Although production of biodiesels from microalgae is proved to be technically feasible, a commercially viable system has yet to emerge. High‐cell‐density fermentation of microalgae can be coupled with photoautotrophic cultivation to produce oils. In this study, by optimizing culturing conditions and employing a sophisticated substrate feed control strategy, ultrahigh‐cell‐density of 286 and 283.5 g/L was achieved for the unicellular alga Scenedesmus acuminatus grown in 7.5‐L bench‐scale and 1,000‐L pilot‐scale fermenters, respectively. The outdoor scale‐up experiments indicated that heterotrophically grown S. acuminatus cells are more productive in terms of both biomass and lipid accumulation when they are inoculated in photobioreactors for lipid production as compared to the cells originally grown under photoautotrophic conditions. Technoeconomic analysis based on the pilot‐scale data indicated that the cost of heterotrophic cultivation of microalgae for biomass production is comparable with that of the open‐pond system and much lower than that of tubular PBR, if the biomass yield was higher than 200 g/L. This study demonstrated the economic viability of heterotrophic cultivation on large‐scale microalgal inocula production, but ultrahigh‐productivity fermentation is a prerequisite. Moreover, the advantages of the combined heterotrophic and photoautotrophic cultivation of microalgae for biofuels production were also verified in the pilot‐scale.

Lgr5+ stem cells are crucial to gut epithelium homeostasis; however, how these cells are maintained is not fully understood. Zinc finger HIT-type containing 1 (Znhit1) is an evolutionarily conserved subunit of the SRCAP chromosome remodeling complex. Currently, the function of Znhit1 in vivo and its working mechanism in the SRCAP complex are unknown. Here we show that deletion of Znhit1 in intestinal epithelium depletes Lgr5+ stem cells thus disrupts intestinal homeostasis postnatal establishment and maintenance. Mechanistically, Znhit1 incorporates histone variant H2A.Z into TSS region of genes involved in Lgr5+ stem cell fate determination, including Lgr5 , Tgfb1 and Tgfbr2 , for subsequent transcriptional regulation. Importantly, Znhit1 promotes the interaction between H2A.Z and YL1 (H2A.Z chaperone) by controlling YL1 phosphorylation. These results demonstrate that Znhit1/H2A.Z is essential for Lgr5+ stem cell maintenance and intestinal homeostasis. Our findings identified a dominant role of Znhit1/H2A.Z in controlling mammalian organ development and tissue homeostasis in vivo.

BACKGROUND Achievement of very high cell concentration is the prerequisite for enhanced porcine interferon‐α (pIFN‐α) production by Pichia pastoris, but it is closely associated with severe ethanol accumulation, leading to instability in pIFN‐α expression. RESULTS By analyzing the transcriptional levels of genes encoding the key enzymes in methanol metabolism, it was found that high (more than 6 g L−1) and long term (more than 4 h) ethanol accumulation in the late glycerol feeding cultivation phase irreversibly repressed alcohol oxidase (AOX) promoter, leading to instability in pIFN‐α production. A novel improved DO‐Stat glycerol feeding strategy based on on‐line ethanol measurement was thus proposed to control ethanol concentration at a low level of 2 g L−1, while maintaining cell growth at comparably high level. With the aid of the proposed strategy, maximum pIFN‐α concentration increased 29.8–75.5% compared with the best one adopting the ‘traditional’ DO‐Stat strategy, when the same methanol induction strategy (methanol/sorbitol co‐feeding ratio of 1:1) was applied. CONCLUSION The proposed improved DO‐Stat strategy is effective in simultaneously achieving very high concentration of the cells with functional cellular skeletons and repressing ethanol accumulation in the glycerol feeding phase, which enhanced and stabilized pIFN‐α production during the induction condition in turn. © 2013 Society of Chemical Industry