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Epimedium total flavonoid capsules (ETFCs), a traditional Chinese patent medicine derived from Epimedium brevicornu Maxim., have been used for centuries to treat primary osteoporosis and are associated with kidney yang deficiency symptoms. Based on the “kidney-brain axis” hypothesis, previous study demonstrated that ETFCs can improve the cognitive function of MCAO rats, and the mechanism may involve the inflammatory response. However, little is known about their therapeutic components and scientific connotations. This study systematically investigates the anti-neuroinflammatory material basis and the mechanisms of ETFCs, integrating UPLC-Q/TOF-MS and UPLC-TQ-MS for chemical profiling, quantitative analysis of key components in rats′ plasma and brain, along with network pharmacology and activity verification. As a result, 65 components were identified. Metabolite profiling showed a total of 130 xenobiotics, highlighting the extensive metabolic transformations. Pharmacokinetic studies showed that primary flavonoid glycosides were quickly absorbed, while secondary glycosides exhibited slower absorption and elimination. In brain tissue, both prototype glycosides and secondary glycosides reached their peak concentrations rapidly, with Tmax between 0.25–1 h, while the prototype glycosides were eliminated after 8 h and secondary glycosides exhibited a secondary peak at 6–8 h. A network pharmacology study revealed that prototypes in blood may play a therapeutic role through targets including AKR1B1, PDE5A, and PTGS2 (COX-2). The LPS-induced BV-2 cell model confirmed ETFCs′ constituents showed inhibitory activities on pro-inflammatory cytokine secretion, mRNA expressions of IL-6, TNF-α, COX-2, iNOS and could down-regulate the protein expressions of COX-2 and iNOS. This research lays the foundation for the further development and utilization of ETFCs.

Abstract Background Acute viral myocarditis (AVMC) is an inflammatory disease of the myocardium. Evidence indicates that dysbiosis of gut microbiome and related metabolites intimately associated with cardiovascular diseases through the gut-heart axis. Methods We built mouse models of AVMC, then applied 16 S rDNA gene sequencing and UPLC-MS/MS metabolomics to explore variations of gut microbiome and disturbances of cardiac metabolic profiles. Results Compared with Control group, analysis of gut microbiota showed lower diversity in AVMC, decreased relative abundance of genera mainly belonging to the phyla Bacteroidetes, and increased of phyla Proteobacteria. Metabolomics analysis showed disturbances of cardiac metabolomics, including 62 increased and 84 decreased metabolites, and mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid hormone biosynthesis, cortisol synthesis and secretion pathway were particularly enriched in AVMC. Among them, such as estrone 3-sulfate, desoxycortone positively correlated with disturbed gut microbiome. Conclusion In summary, both the structure of the gut microbiome community and the cardiac metabolome were significantly changed in AVMC. Our findings suggest that gut microbiome may participate in the development of AVMC, the mechanism may be related to its role in dysregulated metabolites such as steroid hormone biosynthesis.

The benefit of cultivated land use is an essential indicator for measuring the optimal allocation of cultivated land resources and the high-quality development of agriculture. Taking Shiyan City, Xiangyang City, and Suizhou City in Northern Hubei as the research objects, this paper presents an evaluation index system for cultivated land use efficiency from the perspectives of ecology, economy, and society. The entropy TOPSIS method and the obstacle degree model were applied to estimate the cultivated land use efficiency and identify obstacle factors in the three study areas from 2010 to 2020, and the results were as follows. (1) The comprehensive benefit level of cultivated land utilization in Northern Hubei showed an upward trend, and the individual benefit levels of cultivated land utilization in different cities were significantly different. Xiangyang City had outstanding economic performance, Shiyan City had the fastest growth rate of ecological benefits, and various benefits of Suizhou City were “steady”. (2) The fluctuation ranges of the obstacle factors for cultivated land use were relatively large in the Northern Hubei region. From 2010 to 2016, the effective irrigation index, land-averaged fertilizer input level, agricultural input–output ratio, and per capita income of farmers were the main factors restricting the improvement of cultivated land utilization efficiency in Northern Hubei. During 2017–2020, the per capita pesticide input level, per capita grain output, forest coverage rate, land output rate, and agricultural mechanization efficiency became the main obstacles restricting the improvement of cultivated land-use efficiency. (3) All cities of Northern Hubei should take measures according to local conditions, implement specific policies to address the restrictive factors of cultivated land use, improve the level of cultivated land-use benefit in the region, and promote the coordination and unity of the economic, ecological, and social benefits of cultivated land use.

In order to study how to promote the collaborative innovation of green building projects of construction enterprises, this paper establishes an evolutionary game model of suppliers’ participation in collaborative innovation of green building projects of construction enterprises under government governance. Through a numerical simulation, our research analyzes the influence of government tax preference, government infrastructure construction, and environmental pollution punishment on the behavior of the government, suppliers, and construction enterprises. The empirical research shows that the government’s tax incentives will continue to encourage suppliers to choose collaborative innovation. If the government’s short-term tax incentives are small, construction enterprises will evolve in the direction of midway betrayal. When the government’s long-term tax incentives are large, construction enterprises will evolve in the direction of the collaborative innovation of green building projects. Furthermore, the government’s infrastructure support for suppliers to participate in collaborative innovation of green building projects of construction enterprises will encourage suppliers and construction enterprises to choose green building projects for collaborative innovation. With the continuous maturity of green building projects in the construction market, the government has evolved from positive governance to negative governance. The government will take the opportunity to give up infrastructure construction and turn to other supporting policies. Lastly, a low intensity of environmental pollution punishment makes it difficult to promote the construction enterprises to evolve in the direction of collaborative innovation. A moderate intensity of environmental pollution punishment can encourage construction enterprises to evolve in the direction of collaborative innovation, while high-intensity environmental pollution punishment can encourage construction enterprises to choose the direction of midway betrayal. Environmental pollution punishment has no significant impact on suppliers’ selection of collaborative innovation of green building projects in the short term.