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The sesquiterpene α-humulene has been shown to have anti-inflammatory and anticancer activities, which has led to its vast application potential in medicine. However, α-humulene production methods including phytoextraction and chemical synthesis currently were limited to low yield, high costs, and expensive catalysts, which cannot meet the increasing market demand. In this study, Yarrowia lipolytica was developed as a robust cell factory for α-humulene production. The peroxisome in Y. lipolytica was first engineered to boost the synthesis of the sesquiterpene α-humulene. By compartmentalization of the α-humulene biosynthesis pathway, improving ATP and acetyl-CoA supply, and optimizing the gene copy numbers of rate-limiting enzymes, the engineered strain GQ2012 could produce 3.2 g/L α-humulene in a 5 L bioreactor, the highest α-humulene titer reported so far. Our study provides a valuable reference for highly sustainable production of terpenoids by peroxisome engineering in Y. lipolytica.

Arachidonic acid is an essential ω-6 polyunsaturated fatty acid, which plays a significant role in cardiovascular health and neurological development, leading to its wide use in the food and pharmaceutical industries. Traditionally, ARA is obtained from deep-sea fish oil. However, this source is limited by season and is depleting the already threatened global fish stocks. With the rapid development of synthetic biology in recent years, oleaginous fungi have gradually attracted increasing attention as promising microbial sources for large-scale ARA production. Numerous advanced technologies including metabolic engineering, dynamic regulation of fermentation conditions, and multiomics analysis were successfully adapted to increase ARA synthesis. This review summarizes recent advances in the bioengineering of oleaginous fungi for ARA production. Finally, perspectives for future engineering approaches are proposed to further improve the titer yield and productivity of ARA.

From November 1,2018 to January 31,2019 (OP

Non-homologous end-joining (NHEJ)-mediated random integration in

The sesquiterpene α-humulene has been shown to have anti-inflammatory and anticancer activities, which has led to its vast application potential in medicine. However, α-humulene production methods including phytoextraction and chemical synthesis currently were limited to low yield, high costs, and expensive catalysts, which cannot meet the increasing market demand. In this study

This study aimed to investigate relapse risk factors in children with primary nephrotic syndrome (PNS) for prevention and early intervention via logistic regression. One hundred thirty-seven children with PNS were enrolled in this study. Clinical variables were analyzed by single-factor and multiple regression analysis to establish the regression equation. The predictive ability of the regression equation was investigated by the receiver operating characteristic curve (ROC). Files of 17 patients were lost, and 120 patients were enrolled finally in the study, among whom 55 cases (45.8%) had frequently relapsed. Single-factor analysis and multiple regression analysis revealed that concurrent infection on first onset, irregular glucocorticoid therapy, severe hypoalbuminemia, and persistent severe hyperlipidemia were the significant risk factors for frequent relapse on PNS (P.05), among which infection remained to be the main inductive factor. Among the 4 indicators, serum albumin had the best diagnostic efficacy based on the area under the ROC curve (0.933), sensitivity (89.09%), and specificity (81.54%). The area under curve, sensitivity, and specificity for the combined diagnostic model of the 4 indices were 97.8%, 98.18%, and 90.77%, respectively, which had good predictive power for the relapse of patients. Concurrent infection, irregular glucocorticoid therapy, severe hypoalbuminemia, and persistent severe hyperlipemia were all the risk factors for PNS relapse. The established logistic regression model based on these factors above is reliable for predicting frequent PNS relapse. Much attention should be paid to these critical factors, and early intervention should be taken to reduce the incidence of relapse.

Aims. The over-the-scope clip (OTSC) has recently emerged as a new endoscopic device for treating gastrointestinal bleeding, perforations, fistulas, and leaks. A modified OTSC device (full-thickness resection device, FTRD) has been widely used for endoscopic full-thickness resection. However, there is less experience regarding the indications and methods for OTSC removal. We aimed to summarize the existing methods and indications for OTSC removal. Methods. We searched PubMed, Cochrane Library, and ClinicalTrials.gov to identify relevant publications on OTSC removal. The details of OTSC removal, including the methods, indications, success rates, adverse events, and failure causes, were extracted and summarized. A meta-analysis of pooled success rates was conducted using STATA 15.0. Results. Eighteen articles were included. The reported methods for OTSC removal included (1) grasping forceps, (2) the Nd : YAG laser, (3) argon plasma coagulation, (4) the remOVE system, (5) endoscopic mucosal resection/endoscopic submucosal dissection, and (6) ice-cold saline solution. Indications for OTSC removal were (1) poor healing, (2) OTSC misplacement, (3) repeat biopsy/therapy or further treatment, (4) adverse events after OTSC implantation, (5) removal after recovery, and (6) patient wishes. The pooled success rate of OTSC removal was 89% in patients treated with the remOVE system. Minor bleeding, superficial thermal damage, and superficial mucosal tears were common adverse events. Mucosal overgrowth was the main cause of OTSC removal failure. Conclusions. The remOVE system is the best investigated method, with sufficient efficacy and safety for OTSC removal. This is the first systematic review of OTSC removal and provides significant guidance for clinical practice.

Recurrent oral ulcer (ROU) is a common disease, and seriously affects the quality of life. There are obvious advantages in improving clinical symptoms, maturity of regenerated mucosa and healing quality, and reducing recurrence rate of ROU. But there is a lack of sufficient experimental data. Tongue diagnosis is an important basis for disease differentiation, syndrome differentiation and treatment, and clinical efficacy monitoring. Tongue coating can reflect the local and global pathological state. The back of the tongue forms a relatively complete and independent microecosystem. The change of tongue body may be a colony indicator for ROU. The pathogenicity of colonized bacteria in ROU may be used as a potential diagnostic marker. Based on microecology, the author reviews the pathogenesis of ROU and the correlation between microecology and both the therapeutic effect and mechanism of ROU in traditional Chinese medicine. DOI: 10.11855/j.issn.0577-7402.2018.09.15

Glucocorticosteroid (GC) is one of the most effective drugs available for the treatment of primary nephrotic syndrome (PNS) in children. However, some patients show little or no response to GC. The purpose of our research was to observe and describe the different levels of histone deacetylase-2 (HDAC2) expression in peripheral blood lymphocytes in children with PNS compared with various responses to the GC treatment, with the primary aim to assess the correlation between HDAC2 and GC resistance in PNS children. Forty-eight patients with PNS suffering from their first attack prior to GC treatment were chosen as subjects. They were divided into two groups, those who had steroid-sensitive nephrotic syndrome (SSNS; n = 25) and those with steroid-resistant NS (SRNS; n = 23), according to their response to a 6-week course of oral prednisone. Twenty healthy children from the Physical Examination Center in the hospital served as the control group; Peripheral blood was collected at different time points prior to GC treatment and after regular therapy. RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA) techniques were adopted to analyze HDAC2 mRNA, protein expression, and activity, respectively, in peripheral blood lymphocytes. The level of interleukin-8 (IL-8) in serum was measured by an ELISA. Prior to GC treatment, HDAC2 expression level and activity were lower in the SRNS group than in the SSNS and control group. A statistically significant difference in HDAC2 expression and activity were observed after GC treatment between these groups, with HDAC2 expression and activity lower in the SRNS group than in the SSNS and control groups. In the SSNS group, the expression and activity of HDAC2 were higher following GC treatment than prior to GC treatment. There was a clear difference in HDAC2 expression and activity of SRNS at the different time points. No statistically significant difference was found between the two groups. The pre-treatment and post-treatment serum IL-8 levels in the SRNS group were significantly higher than those in the SSNS group. HDAC2 from children with PNS before GC treatment and after regular therapy for 6 weeks was negatively correlated with serum IL-8 level. The GC effect was influenced by the HDAC2 expression and activity, leading to decreased serum IL-8 levels in children with PNS. HDAC2 seems to be one of the markers of GC resistance in children with PNS.

BACKGROUND: Genome-wide association studies on components of the one-carbon metabolic pathway revealed that human vitamin B12 levels could be significantly influenced by variations in the fucosyltransferase 2 (FUT2), cubilin (CUBN), and transcobalamin-I (TCN1) genes. An altered vitamin B12 level is an important factor that disturbs the homeostasis of the folate metabolism pathway, which in turn can potentially lead to the development of congenital heart disease (CHD). Therefore, we investigated the association between the variants of vitamin B12-related genes and CHD in Han Chinese populations. METHODS AND RESULTS: Six variants of the vitamin B12-related genes were selected for analysis in two independent case-control studies, with a total of 868 CHD patients and 931 controls. The variant rs11254363 of the CUBN gene was associated with a decreased risk of developing CHD in both the separate and combined case-control studies. Combined samples from the two cohorts had a significant decrease in CHD risk for the G allele (OR = 0.48, P = 1.7×10⁻⁵) and AG+GG genotypes (OR = 0.49, P = 4×10⁻⁵), compared with the wild-type A allele and AA genotype, respectively. CONCLUSIONS: Considering the G allele of variant rs11254363 of the CUBN gene was associated with an increased level of circulating vitamin B12. This result suggested that the carriers of the G allele would benefit from the protection offered by the high vitamin B12 concentration during critical heart development stages. This finding shed light on the unexpected role of CUBN in CHD development and highlighted the interplay of diet, genetics, and human birth defects.

Aims Elevated homocysteine levels are known to be a risk factor for congenital heart disease (CHD), but the mechanism underlying this effect is unknown. During early embryonic development, homocysteine removal is dictated exclusively by the MTR activity. To examine the role of MTR in CHD risk, we identified genetic variants in MTR and investigated the mechanisms that affect its expression levels and that increase the risk of CHD in Chinese populations. Methods and results The association between regulatory variants of the MTR gene and CHD was examined in three independent case–control studies in a total of 2340 patients with CHD and 2270 controls. The functional consequences of these variants were demonstrated using dual-luciferase assays, real-time polymerase chain reaction (PCR), electrophoretic mobility shift assays, surface plasma resonance, chromatin immunoprecipitation, and bisulfite sequencing, as well as by a group of predicted microRNAs using a gene reporter system. Two regulatory variants of MTR , −186T>G and +905G>A, were associated with an increased risk of CHD in both the separate and combined case–control studies (−186GG P = 1.32 × 10−9; +905AA P = 6.35 × 10−14). Compared with the major allele, the −186G allele exhibited significantly lower promoter activity, decreased hnRNA and mRNA levels, reduced transcription factor binding affinity, and a more highly methylated promoter. The +905A allele exhibited a statistically stronger binding affinity to functional microRNAs that down regulate MTR expression at the translational level. Both of the minor alleles were correlated with elevated plasma homocysteine concentrations, indicating a genetic component for hyperhomocysteinaemia. Conclusions Regulatory variants of the MTR gene increase CHD risk by reducing MTR expression and inducing the homocysteine accumulation and elevation.