Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in ...the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9‐associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR‐185‐5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia‐induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR‐185‐5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT‐PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR‐185‐5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR‐185‐5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.
This paper presents a dual-band dielectric resonator antenna (DRA) with a large frequency ratio at millimeter-wave band. A large frequency ratio of 2.36 is formed by the TE 111 mode and TE 131 mode ...working at 16 GHz and 38 GHz, respectively. These two modes of DRA are excited by a microstrip-fed slot. A 1×4 DRA array is then constructed to achieve high gain in the millimeter-wave range. In addition, this design also features easy fabrication and wideband characteristics achieved through the use of printing circuit board (PCB) technology. The impedance bandwidths of 13.3 - 19 GHz (35.3%) and 36.3 - 40 GHz (9.7%), and the gain of 10.6 and 14.2 dBi can be realized in these two bands, respectively. The good agreement between measurement and simulation suggests that this design has promising potential for application in millimeter-wave communication.
Purpose To measure the density of the superficial retinal small vessel network (SRSVN), superficial retinal capillary network (SRCN), deep retinal capillary network (DRCN) and choriocapillaris, and ...the size of the foveal avascular zone (FAZ) in the superficial retinal layer in normal eyes. Design Prospective observational cross-sectional study. Methods In healthy Chinese volunteers, the retinal and choroidal vasculature was visualized by split-spectrum amplitude decorrelation angiography associated optical coherence tomography (RTVueXR Avanti device; Optovue Inc., Fremont, CA, USA). Results Among 105 healthy participants (age:35.9±13.8 years) mean FAZ measured 0.35±0.12mm2 , and mean density of SRSVN, SRCN, DRCN and choriocapillaris was 8.54±0.92%, 31.8±2.6%, 45.8±3.3%, 44.4±3.3% and 44.5±2.7%, respectively. In multivariate analysis, higher SRSVN density was associated with younger age ( P =0.001;standardized regression coefficient β:-0.28;), male gender ( P =0.008; β:-0.23), lower SRCN density ( P <0.001; β:-0.40), and larger mean choriocapillaris vessel diameter ( P =0.001;β:0.30). Higher SRCN density was correlated with male gender ( P =0.007; β:-0.19), lower SRSVN density ( P <0.001; β:-0.44), and higher density of the radial peripapillary capillary density ( P =0.004; β:0.20). Higher DRCN density was correlated with younger age ( P <0.001; β:-0.31), female gender ( P =0.002; β:0.22), higher SRCN density ( P <0.001; β:0.38), and higher choriocapillaris density ( P <0.001; β:0.39). Higher choriocapillaris network density in the central region was associated with higher DRCN density ( P <0.001; β:0.43) and lower radial peripapillary capillary density ( P =0.005; β:-0.26). All retinal vascular parameters were not significantly correlated with axial length or subfoveal choroidal thickness. Conclusions The density of the macular vascular networks decreases with older age and is independent of axial length and subfoveal choroidal thickness in healthy individuals.
Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat and mediates the beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with ...hepatic steatosis, autophagy, fatty acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism. Fasted FNDC5
mice exhibited severe steatosis, reduced autophagy, and FAO, and enhanced lipogenesis in the liver compared with wild-type mice. Energy deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5
hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin (mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated lipogenesis and steatosis in FNDC5
livers. FNDC5 deficiency exacerbated hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO gene expression in hepatocytes and repaired the attenuated autophagy and palmitate-induced steatosis in FNDC5
hepatocytes. FNDC5 overexpression prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. These results indicate that FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired FAO and autophagy in the liver.
The water‐soluble polypyridine copper complex Cu(F3TPA)(ClO4)2 1; F3TPA=tris(2‐fluoro‐6‐pyridylmethyl)amine catalyzes water oxidation in a pH 8.5 borate buffer at a relatively low overpotential of ...610 mV. Assisted by photosensitizer and an electron acceptor, 1 also exhibits activity as a homogeneous catalyst for photo‐induced O2 evolution with a maximum turnover frequency (TOF) of (1.58±0.03)×10−1 s−1 and a maximum turnover number (TON) of 11.61±0.23. In comparison, the reference Cu(TPA)(ClO4)2 TPA=tris(2‐pyridylmethyl)amine displayed almost no activity under either set of conditions, implying the crucial role of the ligand in determining the behavior of the catalyst. Experimental evidence indicate the molecular catalytic nature of 1, leading to a potentially practical strategy to apply the copper complex in a photoelectrochemical device for water oxidation.
A water‐soluble copper polypyridine complex performs as a homogeneous catalyst for both photo‐induced and electrocatalytic O2 evolution, which allows a derivative to be assembled into a photoelectrochemical device for water oxidation (see figure; ITO=indium–tin oxide, bpy=bipyridine).
Obesity-induced chronic inflammation is critical in the pathogenesis of insulin resistance, and the recruitment and proinflammatory activation of adipose tissue macrophages (ATMs) is important for ...the development of this process. Here, we examined the effects of fibronectin type III domain-containing 5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese mice.
Male wild-type (WT) and FNDC5−/− mice were fed with standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin resistance, macrophage accumulation and polarization and adipose tissue inflammation were determined in mice. Secondly, the macrophage polarity shift was further examined with flow cytometry in isolated stromal vascular fraction (SVF). Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced macrophage polarization, inflammation and the underlying signaling mechanism were investigated in RAW264.7 macrophages and primary mouse peritoneal cavity macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were examined in HFD-induced obese WT and FNDC5−/− mice.
FNDC5 gene deletion aggravated obesity, insulin resistance, fat accumulation and inflammation accompanied with enhanced AMPK inhibition, macrophages recruitment and M1 polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1 macrophage polarization and inflammatory cytokine production via AMPK phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and inflammatory cytokine production in adipose tissue of obese WT and FNDC5−/− mice.
FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays several beneficial roles in obesity and may be used as a therapeutic regimen for preventing inflammation and insulin resistance in obesity and diabetes.
•FNDC5 deficiency aggravates adipose tissue inflammation and insulin resistance in obesity.•FNDC5 attenuates adipose tissue inflammation and insulin resistance in obesity.•FNDC5 inhibits M1 macrophage polarization and inflammatory cytokine production in obesity.•AMPK phosphorylation mediates the beneficial effects of FNDC5.
Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall ...function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling.
Multiple-surface segmentation in optical coherence tomography (OCT) images is a challenging problem, further complicated by the frequent presence of weak image boundaries. Recently, many deep ...learning-based methods have been developed for this task and yield remarkable performance. Unfortunately, due to the scarcity of training data in medical imaging, it is challenging for deep learning networks to learn the global structure of the target surfaces, including surface smoothness. To bridge this gap, this study proposes to seamlessly unify a U-Net for feature learning with a constrained differentiable dynamic programming module to achieve end-to-end learning for retina OCT surface segmentation to explicitly enforce surface smoothness. It effectively utilizes the feedback from the downstream model optimization module to guide feature learning, yielding better enforcement of global structures of the target surfaces. Experiments on Duke AMD (age-related macular degeneration) and JHU MS (multiple sclerosis) OCT data sets for retinal layer segmentation demonstrated that the proposed method was able to achieve subvoxel accuracy on both datasets, with the mean absolute surface distance (MASD) errors of 1.88 ± 1.96
and 2.75 ± 0.94
, respectively, over all the segmented surfaces.
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