ε-Poly-L-lysine (ε-PL) has been widely used as food additive. However, the self-inhibition of ε-PL on cell growth limits the accumulation of ε-PL in the wild-type strain. Here, we screened ε-PL-tolerant strain of Streptomyces sp. with higher ε-PL productivity by genome shuffling and studied the mechanism for the improvement. The initial mutant library was constructed by diethyl sulfate mutagenesis. After four rounds of protoplast fusion, a shuffled strain F4-22 with 3.11 g/L ε-PL productivity in shake flask, 1.81-fold in comparison with that of parent strain, was obtained. The higher aspartokinase activity was induced in F4-22 whereas no obvious changes have been found in ε-PL synthetic and degrading enzymes which indicated that the upstream reregulation of the precursor lysine synthesis rather than lysine polymerization or ε-PL degradation in shuffled strain accounted for the higher productivity. The activities of key enzymes in the central metabolic pathway were also enhanced in F4-22 which resulted in increased vigor of the strain and in delayed strain lysis during fermentation. These improved properties of shuffled strain led to the success of combining general two-stage fermentation into one-stage one in 5-L bioreactor with 32.7 % more ε-PL production than that of parent strain. The strategy used in this study provided a novel strain breeding approach of producers which suffered from ε-PL-like self-inhibition of the metabolites.

No abstract

Objectives Neurocognitive complications significantly reduce long-term health-related quality of life in patients undergoing liver transplantation; however, few studies have focused on their perioperative cognitive status. The authors designed a prospective observational study to determine the incidence and risk factors of posttransplant cognitive dysfunction. Methods This study included patients with end-stage liver disease who were on the liver transplantation waiting list. We performed an investigation with a neuropsychological battery before and 1 week after the successful transplant, analyzed the changes, and further explored the complicated perioperative factors that contribute to cognitive dysfunction. Results A total of 132 patients completed all the investigations. Compared with healthy controls and preoperative cognitive performance, 54 patients experienced deterioration, 50 patients remained unchanged, and 28 patients showed rapid improvement. Logistic regression analysis showed that age [odds ratio (OR) = 1.15, 95% confidence interval (CI, 1.07-1.22), P < 0.001], the model for end-stage liver disease (MELD) score [OR = 1.07, 95% CI (1.03-1.13), P = 0.038], systemic circulation pressure [OR = 0.95, 95% CI (0.91-0.99), P = 0.026] within the first 30 min after portal vein opening, and total bilirubin concentration [OR = 1.02, 95% CI (1.01-1.03), P = 0.036] on the seventh day post-transplant were closely related to the deterioration of cognitive function. ConclusionThe incidences of deterioration, maintenance, and improvement in cognitive function were 40.9%, 37.9%, and 21.2%, respectively. Increasing age, higher MELD score, lower perfusion pressure in the early stage of the new liver, and higher total bilirubin concentration postoperatively may be independent pathogenic factors.

Background Neurocognitive complications seriously affect long-term health-related quality of life in patients after liver transplantation, but what was it like during the transplant? There has been little related research,so it is very necessary to understand the changes in cognition during the perioperative period. Methods This observational study included patients with end-stage liver disease who are waiting for liver transplantation in our center. We performed the individual cognitive function investigation before and one week after successful surgery,then analyze the changes between them and further explore possible ones that cause perioperative cognitive dysfunction among several factors. Results From December 2018 to November 2019, there are 70 patients completed all the investgation. Compared with preoperative cognitive performance, 29 patients experienced deterioration, 14 patients showed significant improvement, and 27 patients remained unchanged. Multi-factor analysis results showed that, a mean arterial pressure <80 mmHg (p=0.035) during the reperfusion phase, sufentanil dosage <1.5 µg kg -1 (p=0.027), and blood transfusion volume >70 ml kg -1 (p=0.047) were closely related to early postoperative cognitive dysfunction. Conclusions The incidences of deterioration, maintenance, and improvement in cognitive function were 41.6%, 38.4%, and 20%, respectively. Massive blood transfusion, hypotension during the reperfusion phase, insufficient intra-operative analgesia, and lower anesthesia depth may be the independent pathogenic factors for deteriorated cognitive function.