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Abstract Background Previous observational studies indicated that atrial fibrillation may increase the risk of breast cancer. Following a breast cancer diagnosis, the chance of developing atrial fibrillation may increase as well. However, it is uncertain whether the link is causal or just due to confounding factors. Objective Using bidirectional Mendelian randomization (MR) analysis, we sought to assess the bidirectional causal relationship between atrial fibrillation and breast cancer from a genetic level. Methods Large genome‐wide association studies yielded summary‐level data for atrial fibrillation and breast cancer. The preliminary estimate was inverse variance weighted (IVW) under a random model. MR–Egger, weighted median, simple mode, weighted mode, and multivariable MR (adjusting body mass index, smoking, and alcohol drinking) were performed as sensitivity analyses. Results Genetically predicted atrial fibrillation presented no statistically significant association with overall breast cancer (odds ratio [OR] = 1.00; 95% confidence interval [CI]: 0.97–1.04; p = 0.79), estrogen receptor (ER) + (OR = 1.00; 95% CI: 0.96–1.03; p = 0.89) or ER− subtypes (OR = 1.00; 95% CI: 0.97–1.04; p = 0.89). Similarly, genetically predicted overall breast cancer (OR = 1.01; 95% CI: 0.98–1.04; p = 0.37), ER+ (OR = 1.02; 95% CI: 0.99–1.05; p = 0.16) or ER− (OR = 0.98; 95% CI: 0.93–1.02; p = 0.32) subtypes had no causal effect on atrial fibrillation. Sensitivity analyses yielded similar results. Individual single nucleotide polymorphism had little effect on the total estimate. We did not observe any evidence of horizontal pleiotropy. Conclusions Our bidirectional MR studies revealed that there may be no causal links between atrial fibrillation and breast cancer.

Abstract Background Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV. Methods MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo. Results MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P

Deep neural networks (DNNs) are vulnerable to adversarial attacks. In particular, object detectors may be attacked by applying a particular adversarial patch to the image. However, because the patch will lose information during the shrinking process, most existing approaches that employ adversarial patches to attack object detectors would diminish the attack success rate on small and medium targets. This paper proposes a Frequency Module(FRAN), a frequency-domain attention module for guiding patch generation to solve this problem. We use FRAN to allow the patched attack to rely on the low-frequency signals which are lost less in the shrinking process. This is the first study to introduce frequency domain attention to optimize the attack capabilities of adversarial patches. Our method increases the attack success rates of small and medium targets by 4.18% and 3.89%, respectively, over the state-of-the-art attack method for fooling the human detector while assaulting YOLOv3 without reducing the attack success rate of big targets.

Abstract The increasing burden of heart failure with preserved ejection fraction (HFpEF) has become a global health problem. HFpEF is characterized by systematic inflammation, cardiac metabolic remodeling, and fibrosis. Eosinophils act as an essential but generally overlooked subgroup of white blood cells, which participate in cardiac fibrosis, as reported in several recent studies. Herein, we explored the role of eosinophils in a “two‐hit” preclinical HFpEF model. The peripheral eosinophil counts were comparable between the normal chow and HFpEF mice. Deficiency of eosinophils failed to alter the phenotype of HFpEF. Conclusively, the development of HFpEF is independent of eosinophils in terms of the functional, biochemical, and histological results.

Abstract Background Bone marrow cells (BMCs), especially mesenchymal stem cells (MSCs), have shown attractive application prospects in acute myocardial infarction (AMI). However, the weak efficacy becomes their main limitation in clinical translation. Based on the anti-inflammation and anti-apoptosis effects of a Chinese medicine-Tongxinluo (TXL), we aimed to explore the effects of TXL-pretreated MSCs (MSCsTXL) in enhancing cardiac repair and further investigated the underlying mechanism. Methods MSCsTXL or MSCs and the derived exosomes (MSCsTXL-exo or MSCs-exo) were collected and injected into the infarct zone of rat hearts. In vivo, the anti-apoptotic and anti-inflammation effects, and cardiac functional and histological recovery were evaluated. In vitro, the apoptosis was evaluated by western blotting and flow cytometry. miRNA sequencing was utilized to identify the significant differentially expressed miRNAs between MSCsTXL-exo and MSCs-exo, and the miRNA mimics and inhibitors were applied to explore the specific mechanism. Results Compared to MSCs, MSCsTXL enhanced cardiac repair with reduced cardiomyocytes apoptosis and inflammation at the early stage of AMI and significantly improved left ventricular ejection fraction (LVEF) with reduced infarct size in an exosome-dependent way. Similarly, MSCsTXL-exo exerted superior therapeutic effects in anti-apoptosis and anti-inflammation, as well as improving LVEF and reducing infarct size compared to MSCs-exo. Further exosomal miRNA analysis demonstrated that miR-146a-5p was the candidate effector of the superior effects of MSCsTXL-exo. Besides, miR-146a-5p targeted and decreased IRAK1, which inhibited the nuclear translocation of NF-κB p65 thus protecting H9C2 cells from hypoxia injury. Conclusions This study suggested that MSCsTXL markedly facilitated cardiac repair via a new mechanism of the exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway, which has great potential for clinical translation.

Abstract Background Bone marrow-derived mesenchymal stem cells (MSCs), which possess immunomodulatory characteristic, are promising candidates for the treatment of acute myocardial infarction (AMI). However, the low retention and survival rate of MSCs in the ischemic heart limit their therapeutic efficacy. Strategies either modifying MSCs or alleviating the inflammatory environment, which facilitates the recruitment and survival of the engrafted MSCs, may solve the problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and combinatorial pretreated MSCs in the treatment of AMI. Methods Exosomes derived from MSCs were delivered to infarcted hearts through intramyocardial injection followed by the intravenous infusion of differentially pretreated MSCs on Day 3 post-AMI. Enzyme linked immunosorbent assay (ELISA) was performed to evaluate the inflammation level as well as the SDF-1 levels in the infarcted border zone of the heart. Echocardiography and histological analysis were performed to assess cardiac function, infarct size, collagen area and angiogenesis. Results Sequential transplantation of exosomes and the combinatorial pretreated MSCs significantly facilitated cardiac repair compared to AMI rats treated with exosomes alone. Notably, compared to the other three methods of cotransplantation, combinatorial pretreatment with hypoxia and Tongxinluo (TXL) markedly enhanced the CXCR4 level of MSCs and promoted recruitment, which resulted in better cardiac function, smaller infarct size and enhanced angiogenesis. We further demonstrated that exosomes effectively reduced apoptosis in MSCs in vitro. Conclusion Sequential delivery of exosomes and pretreated MSCs facilitated cardiac repair post-AMI, and combined pretreatment with hypoxia and TXL better enhanced the cardioprotective effects. This method provides new insight into the clinical translation of stem cell-based therapy for AMI.

Semantic segmentation is increasingly being applied on mobile devices due to advancements in mobile chipsets, particularly in low-power consumption scenarios. However, the lightweight design of mobile devices poses limitations on the receptive field, which is crucial for dense prediction problems. Existing approaches have attempted to balance lightweight designs and high accuracy by downsampling features in the backbone. However, this downsampling may result in the loss of local details at each network stage. To address this challenge, this paper presents a novel solution in the form of a compact and efficient convolutional neural network (CNN) for real-time applications: our proposed model, local spatial perception convolution (LSPConv). Furthermore, the effectiveness of our architecture is demonstrated on the Cityscapes dataset. The results show that our model achieves an impressive balance between accuracy and inference speed. Specifically, our LightSeg, which does not rely on ImageNet pretraining, achieves an mIoU of 76.1 at a speed of 61 FPS on the Cityscapes validation set, utilizing an RTX 2080Ti GPU with mixed precision. Additionally, it achieves a speed of 115.7 FPS on the Jetson NX with int8 precision.

BackgroundCalcific aortic valve disease (CAVD) is one of the most frequently occurring valvular heart diseases among the aging population. Currently, there is no known pharmacological treatment available to delay or reverse CAVD progression. The regulation of gene expression could contribute to the initiation, progression, and treatment of CAVD. Non-coding RNAs (ncRNAs) and transcription factors play essential regulatory roles in gene expression in CAVD; thus, further research is urgently needed.Materials and MethodsThe gene-expression profiles of GSE51472 and GSE12644 were obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified in each dataset. A protein-protein-interaction (PPI) network of DEGs was then constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and functional modules were analyzed with ClusterOne plugin in Cytoscape. Furthermore, Gene Ontology-functional annotation and Kyoto Encyclopedia of Genes and Genomes-pathway analysis were conducted for each functional module. Most crucially, ncRNAs and transcription factors acting on each functional module were separately identified using the RNAInter and TRRUST databases. The expression of predicted transcription factors and key genes was validated using GSE51472 and GSE12644. Furthermore, quantitative real-time PCR (qRT-PCR) experiments were performed to validate the differential expression of most promising candidates in human CAVD and control samples.ResultsAmong 552 DEGs, 383 were upregulated and 169 were downregulated. In the PPI network, 15 functional modules involving 182 genes and proteins were identified. After hypergeometric testing, 45 ncRNAs and 33 transcription factors were obtained. Among the predicted transcription factors, CIITA, HIF1A, JUN, POU2F2, and STAT6 were differentially expressed in both the training and validation sets. In addition, we found that key genes, namely, CD2, CD86, CXCL8, FCGR3B, GZMB, ITGB2, LY86, MMP9, PPBP, and TYROBP were also differentially expressed in both the training and validation sets. Among the most promising candidates, differential expressions of ETS1, JUN, NFKB1, RELA, SP1, STAT1, ANCR, and LOC101927497 were identified via qRT-PCR experiments.ConclusionIn this study, we identified functional modules with ncRNAs and transcription factors involved in CAVD pathogenesis. The current results suggest candidate molecules for further research on CAVD.