Effects of tMa-Xin-Di-Tan decoction on ovalbumin-induced allergic asthma in mice

Purpose: To investigate the effect of the Ma-Xin-Di-Tan (MXDT) decoction on  ovalbumin-induced allergic asthma (AA) in mice.Methods: Asthma was induced in mice by ovalbumin (OVA) injection, and different doses of MXDT (150, 300, and 600 mg/kg/day) were administered orally for 28 days. Pathological changes in lung tissues were examined, while levels of cytokines, including interleukin (IL)-4, IL-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β, were determined using enzyme-linked immunosorbent assays (ELISAs) of the bronchoalveolar lavage fluid. Toll-like receptor (TLR)-4,  GATA-binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine  2,3-dioxygenase (IDO), forkhead box P3 (Foxp3), and T box expressed in T cells (T-bet) levels were determined in lung tissues by western blot analysis.Results: MXDT inhibited the inflammatory reaction of lung tissues in  OVA-challenged mice. After treatment with MXDT, levels of IL-4, IL-6, IL-17, and TGF-β were downregulated, whereas IFN-γ levels were upregulated. In addition,  MXDT decreased TLR-4, GATA-3, and OX40L levels in lung tissues but increased the expression of Foxp3, T-bet, and IDO.Conclusion: MXDT has antiallergic effects on OVA-induced AA in mice; the possible molecular mechanisms might involve the inhibition of inflammatory reactions and modulation of Th1/Th2 cytokine balance.Keywords: Ma-Xin-Di-Tan decoction, Allergic asthma, Inflammatory reactions, Th1/Th

Anti-asthmatic effect of Ping-Chuan Formula in asthmatic mice, and its molecular mechanism of action

Purpose: To investigate the anti-asthmatic effect of Ping-Chuan Formula (PCF) in a mouse model, and the associated molecular mechanisms.Methods: Asthma mice were induced using ovalbumin (OVA), and PCF (600 mg/kg) was administered to the mice for 4 weeks. Sections of lung tissues were examined microscopically. The expressions of interleukins (ILs), interferon (IFN)-γ, transforming growth factor (TGF)-β were assayed, while lung tissue expressions of Toll like receptor (TLR)-4, GATA binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine 2,3-dioxygenase (IDO), and forkhead box P3 (Foxp3) determined. The T box expressed in T cells (T-bet) was evaluated using western blotting. The expressions of MHC II and co-stimulators (CD 11c, CD 80 and CD 86) of dendritic cells (DCs) were determined by flow cytometry.Results: PCF decreased inflammation in lung, and also down-regulated IL-4, -6, -17 and TGF-β (p < 0.01), whereas IL-10 and IFN-γ expressions were up-regulated (p < 0.01). Moreover, PCF decreased the expressions of TLR-4, GATA-3 and OX40L in lung tissue, and promoted Foxp3, IDO and T-bet. Besides, PCF decreased the levels of MHC II and co-stimulators (CD 80 and CD 86) on the surface of DCs.Conclusion: PCF exerts anti-asthmatic effect in mice via inhibition of inflammation, and modulation of MHC II and co-stimulators on the surface of DCs. These findings suggest that PCF is a promising candidate drug for treating asthma in humans

Lifelike Agility and Play on Quadrupedal Robots using Reinforcement Learning and Generative Pre-trained Models

Summarizing knowledge from animals and human beings inspires robotic innovations. In this work, we propose a framework for driving legged robots act like real animals with lifelike agility and strategy in complex environments. Inspired by large pre-trained models witnessed with impressive performance in language and image understanding, we introduce the power of advanced deep generative models to produce motor control signals stimulating legged robots to act like real animals. Unlike conventional controllers and end-to-end RL methods that are task-specific, we propose to pre-train generative models over animal motion datasets to preserve expressive knowledge of animal behavior. The pre-trained model holds sufficient primitive-level knowledge yet is environment-agnostic. It is then reused for a successive stage of learning to align with the environments by traversing a number of challenging obstacles that are rarely considered in previous approaches, including creeping through narrow spaces, jumping over hurdles, freerunning over scattered blocks, etc. Finally, a task-specific controller is trained to solve complex downstream tasks by reusing the knowledge from previous stages. Enriching the knowledge regarding each stage does not affect the usage of other levels of knowledge. This flexible framework offers the possibility of continual knowledge accumulation at different levels. We successfully apply the trained multi-level controllers to the MAX robot, a quadrupedal robot developed in-house, to mimic animals, traverse complex obstacles, and play in a designed challenging multi-agent Chase Tag Game, where lifelike agility and strategy emerge on the robots. The present research pushes the frontier of robot control with new insights on reusing multi-level pre-trained knowledge and solving highly complex downstream tasks in the real world

Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor.

Cholecystokinin A receptor (CCKAR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including Gs, Gi and Gq. However, the basis for G-protein coupling promiscuity and ligand recognition by CCKAR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKAR in complex with Gs, Gi and Gq heterotrimers, respectively. CCKAR presents a similar conformation in the three structures, whereas conformational differences in the 'wavy hook' of the Gα subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8

Energy and Exergy Analysis of Hydrogen-Based Fluidized Bed Direct Reduction towards Efficient Fossil-Free Ironmaking

Hydrogen-based fluidized bed direct reduction (H-FBDR) is an important and promising route for fossil-free ironmaking. In this study, to achieve the optimal operation state of energy use and exergy efficiency, the influences of the metallization process and the ratios of H2 injected on the energy and exergy flows in the H-FBDR process are studied. The results show that the thermodynamically designed two-stage reduction process (first: Fe2O3→FeO; second: FeO→Fe) requires a smaller H2 quantity than other metallization processes. According to the mass, energy, and exergy balance analyses, variations in the H2 consumption, exergy destruction, and energy/exergy losses of the overall system, iron ore preheater (F1), fluidized bed reactor system (R), heat exchanger (E), and gas preheater (F2) with different ratios of H2 injected (η) are derived. The total H2 consumption, total exergy destruction, and energy/exergy losses rise with increasing η, and sharp increases are observed from η = 1.3 to η = 1.8. The exergy efficiencies (φ) can be ranked as φR > φE > φF1 ≈ φF2, and the exergy destruction in components F1 and F2 is mainly caused by the combustion reaction, whereas physical exergy destruction dominates for components R and E. The performances of components F1, E, and F2 degrade from η = 1.0 to η = 1.8, and significant degradation arises when η exceeds 1.3. Thus, considering the H2 consumption, thermodynamic efficiency, and energy/exergy losses, the ratio of H2 injected should be set below 1.3. Notably, although the energy loss in the H-FBDR system is 2 GJ/h at η = 1.3, the exergy loss is only 360 MJ/h, in which the recycled gases from component E occupy 320 MJ/h, whereas the total exergy destruction is 900 MJ/h. Therefore, improving the performance of operation units, particularly the components F1 and F2, is as important as recovering the heat loss from component E for optimizing the H-FBDR process

Efficient Combination of Complex Chromatography, Molecular Docking and Enzyme Kinetics for Exploration of Acetylcholinesterase Inhibitors from Poria cocos

Poria cocos (P. cocos) is a traditional Chinese medicinal product with the same origin as medicine and food. It has diuretic, anti-inflammatory and liver protection properties, and has been widely used in a Chinese medicine in the treatment of Alzheimer’s disease (AD). This study was conducted to explore the activity screening, isolation of acetylcholinesterase inhibitors (AChEIs), and in vitro inhibiting effect of P. cocos. The aim was to develop a new extraction process optimization method based on the Matlab genetic algorithm combined with a traditional orthogonal experiment. Moreover, bio−affinity ultrafiltration combined with molecular docking was used to screen and evaluate the activity of the AChEIs, which were subsequently isolated and purified using high-speed counter−current chromatography (HSCCC) and semi−preparative high-performance liquid chromatography (semi−preparative HPLC). The change in acetylcholinesterase (AChE) activity was tested using an enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on AChE and explore its mechanism of action. Five potential AChEIs were screened via bio−affinity ultrafiltration. Molecular docking results showed that they had good binding affinity for the active site of AChE. Meanwhile, the five active compounds had reversible inhibitory effects on AChE: Polyporenic acid C and Tumulosic acid were non-competitive inhibitors; 3−Epidehydrotumulosic acid was a mixed inhibitor; and Pachymic acid and Dehydrotrametenolic acid were competitive inhibitors. This study provided a basis for the comprehensive utilization of P. cocos and drug development for the treatment of AD

Efficient Combination of Complex Chromatography, Molecular Docking and Enzyme Kinetics for Exploration of Acetylcholinesterase Inhibitors from <i>Poria cocos</i>

Poria cocos (P. cocos) is a traditional Chinese medicinal product with the same origin as medicine and food. It has diuretic, anti-inflammatory and liver protection properties, and has been widely used in a Chinese medicine in the treatment of Alzheimer’s disease (AD). This study was conducted to explore the activity screening, isolation of acetylcholinesterase inhibitors (AChEIs), and in vitro inhibiting effect of P. cocos. The aim was to develop a new extraction process optimization method based on the Matlab genetic algorithm combined with a traditional orthogonal experiment. Moreover, bio−affinity ultrafiltration combined with molecular docking was used to screen and evaluate the activity of the AChEIs, which were subsequently isolated and purified using high-speed counter−current chromatography (HSCCC) and semi−preparative high-performance liquid chromatography (semi−preparative HPLC). The change in acetylcholinesterase (AChE) activity was tested using an enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on AChE and explore its mechanism of action. Five potential AChEIs were screened via bio−affinity ultrafiltration. Molecular docking results showed that they had good binding affinity for the active site of AChE. Meanwhile, the five active compounds had reversible inhibitory effects on AChE: Polyporenic acid C and Tumulosic acid were non-competitive inhibitors; 3−Epidehydrotumulosic acid was a mixed inhibitor; and Pachymic acid and Dehydrotrametenolic acid were competitive inhibitors. This study provided a basis for the comprehensive utilization of P. cocos and drug development for the treatment of AD

Evaluation of Geometrical Influence on the Hydrodynamic Characteristics and Power Absorption of Vertical Axisymmetric Wave Energy Converters in Irregular Waves

To obtain the mechanical energy of waves from arbitrary directions, the vibration absorbers of wave energy converters (WEC) are usually vertically axisymmetric. In such case, the wave-body interaction hydrodynamics is an essential research topic to obtain high-efficiency wave energy. In this paper, a semi-analytical method of decomposing the complex axisymmetric boundary into several ring-shaped stepped surfaces based upon the boundary approximation method (BAM) is introduced and examined. The hydrodynamic loads and parameters, such as the wave excitation forces, added mass and radiation damping of the vertical axisymmetric oscillating buoys, can then be achieved by using the new boundary discretisation method. The calculations of the wave forces and hydrodynamic coefficients show good convergence with the number of discretisation increases. Comparison between the constringent results and the results of the conventional method also verifies the feasibility of the method. Then, simulations and comparisons of the hydrodynamic forces, motions and wave power conversions of the buoys with series draught and displacement ratios in regular and irregular waves are conducted. The calculation results show that the geometrical shape has a great effect on the hydrodynamic and wave power conversion performance of the absorber. In regular waves, though the concave buoy has the lowest wave conversion efficiency, it has the largest frequency bandwidth for a given draught ratio, while in irregular waves, for a given draught ratio, the truncated cylindrical buoy has the best wave power conversion, and for a given displacement of the buoy, the concave buoy shows the best wave power conversion ability

Optimal Configurations of Wave Energy Converter Arrays with a Floating Body

An array of floating point-absorbing wave energy converters (WECs) is usually employed for extracting efficiently ocean wave energy. For deep water environment, it is more feasible and convenient to connect the absorbers array with a floating body, such as a semi-submersible bottom-moored disk, whose function is to act as the virtual seabed. In the present work, an array of identical floating symmetrically distributed cylinders in a coaxial moored disk as a wave energy device is proposed The power take-off (PTO) system in the wave energy device is assumed to be composed of a linear/nonlinear damper activated by the buoys heaving motion. Hydrodynamic analysis of the examined floating system is implemented in frequency domain. Hydrodynamic interferences between the oscillating bodies are accounted for in the corresponding coupled equations. The array layouts under the constraint of the disk, incidence wave directions, separating distance between the absorbers and the PTO damping are considered to optimize this kind of WECs. Numerical results with regular waves are presented and discussed for the axisymmetric system utilizing heave mode with these interaction factors, in terms of a specific numbers of cylinders and expected power production

Association between different combination of measures for obesity and new-onset gallstone disease.

Body mass index(BMI) is a calculation index of general obesity. Waist circumference(WC) is a measure of body-fat distribution and always used to estimate abdominal obesity. An important trait of general obesity and abdominal obesity is their propensity to coexist. Using one single measure of obesity could not estimate persons at risk for GSD precisely.This study aimed to compare the predictive values of various combination of measures for obesity(BMI, WC, waist to hip ratio) for new-onset GSD.We prospectively studied the predictive values of various combination of measures for obesity for new-onset GSD in a cohort of 88,947 participants who were free of prior gallstone disease, demographic characteristics and biochemical parameters were recorded.4,329 participants were identified to have GSD among 88,947 participants during 713 345 person-years of follow-up. Higher BMI, WC and waist to hip ratio (WHtR) were significantly associated with higher risks of GSD in both genders even after adjustment for potential confounders. In males, the hazard ratio for the highest versus lowest BMI, WC, WHtR were 1.63(1.47~1.79), 1.53(1.40~1.68), 1.44(1.31~1.58), respectively. In females, the hazard ratio for the highest versus lowest BMI, WC, WHtR were 2.11(1.79~2.49), 1.85(1.55~2.22), 1.84(1.55~2.19), respectively. In male group, the combination of BMI+WC improved the predictive ability of the model more clearly than other combinations after adding them to the multivariate model in turn, while for females the best predictive combination was BMI+WHtR.Elevated BMI, WC and WHtR were independent risk factors for new-onset GSD in both sex groups after additional adjustment was made for potential confounders. In males, the combination of BMI+WC seemed to be the most predictable model to evaluate the effect of obesity on new-onset GSD, while the best combination in females was BMI+WHtR