Search

Shikimate is a valuable chiral precursor for synthesizing oseltamivir (Tamiflu®) and other chemicals. High production of shikimate via microbial fermentation has attracted increasing attention to overcome the unstable and expensive supply of shikimate extracted from plant resources. The current cost of microbial production of shikimate via engineered strains is still unsatisfactory, and thus more metabolic strategies need to be investigated to further increase the production efficiency. In this study, we first constructed a shikimate E. coli producer through the application of the non-phosphoenolpyruvate: carbohydrate phosphotransferase system (non-PTS) glucose uptake pathway, the attenuation of the shikimate degradation metabolism, and the introduction of a mutant of feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase. Inspired by the natural presence of bifunctional 3-dehydroquinate dehydratase (DHD)-shikimate dehydrogenase (SDH) enzyme in plants, we then designed an artificial fusion protein of DHD-SDH to decrease the accumulation of the byproduct 3-dehydroshikimate (DHS). Subsequently, a repressed shikimate kinase (SK) mutant was selected to promote shikimate accumulation without the supplementation of expensive aromatic substances. Furthermore, EsaR-based quorum sensing (QS) circuits were employed to regulate the metabolic flux distribution between cell growth and product synthesis. The final engineered strain dSA10 produced 60.31 g/L shikimate with a yield of 0.30 g/g glucose in a 5 L bioreactor.

Yi Lao,1 Taidong Li,2 Xin Xie,1 Kangbiao Chen,1 Ming Li,1 Lu Huang1 1The Fourth Department of Medical Oncology, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, Zhanjiang, Guangdong, 524002, People’s Republic of China; 2Department of Thoracic Surgery, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, Zhanjiang, Guangdong, 524002, People’s Republic of ChinaCorrespondence: Lu HuangThe Fourth Department of Medical Oncology, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, No. 2 Mid Renmin Avenue, Zhanjiang, 524002, Guangdong, People’s Republic of ChinaTel +86-0759-2633696Email luternh@163.comBackground: MicroRNA-195-3p (miR-195-3p) plays an important role in some tumors, but its role in LUAD is unclear. This study explored the expression of miR-195-3p in LUAD and the relationship between the expression of miR-195-3p and the clinical and prognostic characteristics of LUAD patients.Methods: MiR-195-3p expression and clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA). Kruskal–Wallis test, Wilcoxon signed rank test, logistic regression, and Cox regression were used to assess the relationship between the expression level of miR-195-3p and clinical features in LUAD tissues. Kaplan–Meier survival curves were used to analyze the effect of miR-195-3p expression levels on the prognosis of LUAD patients. Target genes of miR-195-3p were predicted by several software. GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and immune infiltration analysis were used to analyze the possible regulatory network of miR-195-3p.Results: Compared with normal lung tissue, miR-195-3p is down expressed in LUAD tissue (P < 0.001). The low miR-195-3p expression in LUAD was significantly associated with N stage (P = 0.046), pathologic stage (P = 0.011), and gender (P = 0.010). Low miR-195-3p expression predicted a poorer overall survival (HR: 0.60; 95% CI: 0.45– 0.81; P = 0.001) and disease-specific survival (HR: 0.55; 95% CI: 0.37– 0.80; P = 0.002). The expression of miR-195-3p (HR: 0.488; 95% CI: 0.304– 0.784; P = 0.003) was independently correlated with OS in LUAD patients. High expression of miR-195-3p genes, including ABCC2, AGMAT, ARNTL2, ATP6V0A4, CDC25A, CDK1, FAM111B, GJB2, GRIP1, HMGA2, HOXA9, KIF14, SYT2, and TFAP2A, were associated with poor OS in LUAD. GO and KEGG analysis suggested that miR-195-3p was related to the phagosome pathway. MiR-195-3p may promote the function of B cells, dendritic cells, eosinophils, immature dendritic cells, macrophages, Mast cells, NK cells, plasmacytoid dendritic cells, and follicular helper T cells.Conclusion: Low miR-195-3p expression is significantly associated with poor survival in LUAD, which may be a promising prognostic biomarker for LUAD.Keywords: lung adenocarcinoma, miR-195-3p, gene expression, prognosis, immune infiltration, biomarker

The introduction of gas is the principal difference between external gas-assisted injection molding (EGAIM) and conventional injection molding. In this study, the effects of gas thickness and gas delay time on polymer temperature were discussed. A modified one-dimensional transient heat conduction model of polymer was established to reveal the relationships between polymer temperature and gas thickness and gas delay time in EGAIM. The temperature histories of polymer were obtained by the simulation methods, including Moldflow and ANSYS, and were verified by comparing the experimental data to numerical simulation results. The effects of gas thickness and gas delay time on the temperature histories of polymer will be discussed in detail. The results showed that the polymer temperature is strongly affected by the heat preservation of gas, which in turn, increases with the increase of gas thickness and delay time. This paper provides quantitative methods and theoretical guidance for the study of the effects of gas on the polymer temperature in EGAIM.

External gas-assisted injection molding (EGAIM) has been used to reduce the sink marks of amorphous polymer products, but that of crystalline polymer products has not yet been reported. EGAIM of a crystalline polymer product was investigated in this study, and the influences of process parameters on the sink marks were discussed based on experiments. An isotactic polypropylene (iPP) product was fabricated by EGAIM under different process conditions. A uniform design was applied as an experimental design to investigate the influences of the process parameters on the sink marks. A regression equation was established to describe the quantitative relationship between the important parameters and sink marks in which a data-processing method was applied to determine the optimal value of Fα at significant level α to reduce the possibility of omission of some important parameters. The results show that EGAIM was effective in reducing the sink marks in these iPP products, and the most important parameters were the cooling time, gas pressure, and gas time. This study also provides the quantitative relationship between the important parameters and sink marks as reference for the research of EGAIM on crystalline polymer.

The microstructure of a molded product considerably influences its macroscopic properties. In this study, the influence of molding process on microstructure, tensile property, and surface quality was explored on the glass fiber-reinforced polypropylene (GFRPP) parts molded by rapid heat cycle molding (RHCM) and conversion injection molding (CIM). Tensile strength and surface gloss were chosen to measure macroscopic properties of the molded parts. The microstructure including multilayer, fiber orientation, crystallinity, and fiber-matrix bonding strength were analyzed by simulations, scanning electron microscopy, wide-angle X-ray diffraction, and dynamic mechanical analysis. The relationship between the macroscopic properties and microstructure of the RHCM samples was also discussed. The results indicate that as the mold cavity surface temperature increases, the tensile strength increases firstly and decreases thereafter. The tensile strength of RHCM parts reached the maximum at the mold heating temperature of 60°C. It is also observed that the surface gloss of the sample increases as the mold cavity surface temperature rises, and the increase of surface gloss decreases distinctly with the mold heating temperature higher than 90°C.

Temperature greatly influences the mechanical response of acrylonitrile butadiene styrene (ABS). The tensile behavior of ABS was explored in this study. The tensile experiments were conducted at a wide range of temperatures (from 40°C to 130°C). A model was established to reveal the quantitative relationship between temperature and tensile behavior of ABS. The results of tensile experiments showed that tensile behavior of ABS exhibited glassy state and high-elastics state. The model was also divided into two parts that rely on the boundary of glass transition temperature, in which the parameters of the model were calculated by the fitting method. The model predictions showed a good agreement with the results of the experimental tensile test. This study provides the quantitative relationship between temperature and tensile behavior of ABS, which saves time and experimental costs.

Rapid heat cycle molding (RHCM) is an injection molding process that has been developed in recent years. Recent studies of RHCM have mainly focused on heating technologies and process optimization. Few studies have examined the evolution of crystallization behavior. In this study, a novel method is proposed to determine the crystallization evolution information of polymers during the RHCM process. The influence of temperature and shear rate on crystallization was considered. The non-isothermal crystallization process was first divided into a series of isothermal processes. Next, mathematical model parameters were obtained through isothermal crystallization experiments, and then the crystallization information during the RHCM process could be determined. Finally, for comparison, the degrees of crystallinity for the final product in different positions were measured using wide-angle X-ray diffraction (WAXD). Experimental results showed that the proposed method is both accurate and effective. It is also simple and has broad application prospects in characterizing crystallization information during the molding process.

To improve the heating efficiency and cavity surface temperature uniformity, an optimal design method was developed for the heating system in electrical rapid heat cycle molding mold. First, an electrical rapid heat cycle molding mold was simplified as a single heating cell unit for thermal response analysis based on conformal design theory. Second, a response surface using back propagation neural network was constructed on the ground of initial finite element experiments. Then, a non-dominated sorting genetic algorithm-II combined with the polynomial back propagation neural network model was proposed to capture the Pareto-optimal solutions. Subsequently, the technique for order preference by similarity to ideal solution based on entropy-based weight was adopted as a multi-attribute decision-making method to choose the trade-off optimal design point from the Pareto-optimal set. To gain the optimal design of heating system, the optimized heating cell unit for electrical rapid heat cycle molding mold was calculated and finally mapped into the entire mold. Cavity surface temperature uniformity increased by 17.1%, and heating efficiency increased by 26%. The results show that the temperature distribution uniformity on the mold cavity surface was obviously improved and using this optimization strategy ensured high heating efficiency.