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Epigenetic modifications play an important role in disturbed flow (d‐flow) induced atherosclerotic plaque formation. By analysing a scRNA‐seq dataset of the left carotid artery (LCA) under d‐flow conditions, we found that Jarid1b (KDM5B) was upregulated primarily in a subcluster of endothelial cells in response to d‐flow stimulation. We therefore investigated the mechanism of KDM5B expression and the role of KDM5B in endothelial cell. Intriguingly, activation of Piezo1, a major endothelial mechanosensor, was found to promote KDM5B expression, which was reversed by Piezo1 inhibition in HUVECs. Downstream of Piezo1, ETS1 expression and c‐JUN phosphorylation were enhanced by d‐flow or Piezo1 activation, leading to an increase in KDM5B expression. Furthermore, knockdown of either KDM5B or Piezo1 was found to prevent d‐flow induced H3K4me3 demethylation, which was supported by the pharmacological inhibition of Piezo1 in HUVECs. RNA sequencing on shKdm5b HUVECs implied that KDM5B is associated with endothelial inflammation and atherosclerosis. Using partial carotid ligation surgery on Kdm5bf/fCdh5cre mice with mAAV‐PCSK9D377Y infected, we showed that endothelial KDM5B deficiency reduced atherosclerotic lesions in hypercholesterolemic mice. Our findings indicate that endothelial KDM5B expression induced by d‐flow via the Piezo1 pathway promotes atherosclerotic plaque formation, providing targets for the prevention or therapeutic intervention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD‐associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD‐associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD. [ABSTRACT FROM AUTHOR]

Background: The serum orexin A level was significantly lower among patients with acute ischemic stroke (AIS) and negatively related to the volume of the infarction, but the relationship between serum orexin A and prognosis of AIS was still unclear. We aimed to clarify the association between serum orexin A and the short‐term neurological improvement in patients with mild to moderate AIS. Methods: We consecutively enrolled patients with first ever mild to moderate AIS admitted to hospital within 48 h from symptom onset in this prospective observational study. The serum orexin A concentrations were determined on the second morning since the admission. The short‐term neurological improvement was defined as more than 1 point decrease in the National Institute of Health Stroke Scale score within 7 days after admission. Results: We detected increased serum orexin A level in mild to moderate AIS patients with early onset of stroke‐related insomnia (33.44 vs 18.66 pg/ml, p =.004) as well as in patients with short‐term neurological improvement compared to those without improvement (31.78 vs 16.24 pg/ml, p =.038). The serum orexin A level was positively associated with the short‐term neurological improvement after adjusting for sleep condition and other related variables. Conclusion: Serum orexin A might be a useful biomarker for the assessment of early prognosis in patients with mild to moderate AIS. [ABSTRACT FROM AUTHOR]

Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI‐binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di‐eosin‐glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin‐ or CRP‐stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser‐induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail‐bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent. [ABSTRACT FROM AUTHOR]

HNG, a highly potent mutant of the anti‐Alzheimer peptide‐humanin, has been shown to protect against ischaemia‐reperfusion (I/R) injury. However, the underlying mechanism related to platelet activation remains unknown. We proposed that HNG has an effect on platelet function and thrombus formation. In this study, platelet aggregation, granule secretion, clot retraction, integrin activation and adhesion under flow conditions were evaluated. In mice receiving HNG or saline, cremaster arterial thrombus formation induced by laser injury, tail bleeding time and blood loss were recorded. Platelet microtubule depolymerization was evaluated using immunofluorescence staining. Results showed that HNG inhibited platelet aggregation, P‐selectin expression, ATP release, and αIIbβ3 activation and adhesion under flow conditions. Mice receiving HNG had attenuated cremaster arterial thrombus formation, although the bleeding time was not prolonged. Moreover, HNG significantly inhibited microtubule depolymerization, enhanced tubulin acetylation in platelets stimulated by fibrinogen or microtubule depolymerization reagent, nocodazole, and inhibited AKT and ERK phosphorylation downstream of HDAC6 by collagen stimulation. Therefore, our results identified a novel role of HNG in platelet function and thrombus formation potentially through stabilizing platelet microtubules via tubulin acetylation. These findings suggest a potential benefit of HNG in the management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Semaphorin 7A (Sema7A), a neural guidance cue, was recently identified to regulate atherosclerosis in mice. However, the clinical relevance of Sema7A with atherosclerotic diseases remains unknown. The aim of this study was to investigate the association between serum Sema7A and the risk of acute atherothrombotic stroke (AAS). We measured serum concentrations of Sema7A in 105 newly onset AAS cases and 105 age‐ and sex‐matched controls, showing that median Sema7A level in AAS cases was over three times of that in controls (5.86 vs 1.66 ng/mL). Adjusted for hypertension, body mass index, fasting blood glucose, total cholesterol, triglyceride, high‐density lipoprotein (HDL)‐cholesterol, low‐density lipoprotein (LDL)‐cholesterol, current smoking and alcohol consumption, multivariate logistic regression showed that higher Sema7A was independently associated with the odds of AAS (OR = 6.40, 95% CI: 2.88‐14.25). Each 1‐standard deviation increase in Sema7A was associated with a threefold higher odds of AAS (OR = 3.42, 95% CI: 1.84‐6.35). Importantly, adding Sema7A to a multivariate logistic model containing conventional cardiovascular risk factors improved the area under receiver operating characteristic curves from 0.831 to 0.891 for the association with AAS. In conclusion, elevated serum Sema7A is independently associated with the risk of AAS, suggesting that it may play a potential role in AAS. [ABSTRACT FROM AUTHOR]

Abstract: In order to improve the detonation performances of emulsion explosives, a new type of emulsion explosives sensitized by hydrogen‐storage glass microballoons is proposed. The influences of hydrogen in glass microballoons on explosion characteristics of emulsion explosives were studied. Brisance testing and underwater explosion experiments showed that, compared with traditional emulsion explosives, the shock impulse and specific total energy of hydrogen‐storage glass microballoons sensitized emulsion explosives are improved significantly. The brisance (compression of lead block) of hydrogen‐storage emulsion explosives is 23.0 mm, 3.2 mm more than that of traditional emulsion explosives. Therefore, the hydrogen‐storage glass microballoons could be a promising energetic additive for developing high‐power emulsion explosives. [ABSTRACT FROM AUTHOR]

Experiments were conducted to study the underwater explosion performance of titanium hydride/RDX-based (TiH2/RDX) composite explosive. Cylinder charges with different TiH2 particle sizes and contents were prepared and tested. Explosion parameters like peak overpressure, impulse, shock energy, and bubble energy were analyzed. It was notable that underwater explosion performance of TiH2/RDX composite explosive was promoted by addition of small particle size TiH2 (D50=0.96 μm), in which case increasing TiH2 content also showed a favorable effect. The maximum increments of specific initial shock energy, bubble energy, and total energy were 10.5%, 6.4%, and 7.1% respectively. However, with bigger TiH2 particle sizes (D50=20.78 μm, D50=136.74 μm), the explosion parameters and the TiH2 content showed a negative relationship, which reveals that TiH2 particle size plays an important role in determining the reactivity of TiH2. Meanwhile, the interaction between TiH2 particle size and content was significant. [ABSTRACT FROM AUTHOR]

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. [ABSTRACT FROM AUTHOR]

Segmentation of infarcts at hyperacute stage is challenging as they exhibit substantial variability which may even be hard for experts to delineate manually. In this paper, a sparse representation based classification method is explored. For each patient, four volumetric data items including three volumes of diffusion weighted imaging and a computed asymmetry map are employed to extract patch features which are then fed to dictionary learning and classification based on sparse representation. Elastic net is adopted to replace the traditional L0-norm/L1-norm constraints on sparse representation to stabilize sparse code. To decrease computation cost and to reduce false positives, regions-of-interest are determined to confine candidate infarct voxels. The proposed method has been validated on 98 consecutive patients recruited within 6 hours from onset. It is shown that the proposed method could handle well infarcts with intensity variability and ill-defined edges to yield significantly higher Dice coefficient (0.755 ± 0.118) than the other two methods and their enhanced versions by confining their segmentations within the regions-of-interest (average Dice coefficient less than 0.610). The proposed method could provide a potential tool to quantify infarcts from diffusion weighted imaging at hyperacute stage with accuracy and speed to assist the decision making especially for thrombolytic therapy. [ABSTRACT FROM AUTHOR]