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Background: Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classic epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in patients with hypertension is important for investigating hypertension mechanisms. Methods: Differential genomic DNA methylation in patients with hypertension, individuals with prehypertension, and healthy control individuals was screened using Illumina 450K BeadChip and verified by pyrosequencing. Plasma OVGP1 (oviduct glycoprotein 1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein–protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. Results: We found a hypomethylated site at cg20823859 in the promoter region of OVGP1 and plasma OVGP1 levels were significantly increased in patients with hypertension. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, OVGP1 deficiency attenuated angiotensin II–induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that MYH9 (nonmuscle myosin heavy chain IIA) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. Conclusions: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.

When a detection model that has been well-trained on a set of classes faces new classes, incremental learning is always necessary to adapt the model to detect the new classes. In most scenarios, it is required to preserve the learned knowledge of the old classes during incremental learning rather than reusing the training data from the old classes. Since the objects in remote sensing images often appear in various sizes, arbitrary directions, and dense distribution, it further makes incremental learning-based object detection more difficult. In this article, a new architecture for incremental object detection is proposed based on feature pyramid and knowledge distillation. Especially, by means of a feature pyramid network (FPN), the objects with various scales are detected in the different layers of the feature pyramid. Motivated by Learning without Forgetting (LwF), a new branch is expended in the last layer of FPN, and knowledge distillation is applied to the outputs of the old branch to maintain the old learning capability for the old classes. Multitask learning is adopted to jointly optimize the losses from two branches. Experiments on two widely used remote sensing data sets show our promising performance compared with state-of-the-art incremental object detection methods.

Hierarchical multilabel classification (HMC) assigns multiple labels to each instance with the labels organized under hierarchical relations. In ship classification in remote sensing images, depending on the expert knowledge and image quality, the same type of ships in different remote sensing images may be annotated with different class labels from coarse to fine levels such as merchant ship (MS) or container ship (CTS). In this article, we propose a novel deep network with two output channels and their associated loss functions to learn an HMC classifier using samples labeled at different levels in the hierarchy. In the proposed network, a hierarchy and exclusion (HEX) graph is introduced to model the label hierarchy, which satisfies hierarchical constraints by encoding semantic relations between any two labels. The output nodes of the first channel are organized according to the HEX graph, and its corresponding probabilistic classification loss is built to reflect the hierarchical structure of the HEX graph. On the other hand, the output nodes of the second channel only represent the finest grained (last level in the hierarchy) classes, and its multiclass cross-entropy loss is designed to enhance the discriminative power of the HMC classifier on the last level labels, which is also compatible with constraints in the HEX graph. The combination of these two losses from two output channels can effectively transfer the hierarchical information of ship taxonomy during network training. Experimental results on two commonly used ship datasets demonstrate that the proposed method outperforms the state-of-the-art HMC approaches, and is especially advantageous when trained with fewer fine-grained samples.

Lithium-sulfur batteries (LSBs) are considered the most likely replacement for conventional lithium–ion batteries in next-generation high-energy output solutions based on their high specific capacity (1675 mAh g−1) and high-energy density (2600 Wh kg−1). But, there are some problems that need to be solved urgently. In this work, an environmentally friendly, green, and low-cost ZIF-67-derived cobalt-based sulfate material (CoSO4) combined with carbon nanotubes was proposed as a sulfur host material. Experiments show that the addition of CoSO4 can significantly enhance the transformation of polysulfide and suppress the shuttle effect. The best performance is the CNT-CoSO4-2/S, which has an initial capacity of 1356.9 mAh g−1 at 0.1 C current density. Furthermore, long-term cycle test was carried out at a current density of 0.2 C; the coulombic efficiency was above 98.63% after 200 cycles. This work demonstrates the potential of cobalt-based sulfates as cathode materials for lithium–sulfur batteries.

Sr2+ ions-substituted cobalt ferrite having the composition formula SrxCo1−xFe2O4 (x = 0.05, 0.10, 0.15, and 0.20) was synthesized with sol–gel method. X-ray diffraction (XRD) patterns proved that the samples had a spinel structure. The Fourier-transform infrared (FTIR) spectra showed that the samples have two characteristic bands about the intrinsic vibrations of spinel ferrite. The morphology and chemical elements were tested by scanning electron microscope (SEM) and energy-dispersive spectrometer (EDS). The elemental state of annealed samples was examined by X-ray photoelectron spectroscopy (XPS). The magnetic data showed the coercivity increased from 954.33 Oe to 1545.54 Oe when the Sr2+ ions content increased. The optical absorption properties of annealed samples were investigated by UV–Vis spectroscopy. Complex impedance spectroscopy showed that grain resistance of Sr0.10Co0.90Fe2O4 sample was 443.9 Ω.

Lithium-sulfur batteries have become a potential candidate for a new generation of energy storage devices due to their extremely high theoretical capacity, but their shuttle effect and poor conductivity of sulfur and final discharge products hinder their commercial development. In this paper, ZIF-8 material with a large specific surface area was successfully prepared with metallic zinc as the central atom and dimethylimidazole. After sintering at 800 °C, the mesoporous carbon material was obtained, which increased its physical adsorption of sulfur. At the same time, titanium dioxide was coated on the mesoporous carbon material to obtain a core-shell structure with a specific surface area of up to 556.1 m2/g. The titanium dioxide coating well inhibits the occurrence of the shuttle effect and at the same time improves the cycle stability of the lithium-sulfur battery. The specific discharge capacity of the battery reaches 1351 mAh/g at 0.1 C.

Aim: To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). Materials & methods: RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Results: Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. The circRNAs were involved mainly in lysine degradation and the immune system. Conclusion: This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.

Rationale: The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Methods and Results: Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice. Furthermore, targeting thrombospondin-1 with TAX2 strongly inhibited the proinflammatory process, matrix metalloproteinase (MMP) activity and vascular smooth muscle cells (VSMCs) apoptosis, ultimately decreasing the incidence of dissecting AAA. Restoration of LH1 protein expression in LH1-deficient mice by intraperitoneal injection of an adeno-associated virus normalized thrombospondin-1 levels, subsequently alleviating dissecting AAA formation and preserving aortic structure and function. Consistently, in human AAA specimens, decreased LH1 expression was associated with increased thrombospondin-1 levels. Conclusions: LH1 deficiency contributes to dissecting AAA pathogenesis, at least in part, by upregulating thrombospondin-1 expression, which subsequently enables proinflammatory processes, MMP activation and VSMCs apoptosis. Our study provides evidence that LH1 is a potential critical therapeutic target for AAA.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs., Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Here the authors report altered gut microbiota including low abundance of Hungatella hathewayi in patients with UIAs, and show that supplementation with Hungatella hathewayi or the metabolite taurine prevents UIAs in mice.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Vascular smooth muscle cells (VSMCs) contribute to plaque stability. VSMCs are also a major source of CTH (cystathionine gamma-lyase)-hydrogen sulfide (H2S), a protective gasotransmitter in atherosclerosis. However, the role of VSMC endogenous CTH-H2S in pathogenesis of plaque stability and the mechanism are unknown. In human carotid plaques, CTH expression in ACTA2+ cells was dramatically downregulated in lesion areas in comparison to non-lesion areas. Intraplaque CTH expression was positively correlated with collagen content, whereas there was a negative correlation with CD68+ and necrotic core area, resulting in a rigorous correlation with vulnerability index (r = −0.9033). Deletion of Cth in VSMCs exacerbated plaque vulnerability, and were associated with VSMC autophagy decline, all of which were rescued by H2S donor. In ox-LDL treated VSMCs, cth deletion reduced collagen and heightened apoptosis association with autophagy reduction, and vice versa. For the mechanism, CTH-H2S mediated VSMC autophagosome formation, autolysosome formation and lysosome function, in part by activation of TFEB, a master regulator for autophagy. Interference with TFEB blocked CTH-H2S effects on VSMCs collagen and apoptosis. Next, we demonstrated that CTH-H2S sulfhydrated TFEB at Cys212 site, facilitating its nuclear translocation, and then promoting transcription of its target genes such as ATG9A, LAPTM5 or LDLRAP1. Conclusively, CTH-H2S increases VSMC autophagy by sulfhydration and activation of TFEB, promotes collagen secretion and inhibits apoptosis, thereby attenuating atherogenesis and plaque vulnerability. CTH-H2S may act as a warning biomarker for vulnerable plaque. Abbreviations ATG9A: autophagy related 9A; CTH: cystathionine gamma-lyase; CQ: chloroquine; HASMCs: human aortic smooth muscle cells; H2S: hydrogen sulfide; LAMP1: lysosomal associated membrane protein 1; LAPTM5: lysosomal protein transmembrane 5; NaHS: sodium hydrosulfide hydrate; ox-LDL: oxidized-low density lipoprotein; PPG: DL- propagylglycine; TFEB: transcription factor EB; 3-MA: 3-methyladenine; VSMCs: vascular smooth muscle cells.

To fulfill the increasing energy demand, lithium-sulfur batteries (LIBs) are considered one of the most promising energy storage devices for the next generation because of their high specific capacity (1675[Formula: see text]mAh[Formula: see text]g[Formula: see text] and high energy density (2600[Formula: see text]Wh[Formula: see text]kg[Formula: see text]. However, the low conductivity of electrode materials, large volume expansion rate and shuttle effect, rapid decline of battery capacity and low cycle lifetime have restricted the commercialization of LIBs. In this paper, a type of silver-coated Co@NC porous carbon (ZIF-67 derivatives) is used as the principal material of the lithium-sulfur battery cathode (denoted Ag–Co@NC). These composites not only confine the active materials to the ordered pore structure composites but also inhibit the free migration of polysulfide and improve the redox reaction. Furthermore, uniformly modified silver nanoparticles are beneficial for enhancing the conductivity of Li2S, thus exhibiting good rate performance and capacity and effectively improving the electrochemical performance of the material.

Background: We used a targeted metabolomics approach to identify fatty acid (FA) metabolites that distinguished patients with coronary artery ectasia (CAE) from healthy Controls and patients with coronary artery disease (CAD).Materials and methods: Two hundred fifty-two human subjects were enrolled in our study, such as patients with CAE, patients with CAD, and Controls. All the subjects were diagnosed by coronary angiography. Plasma metabolomic profiles of FAs were determined by an ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometric (UPLC-QqQ-MS/MS).Results: Ninety-nine plasma metabolites were profiled in the discovery sets (n = 72), such as 35 metabolites of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), 10 FAs, and 54 phospholipids. Among these metabolites, 36 metabolites of AA, EPA, and DHA showed the largest difference between CAE and Controls or CAD. 12-hydroxyeicosatetraenoic acid (12-HETE), 17(S)-hydroxydocosahexaenoic acid (17-HDoHE), EPA, AA, and 5-HETE were defined as a biomarker panel in peripheral blood to distinguish CAE from CAD and Controls in a discovery set (n = 72) and a validation set (n = 180). This biomarker panel had a better diagnostic performance than metabolite alone in differentiating CAE from Controls and CAD. The areas under the ROC curve of the biomarker panel were 0.991 and 0.836 for CAE versus Controls and 1.00 and 0.904 for CAE versus CAD in the discovery and validation sets, respectively.Conclusions: Our findings revealed that the metabolic profiles of FAs in the plasma from patients with CAE can be distinguished from those of Controls and CAD. Differences in FAs metabolites may help to interpret pathological mechanisms of CAE.

We present a novel stacked autoencoder framework for feature extraction to improve classification of hyperspectral image, leveraging graph regularization to address the shortcomings of classical autoencoder that mainly focuses on learning spectral features. In the proposed method, we firstly construct a graph to represent the spectral-spatial similarity between pixels in a hyperspectral image by measuring their spatial and spectral distances. And then the graph regularized autoencoder is learned to transform the original spectral signatures of pixels into a new feature space used for the downstream pixel classification or other tasks. Our feature extraction method can preserve the intrinsic spectral-spatial distribution in a hyperspectral image and obtain more discriminative and robust features. The experiments on pixel classification show the competitive performance compared with classical autoencoder based and manifold learning based feature extraction approaches.

Objectives Lacunar stroke had an unfavorable prognosis in the long term with a high risk of recurrent stroke, aspirin has been widely used to prevent ischemic stroke, but data on the effect of antiplatelet therapy on lacunar infarction are limited. We investigated the long-term effect of aspirin treatment on stroke recurrence risk in patients with lacunar stroke in a multicenter prospective cohort. Methods Between November 2000 and November 2001, 2000 consecutive stroke patients (age 35-74 years) were recruited from seven clinical centers. For the present study, a total of 544 patients with lacunar infarction were finally included in the analysis. The patients were divided into two groups (aspirin group, n = 342 and non-aspirin group, n = 202).The effect of aspirin on stroke recurrence was evaluated by using Kaplan-Meier analysis and Cox regression models. Results During a median 4.1-year follow-up for 544 patients with lacunar stroke, 99 recurrent strokes, 125 major vascular events (stroke, myocardial infarction, and vascular death), 31 vascular deaths, and 59 all-cause deaths were identified. Kaplan-Meier analysis showed that aspirin non-users had a higher risk of future recurrent stroke and of vascular events than did aspirin users (log-rank test, P = 0.049, 0.047, respectively). Aspirin significantly reduced the stroke recurrence in patients with lacunar stroke analyzed with multivariate stepwise analysis using model of Cox proportional hazards with backward elimination (HR = 0.67, 95% CI 0.45-0.99). Conclusion We concluded that aspirin significantly reduced stroke recurrence in patients with lacunar stroke.

Background: Fast resting heart rate (RHR) is easily neglected in clinical practice of hypertension treatment.Aims: We aimed to investigate the prevalence of fast RHR and associated factors in hyper...

BACKGROUND AND PURPOSE This study aimed to test the hypothesis that long noncoding RNA (lncRNA) AL110200 exerts a proinflammatory effect on atherosclerosis and that the variant rs901681 contributes to ischaemic stroke incidence and recurrence. METHODS The expression of AL110200 was analyzed in THP-1 cells treated with oxidized low-density lipoprotein and in human peripheral blood in a coronary heart disease and control population to determine the role of AL110200 in atherosclerosis. The effect of AL110200 on cell adhesion and invasion was tested. The plasma level of leukotriene B4 and rs901681 genotype distribution were assessed in 220 participants. In 1004 ischaemic stroke patients and 1434 controls, the association between rs901681 and stroke incidence was analyzed by logistic regression, and the association of rs901681 and stroke prognosis was analyzed using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS Increased expression of AL110200 was observed in THP-1 cells under oxidized low-density lipoprotein treatment. Knockdown of AL110200 reduced the adhesive and invasive ability of THP-1 cells. AL110200 expression in peripheral blood was significantly higher in the coronary heart disease group than in the controls. The GG genotype of rs901681 is associated with reduced plasma leukotriene B4. In the ischaemic stroke population, rs901681 was not associated with ischaemic stroke incidence (p = 0.686). Patients carrying rs901681 GG had a lower risk for stroke recurrence at age ≥60 years (p = 0.001), cardiovascular stroke death (p = 0.022) and all-cause mortality (p = 0.034) in the all-age group. CONCLUSIONS AL110200 might exert a proinflammatory effect on atherosclerosis, and the variant rs901681 might be a strong predictor of stroke prognosis in ischaemic stroke patients.