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Background: Inflammation is related to cardiovascular disease. Among the many inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) were considered as novel predictors for atherosclerosis outcomes. We aimed to investigate the impact of these inflammatory markers on the prognosis of patients with atrial fibrillation (AF). Methods: We obtained data on AF patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. These patients were classified into two groups based on their survival status within 30 days. Then, they were divided into three groups based on the tertile of baseline NLR, PLR, and SII, respectively. We comprehensively explored the relationship between those inflammatory indicators and all-cause mortality in patients with AF by Kaplan-Meier analysis, multivariate Cox regression analysis, receiver operating characteristic (ROC) analyses, restricted cubic spline regression (RCS), and subgroup analysis. Results: A total of 4562 patients with AF were included. Statistically significant differences were found between survivor and non-survivor groups for NLR, PLR and SII. Patients in the high tertile of the NLR had a higher mortality rate than those in the low and intermediate tertiles, as did patients in the PLR and the SII. NLR, PLR and SII were independently associated with increased risk of all-cause mortality. RCS showed that the 30-day and 365-day risk of death were linearly associated with increases in NLR, PLR, and SII, respectively. Conclusion: NLR, PLR, and SII have the potential to be used as indicators for stratifying the risk of mortality in critically ill patients with AF.

Hantaviruses encompass rodent-borne zoonotic pathogens that cause severe hemorrhagic fever disease with high mortality rates in humans. Detection of infectious virus titer lays a solid foundation for virology and immunology researches. Canonical methods to assess viral titers rely on visible cytopathic effects (CPE), but Hantaan virus (HTNV, the prototype hantavirus) maintains a relatively sluggish life cycle and does not produce CPE in cell culture. Here, an in-cell Western (ICW) assay was utilized to rapidly measure the expression of viral proteins in infected cells and to establish a novel approach to detect viral titers. Compared with classical approaches, the ICW assay is accurate and time- and cost-effective. Furthermore, the ICW assay provided a high-throughput platform to screen and identify antiviral molecules. Potential antiviral roles of several DExD/H box helicase family members were investigated using the ICW assay, and the results indicated that DDX21 and DDX60 reinforced IFN responses and exerted anti-hantaviral effects, whereas DDX50 probably promoted HTNV replication. Additionally, the ICW assay was also applied to assess NAb titers in patients and vaccine recipients. Patients with prompt production of NAbs tended to have favorable disease outcomes. Modest NAb titers were found in vaccinees, indicating that current vaccines still require improvements as they cannot prime host humoral immunity with high efficiency. Taken together, our results indicate that the use of the ICW assay to evaluate non-CPE Hantaan virus titer demonstrates a significant improvement over current infectivity approaches and a novel technique to screen antiviral molecules and detect NAb efficacies.

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.