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Characterization of gene regulatory mechanisms in cancer is a key task in cancer genomics. CCCTC-binding factor (CTCF), a DNA binding protein, exhibits specific binding patterns in the genome of cancer cells and has a non-canonical function to facilitate oncogenic transcription programs by cooperating with transcription factors bound at flanking distal regions. Identification of DNA sequence features from a broad genomic region that distinguish cancer-specific CTCF binding sites from regular CTCF binding sites can help find oncogenic transcription factors in a cancer type. However, the presence of long DNA sequences without localization information makes it difficult to perform conventional motif analysis. Here, we present DNAResDualNet (DARDN), a computational method that utilizes convolutional neural networks (CNNs) for predicting cancer-specific CTCF binding sites from long DNA sequences and employs DeepLIFT, a method for interpretability of deep learning models that explains the model's output in terms of the contributions of its input features. The method is used for identifying DNA sequence features associated with cancer-specific CTCF binding. Evaluation on DNA sequences associated with CTCF binding sites in T-cell acute lymphoblastic leukemia (T-ALL) and other cancer types demonstrates DARDN's ability in classifying DNA sequences surrounding cancer-specific CTCF binding from control constitutive CTCF binding and identifying sequence motifs for transcription factors potentially active in each specific cancer type. We identify potential oncogenic transcription factors in T-ALL, acute myeloid leukemia (AML), breast cancer (BRCA), colorectal cancer (CRC), lung adenocarcinoma (LUAD), and prostate cancer (PRAD). Our work demonstrates the power of advanced machine learning and feature discovery approach in finding biologically meaningful information from complex high-throughput sequencing data. [ABSTRACT FROM AUTHOR]

Inflammation resolution is an active process via specialized pro-resolving mediators (SPMs) to fight invading microbes and repair tissue injury. RvD1 and RvD2 are SPMs produced from DHA during inflammation responses and show a benefit in treating inflammation disorders, but it is not completely understood how they act on vasculature and immune cells in the lung to promote inflammation resolution programs. Here, we studied how RvD1 and RvD2 regulated the interactions between endothelial cells and neutrophils in vitro and in vivo. In an acute lung inflammation (ALI) mouse model, we found that RvD1 and RvD2 resolved lung inflammation via their receptors (ALX/GPR32 or GPR18) and enhanced the macrophage phagocytosis of apoptotic neutrophils, which may be the molecular mechanism of lung inflammation resolution. Interestingly, we observed the higher potency of RvD1 over RvD2, which may be associated with unique downstream signaling pathways. Together, our studies suggest that the targeted delivery of these SPMs into inflammatory sites may be novel strategies with which to treat a wide range of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Pursuing oxygen evolution reaction (OER) catalysts with high activity and stability is attracting many researchers. Here, we first designed and synthesized a biphasic three-dimensional structured catalyst of nickel–cobalt sulfide NiCo2S4-NiS2/CFP, which is a nickel–cobalt sulfide composite decorated on carbon fiber paper (CFP) by a one-step hydrothermal method. It exhibited an overpotential of about 165 mV at a current density of 10 mA cm−2 and a small Tafel slope of 81.54 mV dec−1. Furthermore, the long-term stability of the NiCo2S4-NiS2/CFP nanocomposite was 90.0% of the initial current density even after 12 h. The excellent catalytic performance of the NiCo2S4-NiS2/CFP nanocomposite can be attributed to several aspects. Firstly, the petal-like morphology of the NiCo2S4-NiS2 nanocomposite exposes more active sites. Secondly, the stability of the composite catalyst is significantly enhanced by its firm anchoring on the CFP. Thirdly, the catalytic performance was significantly improved by the addition of mixed valence of Ni or Co on the {111} plane of spinel NiCo2S4. Finally, the three-dimensional CFP substrate provides an efficient pathway and a stable integrated structure for the transmission of electrons and ions. Our one-step hydrothermal synthesis method provides a simple and economical way to obtain high-performance and robust OER catalysts. [ABSTRACT FROM AUTHOR]

The application of voxel-mirrored homotopic connectivity (VMHC) analysis to study the central mechanism of migraine has been limited. Furthermore, little is known about inter-hemispheric functional connectivity (FC) alterations during resting state in female patients with migraine. This study aimed to investigate potential interictal VMHC impairments in migraine without aura (MwoA) patients and the relationship between connectivity alterations and clinical parameters. Resting-state functional magnetic resonance imaging data and clinical information were acquired from 43 female MwoA patients and 43 matched healthy controls. VMHC analysis was used to compare differences between these two groups, and brain regions showing significant differences were chosen as a mask to perform a seed-based FC group comparison. Subsequent correlation analysis was conducted to explore the relationship between abnormal inter-hemispheric FC and clinical data. Compared with healthy controls, female MwoA patients revealed significantly decreased VMHC in the bilateral cerebellum; cuneus; and lingual, middle occipital, precentral and postcentral gyri. Seed-based FC analysis indicated disrupted intrinsic connectivity in the cerebellum, and default mode, visual and sensorimotor network. These VMHC and FC abnormalities were negatively correlated with clinical indexes including duration of disease, migraine days and visual analogue scale. These inter-hemispheric FC impairments and correlations between abnormal VMHC and FC and clinical scores may improve our understanding of the central mechanism of female-specific migraine. [ABSTRACT FROM AUTHOR]

(1) Aim: We aim to evaluate the association between arousals during sleep and subclinical coronary atherosclerosis detected by coronary computed tomography angiography (CTA) in patients with obstructive sleep apnea (OSA). (2) Methods: This was a cross-sectional study. Consecutive newly diagnosed OSA patients, who underwent coronary CTA examinations within 3 months of the sleep study, were eligible. We used the arousal index (ArI) derived from polysomnography to assess arousals during sleep and a semi-automated plaque quantification software to characterize and quantify the subclinical coronary atherosclerosis. Multiple regression models were used to evaluate the associations of the ArI with the coronary atherosclerotic plaque presence, volume, and composition. (3) Results: A total of 99 patients with OSA were included in the study. In the multivariable models, patients with a high ArI (ArI > 32.2 events/h) were more likely to have coronary plaques compared to those with a low ArI (ArI ≤ 32.2 events/h) (OR: 3.29 [95% CI: 1.284 to 8.427], p = 0.013). Furthermore, the ArI exhibited significant associations with total (β = 0.015), noncalcified (β = 0.015), and low-attenuation (β = 0.012) coronary plaque volume after accounting for established risk factors (p = 0.008, 0.004, and 0.002, respectively). However, no association between the ArI and calcified plaque volume was found. (4) Conclusion: Repetitive arousals during sleep are associated with an increased coronary plaque burden in patients with OSA, which remained robust after adjusting for multiple established cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Dietary omega 3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been reported to be beneficial for cardiovascular diseases and cancer. Such diseases share a common pathophysiological feature of inflammation responses, such as unbalanced oxidative stress and increased cytokine release. PUFAs show anti-inflammatory effects, and thus, they are potential therapeutics to treat inflammatory disorders. Here, we proposed a novel liposomal formulation of EPA (EPA-liposomes), and the liposome was PEGylated to increase their stability. In the study, we measured the physicochemical characteristics of EPA-liposomes and their anti-inflammatory effects in neutrophil-like cells (HL 60 cells). The results showed that EPA-liposomes dramatically decreased the production of NO, ROS, and cytokines compared to EPA alone, and the molecular mechanism is associated with biosynthesis of RvE1 from EPA, and RvE1 binds to GPCRs to mediate the anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Neutrophils and macrophages are major components of innate systems, playing central roles in inflammation responses to infections and tissue injury. If they are out of control, inflammation responses can cause the pathogenesis of a wide range of diseases, such as inflammatory disorders and autoimmune diseases. Precisely regulating the functions of neutrophils and macrophages in vivo is a potential strategy to develop immunotherapies to treat inflammatory diseases. Advances in nanotechnology have enabled us to design nanoparticles capable of targeting neutrophils or macrophages in vivo. This review discusses the current status of how nanoparticles specifically target neutrophils or macrophages and how they manipulate leukocyte functions to inhibit their activation for inflammation resolution or to restore their defense ability for pathogen clearance. Finally, we present a novel concept of hijacking leukocytes to deliver nanotherapeutics across the blood vessel barrier. This review highlights the challenges and opportunities in developing nanotherapeutics to target leukocytes for improved treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Stroke is a severe brain disease leading to disability and death. Ischemic stroke dominates in stroke cases, and there are no effective therapies in clinic, partly due to the challenges in delivering therapeutics to ischemic sites in the brain. This review is focused on the current knowledge of pathogenesis in ischemic stroke, and its potential therapies and diagnosis. Furthermore, we present recent advances in developments of nanoparticle-based therapeutics for improved treatment of ischemic stroke using polymeric NPs, liposomes and cell-derived nanovesicles. We also address several critical questions in ischemic stroke, such as understanding how nanoparticles cross the blood brain barrier and developing in vivo imaging technologies to address this critical question. Finally, we discuss new opportunities in developing novel therapeutics by targeting activated brain endothelium and inflammatory neutrophils to improve the current therapies for ischemic stroke. [ABSTRACT FROM AUTHOR]