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Pei-Wen Liu,* Ming-Xia Yue,* Rui Zhou, Juan Niu, Du-Juan Huang, Tao Xu, Pei Luo, Xiao-Hong Liu, Jun-Wei Zeng Department of Physiology, Zunyi Medical College, Guizhou, China *These authors contributed equally to this work Objective: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. Dorsal horn P2Y12 and P2Y13 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known whether P2Y12 and P2Y13 receptors activation is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in cultured dorsal spinal cord microglia. For this reason, we examined the effects of ADPβs (ADP analog) on the expression and the release of IL-1β, IL-6, and TNF-α.Methods and results: In this study, we observed the effect of P2Y receptor agonist ADPβs on the expression and release of IL-1β, IL-6 and TNF-α by using real-time fluorescence quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). ADPβs induced the increased expression of Iba-1, IL-1β, IL-6 and TNF-α at the level of messenger RNA (mRNA). ADPβs-evoked increase in Iba-1, IL-1β, IL-6 and TNF-α mRNA expression was inhibited only partially by P2Y12 receptor antagonist MRS2395 or P2Y13 receptor antagonist MRS2211, respectively. Similarly, ADPβs-evoked release of IL-1β, IL-6 and TNF-α was inhibited only partially by MRS2395 or MRS2211. Furthermore, ADPβs-evoked increased expression of Iba-1, IL-1β, IL-6 and TNF-α mRNA, and release of IL-1β, IL-6 and TNF-α were nearly all blocked after co-administration of MRS2395 plus MRS2179. Further evidence indicated that P2Y12 and P2Y13 receptor-evoked increased gene expression of IL-1β, IL-6 and TNF-α were inhibited by Y-27632 (ROCK inhibitor), SB203580 (P38MAPK inhibitor) and PDTC (NF-κb inhibitor), respectively. Subsequently, P2Y12 and P2Y13 receptor-evoked release of IL-1β, IL-6 and TNF-α, were also inhibited by Y-27632, SB203580 and PDTC, respectively.Conclusion: These observations suggest that P2Y12 and P2Y13 receptor-evoked gene expression and release of IL-1β, IL-6 and TNF-α are associated with ROCK/P38MAPK/NF-κb signaling pathway. Keywords: glial activation, P2 receptor, NF-kB, p38 mitogen-activated protein kinasez

Soil-borne fungi influence coexistence of plant species in mesic environments, but much less is known about their effects on demographic processes relevant to coexistence in arid and semi-arid systems. We isolated 43 fungal strains that naturally colonize seeds of an invasive winter annual (Brassica tournefortii) in the Sonoran Desert, and evaluated the impact of 18 of them on seed germination and mortality of B. tournefortii and a co-occurring native annual (Plantago ovata) under simulated summer and winter temperatures. Fungi isolated from B. tournefortii seeds impacted germination and mortality of seeds of both plant species in vitro. Seed responses reflected host-specific effects by fungi, the degree of which differed significantly between the strains, and depended on the temperature. In the winter temperature, ten fungal strains increased or reduced seed germination, but substantial seed mortality due to fungi was not observed. Two strains increased germination of P. ovata more strongly than B. tournefortii. In the summer temperature, fungi induced both substantial seed germination and mortality, with ten strains demonstrating host-specificity. Under natural conditions, host-specific effects of fungi on seed germination may further differentiate plant species niche in germination response, with a potential of promoting coexistence. Both host-specific and non-host-specific effects of fungi on seed loss may induce polarizing effects on plant coexistence depending on the ecological context. The coexistence theory provides a clear framework to interpret these polarizing effects. Moreover, fungi pathogenic to both plant species could induce host-specific germination, which challenges the theoretical assumption of density-independent germination response. These implications from an in vitro study underscore the need to weave theoretical modeling, reductive empirical experiments, and natural observations to illuminate effects of soil-borne fungi on coexistence of annual plant species in variable desert environments.

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers. [ABSTRACT FROM AUTHOR]