Effect of a combination of donepezil tablets and butylphthalide soft capsules on neurological function in dementia patients, and its effect on serum inflammatory factors

Purpose: To determine the effect of combined use of donepezil tablets and butylphthalide soft capsules in the treatment of patients with vascular dementia, and its effect on serum inflammatory factor levels and neurological functional recovery of patients.Methods: 120 patients with vascular dementia were selected and assigned to group A (n = 60) and group B (n = 60). All patients were treated with donepezil tablets, while patients in group A were, in addition, treated with butylphthalide soft capsules. Mini mental state examination (MMSE) scores, clinical dementia rating scale (CDRS) scores, activities of daily living (ADL) scores, incidence of adverse reactions, serum inflammatory factor levels and neurological functional recovery were determined.Results: There was significantly higher MMSE score in group A than in B, while CDRS score was lower in group A. The ADL scores and inflammatory factor levels were lower in group A than in B (p < 0.001), while neurological functional recovery was markedly better in A (p < 0.001). Incidents of unwanted events were comparable in groups A and B, and there were no serious complications in the patients.Conclusion: The combination therapy of donepezil tablets and butylphthalide soft capsules reduces inflammatory factor levels and improved cognitive level and quality of life of patients with vascular dementia. It also produces good neurological functional recovery and low incidence of adverse reactions. Therefore, this treatment strategy has potentials for the management of vascular dementia

Spatial scale effect of surface routing and its parameter upscaling for urban flood simulation using a grid‐based model

Urban catchments are characterized by a wide variety of complex juxtapositions and surface compositions that are linked to multiple overland flow paths. Their extremely high spatial heterogeneity leads to great sensitivity of hydrologic simulation to the scale variation of calculation units. Although extensive efforts have been made for investigating the scale effects and indicate its significance, less is understood of how routing features vary with spatial scales and further how the variation of routing features influences the hydrological response. In this paper, a grid-based distributed urban hydrological model is applied to study spatial scale effects ranging from 10 to 250 m. Two parameters are proposed to quantitatively depict the routing features of overland flow specified for impervious and pervious areas. The results show that routing features are quite sensitive to spatial resolution. Large differences among simulations exist in the infiltration amounts attributed to the combined effects of the two routing parameters, which leads to opposite effects for both total flow volume and peak flow for various rainfall events. The relationship of the key model parameters at different spatial resolutions can be explicitly expressed by corresponding routing features. With this relationship, parameters transfer among different spatial scales can be realized to obtain consistent simulation results. This study further revealed the quantitative relationship between spatial scales, routing features and the hydrologic processes, and enabled accurate and efficient simulations required by real time flooding forecasting and land-atmosphere coupling, while fully taking the advantages of detailed surface information. Plain Language Summary Given the inherent complex underlying surface compositions and overland flow paths in urban areas, underlying high spatial resolution surface data eventually become necessary. Unfortunately, high resolution modelling in urban catchment is still challenging in terms of computational restricts, proper setting up of parameters etc., due to the high spatial heterogeneity. Practical simulation requirements often limit the use of high resolution models, as in the case of real time prediction of urban flooding, the coupling of land-atmosphere processes. Therefore, it is necessary to investigate the scale effects and its mechanism, and then to explore an accommodation approach to enable precise flooding prediction with a coarse model. For grid-based and distributed hydrologic models, the mosaic method can basically eliminate the scale effects on the runoff generation process. However, the scale effects on overland flow routing remain insufficiently understood, and to help understand the scale effects, simulations were performed under five different resolutions, ranging from 10 m to 250 m, for various rainfall events. Two physical parameters are introduced to quantify the scale effects on routing features. Three variables are concurrently calculated to assess the effects on modeling outputs. The results indicate that routing features are sensitive to changes in spatial resolution, which results in opposite effects on simulation results under different rainfall conditions. In conclusion, an accommodation approach is proposed based on the affecting mechanism

Sequence homolog-based molecular engineering for shifting the enzymatic pH optimum

AbstractCell-free synthetic biology system organizes multiple enzymes (parts) from different sources to implement unnatural catalytic functions. Highly adaption between the catalytic parts is crucial for building up efficient artificial biosynthetic systems. Protein engineering is a powerful technology to tailor various enzymatic properties including catalytic efficiency, substrate specificity, temperature adaptation and even achieve new catalytic functions. However, altering enzymatic pH optimum still remains a challenging task. In this study, we proposed a novel sequence homolog-based protein engineering strategy for shifting the enzymatic pH optimum based on statistical analyses of sequence-function relationship data of enzyme family. By two statistical procedures, artificial neural networks (ANNs) and least absolute shrinkage and selection operator (Lasso), five amino acids in GH11 xylanase family were identified to be related to the evolution of enzymatic pH optimum. Site-directed mutagenesis of a thermophilic xylanase from Caldicellulosiruptor bescii revealed that four out of five mutations could alter the enzymatic pH optima toward acidic condition without compromising the catalytic activity and thermostability. Combination of the positive mutants resulted in the best mutant M31 that decreased its pH optimum for 1.5 units and showed increased catalytic activity at pH < 5.0 compared to the wild-type enzyme. Structure analysis revealed that all the mutations are distant from the active center, which may be difficult to be identified by conventional rational design strategy. Interestingly, the four mutation sites are clustered at a certain region of the enzyme, suggesting a potential “hot zone” for regulating the pH optima of xylanases. This study provides an efficient method of modulating enzymatic pH optima based on statistical sequence analyses, which can facilitate the design and optimization of suitable catalytic parts for the construction of complicated cell-free synthetic biology systems

Analysis of the Material Basis of Uric Acid-Lowering Activity of Gynura procumbens Extracts

In order to investigate the material basis of the uric acid-lowering activity of Gynura procumbens, G. procumbens extracts obtained by hot reflux extraction with different ethanol concentrations (0%, 30% and 70%) were evaluated for bioactive ingredients, xanthine oxidase (XOD) inhibitory activity and antioxidant activity. The extracts were analyzed and identified by non-targeted metabolomics. Meanwhile, the 30% and 70% ethanol extracts, which exhibited high XOD inhibitory activity, was evaluated for uric acid-lowering activity in a mouse model of hyperuricemia induced by hypoxanthine and potassium oxonate. The results showed that the XOD inhibitory activity of the extracts was significantly positively correlated with the total flavonoid and total organic acid contents (P < 0.05 and P < 0.01, respectively), and the superoxide anion scavenging capacity was significantly positively correlated with the total phenol content (P < 0.01). A total of 705 differential metabolites were detected by non-targeted metabolomics. In vitro experiments revealed that naringenin, 1,5-dicaffeoylquinic acid, α-linolenic acid, ferulic acid and diosmetin were the key contributors to the uric acid-lowering activity of G. procumbens. Both 30% and 70% ethanol extracts alleviated hyperuricemia by lowering serum uric acid and inhibiting XOD (P < 0.01), and alleviated hyperuricemia-induced oxidative liver damage. In this study, through in vivo and in vitro experiments, the uric acid lowering activity of G. procumbens was verified, and the basis of the uric acid lowering substance was discussed, which could provide a theoretical basis for the preparation of uric acid-lowering substances from G. procumbens and the development of functional foods with uric acid-lowering activity