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Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymal-transition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH., Pulmonary arterial hypertension (PAH) is a heterogeneous disease, causing severe breathing problems and cardiac morbidity. Here, the authors study chromatin marks in pulmonary arterial endothelial cells from PAH patients and controls and find changes in transcription factor and enhancer activity that suggest an aberrant response to signalling in PAH.

Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.

The hybrid laser arc welding (HLAW) of 42CrMo quenched and tempered steel was conducted. The effect of the processing parameters, such as the relative positions of the laser and the arc, the shielding gas flow rate, the defocusing distance, the laser power, the wire feed rate and the welding speed, on the pore formation was analyzed, the morphological characteristics of the pores were analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The results showed that the majority of the pores were invasive. The pores formed at the leading a laser (LA) welding process were fewer than those at the leading a arc (AL) welding process. Increasing the shielding gas flow rate could also facilitate the reduction of pores. The laser power and the welding speed were two key process parameters to reduce the pores. The flow of the molten pool, the weld cooling rate and the pore escaping rate as a result of different parameters could all affect pore formation. An ideal pore-free weld was obtained for the optimal welding process parameters.