Multiplex modification of Yarrowia lipolytica for enhanced erythritol biosynthesis from glycerol through modularized metabolic engineering.

Erythritol is a novelty 4-carbon sugar polyol and has great potential to be used as the precursor of some platform chemicals. The increasing cost of glucose poses researchers shifting insights to the cheaper biodiesel raw materials. Herein, we engineered a non-degradation, non-byproducts Yarrowia lipolytica for the erythritol production with high-titer from glycerol. Initially, the degradation and competition modules were blocked by URA3 counter-selection marker. Subsequently, a shortened biosynthetic pathway was explored to elevate its synthetic flux by multi-modules combination expression of functional genes. Furthermore, a screened glycerol transporter ScFPS1 was integrated into ERY6 genome to promote the glycerol uptake. The constructed strain ERY8 produced 176.66 g/L erythritol in the 5-L bioreactor with a yield and productivity of 0.631 g/g and 1.23 g/L/h, respectively, which achieved the highest fermentation production efficiency till date. This study proposed a novel multi-modules combination strategy for effectively engineering Y. lipolytica to produce erythritol using glycerol.

Establishment and Validation of a Nomogram for Nasopharyngeal Carcinoma Patients Concerning the Prognostic Effect of Parotid Lymph Node Metastases / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk. @*Materials and Methods@#Clinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation.ResultTotally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort. @*Conclusion@#NPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis.

A novel sandwiched electrochemiluminescence immunosensor for the detection of carcinoembryonic antigen based on carbon quantum dots and signal amplification.

In this study, a novel sandwiched electrochemiluminescence (ECL) immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. The nanocomposite of polydopamine and Ag nanoparticles (PDA-AgNPs) was prepared by the redox reaction between Ag+ and dopamine. This nanocomposite not only provided an effective matrix for the immobilization of primary antibody (Ab1) but also enhanced the conductivity of the electrode. Carbon quantum dots (CQDs) were immobilized on the poly(ethylenimine) functionalized graphene oxide (PEI-GO) through amido-bond. Then Au nanoparticles were decorated on the CQDs modified PEI-GO matrix, and the resulted complex AuNPs/CQDs-PEI-GO was introduced to link secondary antibody (Ab2). The CQDs can be connected to the electrode surface through the combination of CEA with Ab1 and Ab2, and then the amplified electrochemiluminescence signal of CQDs was obtained with the synergistic effect of AgNPs, polydopamine, AuNPs and PEI-GO. Under the optimal conditions, the ECL intensity was proportional to the logarithm value of CEA concentration in the linear range from 5pgmL-1 to 500ngmL-1 with a detection limit of 1.67pgmL-1 for CEA detection. The immunosensor was applied for the CEA detection in real samples with satisfactory results. The proposed ECL immunosensor showed good performance with high sensitivity, specificity, reproducibility, stability and will be potential in clinical detection.

Clinical effects of the circumcision stapler, foreskin cerclage, and traditional circumcision: A comparative study / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the clinical effects of the circumcision stapler, circumcision cerclage, and traditional circumcision in the treatment of phimosis and redundant prepuce.</p><p><b>METHODS</b>Using the circumcision stapler (group A), foreskin cerclage (group B), and traditional circumcision (group C), we treated 276 patients with phimosis or redundant prepuce. We made comparisons among the three groups in the operation time, intraoperative blood loss, intraoperative and 24-hour postoperative pain scores, and incidence of postoperative complications. Results: The operation time, intraoperative blood loss, and intraoperative pain score were (6.52 ± 2.45) min, (1.93 ± 0.82) ml, and 1.37 ± 0.68 in group A and (7.24 ± 1.86) min, (1.51 ± 0.72) ml, and 1.20 ± 0.79 in group B, all significantly lower than (28. 36 ± 4.22) min, (9.52 ± 3.29) ml, and 3.06 ± 0.75 in group C (P <0.05). The 24-hour postoperative pain score was remarkably higher in group B than in A and C (3. 18 ± 0. 82 vs 1. 85 ± 0. 63 and 1. 82 ± 0. 75, P <0. 05). The incidence rate of postoperative complications was markedly lower in group A than in B (5. 43% vs 14. 13%, P < 0.05), but with no significant differences between either A and C or B and C (P >0.05).</p><p><b>CONCLUSION</b>The circumcision stapler, with its advantages of simple operation, minimal invasiveness, fewer complications, and better cosmetic result, deserves a wider clinical application.</p>