No abstract

Fungal denitrification is a dissimilating metabolic mechanism for nitrate and was first described in Fusarium oxysporum. Here we investigated regulatory systems of expression of CYP55, which encodes cytochrome P450 (P450nor) and is essential for the fungal denitrification. Promoter-reporter analysis of F. oxysporum CYP55 using Escherichia coli beta-galactosidase showed that the region between nucleotides -526 and -515 was critical for induction by nitrate. It contained a nucleotide sequence similar to the binding consensus sequence of the pathway-specific transcriptional factor NirA, which induces expression of the nitrate-assimilatory genes of Aspergillus nidulans in the presence of nitrate. This indicates that expression of the nitrate dissimilatory gene (CYP55) is concomitantly regulated with the nitrate-assimilatory genes. The deletion studies also indicated that the nucleotide sequence between -118 and -107, which was similar to the binding consensus of the yeast Rox1p, which represses the anoxic genes under aerobic conditions, was responsible for repression of CYP55 under aerobic conditions. These results indicate that the fungus adapts to the denitrifying conditions by a combination of NirA- and Rox1-like transcription factors.

NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.

BackgroundIschaemic stroke and transient ischaemic attack (TIA) share a common cause. We aim to develop and validate a concise prognostic nomogram for patients with minor stroke and TIA.MethodsA total of 994 patients with minor stroke and TIA were included. They were split into a derivation (n=746) and validation (n=248) cohort. The modified Rankin Scale (mRS) scores 3 months after onset were used to assess the prognosis as unfavourable outcome (mRS≥2) or favourable outcome (mRS<2).ResultThe final model included seven independent predictors: gender, age, baseline National Institute of Health Stroke Scale (NIHSS), hypertension, diabetes mellitus, white blood cell and serum uric acid. The Harrell’s concordance index (C-index) of the nomogram for predicting the outcome was 0.775 (95% CI 0.735 to 0.814), which was confirmed by the validation cohort (C-index=0.787 (95% CI 0.722 to 0.853)). The calibration curve showed that the nomogram-based predictions were consistent with actual observation in both derivation cohort and validation cohort.ConclusionThe proposed nomogram showed favourable predictive accuracy for minor stroke and TIA. This has the potential to contribute to clinical decision-making.