexpression of RXRα/385 mutant decreased autophagic flux in RAW264.7 cells. Finally, K-80003 strongly inhibited 7-KC-induced RXRα cytoplasmic translocation.Conclusions and Implications: K-80003 suppressed atherosclerotic plaque progression and destabilization by promoting macrophage autophagic flux and consequently inhibited the p62/SQSTM1-mediated NF-κB proinflammatory pathway. Thus, targeting RXRα-mediated autophagy-inflammation axis by its noncanonical modulator may represent a promising strategy to treat atherosclerosis. [ABSTRACT FROM AUTHOR]

Shale gas resources are considered to be extremely abundant in southern China, which has dedicated considerable attention to shale gas exploration in recent years. Exploration of shale gas has considerably progressed and several breakthroughs have been made in China. However, shale gas explorations are still scarce. Summary and detailed analysis studies on black shale reservoirs are still to be performed for many areas. This lack of information slows the progress of shale gas explorations and results in low quantities of stored black shale. The Carboniferous Dawuba Formation, which is widely distributed and considerably thick, is one of the black shale formations targeted for shale gas exploration in southern China in the recent years. The acquisition and analysis of total organic carbon, vitrinite reflectance, types of organic matter, mineral composition, porosity, and permeability are basic but important processes. In addition, we analyzed the microscopic pores present in the shale. This study also showesd the good gas content of the Dawuba Formation, as well as the geological factors affecting its gas content and other characteristics. To understand the prospect of exploration, we compared this with other shale reservoirs which have been already successfully explored for gas. Our comparison showesd that those shale reservoirs have similar but not identical geological characteristics. [ABSTRACT FROM AUTHOR]

Implantation of leadless pacemaker is efficacy and safety compared with the traditional pacemaker in structurally normal hearts. However, delivery experience of leadless pacemaker in patients with severe right heart enlargement remains limited. We present the rare case of a patient with giant right heart and moderate to severe tricuspid regurgitation implanted with a leadless Micra transcatheter pacemaker system. The extension of the Micra delivery catheter can be improved by using a single‐loop snare on the catheter proximal to appropriate right ventricle (RV) pacing position. The snare‐kissing‐catheter technique can aid in successful deployment in the setting of challenging right heart enlargement. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a leading cause of death worldwide, requiring the development of new therapeutic strategies including stem cell therapy. Pentraxins (PTXs) are a superfamily of proteins highly involved in different myocardial disorders, and thus this study aimed to identify the modulation of long pentraxin 3 (PTX3) in the differentiation of mouse embryonic stem cells (mESCs) toward cardiomyocytes. Cell toxicity of PTX3 was detected by MTT and LDH assays in mESCs. Embryoid bodies (EBs) were differentiated using hanging drop method, and the beating was observed under microscope. Expressional levels of early cardiac progenitor marker genes were assessed by qRT‐PCR. Expression of marker proteins in early myocardial development and the activation of JNK signaling pathway was evaluated by Western blot. PTX3 treatment at 50 ng/mL significantly promoted the expression of cardiac‐specific marker genes including Nkx2.5, Mef2c, Tbx5, dHand, and αMHC, and increased the expression of cardiac maturity indicative markers including connexin 43 and troponin C1. PTX3 enhanced the phosphorylation of JNK across the incubation duration, whereas the activation of p38 remained the same as control group. Co‐treatment of JNK signaling pathway inhibitor SP600125 impaired the PTX3‐promoted transcription of Nkx2.5, Mef2c, Tbx5, dHand, and αMHC. This study revealed the promotion of PTX3 in the differentiation of mESCs into cardiomyocytes and the underlying mechanism. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no‐reflow in a canine model of acute myocardial infarction after reperfusion. Methods: The canine myocardial no‐reflow model was established by a 3‐hour occlusion of the left anterior desecending coronary artery followed by a 2‐hour reperfusion. Twenty‐four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS + tirofiban), and (4) ETUS alone. Results: The area of no‐reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS + tirofiban group having the smallest area. Also, the ETUS + tirofiban group had the highest recanalized rate of microvessels in the no‐reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS + tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia‐inducible factor‐1α (HIF‐1α) was significantly increased in the ETUS + tirofiban group, compared with the other groups. Conclusions: The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no‐reflow. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, antidiabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting that it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor-α ( RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes. Microscopic and molecular analyses further indicated that the detrimental effects of RORα deficiency were associated with aggravated myocardial apoptosis, autophagy dysfunction, and oxidative stress by disrupting antioxidant gene expression. By contrast, restoration of cardiac RORα levels in transgenic mice significantly improved cardiac functional and structural parameters at 8 weeks after diabetes induction. Consistent with genetic manipulation, pharmacological activation of RORα by melatonin and SR1078 (a synthetic agonist) showed beneficial effects against diabetic cardiomyopathy, while the RORα inhibitor SR3335 significantly exacerbated cardiac impairments in diabetic mice. Collectively, these findings suggest that cardiac-targeted manipulation of nuclear melatonin receptor RORα may hold promise for delaying diabetic cardiomyopathy development. [ABSTRACT FROM AUTHOR]

Circadian rhythm disruption or decrease in levels of circadian hormones such as melatonin increases ischemic heart disease risk. The nuclear melatonin receptors RORs are pivotally involved in circadian rhythm regulation and melatonin effects mediation. However, the functional roles of RORs in the heart have never been investigated and were therefore the subject of this study on myocardial ischemia/reperfusion ( MI/R) injury pathogenesis. ROR α and ROR γ subtypes were detected in the adult mouse heart, and ROR α but not ROR γ was downregulated after MI/R. To determine the pathological consequence of MI/R-induced reduction of ROR α, we subjected ROR α-deficient staggerer mice and wild-type ( WT) littermates to MI/R injury, resulting in significantly increased myocardial infarct size, myocardial apoptosis and exacerbated contractile dysfunction in the former. Mechanistically, ROR α deficiency promoted MI/R-induced endoplasmic reticulum stress, mitochondrial impairments, and autophagy dysfunction. Moreover, ROR α deficiency augmented MI/R-induced oxidative/nitrative stress. Given the emerging evidence of ROR α as an essential melatonin effects mediator, we further investigated the ROR α roles in melatonin-exerted cardioprotection, in particular against MI/R injury, which was significantly attenuated in ROR α-deficient mice, but negligibly affected by cardiac-specific silencing of ROR γ. Finally, to determine cell type-specific effects of ROR α, we generated mice with cardiomyocyte-specific ROR α overexpression and they were less vulnerable to MI/R injury. In summary, our study provides the first direct evidence that the nuclear melatonin receptor ROR α is a novel endogenous protective receptor against MI/R injury and an important mediator of melatonin-exerted cardioprotection; melatonin- ROR α axis signaling thus appears important in protection against ischemic heart injury. [ABSTRACT FROM AUTHOR]

Background Sympathetic activation and parasympathetic withdrawal are important characteristics of heart failure. Recent studies demonstrate that galanin reduces the discharge of acetylcholine and inhibits vagal bradycardia by acting on galanin receptor type 1 (GalR1). We speculated that blocking GalR1 is beneficial for heart failure. Methods Rats with heart failure were induced by myocardial infarction. The rats were injected intraperitoneally with galanin receptor antagonist M40 solution (30 nmol/kg) or saline for 4 weeks. Cardiac function was assessed by echocardiography and brain natriuretic peptide ( BNP) in plasma. The ratio of heart weight to body weight ( HW/ BW), hematoxylin-eosin ( HE), and Masson trichrome stain was used to evaluate cardiac remodeling. Tumor necrosis factor- α ( TNF- α), interleukin 6 ( IL-6) in plasma, and sarco(endo)plasmic reticulum Ca2+- ATPase ( SERCA2) in heart tissue were detected to confirm the mechanism of the cardioprotection effect. Results Compared with rats injected with saline, M40 effectively improved cardiac function of contraction; decreased BNP, IL-6, and HW/ BW (all P < 0.05); attenuated cardiac fibrosis; and upregulated SERCA2 ( P < 0.05). Conclusion M40 improves cardiac function and attenuates remodeling, suggesting that galanin receptor antagonist may be a potential therapeutic agent for HF. [ABSTRACT FROM AUTHOR]

Key Clinical Message Coughing could induce symptomatic, frequent atrial premature contractions ( APCs), and episodes of atrial tachycardia ( AT) in a rare case. If multiple arrhythmic drugs therapy failed to control the symptoms, catheter ablation was an effective therapeutic option for abolishing such atrial tachyarrhythmias guided by the electroanatomic mapping systems. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a multi-system inflammatory disorder. We report the case of a BD patient with severe aortic root vasculitis. Two-dimensional transthoracic echocardiography (2DE) images suggested left Valsalva sinus aneurysm ruptured into the left ventricular outflow tract. However, preoperative transesophageal real-time 3-dimensional echocardiography (3DE) revealed that the aneurysm-like structure involved most of the left ventricular outflow tract wall, leading to the diagnosis of aortic root dissection associated with perforation of the left Valsalva sinus and prolapse of the exfoliated endocardium into the left ventricular outflow tract. These findings were confirmed by open heart surgery. 3DE was helpful differentiating aortic root dissection from Valsalva sinus aneurysm rupture, especially by demonstrating the extent of aneurysm-like structure in the left ventricular outflow tract. [ABSTRACT FROM AUTHOR]

Term proximity is effective for many information retrieval (IR) research fields yet remains unexplored in blogosphere IR. The blogosphere is characterized by large amounts of noise, including incohesive, off-topic content and spam. Consequently, the classical bag-of-words unigram IR models are not reliable enough to provide robust and effective retrieval performance. In this article, we propose to boost the blog postretrieval performance by employing term proximity information. We investigate a variety of popular and state-of-the-art proximity-based statistical IR models, including a proximity-based counting model, the Markov random field (MRF) model, and the divergence from randomness (DFR) multinomial model. Extensive experimentation on the standard TREC Blog06 test dataset demonstrates that the introduction of term proximity information is indeed beneficial to retrieval from the blogosphere. Results also indicate the superiority of the unordered bi-gram model with the sequential-dependence phrases over other variants of the proximity-based models. Finally, inspired by the effectiveness of proximity models, we extend our study by exploring the proximity evidence between uery terms and opinionated terms. The consequent opinionated proximity model shows promising performance in the experiments. [ABSTRACT FROM AUTHOR]

Background Previously developed techniques for pacemaker lead introduction usually require some form of image guidance to facilitate the axillary vein puncture process. The existing blind vein puncture methods have not gained widespread acceptance. We aimed to investigate whether our blind vein puncture approach is effective and safe. Methods We compared the patient characteristics and clinical outcomes of 600 consecutive patients who underwent different blind axillary vein puncture procedures. In group I, a steep needle puncture method was used, whereas in group II a shallow needle puncture technique was used. Results The shallow needle puncture method was associated with a higher success rate than the steep needle puncture method (94% vs 54%, P < 0.00001). The shallow needle puncture method was also associated with a much shorter puncture and lead insertion time (7 ± 2 minutes vs 10 ± 3 minutes, P = 0.02). Conclusion Our shallow needle puncture technique does not require any extra equipment. In addition, this method is effective and safe and may be used as the initial attempt for venous access during pacemaker implantation. [ABSTRACT FROM AUTHOR]

The structural dynamics of 4-pyrimidone (4PMO) in the A- and B-band absorptions was studied by using the resonance Raman spectroscopy combined with quantum chemical calculations to better understand whether the excited state intramolecular proton-transfer (ESIPT) reaction occurs in Franck-Condon regions or not. The transition barrier for the ground state proton-transfer tautomerization reaction between 3(H) (I) and hydroxy (II) was determined to be 165 kJ·mol−1 in vacuum on the basis of the B3LYP/6-311++G(d,2p) level of theory calculations. Two ultraviolet absorption bands of 4PMO were, respectively, assigned as πH→π*L and πH→π*L+1 transitions. The vibrational assignments were done on the basis of the Fourier transform (FT)-Raman and FT-infrared (IR) measurements, the density-functional theory computations and the normal mode analysis. The A- and B-band resonance Raman spectra of 4PMO were measured in water, methanol and acetonitrile. The structural dynamics of 4PMO was obtained through the analysis of the resonance Raman intensity pattern. We discuss the similarities in the structural dynamics of 4PMO and 2-thiopyrimidone (2TPM), and the results were used to correlate to the intramolecular hydrogen-atom-transfer process as observed by matrix-isolation IR experiments for 4PMO. A variety of NH/CH bend modes + C = O stretch mode mark the hydrogen-detachment-attachment or ESIPT reaction initiated in Franck-Condon region for 4PMO and 2TPM. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Optimal duration of dual-antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation remains uncertain. The aim of this study was to perform a meta-analysis of trials evaluating the effect of DAPT duration on long-term clinical outcomes after DES implantation. The authors searched OvidMEDLINE, EMBASE, and the Cochrane Library for both randomized controlled trials and nonrandomized studies that evaluated DAPT duration on long-term clinical outcomes after DES implantation. The end point was the cumulative incidence of the composite of all-cause death and nonfatal myocardial infarction (MI) at maximum follow-up. Quantitative analysis was performed to estimate the pooled hazard ratios (HRs) for the effect of DAPT duration. The pooled effect of DAPT discontinuation before 6 months significantly increased risk of death and nonfatal MI (HR, 1.46; 95% confidence interval, 1.18-1.80), but DAPT beyond 12 months did not reduce the incidence of the composite end point compared with drug discontinuation at 12 months (HR, 0.91; 95% confidence interval, 0.75-1.10). In conclusion, the current evidence suggests that 6 to 12 months of DAPT may be optimal after DES implantation. [ABSTRACT FROM AUTHOR]

Wikipedia is characterized by its dense link structure and a large number of articles in different languages, which make it a notable Web corpus for knowledge extraction and mining, in particular for mining the multilingual associations. In this paper, motivated by a psychological theory of word meaning, we propose a graph-based approach to constructing a cross-language association dictionary ( CLAD) from Wikipedia, which can be used in a variety of cross-language accessing and processing applications. In order to evaluate the quality of the mined CLAD, and to demonstrate how the mined CLAD can be used in practice, we explore two different applications of the mined CLAD to cross-language information retrieval ( CLIR). First, we use the mined CLAD to conduct cross-language query expansion; and, second, we use it to filter out translation candidates with low translation probabilities. Experimental results on a variety of standard CLIR test collections show that the CLIR retrieval performance can be substantially improved with the above two applications of CLAD, which indicates that the mined CLAD is of sound quality. [ABSTRACT FROM AUTHOR]

Background: Although international guidelines recommend an early invasive intervention for the treatment of patients presenting with acute coronary syndrome (ACS), the optimal timing of this intervention remains uncertain. We aimed to determine the best time period for an early invasive intervention in ACS patients. Methods: Literature searches for controlled trials on ACS (1970-Sep. 2010) were conducted. Patients with moderate to high risk of ACS sent to the catheterization laboratory within 72 hours of admission/symptom onset were analyzed. The major outcome was the rate of death or recurrent myocardial infarction (re-MI). Results: A total of 10 trials with 39,453 patients were eligible. Intervention performed within 24-48 hours was associated with a significantly lower death or re-MI rate compared with intervention after 48 hours (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.52-0.79; P < 0.0001). Death or re-MI was also reduced in the 12-24 hour group relative to the 24-48 hour group (8.4% vs. 10.8%; OR 0.85; 95% CI 0.75-0.97; P = 0.01). Performing angiography within <12 hours provided no benefit over 12-24 hours (P > 0.05). Interestingly, intervention before 3 hours was associated with a higher rate of death or re-MI compared with intervention within 3-48 hours (P = 0.0008). Conclusions: Intervention following ACS should be undertaken within 24 hours; however, immediate (<3 hours) angiography does not provide any benefit and may even be harmful. (J Interven Cardiol 2012;25:10-18) [ABSTRACT FROM AUTHOR]

Background: Arterial stiffening and atherosclerosis tend to coexist. Strain imaging, using a 2-dimensional speckle tracking (2D-ST) method, has been used for arterial stiffness assessment and early identification of atherosclerosis. We investigated whether the ascending aortic strain assessed by 2D-ST echocardiography at rest can predict the presence of coronary artery disease (CAD)., Methods and Results: Two hundred seventy-one consecutive patients with suspected stable angina pectoris sequentially underwent exercise treadmill testing, 2-dimensional echocardiography, M-mode echocardiography, 2D-ST echocardiography, and coronary angiography. Circumferential ascending aortic strain (CAAS) and radial ascending aortic strain were assessed by 2D-ST echocardiography. Ninety-two patients with coronary lumen area stenosis ≥70% were categorized as having significant CAD. Global CAAS was significantly lower in patients with significant CAD (7.41±2.30% versus 11.54±4.03%; P <0.001) and remained an independent predictor of significant CAD (odds ratio, 0.64 [0.54-0.75]; P <0.001) after multivariate regression. Based on the receiver operating characteristic curve for diagnosing significant CAD, the optimal cut-off value of global CAAS was ≤9.22% (sensitivity, 86%; specificity, 70%; area under curve=0.82; P <0.001). Global CAAS decreased with increasing severity of CAD and was significantly associated with 3-vessel disease (odds ratio, 0.58 [0.42-0.79]; P <0.001). Diagnostics for significant CAD were remarkably better for global CAAS combined with exercise treadmill testing than for exercise treadmill testing alone (area under curve=0.88 versus 0.78; P <0.001)., Conclusions: Global CAAS assessed by 2D-ST echocardiography at rest was able to predict the presence of significant CAD and identify multivessel disease. In addition, global CAAS combined with exercise treadmill testing remarkably improved the diagnostics for significant CAD., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)