Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

Objective: To investigate the knowledge, attitude, and practice on disposable plastic tableware and self reported gastrointestinal symptoms in college students. Methods: Stratified sampling method was applied in 338 students of a medical university during the 2020-2021 academic year. The study investigated knowledge, attitude and practice on disposable plastic tableware and self reported gastrointestinal symptoms among students. Results: There were 24.0% students were unaware of the specific material of plastic tableware, 82.0% students had no idea about the meaning of "plastic products logo". About 94.1% of the students thought that plastic tableware might contaminate food, and female students (97.1%) were more worried than male (86.3%) ( χ 2=14.32, P <0.05). The attitude towards the use of disposable tableware was not consistent with the cumulative use score of disposable plastic tableware ( F=1.31, P =0.25),students with high consumption had higher score of accumulative use of disposable plastic tableware ( F=8.32, P <0.01). About 18.3% of the students were prone to report gastrointestinal symptoms. The cumulative scores of disposable plastic tableware weekly using frequency in students who reported gastrointestinal symptoms(14.85±4.01) was still higher than that of no gastrointestinal symptoms group(13.78±3.50), regardless of the effect of takeout ordering frequency( F=4.53，P = 0.03 ). Conclusion College students have limited knowledge of disposable plastic products. However, the use of disposable plastic products may be associated with gastrointestinal diseases. It is suggested to active the propaganda and education, to reduce the use of disposable tableware, and enhance the awareness of health and environment.