RESUMO
Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified.
RESUMO
The acceleration and deceleration (AD) motions are the basic motion modes of robot astronauts moving in a space station. Controlling the locomotion of the robot astronaut is very challenging due to the strong nonlinearity of its complex multi-body dynamics in a gravity-free environment. However, after training, humans can move well in space stations by pushing the bulkhead, and the motion mechanism of humans is a good reference for robot astronauts. The contribution of this study is modeling the human AD motion in a microgravity environment and proposing a human-like control method for robot astronauts moving in space stations. Specifically, the movement and contact force data of the human body during AD motion were collected on an air-floating platform. Through human AD modeling analysis, the mechanism of human motion is discovered, and semi-sinusoidal primitives of contact forces are proposed for AD motion. Then, a dynamic guidance model of human AD motion is built to complete motion planning under contact constraints, which is used as the expected model for the AD control of robot astronauts. Benefiting from the force primitives, accurate and safe planning of human-like AD motion can be completed. The characteristics and mechanism of human AD motion have been analyzed from the perspective of optimization. Lastly, based on the proposed dynamic guidance model, the AD motion policy is mapped to the robot astronaut system via a system control method based on the equivalent mapping of dynamic responses (force, velocity and pose). Through comparative analysis with real human motion data and simulation results under different conditions, the proposed AD control method can achieve human-like motion efficiently and stably. Even when confronted with errors in the robot's contact velocities and inertia parameters, the method can significantly reduce the motion errors while ensuring stability.
Assuntos
Aceleração , Astronautas , Desaceleração , Robótica , Voo Espacial , Ausência de Peso , Humanos , Algoritmos , Simulação por Computador , Astronave , Movimento (Física) , Movimento/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used in the treatment of ulcerative colitis (UC) and has good antioxidant and anti-inflammatory effects, but its specific active ingredients and mechanisms of action are still unknown. THE PURPOSE OF THE STUDY: To elucidate the specific molecular mechanisms of licorice in the treatment of UC and to experimentally verify its activity. METHODS: Through network pharmacology, the active ingredients of licorice and the molecular targets of UC were identified. A traditional Chinese medicine (TCM)-components-target-disease network diagram was established, and the binding energies of the active ingredient and targets of licorice were verified by molecular docking. A BALB/c mice model of UC was established by treatment with 3% dextran sulfate sodium (DSS). The effect of licorice on colon tissue injury was histologically assessed. The expression of IL-6 and IL-17 in colon tissue was detected by immunohistochemistry (IHC). Transmission electron microscopy (TEM) was used to observe morphological changes in mitochondria in the colon. Caco2 cells were treated with lipopolysaccharide (LPS) for 24 h to establish the cell inflammatory damage model, and cells were exposed to different concentrations of drug-containing serum of Licorice (DCSL) for 24 h. In cells treated with the drug, the contents of oxidation markers were measured and ELISA was used to determine the levels of inflammatory factors in the cells. TEM was used to observe morphological changes in mitochondria. ZO-1 and occludin were detected by Western blotting. DCSL effects on autophagy were evaluated by treating cells with DCSL and autophagy inhibitor for 24 h after LPS injection. Small interfering ribonucleic acid (si-RNA) was used to silence Nrf2 gene expression in Caco2 cells to observe the effects of DCSL on autophagy through the Nrf2/PINK1 pathway. Nrf2, PINK1, HO-1, Parkin, P62, and LC3 were detected by Western blotting. RESULTS: Ninety-one active ingredients and 339 action targets and 792 UC disease targets were identified, 99 of which were overlapping targets. Molecular docking was used to analyze the binding energies of liquiritin, liquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid to the targets, with glycyrrhetinic acid having the strongest binding energy. In the UC mouse model, licorice improved colon histopathological changes, reduced levels of IL-6 and IL-17 and repaired mitochondrial damage. In the LPS-induced inflammation model of Caco2 cells, DCSL decreased MDA, IL-1ß, Il-6, and TNF-α levels and increased those of Superoxide Dismutase (SOD), glutathione peroxidase (GSH-PX), and IL-10, and improved the morphological changes of mitochondria. Increased expression of Nrf2, PINK1, Parkin, HO-1, ZO-1, occludin, P62, and LC3 promoted autophagy and reduced inflammation levels. CONCLUSION: Licorice improves UC, which may be related to the activation of the Nrf2/PINK1 signaling pathway that regulates autophagy.