922 research outputs found

    Efficacy and safety of olmesartan medoxomil‐amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single‐arm, multi‐center, real‐world study

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    Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients’ and physicians’ satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug‐related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM‐AML tablet is one of the best antihypertensive agents in patients with essential hypertension

    A short‐chain carbonyl reductase mutant is an efficient catalyst in the production of (R)‐1,3‐butanediol

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    Abstract R‐1,3‐butanediol (R‐1,3‐BDO) is an important chiral intermediate of penem and carbapenem synthesis. Among the different synthesis methods to obtain pure enantiomer R‐1,3‐BDO, oxidation–reduction cascades catalysed by enzymes are promising strategies for its production. Dehydrogenases have been used for the reduction step, but the enantio‐selectivity is not high enough for further organic synthesis efforts. Here, a short‐chain carbonyl reductase (LnRCR) was evaluated for the reduction step and developed via protein engineering. After docking result analysis with the substrate 4‐hydroxy‐2‐butanone (4H2B), residues were selected for virtual mutagenesis, their substrate‐binding energies were compared, and four sites were selected for saturation mutagenesis. High‐throughput screening helped identify a Ser154Lys mutant which increased the catalytic efficiency by 115% compared to the parent enzyme. Computer‐aided simulations indicated that after single residue replacement, movements in two flexible areas (VTDPAF and SVGFANK) facilitated the volumetric compression of the 4H2B‐binding pocket. The number of hydrogen bonds between the stabilized 4H2B‐binding pocket of the mutant enzyme and substrate was higher (from four to six) than the wild‐type enzyme, while the substrate‐binding energy was decreased (from −17.0 kJ/mol to −29.1 kJ/mol). Consequently, the catalytic efficiency increased by approximately 115% and enantio‐selectivity increased from 95% to 99%. Our findings indicate that compact and stable substrate‐binding pockets are critical for enzyme catalysis. Lastly, the utilization of a microbe expressing the Ser154Lys mutant enzyme was proven to be a robust process to conduct the oxidation–reduction cascade at larger scales

    Impact of caregivers' psychological and caregiving status on recruitment, conversion, and retention in stem cell therapy trials for cerebral palsy: A prospective survey analysis

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    Abstract Aim To examine specific correlates that may affect retention outcomes of neural stem cell therapy trials in families screened for cerebral palsy. Design A prospective correlational study. Methods Primary caregivers completed surveys of psychological resilience, care burden and family caregiver tasks. The overall data and differences between groups were analysed and compared. Results Resilience was negatively correlated with the care ability and closely related to the monthly household income and educational level of the caregivers. Factors affecting the final retention rate included the type of disease, number of combined disorders, monthly household income, primary caregivers' education level and resilience. Conclusion Economic level, literacy and psychological status may affect trial retention. These findings can provide tips for preparing for subsequent screening, identification and intervention in stem cell clinical trials. Implication for the Profession and/or Patient Care The study results may provide nursing care tips to make recruitment more efficient, reduce trial costs, support patient‐centredness and accelerate trial progress. No Patient or Public Contribution The target population involves the primary caregivers of children living with cerebral palsy. However, neither patients nor the public contributed to the design or conduct of the study, analysis, or interpretation of the data, or preparation of the manuscript

    The Design and Technology Development of the JUNO Central Detector

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    International audienceThe Jiangmen Underground Neutrino Observatory (JUNO) is a large scale neutrino experiment with multiple physics goals including deter mining the neutrino mass hierarchy, the accurate measurement of neutrino oscillation parameters, the neutrino detection from the super nova, the Sun, and the Earth, etc. JUNO puts forward physically and technologically stringent requirements for its central detector (CD), including a large volume and target mass (20 kt liquid scintillator, LS), a high energy resolution (3% at 1 MeV), a high light transmittance, the largest possible photomultiplier (PMT) coverage, the lowest possible radioactive background, etc. The CD design, using a spherical acrylic vessel with a diameter of 35.4 m to contain the LS and a stainless steel structure to support the acrylic vessel and PMTs, was chosen and optimized. The acrylic vessel and the stainless steel structure will be immersed in pure water to shield the radioactive back ground and bear great buoyancy. The challenging requirements of the acrylic sphere have been achieved, such as a low intrinsic radioactivity and high transmittance of the manufactured acrylic panels, the tensile and compressive acrylic node design with embedded stainless steel pad, one-time polymerization for multiple bonding lines. Moreover, several technical challenges of the stainless steel structure have been solved: the production of low radioactivity stainless steel material, the deformation and precision control during production and assembly, the usage of high strength stainless steel rivet bolt and of high friction efficient linkage plate. Finally, the design of the ancillary equipment like the LS filling, overflowing and circulating system was done

    The relationship between the interactive behavior of industry–university–research subjects and the cooperative innovation performance: The mediating role of knowledge absorptive capacity

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    IntroductionIndustry–university–research cooperation innovation, which is often characterized by resource complementarity and the sharing technology, has become one of the most preferred innovation cooperation methods for enterprises. However, various problems still occur in the process of industry–university–research cooperations, such as poor innovation performance and difficulty in sustaining cooperation. Existing studies mostly focus on the macroscopic perspectives of geographic location, cooperation scale, concentration, and diversification of industry–university–research cooperation subjects, and fail to explore the microscopic behavioral mechanisms.MethodsTherefore, this paper establishes the interactive behavior of industry–university–research subjects and defines its concepts and dimensions in an attempt to provide a mechanism for improving the cooperative innovation performance of industry–university–research from the micro-behavioral perspective. On the basis of theoretical analysis, this paper develops a model of the relationship between cooperative trust, cooperative communication, and cooperative innovation performance for interactive behavior, while exploring the mediating role of knowledge absorptive capacity. The model was validated by stepwise regression using data from 325 questionnaires.ResultsThe paper found that cooperative trust and cooperative communication in the cooperative interactive behavior of industry–university–research positively contribute to the improvement of cooperative innovation performance. Knowledge absorptive capacity plays a partially mediating role between the interactive behaviors and cooperative innovation performance. More specifically, knowledge absorptive capacity partially mediates cooperative communication in cooperative innovation performance and completely mediates cooperative trust in cooperative innovation performance. The results are largely consistent with the results of the heterogeneity analysis of the sample.DiscussionThis paper not only explains why the cooperative innovation performance of industry–university–research is poor from the perspective of interactive behavior, but also enriches the research perspective of industry–university–research and provides theoretical support for enterprises to optimize the relationship between industry, university, and research institutes

    Identification of Key Genes Induced by Different Potassium Levels Provides Insight into the Formation of Fruit Quality in Grapes

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    Inadequate potassium (K) availability is a common abiotic stress that limits the growth and quality of fruit trees. Few studies have investigated the physiological and molecular responses of grapes at different potassium levels. In this study, an integrated approach was developed for grapevines grown at four different potassium fertilization levels [0 (K0-CK), 150 (K150), 300 (K300), and 450 (K450) g/plant] in combination with metabolite measurements and transcript analysis. The results showed that different K levels affected the accumulation of sugars and anthocyanins in the fruit. At 78 days after bloom (DAB), the K150, K300, and K450 treatments increased soluble sugar content by 37.39%, 31.10% and 32.59%, respectively, and anthocyanin content by 49.78%, 24.10%, and 13.06%, respectively, compared to K0. Weighted gene co-expression network analysis (WGCNA) of DEGs identified a network of 11 grapevines involved. During fruit development, potassium application promoted the accumulation of anthocyanins and sugars in fruit by regulating the up-regulation of GST, AT, UFGT and SPS, HT, PK gene expressions. These results suggest that potassium deficiency inhibits anthocyanin and sugar metabolism. In addition, it promotes the up-regulation of KUP expression, which is the main cause of K accumulation in fruits. Together, our data revealed the molecular mechanism in response to different K levels during fruit quality formation and provides the scientific foundation for the improvement of fruit quality by adding K fertilizer

    Influence of Li+/Al3+ on the corrosion behavior of Li-Al layered double hydroxides (LDHs) film on LA51 magnesium alloys

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    A hierarchical superhydrophobic Al-Li layered double hydroxide (LDH) films with different Li+/Al3+ molar ratios of 1:1, 1:2, 2:1, pH value of 11.5 and reaction temperature of 125 °C, have been fabricated on the surface of Mg-5Li-1Al (LA51) alloys by hydrothermal method following the characteristics of controllable cation structure and exchangeable anion between layers. The properties of the films were investigated by X-ray diffractometer (XRD), scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). XRD and SEM results indicate that the Al-Li LDH films are successfully prepared on LA51 alloys. The contact angle (CA) was measured to be about 100.7°, indicating that the surface wettability of the film converted from hydrophilic to hydrophobic by surface modification. The corrosion resistance of Al-Li LDH films was evaluated by Tafel polarization curve and electrochemical impedance spectroscopy (EIS). Surprisingly, Tafel polarization curve and EIS test reveal that the Al-Li LDH films prepared at the molar ratio of Li+/Al3+ 1:2, pH 11.5 and temperature 125 °C have better corrosion resistance in 0.1 M NaCl neutral solution. In addition, the formation mechanism and corrosion mechanism of the films on the surface of LA51 alloy are also proposed. It provides innovative synthetic materials and novel design ideas for the preparation of high-efficiency anti-corrosion coatings on LA51 alloys, whose application can be extended in industrial fields

    Cooperation between dual metal atoms and nanoclusters enhances activity and stability for oxygen reduction and evolution

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    We have achieved the synthesis of dual-metal single atoms and atomic clusters that co-anchor on a highly graphitic carbon support. The catalyst comprises Ni4 (and Fe4) nanoclusters located adjacent to the corresponding NiN4 (and FeN4) single-atom sites, which is verified by systematic X-ray absorption characterization and density functional theory calculations. A distinct cooperation between Fe4 (Ni4) nanoclusters and the corresponding FeN4 (NiN4) atomic sites optimizes the adsorption energy of reaction intermediates and reduces the energy barrier of the potential-determining steps. This catalyst exhibits enhanced oxygen reduction and evolution activity and long-cycle stability compared to counterparts without nanoclusters and commercial Pt/C. The fabricated Zn-air batteries deliver a high power density and long-term cyclability, demonstrating their prospects in energy storage device applications.Z.W. thanks Soochow University, China, for providing financial support (2111500622). This work was also supported by National Research Foundation-Competitive Research Programs (NRF-CRP22-2019-0007) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022M3H4A4086103). The experiments at PAL were supported in part by MOST and POSTECH. Y.L. acknowledges the Open Project of Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of Education, Shaanxi University of Science and Technology (KFKT2023-01)
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