Etiology and Chinese Medicine Screening of Severe COVID-19 Based on Multiomics and Serum Pharmacology

Background At present, scholars believe that severe COVID-19 is related to a variety of basic diseases, and we also observe this point using multi-omics method. The latest sequencing data of severe COVID-19 patients were combined to analyze the pathological mechanism, and pharmacological experimental research on local drugs was conducted, and a compound ingredient was found to have potential medicinal value. Results Here, we observed, for patients with severe COVID-19 disease, the differential miRNA expression is mainly low but having higher expression of mRNA. These differential mRNA expressions are associated with the activation of inflammatory pathways and ultimately with hypoxia and coagulation. Using database analysis, we found that Yi Xin Tong Mai Granule(YXTMG) might regulate COVID-19 through Toll-like receptor signaling pathway by acting on different immune targets. We found a new molecular mechanism for COVID-19 to turn the crisis around, the down-regulated miR-181a-5p mediates the up-regulation of PLAU and SERPINE1 molecules to cause cardiovascular adverse events, and YXTMG may prevent it. At the same time, molecular docking indicated that the its various components have anti-inflammatory activity. In vitro studies, we confirmed that YXTMG had antioxidant and anti-inflammatory activities. Conclusions The study has supplemented the potential mechanism for the conversion of mild to critical COVID-19 disease and screened the Chinese medicines for improving these factors, providing methodological reference for disease pathology and drug development.

Data Mining Statewide Department of Transportation Volumetrically Designed Asphalt Mixture Records

In recent years, the asphalt paving industry has been strained by numerous factors including increased asphalt binder costs, funding that has not kept up with material costs, increased societal pressure to recycle, and deteriorating pavement networks. Mix design should account for the market in which it is used, which is very different now than when today’s volumetric mix design practices were developed (many of the aforementioned factors were less present). Given this reality, a statewide database of all 1,452 approved mix designs in Mississippi from 2005 to 2018 was compiled and analyzed, and the objective of this paper is to present findings, trends, and unintended consequences of exclusive reliance on volumetrics. With volumetrics-only mix design, asphalt content is primarily controlled by voids in mineral aggregate (VMA), which is influenced by aggregate bulk specific gravity (Gsb). Minor Gsb deviations (i.e., within AASHTO d2 s limits), can significantly affect VMA, so much so that 99% of Mississippi’s mixes could be failing VMA while reported VMA passes. This allows mix manipulation and economization, with 0.8% asphalt content reductions possible while still meeting volumetric requirements. Recycled materials can exacerbate this issue, and common approaches to increase asphalt content (decreasing design gyration level or using finer gradations) are ineffective with fixed VMA requirements. Overall, the mix design database analysis agrees with numerous smaller studies but does so with an entire state’s actual practice. This presents a compelling case that volumetrics-only mix design has limitations, and supports ongoing efforts to reintegrate mechanical tests.