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Objective To investigate the effect of silencing alpha tubulin acetyltransferase 1 (α-TAT1) on migration behavior of endothelial cells induced by hepatopulmonary syndrome (HPS). Methods Online database Tabula Muris was used to analyze the expression of α-TAT1 in various cell subsets in the lungs. Twenty-four male SD rats were randomly divided into control group (Sham group, n=6) and common bile duct ligation group (HPS group, n=18). The rats in HPS group were euthanasized at 2 and 4 weeks after modelling, and then the expression of α-TAT1 in pulmonary vascular endothelial cells was detected by immunofluorescence colocalization. The sera from the Sham and HPS rats were used to stimulate human umbilical vein endothelial cells (HUVECs) for 12 and 24 h, respectively. Then the obtained HUVECs were divided into 4 groups: Sham serum + siRNA NC group, Sham serum + siRNA α-TAT1 group, HPS serum+ siRNA NC group, HPS serum + siRNA α-TAT1 group. The expression levels of α-TAT1 and Ace-α-tubulin in HUVECs were detected by Western blotting. Immunofluorescence assay was applied to observe the levels of polymerized microtubules of α-Tubulin in HUVECs after nocodazole (10 μmol/L) pretreatment to evaluate the stability of microtubule structure. Cell scratch assay combined with cell immunofluorescence assay was employed to observe the nuclear localization of Golgi apparatus and cell migration ability of HUVECs. The angiogenesis ability of HUVECs was tested by in vitro angiogenesis test. Results In vivo and in vitro experiments showed that the expression of α-TAT1 in endothelial cells was significantly increased after HPS inducement. The expression levels of α-TAT1 and Ace-α-tubulin were significantly down-regulated, and the stability of microtubules was weakened in the siRNA α-TAT1 interference group (P < 0.01). In addition, the distribution of GM130 labeled Golgi apparatus in the protrusion of HUVECs was down-regulated in the siRNA α-TAT1 interference group, as well as the migration ability (P < 0.01). And the length of angiogenesis and network level were also significantly declined (P < 0.01). Conclusion Silencing α-TAT1 reduces the migration and angiogenesis of endothelial cells in HPS, which was associated with weakened stabilization of microtubule.

BackgroundCoronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.MethodsWe performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.ResultsWe replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P

P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 μW m−1 K−2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm−2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value. The authors fabricate p-type Fe3CoSb12-based skutterudite films exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and pulsed laser deposition techniques. [ABSTRACT FROM AUTHOR]

Objective: The post-hoc analysis aimed to explore the effect of ticagrelor plus aspirin (T+A) or ticagrelor alone (T) vs aspirin alone (A) on saphenous vein (SV) graft patency 1 year after coronary-artery bypass grafting (CABG) under different baseline levels of low-density lipoprotein cholesterol (LDL-C). Methods: All the 500 patients with 1460 SV grafts from the DACAB trial (NCT02201771) were stratified into subgroup LDL-Low (baseline LDL-C<1.8mmol/L, 148 patients with 430 SV grafts) & subgroup LDL-High (baseline LDL-C≥ 1.8mmol/L, 352 patients with 1030 SV grafts). The primary outcome was the 1-year SV graft patency (Fitzgibbon grade A). The generalized estimating equation model was applied in grafts outcome analyses. Results: The mean baseline LDL-C were 1.4mmol/L and 2.6mmol/L while mean follow-up LDL-C were 1.6mmol/L and 2.3mmol/L for subgroup LDL-Low and subgroup LDL-High, respectively. The baseline and 1-year statin use were comparable between the two subgroups (baseline, LDL-Low: 94.6% [140 of 148 patients], LDL-High: 93.5% [329 of 352 patients], P=0.633; 1-year, LDL-Low: 96.0% [142 of 148 patients], LDL-High: 95.7% [337 of 352 patients], P=0.916).For subgroup LDL-Low and subgroup LDL-High, the 1-year SV graft patency rates were constant significant higher with T+A vs A (LDL-Low: adjusted OR=0.41 [95%CI, 0.17 to 0.97]; LDL-High: adjusted OR=0.38 [95%CI, 0.20 to 0.71]; Inter P=0.679), but may not with T vs A (LDL-Low: adjusted OR=0.24 [95%CI, 0.08 to 0.67]; LDL-High: adjusted OR=0.93 [95%CI, 0.53 to 1.63]; Inter P=0.030). The 1-year SV graft patency were 83.8% (359 of 430 grafts) in subgroup LDL-Low and 82.3% (848 of 1030 grafts) in subgroup LDL-High. No statistically significant difference was observed between the two subgroups (adjusted OR=0.96 [95%CI, 0.62 to 1.50], P=0.857). Conclusion: For 1-year SV graft patency post-CABG, T+A was more effective than A alone in both subgroup LDL-Low and LDL-High; T alone might be more effective than A alone in subgroup LDL-Low. No statistically significant difference of 1-year SV graft patency were observed between subgroup LDL-Low and LDL-High in the DACAB trial. [ABSTRACT FROM AUTHOR]