Effects of Active Site Inhibitors on APN-dependent Coronavirus Entry

University of Minnesota M.S. thesis. June 2017. Major: Pharmacology. Advisor: Fang Li. 1 computer file (PDF); v, 41 pages.Aminopeptidase N(APN) has been shown as a receptor of several coronaviruses, such as HCoV-229E, TGEV, CCoV and FeCoV. Bestatin and Actinonin are inhibitors which can block APN enzymatic activity. These inhibitors bind to the catalytic site of APN, while viruses bind to the outer surface of APN. Here we investigate the mechanism of APN inhibition on protein-protein binding, receptor expression and coronavirus entry. We find that these chemical compounds can inhibit the protein-protein interaction between APN and Coronavirus spike; these inhibitors can also regulate APN RNA and protein expression; additionally, these compounds can inhibit the pseudovirus entry of HCoV-229E into human cells at a certain level. Additionally, coronavirus spike-treated human cells show a decrease in APN expression. This phenomenon may reveal an adaptation of cells to the different treatments and conditions. Our research may provide a new potential strategy for antiviral treatment

Recent advances in the repair of degenerative intervertebral disc for preclinical applications

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients’ quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology

Design and Cosimulation of Twelve-Pole Heteropolar Radial Hybrid Magnetic Bearing

This paper presents a twelve-pole heteropolar radial hybrid magnetic bearing (HRHMB) structure. Firstly, the structure and equivalent magnetic circuit (EMC) are designed. And the radial electromagnetic force characteristics are calculated by the EMC model. At the same time, the rationality of EMC model is verified by the finite-element method (FEM) of Magnet software. Then, the 2-D model of the twelve-pole HRHMB is established in Magnet software. The flux density variations of twelve-pole HRHMB and eight-pole HRHMB under different currents are compared by using the FEM. Finally, a method of Magnet-Simulink cosimulation is proposed to analyze the suspension characteristics of the twelve-pole HRHMB and compared with the eight-pole HRHMB. Thus, the effective combination of theoretical analysis, FEM analysis, and Magnet-Simulink cosimulation analysis is realized in the design of HRHMB. The results of Magnet-Simulink cosimulation show that the twelve-pole HRHMB has the advantages of low power consumption, small coupling, large construction dynamic stiffness, and better suspension characteristics than the eight-pole HRHMB

The effect of different evapotranspiration methods on portraying soil water dynamics and ET partitioning in a semi-arid environment in Northwest China

Different methods for assessing evapotranspiration (ET) can significantly affect the performance of land surface models in portraying soil water dynamics and ET partitioning. An accurate understanding of the impact a method has is crucial to determining the effectiveness of an irrigation scheme. Two ET methods are discussed: one is based on reference crop evapotranspiration (ET₀) theory, uses leaf area index (LAI) for partitioning into soil evaporation and transpiration, and is denoted as the ET_ind method; the other is a one-step calculation of actual soil evaporation and potential transpiration by incorporating canopy minimum resistance and actual soil resistance into the Penman–Monteith model, and is denoted as the ET_dir method. In this study, a soil water model, considering the coupled transfer of water, vapor, and heat in the soil, was used to investigate how different ET methods could affect the calculation of the soil water dynamics and ET partitioning in a crop field. Results indicate that for two different ET methods this model varied concerning the simulation of soil water content and crop evapotranspiration components, but the simulation of soil temperature agreed well with lysimeter observations, considering aerodynamic and surface resistance terms improved the ET_dir method regarding simulating soil evaporation, especially after irrigation. Furthermore, the results of different crop growth scenarios indicate that the uncertainty in LAI played an important role in estimating the relative transpiration and evaporation fraction. The impact of maximum rooting depth and root growth rate on calculating ET components might increase in drying soil. The influence of maximum rooting depth was larger late in the growing season, while the influence of root growth rate dominated early in the growing season

Three-year follow-up of a novel orthopedic ward fracture liaison services (OWFLS) model

Objective We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. Methods This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020. We compared rates of bone metabolic index testing, treatment, and adherence; symptomatic improvement; and recurrent fracture between groups. Results Rates of bone metabolism index testing (50% vs. 0%) and medication use (94.2% vs. 64.2%) were significantly higher after OWFLS implementation. There was no significant difference in adherence rates at 3 months between groups (97.3% vs. 93.5%). Adherence rates at 1 and 3 years were better in group B than A (73.5% vs. 51.9%; 57.5% vs. 26%, respectively). Recurrence of bone pain at 1 and 3 years was significantly lower in group B than A (20.4% vs. 46.8%; 45.1% vs. 76.6%, respectively). Conclusions OWFLS improved the detection rate of bone metabolism indicators, treatment rate, and patient adherence and reduced recurrence of bone pain. OWFLS may be suitable for settings lacking human resources

Data underlying the research on Seasonal and interannual variation in evapotranspiration, energy flux, and Bowen ratio over a dry semi-humid cropland in Northwest China

In this dataset, we report on five years of energy flux measurements observed by EC over the Guanzhong Plain cropland. The objectives of this study were to (1) characterize seasonal variation in ET and its components in order to identify the important controlling environmental factors; (2) investigate seasonal variation in energy fluxes and determine the energy budget; and (3) assess the effects of crop growth on ET, Bowen ratio (β), the Priestley-Taylor coefficient (α), and canopy conductance (Gc) and examine the relationships between Gc and other surface parameters

Integrated modeling of canopy photosynthesis, fluorescence, and the transfer of energy, mass, and momentum in the soil–plant–atmosphere continuum (STEMMUS–SCOPE v1.0.0)

Root water uptake by plants is a vital process that influences terrestrial energy, water, and carbon exchanges. At the soil, vegetation, and atmosphere interfaces, root water uptake and solar radiation predominantly regulate the dynamics and health of vegetation growth, which can be remotely monitored by satellites, using the soil-plant relationship proxy-solar-induced chlorophyll fluorescence. However, most current canopy photosynthesis and fluorescence models do not account for root water uptake, which compromises their applications under water-stressed conditions. To address this limitation, this study integrated photosynthesis, fluorescence emission, and transfer of energy, mass, and momentum in the soil-plant-Atmosphere continuum system, via a simplified 1D root growth model and a resistance scheme linking soil, roots, leaves, and the atmosphere. The coupled model was evaluated with field measurements of maize and grass canopies. The results indicated that the simulation of land surface fluxes was significantly improved by the coupled model, especially when the canopy experienced moderate water stress. This finding highlights the importance of enhanced soil heat and moisture transfer, as well as dynamic root growth, on simulating ecosystem functioning

Seasonal variation and controlling factors of evapotranspiration over dry semi-humid cropland in Guanzhong Plain, China

The Guanzhong Plain is a critical food production area in the Yellow River Basin that frequently suffers from water shortages. In this study, long-term (June 2013 to June 2018) water and energy fluxes were observed, and path analysis was conducted over an irrigated winter wheat (Triticum aestivum L.) / summer maize (Zea mays L.) rotation field to identify the controlling factors of evapotranspiration (ET). Total ET for each crop year ranged from 627 to 775 mm, with an average growing season ET of 398 mm for wheat and 310 mm for maize. There is significant seasonal variation in both ET and surface conductance (Gs). Daily ET varied from 0.0 to 6.0 mm d–1 for wheat and 0.0 to 6.7 mm d–1 for maize. The peak daily values of Gs were 29.5 mm s–1 for wheat and 19.5 mm s–1 for maize. The direct and indirect effects of environmental and biological factors—net radiation (Rn), surface conductance (Gs), saturation vapor pressure deficit (VPD), leaf area index (LAI), air temperature (Tair), and volumetric soil water content (VWC)—on ET were calculated using the path analysis method. Rn was determined to be the primary controlling factor of ET for both the summer maize and winter wheat growing seasons. Also, Gs was found to be another controlling factor that has more controlling power in the summer maize growing season than in the winter wheat season. VPD had a significant positive and direct effect on ET for both of the crop seasons, while it had a significant negative and indirect effect on ET through Gs in the summer maize season. VWC and Tair only directly affected the wheat ET. In addition, VWC had two significant paths that can indirectly affect ET through LAI and Gs. The revealed seasonal patterns and controlling factors of evapotranspiration in this agroecosystem provide a theoretical basis for optimizing water resources management of the Yellow River