A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor

BACKGROUND: Enterovirus 71 (EV71), one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection. PRESENTATION OF THE HYPOTHESIS: The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation. TESTING THE HYPOTHESIS: CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. The potential bioavailability and efficacy of the targeted complement inhibitor are evaluated by histology, immunofluorescence staining and radiolabeling. IMPLICATIONS OF THE HYPOTHESIS: CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection

Soil Microbial Co-Occurrence Patterns under Controlled-Release Urea and Fulvic Acid Applications

The increasing amount of agricultural applications of controlled-release urea (CRU) and fulvic acids (FA) demands a better understanding of FA’s effects on microbially mediated nitrogen (N) nutrient cycling. Herein, a 0–60 day laboratory experiment and a consecutive pot experiment (2016–2018) were carried out to reveal the effects of using CRU on soil microbial N-cycling processes and soil fertility, with and without the application of FA. Compared to the CRU treatment, the CRU+FA treatment boosted wheat yield by 22.1%. To reveal the mechanism of CRU+FA affecting the soil fertility, soil nutrient supply and microbial community were assessed and contrasted in this research. From 0–60 days, compared with the CRU treatment, leaching NO3−-N content of CRU+FA was dramatically decreased by 12.7–84.2% in the 20 cm depth of soil column. Different fertilizers and the day of fertilization both have an impact on the soil microbiota. The most dominant bacterial phyla Actinobacteria and Proteobacteria were increased with CRU+FA treatment during 0–60 days. Network analysis revealed that microbial co-occurrence grew more intensive during the CRU+FA treatment, and the environmental change enhanced the microbial community. The CRU+FA treatment, in particular, significantly decreased the relative abundance of Sphingomonas, Lysobacter and Nitrospira associated with nitrification reactions, Nocardioides and Gaiella related to denitrification reactions. Meanwhile, the CRU+FA treatment grew the relative abundance of Ensifer, Blastococcus, and Pseudolabrys that function in N fixation, and then could reduce NH4+-N and NO3−-N leaching and improve the soil nutrient supply. In conclusion, the synergistic effects of slow nutrition release of CRU and growth promoting of FA could improve the soil microbial community of N cycle, reduce the loss of nutrients, and increase the wheat yield