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Objective To investigate the mechanism of kaempferol in the treatment of rheumatoid arthritis (RA) based on network pharmacology and in vitro experiments. Methods Kaempferol targets were queried by TCMSP and SwissTarget databases, and RA related functional targets were searched in the GeneCards and DisGeNET databases. After the cross between kaempferol and RA targets through Venny2.1.0, STRING database was used for protein-protein interaction (PPI) analysis, and molecular docking between kaempferol and the targets was conducted. Mouse mononuclear leukemia RAW264.7 cells were treated by lipopolysaccharide (LPS) and kaempferol, and divided into control group, LPS group, LPS+Kaempferol group. MTT assay was used to determine the cytotoxicity of RAW264.7 cells after kaempferol treatment. LPS-induced RAW264.7 cells were used to construct a cellular inflammatory model. The change in aging and aging-related inflammatory factors were detected in each treatment group. The content of β-galactosidase was detected by SA-β-Gal, and the expression of IL-6 was detected by cellular immunofluorescence assay. Results A total of 138 targets of kaempferol and 76 potential targets of kaempferol against RA were obtained. PPI analysis showed that TNF, EGFR, PTGS2 and AKT1 may be the core targets of kaempferol against RA. The results of molecular docking indicated that kaempferol could form stable complexes with the core targets of TNF, EGFR, PTGS2 and AKT1. The results of MTT assay displayed that the treatment of 0.125 to 16 μmol/L kaempferol for 24 h promoted the proliferation of RAW264.7 cells (P < 0.05), the doses of 0.125 to 8 μmol/L for 48 h exerted similar effect on the proliferation (P < 0.05), but the dose of 0.125 to 16 μmol/L for 72 h had no such significant effect. The results of qPCR and Western blotting showed that kaempferol decreased the expression of cell senescence markers p16 and p21 and promoted the expression of cell cycle markers CCND1 and CCNE1 (P < 0.05). Cellular immunofluorescence assay indicated that kaempferol reduced the expression of IL-6 (P < 0.05). SA-β-Gal staining displayed that LPS treatment promoted β-galactosidase level in RAW264.7 cells (P < 0.05), and this effect was reversed by kaempferol treatment (P < 0.05). Conclusion Kaempferol may regulate the expression of IL-1β, IL-6 and TNF-α and p16/p21 senescence related genes, prevent premature aging of immune cells, and thus play a therapeutic role for RA. [

As an important emission reduction source for the transportation industry, biofuel has received strong support from the Chinese government. However, the development of the biofuel industry is still struggling. The high degree of uncertainty makes the development of the industry face huge challenges. Kitchen waste, as a biodiesel raw material with a large yield, has good development prospects. Reuse of kitchen waste can solve public health and safety problems. This paper proposes a two-stage stochastic programming model under supply disturbance to optimize the supply chain from the perspective of contract. Then current three main flow directions of kitchen waste are analysed and the reasonable price for biodiesel operators to purchase is determined. By signing contracts with the biodiesel operators, restaurant is guaranteed and encouraged to provide a certain percentage of kitchen waste to meet the demand for biodiesel production. Using actual case in the Yangtze River Delta region, the performance of the stochastic programming model under disturbance was compared. Through the sensitivity analysis of different parameters, this paper determines the influence of its supply chain network design and expected total system cost. Through the optimization of the waste cooking oil (WCO) for biodiesel supply chain, this paper can effectively improve the efficiency of the supply chain, reduce system costs, increase the profits of biofuel operators, and promote the sustainable development of the biofuel industry., Author(s): Nana Geng [1]; Qihong Fu [1]; Yixiang Sun (corresponding author) [2] 1. Introduction In China, with the expansion of the bioenergy development planning in recent years, the amount of [...]

With the rapid development of air transportation, the complexity, importance, and severity of civil aviation safety have gradually become prominent. It is essential to use various data to analyze and predict the level of aviation safety. This paper used a combined prediction model based on Induced Ordered Weighted Averaging (IOWA) operator to forecast the civil aviation incident rate. We compiled and calculated civil aviation incident data and total flight hours from 2008 to 2019 in China and took the civil aviation incident rate (incident numbers per ten thousand flight hours) as the prediction object. First, this paper used the nonlinear regression model, Grey Verhulst model, and Holt-Winters exponential smoothing model to forecast the civil aviation incident rate individually. Then, it used the smallest sum of squared errors as the principle to use a combined prediction model based on the IOWA operator. It can be seen from the experimental results that the prediction accuracy of the combined model is better than single models. Finally, this paper forecasted the civil aviation incident rate in 2020 and 2021. The results showed that the predicted rates are 0.524 and 0.551. Most notably the incident rate will increase significantly compared with 2019., Author(s): Yixiang Sun [1]; Nana Geng (corresponding author) [2] 1. Introduction Safety is the primary prerequisite for the development of civil aviation. In recent years, the safety level of civil [...]

In order to further explore the important impact of inbound tourism on economic development, six cities such as X city are selected as the research objects. Based on the panel threshold regression model and relevant data, the dynamic nonlinear relationship between inbound tourism and the economic development of the tertiary industry is explored through mathematical empirical analysis. The specific research results are as follows. The inbound tourism of X city develops rapidly and is in the stage of accelerating development. Meanwhile, the development of inbound tourism in X city has a certain pulling effect on the development of related industries and the tertiary industry. Among them, the elasticity coefficients of inbound tourism in X city to transportation industry, accommodation and catering industry, wholesale and retail industry, finance and insurance industry, and real estate industry are 1.137, 1.104, 1.134, 1.105, and 1.062, respectively; the elasticity coefficient to the income of the tertiary industry is 0.436. Moreover, the analysis of the relationship between inbound tourism and the development of the tertiary industry in six cities shows that there is a dynamic nonlinear relationship between them, and the research results are in line with the expected hypothesis. The research results can provide scientific and effective reference for the follow-up study of inbound tourism and economics. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA., Objectives: To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA., Methods: The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1., Results: It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal's.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14-3-3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity., Conclusion: CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)