Chronic myocardial infarction (MI) results in the formation of arrhythmogenic substrates, causing lethal ventricular arrhythmia (VA). We aimed to determine whether mesenchymal stem cells (MSCs) ...carrying a hepatocyte growth factor (HGF) gene modification (HGF-MSCs) decrease the levels of arrhythmogenic substrates and reduce the susceptibility to developing VA compared with unmodified MSCs and PBS in a swine infarction model.
The left descending anterior artery was balloon-occluded to establish an MI model. Four weeks later, the randomly grouped pigs were administered MSCs, PBS or HGF-MSCs via thoracotomy. After an additional four weeks, dynamic electrocardiography was performed to assess heart rate variability, and programmed electrical stimulation was conducted to evaluate the risk for VA. Then, the pigs were euthanized for morphometric, immunofluorescence and western blot analyses.
The HGF-MSC group displayed the highest vessel density and Cx43 expression levels, and the lowest levels of apoptosis, and tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) expression. Moreover, the HGF-MSC group exhibited a decrease in the number of sympathetic nerve fibers, substantial decreases in the low frequency and the low-/high- frequency ratio and increases in the root mean square of successive differences (rMSSD) and the percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50), compared with the other two groups. Finally, the HGF-MSC group displayed the lowest susceptibility to developing VA.
HGF-MSCs displayed potent antiarrhythmic effects, reducing the risk for VA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to identify radiomic features of primary tumor and develop a model for indicating extrahepatic metastasis of hepatocellular carcinoma (HCC). Contrast-enhanced computed tomographic ...(CT) images of 177 HCC cases, including 26 metastatic (MET) and 151 non-metastatic (non-MET), were retrospectively collected and analyzed. For each case, 851 radiomic features, which quantify shape, intensity, texture, and heterogeneity within the segmented volume of the largest HCC tumor in arterial phase, were extracted using Pyradiomics. The dataset was randomly split into training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was performed to augment the training set to 145 MET and 145 non-MET cases. The test set consists of six MET and six non-MET cases. The external validation set is comprised of 20 MET and 25 non-MET cases collected from an independent clinical unit. Logistic regression and support vector machine (SVM) models were identified based on the features selected using the stepwise forward method while the deep convolution neural network, visual geometry group 16 (VGG16), was trained using CT images directly. Grey-level size zone matrix (GLSZM) features constitute four of eight selected predictors of metastasis due to their perceptiveness to the tumor heterogeneity. The radiomic logistic regression model yielded an area under receiver operating characteristic curve (AUROC) of 0.944 on the test set and an AUROC of 0.744 on the external validation set. Logistic regression revealed no significant difference with SVM in the performance and outperformed VGG16 significantly. As extrahepatic metastasis workups, such as chest CT and bone scintigraphy, are standard but exhaustive, radiomic model facilitates a cost-effective method for stratifying HCC patients into eligibility groups of these workups.
Evidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we ...investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding.
This is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range IQR: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval CI 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma-related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence.
In this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma-related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A highly efficient palladium‐catalyzed asymmetric synthesis of N‐substituted 4‐quinolones was developed via C−N coupling reaction. Various chiral quinolones were readily obtained with desirable ...enantioselectivity (up to 95% ee) and excellent yield (up to 99%), enabled by a simple system of palladium acetate and chiral ferrocene bisphosphine as auxiliary ligand. The corresponding racemic derivatives can also be synthesized by a transition metal‐free strategy of potassium hydroxide in DMSO. The influence of temperature on the configurational stability of these C−N axially chiral compounds was also investigated. The efficient functionalization at 3‐position further expands the application range of this synthetic technique.
The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this ...relationship.
Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations.
In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001).
A higher TyG index is an independent and causal risk factor for incident HF in the general population.
URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current theories of pre-attentive deviant detection postulate that before the Superior Temporal Cortex (STC) detects a change, the Inferior Frontal Cortex (IFC) engages in stimulus analysis, which is ...particularly critical for ambiguous deviations (e.g., deviant preceded by a short train of standards). These theories rest on the assumption that IFC and STC are functionally connected, which has only been supported by correlational brain imaging studies. We examined this functional connectivity assumption by applying Transcranial Magnetic Stimulation (TMS) to disrupt IFC function, while measuring the later STC mismatch response with the event-related optical signal (EROS). EROS can localize brain activity in both spatial and temporal dimensions via measurement of optical property changes associated with neuronal activity, and is inert to the electromagnetic interference produced by TMS. Specifically, the STC mismatch response at 120–180 ms elicited by a deviant preceded by a short standard train when IFC TMS was applied at 80 ms was compared with the STC mismatch responses in temporal control (TMS with 200 ms delay), spatial control (sham TMS at vertex), auditory control (TMS pulse noise only), and cognitive control (deviant preceded by a long standard train) conditions. The STC mismatch response to deviants preceded by the short train was abolished by TMS of the IFC at 80 ms, while the STC responses remained intact in all other control conditions. These results confirm the involvement of the IFC in the STC mismatch response and support a functional connection between IFC and STC.
•We examined the IFC-STC functional connectivity in pre-attentive change detection.•The IFC was disrupted by TMS while optical mismatch response at STC was recorded.•TMS on the IFC at 80 ms after stimulus onset abolished the STC mismatch response.•But this TMS effect was specific to deviants preceded by a short train of standards.•Our results support a functional connection between IFC and STC.
Colossal permittivity (CP) materials have shown great technological potential for advanced microelectronics and high-energy-density storage applications. However, developing high performance CP ...materials has been met with limited success because of low breakdown electric field and large dielectric loss. Here, composite films have been developed based on surface hydroxylated ceramic fillers, (Er + Nb) co-doped TiO
2
embedded in poly(vinylidene fluoride trifluoroethylene) matrix by a simple technique. We report on simultaneously observing a large dielectric constant up to 300, exceptional low dielectric loss down to 0.04 in the low frequency range, and an acceptable breakdown electric field of 813 kV cm
−1
in the composites. Consequently, this work may pave the way for developing highly stable and superior dielectrics through a simple and scalable route to meet requirements of further miniaturization in microelectronic and energy-storage devices.
Colossal permittivity (CP) materials have shown great technological potential for advanced microelectronics and high-energy-density storage applications.
Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with ...blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.
We report herein the acid-catalyzed regioselective remote heteroarylation and reductive alkylation of alkenes. Various alkenes, including mono-, di-, and tri-substituted alkenes and cyclic alkenes, ...are applicable to this reaction. This method exhibits broad substrate scope, high functional group tolerance and high atomic economy. In addition, both gram-scale synthesis and product transformations demonstrate the potential utility of this reaction. It also provides an efficient and novel pathway to establish the valuable framework of 1,1-diaryl alkanes. Further mechanistic studies suggested that TfOH in situ generated by Cu(OTf) 2 and trace H 2 O catalyzed the alkene migration. Then, heteroarylation was conducted by Friedel–Crafts type alkylation.
•A new indolyphosphine bearing multi-electron-donating methoxy groups is disclosed.•The new catalyst system was found to be highly effective in facilitating aromatic C–N bond-forming reaction.•The ...amination process can be accomplished even at parts per million levels of Pd catalyst.
A new indolyphosphine ligand bearing multi-electron-donating methoxy groups has been designed for Pd-catalyzed Buchwald-Hartwig amination. It is worth noting that this new catalyst system was found to be highly effective in facilitating the cross-coupling reaction even at parts per million levels of palladium catalyst. A wide range of aryl chlorides as well as amine nucleophiles were successfully employed for the aromatic C–N bond-forming reaction. Remarkably, the extremely steric congested amine (i.e. 2,6-diisopropylaniline) was also coupled well with aryl chloride under the newly developed catalyst system.
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