Natural products containing benzoheterocyclic skeletons are widely found in plants and exhibit various pharmacological activities. To address the current limited availability of these compounds, we ...herein demonstrate the production of benzopyran, furanocoumarins, and pyranocoumarins in Streptomyces xiamenensis by employing prenyltransferases and two substrate-promiscuous enzymes, XimD and XimE. To avoid the degradation in S. xiamenensis, furanocoumarins and pyranocoumarins were also successfully produced in Escherichia coli. The production of linear furanocoumarins (marmesin) and angular pyranocoumarins (decursinol) reached 3.6 and 3.7 mg/L in shake flasks, respectively. To the best of our knowledge, this is the first report of the microbial production of the plant metabolites furanocoumarins and pyranocoumarins. Our study complements the missing link in the biosynthesis of pyranocoumarins by leveraging the catalytic promiscuity of microbial enzymes.
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IJS, KILJ, NUK, PNG, UL, UM
Background
Previous studies have indicated that neurite orientation dispersion and density imaging (NODDI) could be used as a biomarker for detecting microstructural changes of brain.
Purpose
To ...quantitatively evaluate the changes in basal ganglia (BG) and thalamus in Wilson's disease (WD) by NODDI and assess the correlation between parameters and disease severity.
Study Type
Prospective case–control study.
Population
In total, 24 WD patients and 25 age‐ and sex‐matched normal controls were involved in this study.
Field Strength/Sequence
EPI diffusion‐weighted MR images (b‐values = 0, 1000, and 2000 with 30 diffusion gradient directions) were acquired on a 3T scanner.
Assessment
Diffusion data were analyzed using voxel‐based analysis. NODDI indices including intracellular volume fraction (Vic), orientation dispersion index (ODI), and isotropic volume fraction (Viso) were estimated from the BG and thalamus. The disease severity was assessed by two experienced neurologists based on the Global Assessment Scale (GAS). The relative importance of NODDI indices in diagnosing WD and predictive accuracy were also analyzed.
Statistical Testing
The Shapiro–Wilk test, Student's t‐test, χ2 test, Mann–Whitney–Wilcoxon test, Spearman rank correlation coefficient analysis and random‐forest analysis were used for statistical analyses.
Results
The Vic and ODI in the BG and thalamus were significantly lower in WD patients than normal controls, while the Viso in the BG and thalamus were significantly higher (P < 0.01). The Vic in the putamen and ODI in the globus pallidus were negatively correlated with clinical severity (rvic = −0.727, P < 0.001; rodi = −0.705, P < 0.001). The Vic in the putamen was the most valuable predictor for diagnosing WD and the prediction accuracy of NODDI was 95.92%.
Data Conclusion
NODDI can effectively evaluate the changes of microstructure and metabolism during copper deposition in WD, and thus, it is likely to be useful in detecting the changes in the brain of this disease and assessing its progression.
Level of Evidence: 2
Technical Efficacy Stage 2
J. MAGN. RESON. IMAGING 2018;48:423–430.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Porcine ENPP1 mRNA is predominantly expressed in muscle.•ENPP1 overexpression stimulates PRV infection.•ENPP1 knockdown decreases PRV infection.•ENPP1 inhibits PRV- and cGAMP-induced IRF3 activation ...and IFN-β secretion.
In a previous study, we demonstrated that porcine cyclic GMP–AMP (cGAMP) synthase (cGAS) catalyzes cGAMP production and is an important DNA sensor for the pseudorabies virus (PRV)-induced activation of interferon β (IFN-β). Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) has recently been identified as the hydrolase of cGAMP in rodents, but its role in porcine cells is not clear. Our recent study demonstrated that porcine ENPP1 is responsible for the homeostasis of cGAMP and is critical for PRV infection. Porcine ENPP1 mRNA is predominantly expressed in muscle. PRV infection was enhanced by ENPP1 overexpression and attenuated by silencing of ENPP1. During PRV infection, the activation of IFN-β and NF-κB was reduced in ENPP1 overexpressed cells and promoted in ENPP1 knockdown cells. Investigation of the molecular mechanisms of ENPP1 during PRV infection showed that ENPP1 hydrolyzed cGAMP in PRV-infected or cGAMP-transfected cells and inhibited IRF3 phosphorylation, reducing IFN-β secretion. These results, combined with those for porcine cGAS, demonstrate that ENPP1 acts coordinately with cGAS to maintain the reservoir of cGAMP and participates in PRV infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Systemic inflammation and host immunological nutritional status play important roles in the tumorigenesis of malignant cancer. A novel prognostic inflammation score (PIS) based on preoperative serum ...albumin and neutrophil to lymphocyte ratio (NLR) was designed. We explored its prognostic value in ovarian cancer.
143 patients with ovarian cancer were enrolled in this retrospective study. The association of the PIS with clinicopathologic parameters was analyzed. The prognostic significance was determined by univariate and multivariate cox survival analyses.
Both univariate and multivariate analyses showed that NLR and albumin were independent prognostic factors for overall survival (OS) and progression-free survival (PFS). An inverse correlation was observed between the NLR and serum albumin concentration. The novel prognostic inflammation score (PIS) was shown to be a significant predictor for OS and PFS (both P<0.001) according to multivariate analysis. Additionally, low PIS was associated with advanced tumor stage (P<0.001), metastasis (P<0.001) and preoperative high PLR (P<0.001).
The PIS is a novel but promising prognostic score in ovarian cancer. It is a significant prognostic marker adjusted for clinicopathologic characteristics to further identify patients' survival differences.
•NLR and albumin were independent predictors for overall and progression-free survival.•Prognostic inflammation score (PIS) is a novel but promising prognostic score in ovarian cancer.•The PIS carries a significant value for survival prediction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism ...under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Historically, coal has been a primary input driving China's economic growth. However, it has impacted air quality significantly and negatively in the past decades. Among all efforts and measures, the ...Residential Coal Switch Policy (RCSP), implemented in the 1990s, is considered the most fundamental but challenging pathway toward reducing pollution. This study offers a comprehensive policy panorama to policymakers and researchers, explaining the dynamic evolution of the RCSP under varying objectives and constraints. Based on 66 policy documents issued by the central government during the years 2012–2019, the study reviews the RCSP systematically and presents three development stages. We create an index to measure policy-enforcement intensity at each stage and find that policymakers have become more sophisticated in identifying specific target groups, increasing the use of target-management tools over time. Results indicate that most of the Beijing-Tianjin-Hebei and surrounding areas have achieved and exceeded established targets. Command and control, financial support, competitive funds, and residential willingness to pay for air quality are the primary factors related to achievement. Future challenges are also presented, including the unsustainability of subsidies, the absence of building-reconstruction investment, and the scarcity of clean energy.
•We offer a comprehensive policy panorama to explain the evolution of the RCSP.•We create an index to measure policy-enforcement intensity at three development stages.•Most of the BTH and surrounding areas have achieved and exceeded established targets.•We discussed the driving factors and challenges of RCSP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hydrogen is a promising alternative energy source for sustainable development worldwide. Despite being the world's largest hydrogen producer, China's hydrogen energy development is uneven across ...regions and sectors. The lack of a comprehensive and systematic analysis makes it difficult for policymakers to identify critical areas and links for targeted action. This study aims to establish a comprehensive multi-indicator framework based on a supply-demand-policy model to rank the city's hydrogen development potential. Findings are as follows. First, demand, supply, and policy environment shape the hydrogen market. Second, the development potential of hydrogen varies considerably across regions, and regional development is dependent largely on leading cities. Third, four hydrogen development patterns have been identified: advantage-demonstration, policy-guided, market-driven, and potential-enhancing. This research provides theoretical support and practical guidance for building a hydrogen-based society and may also be applied to similar energy sources.
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•This study offers a panorama of China's hydrogen industry.•Demand, supply, and policy environment shape China's hydrogen market.•A multi-criteria economic analysis framework is established to evaluate the potential rankings of hydrogen.•Considerable heterogeneity exists across regions and four patterns are identified.•Governments and investors should explore differentiated development plans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this manuscript, we demonstrated a highly efficient DCJTB emission with delayed fluorescent exciplex TCTA:3P-T2T as the host. For the 1.0% DCJTB doped concentration, a maximum luminance, current ...efficiency, power efficiency and EQE of 22,767 cd m(-2), 22.7 cd A(-1), 21.5 lm W(-1) and 10.15% were achieved, respectively. The device performance is the best compared to either red OLEDs with traditional fluorescent emitter or traditional red phosphor of Ir(piq)3 doped into CBP host. The extraction of so high efficiency can be explained as the efficient triplet excitons up-conversion of TCTA:3P-T2T and the energy transfer from exciplex host singlet state to DCJTB singlet state.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Digital services of the public sector are regarded as one of the most crucial aspects of the administrative system's reform. However, empirical studies on digital services are insufficient, ...especially for service performance evaluation. This paper establishes a conceptual framework to model service performance with quantity and quality output measures. Based on the panel data of Chinese cities from 2017 to 2020, we employ a one-step stochastic frontier analysis (SFA) to estimate the city's digital government service efficiency (DGSE) and examine its drivers. The findings suggest that the proposed analytical framework is applicable to the public sector performance measurement when quantitative and qualitative outputs are considered. Second, Chinese cities' DGSE levels ranged from 0.149 to 0.999, with a mean of 0.798. The DGSE score also shows significant spatio-temporal heterogeneity, with the eastern area performing best, followed by the middle and western regions, and the northeastern region performing the worst. Further, exogenous factors such as fiscal decentralization, public-private partnership, urban scale, the mayor's ability, and policy intervention substantially affect the DGSE level. The results have significant policy implications for governments' digital transition in the ongoing global digital era.
•A conceptual framework to model service performance is established.•The Chinese city's digital government service efficiency is measured.•The government's service performance shows great spatio-temporal heterogeneity.•The fiscal decentralization, public-private partnership, urban scale, the mayor's ability, and policy intervention are determinants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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