Aberrant Notch signalling contributes to hypertrophic scar formation by modulating the phenotype of keratinocytes.

Hypertrophic scar (HS) is characterized by fibroblast hyperproliferation and excessive matrix deposition. Aberrant keratinocyte differentiation and their abnormal cytokine secretion are said to contribute to HS by activating fibroblasts. However, the signalling pathway causing the aberrant keratinocytes in HS has remained unidentified thus far. Given that Notch signalling is crucial in initiating keratinocyte differentiation, we hypothesized that Notch signalling contributes to HS by modulating the phenotype of keratinocytes. We found that Notch1, Notch intracellular domain, Jagged1 and Hes-1 were overexpressed in the epidermis of patients with HS. Supernatants from recombinant-Jagged1-treated keratinocyte cultures could accelerate dermal fibroblast proliferation and collagen production. Furthermore, Jagged1 induced keratinocyte differentiation and upregulated the expression of fibrotic factors, including transforming growth factors ß1 and ß2 , insulin-like growth factor-1, connective tissue growth factor, vascular endothelial growth factor and epidermal growth factor, while DAPT (a Notch inhibitor) significantly suppressed these processes. In a rabbit ear model of HS, local application of DAPT downregulated the production of fibrotic factors in keratinocytes, together with ameliorated scar hyperplasia. Our findings suggest that Notch signalling contributes to HS by modulating keratinocyte phenotype. These results provide new insights into the pathogenesis of HS and indicate a potential therapeutic target.

Role of sufficient phosphorus in biodiesel production from diatom Phaeodactylum tricornutum.

In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N-P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality.

Polyphosphate during the Regreening of Chlorella vulgaris under Nitrogen Deficiency.

Polyphosphate (Poly-P) accumulation has been reported in Chlorella vulgaris under nitrogen deficiency conditions with sufficient P supply, and the process has been demonstrated to have great impact on lipid productivity. In this article, the utilization of polyphosphates and the regreening process under N resupplying conditions, especially for lipid production reviving, were investigated. This regreening process was completed within approximately 3-5 days. Polyphosphates were first degraded within 3 days in the regreening process, with and without an external P supply, and the degradation preceded the assimilation of phosphate in the media with an external P offering. Nitrate assimilation was markedly influenced by the starvation of P after polyphosphates were exhausted in the medium without external phosphates, and then the reviving process of biomass and lipid production was strictly impeded. It is, thus, reasonable to assume that simultaneous provision of external N and P is essential for overall biodiesel production revival during the regreening process.

The mechanism of carbon source utilization by microalgae when co-cultivated with photosynthetic bacteria.

Microalgae-photosynthetic bacteria (PSB) co-culture, which is promising for wastewater treatment and lipid production, is lacking of study. In this work, the combinations of 3 microalgae and 3 PSB strains were firstly screened and then different inoculation ratios of the co-cultures were investigated. It was found the best promotion was Chlorella pyrenoidosa/Rhodobacter capsulatus co-culture (1:1), where the biomass productivity, acetate assimilation rate and lipid productivity were 1.64, 1.61 and 2.79 times than that of the sum of pure microalgae and PSB cultures, respectively. Meanwhile, the inoculation ratio significantly affected the growth rate and lipid productivity of co-culture systems. iTRAQ analysis showed that PSB played a positive effect on acetate assimilation, TCA cycle and glyoxylate cycle of microalgae, but decreased the carbon dioxide utilization and photosynthesis, indicating PSB promoted the microalgae metabolism of organic carbon utilization and weakened inorganic carbon utilization. These findings provide in-depth understanding of carbon utilization in microalgae-PSB co-culture.

Biosynthesis of high yield fatty acids from Chlorella vulgaris NIES-227 under nitrogen starvation stress during heterotrophic cultivation.

In this study the heterotrophic cultivation of Chlorella vulgaris NIES-227 fed with glucose was investigated systematically using six media types; combinations of nitrogen repletion/depletion and phosphorus repletion/limitation/depletion. It was found that a high yield of fatty acids (0.88 of fed glucose-COD) and a high content of fatty acid methyl esters (FAMEs) (89% of dry weight) were obtained under nitrogen starved conditions. To our knowledge it is the first report on such high COD conversion yield and FAME content in microalgae. The dominant fatty acid (>50%) was methyl oleate (C18:1), a desirable component for biodiesel synthesis. FAME content under nitrogen starved conditions was significantly higher than under nitrogen sufficient conditions, while phosphorus had no significant influence, indicating that nitrogen starvation was the real "fatty acids trigger" in heterotrophic cultivation. These findings could simplify the downstream extraction process, such as the extrusion of oil from soybeans, and could reduce operating costs by improving the fatty acid yield from waste COD.

Effect of phosphorus on biodiesel production from Scenedesmus obliquus under nitrogen-deficiency stress.

In order to study the effect of phosphorus on biodiesel production from Scenedesmus obliquus especially under nitrogen deficiency conditions, six types of media with combinations of nitrogen repletion/depletion and phosphorus repletion/limitation/depletion were investigated in this study. It was found that nitrogen starvation compared to nitrogen repletion enhanced biodiesel productivity. Moreover, biodiesel productivity was further strengthened by varying the supply level of phosphorus from depletion, limitation, through to repletion. The maximum FAMEs productivity of 24.2 mg/L/day was obtained in nitrogen depletion with phosphorus repletion, which was two times higher than that in nutrient complete medium. More phosphorus was accumulated in cells under the nitrogen starvation with sufficient phosphorus condition, but no polyphosphate was formed. This study indicated that nitrogen starvation plus sufficient P supply might be the real "lipid trigger". Furthermore, results of the current study suggest a potential application for utilizing microalgae to combine phosphorus removal from wastewater with biodiesel production.

Phosphorus plays an important role in enhancing biodiesel productivity of Chlorella vulgaris under nitrogen deficiency.

To investigate the role of phosphorus in lipid production under nitrogen starvation conditions, five types of media possessing different nitrogen and phosphorus concentrations or their combination were prepared to culture Chlorella vulgaris. It was found that biomass production under nitrogen deficient condition with sufficient phosphorus supply was similar to that of the control (with sufficient nutrition), resulting in a maximum lipid productivity of 58.39 mg/L/day. Meanwhile, 31P NMR showed that phosphorus in the medium was transformed and accumulated as polyphosphate in cells. The uptake rate of phosphorus in cells was 3.8 times higher than the uptake rate of the control. This study demonstrates that phosphorus plays an important role in lipid production of C. vulgaris under nitrogen deficient conditions and implies a potential to combine phosphorus removal from wastewater with biodiesel production via microalgae.