Genome-Scale Metabolic Model of Actinosynnema pretiosum ATCC 31280 and Its Application for Ansamitocin P-3 Production Improvement

Actinosynnema pretiosum ATCC 31280 is the producer of antitumor agent ansamitocin P-3 (AP-3). Understanding of the AP-3 biosynthetic pathway and the whole metabolic network in A. pretiosum is important for the improvement of AP-3 titer. In this study, we reconstructed the first complete Genome-Scale Metabolic Model (GSMM) Aspm1282 for A. pretiosum ATCC 31280 based on the newly sequenced genome, with 87% reactions having definite functional annotation. The model has been validated by effectively predicting growth and the key genes for AP-3 biosynthesis. Then we built condition-specific models for an AP-3 high-yield mutant NXJ-24 by integrating Aspm1282 model with time-course transcriptome data. The changes of flux distribution reflect the metabolic shift from growth-related pathway to secondary metabolism pathway since the second day of cultivation. The AP-3 and methionine metabolisms were both enriched in active flux for the last two days, which uncovered the relationships among cell growth, activation of methionine metabolism, and the biosynthesis of AP-3. Furthermore, we identified four combinatorial gene modifications for overproducing AP-3 by in silico strain design, which improved the theoretical flux of AP-3 biosynthesis from 0.201 to 0.372 mmol/gDW/h. Upregulation of methionine metabolic pathway is a potential strategy to improve the production of AP-3

Association of glucocorticoid receptor gene polymorphism and occupational stress with hypertension in desert petroleum workers in Xinjiang, China

Abstract Background The aim of this study was to investigate the occupational stress and hypertension in desert petroleum workers in Xinjiang, and to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. Methods Using cluster sampling, 1280 desert petroleum workers of 3 petroleum fields in Xinjiang Karamay were randomly selected as the target group for this study. According to the inclusion criteria, a total of 1080 workers were included as the baseline for this study. We followed these workers for 2 years to investigate their occupational stress and hypertension. The polymorphism of GR gene was detected by polymerase chain reaction-restriction fragment length polymorphism. We applied appropriate statistical methods to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. Results After 2 years of follow-up, there were 995 desert petroleum workers in the queue. The study showed that the incidence of hypertension in desert petroleum workers were 19.4%. Compared with the baseline data, the level of occupational stress increased, and with the increase of occupational stress, the incidence of hypertension was gradually increasing. A positive relationship was observed in the GR BCL1 gene polymorphisms and hypertension. Relative to the CC genotype, carries of the GG genotype had a significantly higher risk of hypertension (OR = 2.830). With the combination of genotype CG and GG, carries of CG and GG increased the risk of hypertension (adjusted OR = 2.238, 95%CI:1.104–4.940). There was no significant association between GR G678S gene polymorphisms and hypertension. Conclusion GR gene polymorphism and occupational stress of desert petroleum workers were important risk factors for hypertension

Prognostic and clinicopathological value of Beclin-1 expression in hepatocellular carcinoma: a meta-analysis

Abstract Background The abnormal expression of Beclin-1 has recently been investigated in a variety of tumors. However, previous studies have obtained contradicting results regarding the clinical and prognostic value of Beclin-1 in hepatocellular carcinoma (HCC). We performed a meta-analysis to clarify the prognostic value of Beclin-1 and its correlations with clinical pathological parameters in HCC. Methods Relevant studies were systematically retrieved from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wan Fang and Chinese VIP databases. We used the Newcastle-Ottawa scale (NOS) to estimate the quality of the involved studies. Results Ten eligible studies with 1086 HCC patients were included in this study. Our results showed that decreased Beclin-1 expression in HCC related to histological grade [poor-undifferentiated vs. well-moderate: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.65–3.32, P < 0.00001]. The pooled hazard ratio (HR) (HR = 1.43, 95% CI = 1.17–1.75, P = 0.0004) indicated that decreased Beclin-1 expression correlated with poor overall survival (OS). Conclusions This meta-analysis indicated that decreased Beclin-1 expression might relate to poor differentiation and unfavorable outcome in HCC

Analysis of Occupational Stress and Its Relationship with Secretory Immunoglobulin A in the Xinjiang Plateau Young Military Recruits

Background. With the continuous improvement of the modernization of the Chinese military and the major adjustments made by the state to the recruitment policy, the newly recruited military undergone multiple pressures such as targeted high-intensity military training and environmental changes. The mental health of military has become a crucial factor of improving the fighting capacity effectiveness of the troops. Objectives. To explore occupational stress of young recruits in the Xinjiang plateau environment during their basic military training period and analyze the relationship between occupational stress and secretory immunoglobulin A (sIgA) levels. Methods. Using multistage stratified cluster random sampling, 625 recruits stationed at Xinjiang plateau command in 2014 were enrolled as subjects. Occupational stress was assessed by the Occupational Stress Inventory Revised Edition (OSI-R). sIgA in saliva was quantified by enzyme-linked immunosorbent assay. The resulting data were analyzed using descriptive statistics, nonparametric tests, and correlation analysis. Results. Based on demographic characteristics, occupational stress was higher in the urban group than the rural group, coping ability for stress was greater in individuals who were students before joining the army than nonstudents, occupational stress was higher in smokers than nonsmokers, and coping ability for stress was higher in nonsmokers than in smokers (all P0.05). Salivary sIgA level was higher in the high occupational stress group than in the low stress group (P<0.01). Salivary sIgA was positively correlated with scores on the occupational role and personal strain questionnaires (rs=0.229, rs=0.268, P<0.01). Conclusion. Demographic characteristics influenced occupational stress among young recruits in cold and high-altitude area. Further, there were some relationships between occupational stress and salivary sIgA in young military recruits