Hydrogen sulfide mitigates ox­LDL­induced NLRP3/caspase­1/GSDMD dependent macrophage pyroptosis by S­sulfhydrating caspase­1.

Macrophage pyroptosis mediates vascular inflammation and atherosclerosis (AS). Hydrogen sulfide (H2S) exerts a protective role in preventing inflammation and AS. However, its molecular mechanisms of regulating the pyroptosis signaling pathway and inhibiting macrophage pyroptosis remain unexplored. The present study aimed to determine whether H2S mitigates macrophage pyroptosis by downregulating the pyroptosis signaling pathway and S­sulfhydrating caspase­1 under the stimulation of oxidized low­density lipoprotein (ox­LDL), a pro­atherosclerotic factor. Macrophages derived from THP­1 monocytes were pre­treated using exogenous H2S donors sodium hydrosulfide (NaHS) and D,L­propargylglycine (PAG), a pharmacological inhibitor of endogenous H2S­producing enzymes, alone or in combination. Subsequently, cells were stimulated with ox­LDL or the desulfhydration reagent dithiothreitol (DTT) in the presence or absence of NaHS and/or PAG. Following treatment, the levels of H2S in THP­1 derived macrophages were measured by a methylene blue colorimetric assay. The pyroptotic phenotype of THP­1 cells was observed and evaluated by light microscopy, Hoechst 33342/propidium iodide fluorescent staining and lactate dehydrogenase (LDH) release assay. Caspase­1 activity in THP­1 cells was assayed by caspase­1 activity assay kit. Immunofluorescence staining was used to assess the accumulation of active caspase­1. Western blotting and ELISA were performed to determine the expression of pyroptosis­specific markers (NLRP3, pro­caspase­1, caspase­1, GSDMD and GSDMD­N) in cells and the secretion of pyroptosis­related cytokines [interleukin (IL)­1ß and IL­18] in the cell­free media, respectively. The S­sulfhydration of pro­caspase­1 in cells was assessed using a biotin switch assay. ox­LDL significantly induced macrophage pyroptosis by activating the pyroptosis signaling pathway. Inhibition of endogenous H2S synthesis by PAG augmented the pro­pyroptotic effects of ox­LDL. Conversely, exogenous H2S (NaHS) ameliorated ox­LDL­and ox­LDL + PAG­induced macrophage pyroptosis by suppressing the activation of the pyroptosis signaling pathway. Mechanistically, ox­LDL and the DTT increased caspase­1 activity and downstream events (IL­1ß and IL­18 secretion) of the caspase­1­dependent pyroptosis pathway by reducing S­sulfhydration of pro­caspase­1. Conversely, NaHS increased S­sulfhydration of pro­caspase­1, reducing caspase­1 activity and caspase­1­dependent macrophage pyroptosis. The present study demonstrated the molecular mechanism by which H2S ameliorates macrophage pyroptosis by suppressing the pyroptosis signaling pathway and S­sulfhydration of pro­caspase­1, thereby suppressing the generation of active caspase-1 and activity of caspase-1.

Application of Human-Computer Interaction System in Regional Tourism Competitiveness Analysis under IoT Background.

With the continuous development of Internet of Things technology, this technology is not limited to the laboratory but is more and more applied in the process of commercialization. Large-scale machine communication is one of the three most important scenarios for 5G applications. Its features include larger uplink access, smaller data packets, higher device energy consumption requirements, lower device transmission speed, higher latency, and bursty communication. With the development of the Internet of Things in the 5G era, interpersonal interaction experience has been further optimized and welcomed by the market and adopt Qt/embedded multilayer menu design mode to improve our computer system interaction to facilitate the operation and Maintenance system. The software function of the human-computer interaction system has reached the expected result. By constructing the application of a human-computer interaction system in the analysis of regional tourism competitiveness, we analyze the temporal and spatial changes of tourism competitiveness in four major economic regions in China and combine multiple linear regression and geographic detector models to analyze China's tourism competitiveness. On this basis, we propose to further enhance the tourism competitiveness of areas with weak tourism development infrastructure and encourage potential tourism development areas to complement each other with high-quality resources between regions.

The Performance Appraisal System of Country Well-Facilitated Farmland Based on AHP-Object Metatopological Model.

Performance appraisal of well-facilitated farmland projects has positive significance for promoting the development of modern agriculture in rural areas and carrying out rural revitalization. Based on the AHP-object metatopological model, a well-facilitated farmland project performance appraisal system is proposed to analyze the county performance of well-facilitated farmland construction. In this study, Fangcheng County, Henan Province, is selected as the research sample area and evaluated by applying the established index system. The results show that the overall performance grade of the well-facilitated farmland project in Fangcheng County is at an excellent level with both excellent and good rates reaching more than 90%, the output is slightly lower with excellent and good rates reaching 73%, and the benefit is the worst with excellent and good rates at 53%. These indicate that the construction effect of the well-facilitated farmland project in Fangcheng County is at a good level, but the benefits are not as satisfactory as expected. In the overall appraisal, excellent accounts for 48.1%, good accounts for 26.9%, average accounts for 16.3%, and poor accounts for 8.7%. Fangcheng County has achieved a good performance level in the construction of a well-facilitated farmland project in 2019, with almost full completion of project objectives and compliance with implementation standards. This study provides a system of county performance appraisal methods for well-facilitated farmland as well as its practical application in county-level units.