In scale-up of bioprocesses from shake flasks to fermentors, NVP-BKM120 acetate production tends to increase and is usually regarded as a cause of the decline in protein expression. For decades many researchers have focused on strategies that reduce acetate accumulation. Briefly, the approaches developed involve process optimization and host organism modification. Eiteman and Altman suggested that E. coli cells produce acetate when they have surpassed a threshold value of the specific rate of glucose consumption and that only under glucose limitation is the specific growth rate directly related to acetate production. Limiting the glucose concentration of the medium is regarded as a valid strategy for reducing acetate accumulation. Akesson and coworkers developed an automated glucose feeding strategy by controlling dissolved oxygen through manipulating the stirrer speed and successfully reduced acetate accumulation to less than 60 mg/L. An alternative is to reduce glucose uptake of the host cells by genetic modification. Accumulation of acetate has long been an issue for recombinant protein production by E. coli cells. Initial efforts focused mainly on reducing acetate excretion, generally by deleting genes in the pathways of glucose uptake and acetate formation, or controlling the glucose feed rate. Recently, improvements in acetate tolerance by genetic strategies and medium supplementation with certain amino acids and pyrimidines have shown much promise. The overall objective of our study was to use the simple approach of an alkaline pH shift to increase the acetate tolerance of E. coli BL21 cells, a popular strain currently used in recombinant protein expression. Pulmonary arterial hypertension is a severe and progressive disease, with sustained elevation of pulmonary arterial pressure and a poor prognosis. Considerable studies have been focused on understanding the mechanisms of PAH, yet the underlying mechanisms have not been comprehensively understood. Recent advance found that abnormal bone morphogenetic proteins signaling deregulated the cell growth and differentiation, and contributed to pulmonary artery remodeling in the process of PAH. Furthermore, substantial evidence indicates that BMP signals are important mediators in calcification of the intima and tunica media, which may lead to severe PAH. BMPs belong to the TGF-b superfamily, which bind and activate heteromeric complexes of type I and type II receptors, while BMP signals regulate through binding the complex of type receptor I and type receptor II. Among these receptors, BMPRII is the most common single culprit gene. The expression of BMPRII significantly decreased in pulmonary artery isolated from patients with primary PAH and in some animal models of PAH induced by monocrotaline, chronic hypoxia or transgenic mice. Moreover, it is generally accepted that mutations in the gene encoding BMPRII are responsible for patients with PAH and BMPRII expression is also decreased in PAH patients without BMPRII mutations, indicating that BMPRII signaling plays a crucial role in the development of PAH. In contrast, BMPRII-targeted therapy significantly reduced pulmonary arterial pressure, right ventricular hypertrophy and muscularization.