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It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates β3 adrenergic receptor (β3 AR). However, the effect of selective β3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. We generated a CIH-induced atherosclerosis model through exposing ApoE−/− mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5–21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective β3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. The expression of β3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE−/− mice in CIH but not in normoxia. Mechanistically, mirabegron activated β3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, β3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via β3 AR–mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the β3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated.Methods: This study involved ApoE−/− mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5–20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups.Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways.Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

A novel vertical cascaded planar electromagnetic bandgap (EBG) structure is proposed for SSN suppression with the ultra- wideband at the restraining depth of i30dB by analyzing the simultaneous switching noise (SSN) suppression mechanism and the equivalent circuit model for EBG structure. Moreover, the SSN suppression bandwidth can be broadened by using difierent novel EBG structures required by vertically cascading difierent planar EBG structures. In addition, the structure is verifled to meet signal integrity (SI) by the time-domain simulation. The tested results show that the presented EBG is accordant to the simulated results of the theory method by the vector network analyzer. The proposed structures provide a new designing method for EBG structures to improve the ability of suppressing SSN.

With the ultrasound was put into the experiment of cast-rolling lead alloy strip, it broke the dendrite structures and enhanced the under-cooling by the effect of cavity and acoustic streaming. The microstructure comparison of ultrasound and general cast-rolling shows that: The grain size of general cast-rolled lead strip is big; the grain boundary is coarse and the organization structure is uneven. However, the grain structure is refined, smaller grains and uniform organization structure is acquired with ultrasound treatment. Besides, the mechanical properties test results of the two kinds lead alloys shows that the ultrasound cast-rolling lead alloys are better than general cast-rolling. The tensile strength, yield strength and elongation of ultrasound cast-rolling lead strip are increased by 11.30%, 22.15% and 21.74% than that of general cast-rolling lead strip.

Coupling factor 6 (CF6) is a novel endogenous inhibitor of prostacyclin. Plasma CF6 and 6-keto-PGF(1a) were measured by radioimmunoassay in 70 consecutively recruited patients with type 2 diabetes and in 56 healthy controls. A significantly increased plasma CF6 level was found in diabetics compared with controls. The CF6 level was inversely correlated with plasma 6-keto-PGF(1a) level and positively correlated with blood glucose and lipids. These results suggest that CF6 might be an obvious marker of impaired endothelium and might contribute to vascular damage in diabetes.

Previous studies have shown that mitochondrial coupling factor 6 (CF6) is an endogenous peptide that inhibits prostacyclin (PGI2) synthesis in vascular endothelial cells. In this study, we measured the plasma CF6 level of patients with acute myocardial infarction (AMI) to observe dynamic changes of CF6. All patients showed elevated plasma CF6 levels upon admission for treatment of AMI. Their CF6 levels peaked approximately 72 h after the onset of AMI and remained high for 7 days. At 7 days, their CF6 levels decreased to the level seen upon admission, but not to within a normal range. Hyperlipidemic patients had significantly greater CF6 levels at 24 h after onset of AMI than patients with a normal lipid profile. On admission, the plasma CF6 level in patients with a cardiac function of Killip class ≥II was higher than that in patients with a Killip class I cardiac function. At 3 days after the onset of AMI, the plasma CF6 levels of patients with a creatinine kinase (CK) peak value ≥1,500 units/l were significantly higher than those of patients with a CK peak value

Objective: To observe the levels of plasma adiponectin and to explore the relationship between the levels of plasma adiponectin and drug efficacy in geratic patients with benign prostate hyperplasia. Methods: 70 cases of geratic men with benign prostate hyperplasia in hospital, according to the International Prostate Symptom Score (IPSS) were divided into 3 groups, 12 cases of mild group, 30 cases of moderate group and 28 cases of severe group. Plasma adiponectin concentration was measured in these cases. The differences of adiponectin levels were compared among the groups. 57 cases with IPSS moderate and above were treated with medication. The levels of adiponectin and prostate volume reduced were compared between the different efficacy groups. Results: Plasma adiponectin levels were significantly reduced according to the severity of prostate symptom in the patients with benign prostatic hyperplasia ( P ＜0.001). Adiponectin levels correlateiy negatively with IPSS ( r ＝ －0.696, P ＜0.01). The levels of adiponectin were (8.16±2.03)mg/L in efficacy group and (6.85±1.92)mg/L in without efficacy group, and there were significant differences between two groups ( P ＝0.024).There were more obvious prostate volume reduced in the efficacy group than those in without efficacy group ( P ＜0.01). Conclusions: Adiponectin levels may reflect the severity of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia. The patients with low adiponectin levels have poor efficacy by medication treatment. The decrease of adiponectin may be involved in the pathogenesis of prostate hyperplasia.