Enhancing Gastrodin Production in Yarrowia lipolytica by Metabolic Engineering.

Gastrodin, 4-hydroxybenzyl alcohol-4-O-ß-D-glucopyranoside, has been widely used in the treatment of neurogenic and cardiovascular diseases. Currently, gastrodin biosynthesis is being achieved in model microorganisms. However, the production levels are insufficient for industrial applications. In this study, we successfully engineered a Yarrowia lipolytica strain to overproduce gastrodin through metabolic engineering. Initially, the engineered strain expressing the heterologous gastrodin biosynthetic pathway, which comprises chorismate lyase, carboxylic acid reductase, phosphopantetheinyl transferase, endogenous alcohol dehydrogenases, and a UDP-glucosyltransferase, produced 1.05 g/L gastrodin from glucose in a shaking flask. Then, the production was further enhanced to 6.68 g/L with a productivity of 2.23 g/L/day by overexpressing the key node DAHP synthases of the shikimate pathway and alleviating the native tryptophan and phenylalanine biosynthetic pathways. Finally, the best strain, Gd07, produced 13.22 g/L gastrodin in a 5 L fermenter. This represents the highest reported production of gastrodin in an engineered microorganism to date, marking the first successful de novo production of gastrodin using Y. lipolytica.

Elevated circulating inflammatory biomarker levels in the SIRT1-NF-κB-sCD40L pathway in patients with acute myocardial infarction: a case-control study.

BACKGROUND: Inflammation plays a key role in atherosclerosis development and progression. However, the role of novel inflammatory biomarker pathways, namely the SIRT1-NF-κB-sCD40L, in the etiopathogenesis of human atherosclerosis remains undefined. This study was designed to evaluate the changes and clinical implications of these inflammatory mediators in the plasma of patients with acute myocardial infarction (AMI). METHODS: The peripheral arterial blood of 88 participants (68 patients with AMI and 20 age-matched controls), was drawn prior to performing coronary angiography (CAG). The SIRT1, NF-κB, and sCD40L plasma levels were quantified using ELISA. Spearman's analysis was used to evaluate the correlation between the three inflammatory markers, while Pearson's test assessed their potential correlation with cardiac troponin T (TNT) levels. Sensitivity, specificity, and area under the ROC curve (AUC) were calculated as measures of diagnostic accuracy. RESULTS: Patients with AMI showed higher levels of circulating SIRT1, NF-κB, and sCD40L compared to the age-matched controls (p < 0.05). However, the plasma concentrations of these three inflammatory mediators did not differ between the ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients. Additionally, in patients with AMI, the SIRT1 level was positively correlated with NF-κB and sCD40L levels (p < 0.001). Likewise, the levels of SIRT1, NF-κB and sCD40L were positively correlated with TNT levels (p < 0.001). More importantly, the ROC analysis showed that the diagnostic accuracy of AMI was significantly higher when NF-κB or sCD40L level was used in combination with TNT levels (p < 0.05). CONCLUSIONS: The levels of the circulating inflammatory biomarkers, including SIRT1, NF-κB, and sCD40L, were significantly elevated in patients with AMI. These novel biomarkers can improve the diagnostic accuracy of AMI when combined with TNT.KEY MESSAGESAMI is a potentially lethal CAD and is the leading cause of mortality and morbidity worldwide. Inflammation plays a key role in atherosclerosis development and progression. The levels of the circulating novel inflammatory biomarkers, including SIRT1, NF-κB, and sCD40L, were significantly elevated in patients with AMI.The SIRT1 level was positively correlated with NF-κB and sCD40L levels in patients with AMI.The levels of SIRT1, NF-κB and sCD40L were positively correlated with TNT levels.The ROC analysis showed that the diagnostic accuracy of AMI was significantly higher when NF-κB or sCD40L level was used in combination with TNT levels.SIRT1/NF-κB/sCD40L axis inhibition is a potential new target for AMI treatment.

Association between physical activity and resistant hypertension in treated hypertension patients: analysis of the national health and nutrition examination survey.

INTRODUCTION: Current guidelines suggest that regular aerobic training might lower blood pressure in hypertensive individuals. However, evidence linking resistant hypertension (RH) with total daily physical activity (PA), including work-, transport-, and recreation-related PA, is limited. Therefore, this study assessed the association between daily PA and RH. METHOD: A cross-sectional study was conducted using data acquired from a nationwide survey in the US (the National Health and Nutrition Examination Survey, NHANES). The weighted prevalence of RH was calculated, and moderate and vigorous daily PA was assessed using the Global Physical Activity Questionnaire (GPAQ). A multivariate logistic regression model determined the association between daily PA and RH. RESULTS: A total of 8,496 treated hypertension patients were identified, including 959 RH cases. The unweighted prevalence of RH among treated hypertension cases was 11.28%, while the weighted prevalence was 9.81%. Participants with RH had a low rate of recommended PA levels (39.83%), and daily PA and RH were significantly associated. PA exhibited significant dose-dependent trends with a low probability of RH (p-trends < 0.05). Additionally, participants with sufficient daily PA had a 14% lower probability of RH than those with insufficient PA [fully adjusted odds ratio (OR) = 0.86; 95% confidence interval (CI) = 0.74-0.99). CONCLUSION: The present study revealed that RH has an incidence of up to 9.81% in treated hypertension patients. Hypertensive patients tended to be physically inactive, and insufficient PA and RH were significantly associated. Sufficient daily PA should be recommended to reduce the RH probability among treated hypertension patients.

Rural Spatial Differentiation and Revitalization Approaches in China: A Case Study of Qingdao City.

Rural revitalization, as a major strategy with the goal of realizing the overall development of strong agriculture industries, beautiful rural areas, and rich farmers, is an effective way of alleviating the loss of talent, land, capital, and other elements in rural areas and a possible cure for "rural diseases". However, "rural diseases" faced by villages are very different, and thus exploring suitable strategies for rural revitalization is beneficial to the implementation of rural revitalization strategies and the promotion of urban-rural integration. Based on location theory, this paper constructs a point-axis-domain three-dimensional spatial location theory model that integrates market location, traffic location, and natural location and combines the coupling coordination model to comprehensively study the vitality and development directions of Qingdao's rural areas. Results found that Qingdao's high-level and medium-high-level coupling coordination areas are the main types of coupling coordination, accounting for 45.19% and 47.48%, respectively. Based on the development status of Qingdao, this study explores development directions for rural revitalization poles as well as high-level, medium-high-level, and medium-level coupling coordination areas and suggests the following: rural revitalization poles should play a demonstration role in rural revitalization in terms of industrial development, rural civilization, social governance, public service construction, etc.; high-level coupling coordination areas should focus on building modern hi-tech agriculture and rural marine tourism industries; medium-high-level coupling coordination areas should strengthen the building of satellite towns and promote industrial transformation and upgrading; medium-level coupling coordination areas should actively develop ecological environment conservation models and establish a characteristic mountainous eco-tourism industry. Thus, the findings provide important scientific reference for the implementation of rural revitalization.