Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA. Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation. Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1ß and NCF1 were determined through protein-protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol. Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution. Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1ß) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol, an active component of Sinomenium acutum, in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.

Temporal Activity Patterns of Sympatric Species in the Temperate Coniferous Forests of the Eastern Qinghai-Tibet Plateau.

Temporal niche partitioning is an important strategy for sympatric species or populations when utilizing limited resources while minimizing competition. Different resource availability across seasons may also influence the intensity of competition, resulting in a varied temporal niche partitioning pattern between species. These competitive interactions are important drivers for the formation of biodiversity patterns and species coexistence on the eastern Qinghai-Tibet Plateau. To clarify these interspecies relationships among sympatric species, we carried out a camera trap survey from 2017 to 2020. We deployed 60 camera traps in the temperate coniferous forests of the eastern Qinghai-Tibet Plateau. We analyzed the daily activity patterns of birds and mammals to reveal the temporal niches and seasonal relationships among the species-specific activity rhythms. The results are summarized as follows: (1) Eight major species, including mammals and birds, have different temporal peak activity rhythms to reduce intense competition for resources. (2) The activity rhythm of a species varies seasonally, and the competition among species is more intense in the warm season than in the cold season. (3) Among 15 pairs of competitor species, seven pairs had significantly different coefficients, with higher winter values than summer values, perhaps due to the abundance of resources in summer and the scarcity of resources in winter causing intensified competition. Among the predators and prey, the summertime coefficients were higher than those in winter, perhaps due to the need to replenish energy during the summer breeding season. The main purpose of animals in winter is to survive the harsh environment. Our results provide important information on temporal and interspecies relationships and contribute to a better understanding of species-coexistence mechanisms.

Nitrogen Addition Affects Ecosystem Carbon Exchange by Regulating Plant Community Assembly and Altering Soil Properties in an Alpine Meadow on the Qinghai-Tibetan Plateau.

Nitrogen (N) deposition can affect the global ecosystem carbon balance. However, how plant community assembly regulates the ecosystem carbon exchange in response to the N deposition remains largely unclear, especially in alpine meadows. In this study, we conducted a manipulative experiment to examine the impacts of N (ammonium nitrate) addition on ecosystem carbon dioxide (CO2) exchange by changing the plant community assembly and soil properties at an alpine meadow site on the Qinghai-Tibetan Plateau from 2014 to 2018. The N-addition treatments were N0, N7, N20, and N40 (0, 7, 20, and 40 kg N ha-1year-1) during the plant growing season. The net ecosystem CO2 exchange (NEE), gross ecosystem productivity (GEP), and ecosystem respiration (ER) were measured by a static chamber method. Our results showed that the growing-season NEE, ER and GEP increased gradually over time with increasing N-addition rates. On average, the NEE increased significantly by 55.6 and 65.2% in N20 and N40, respectively (p < 0.05). Nitrogen addition also increased forage grass biomass (GB, including sedge and Gramineae) by 74.3 and 122.9% and forb biomass (FB) by 73.4 and 51.4% in N20 and N40, respectively (p < 0.05). There were positive correlations between CO2 fluxes (NEE and GEP) and GB (p < 0.01), and the ER was positively correlated with functional group biomass (GB and FB) and soil available N content (NO3 --N and NH4 +-N) (p < 0.01). The N-induced shift in the plant community assembly was primarily responsible for the increase in NEE. The increase in GB mainly contributed to the N stimulation of NEE, and FB and the soil available N content had positive effects on ER in response to N addition. Our results highlight that the plant community assembly is critical in regulating the ecosystem carbon exchange response to the N deposition in alpine ecosystems.