Background: Blood urea nitrogen to albumin ratio (BAR) has been implicated in predicting outcomes of various inflammatory-related diseases. However, the predictive value of BAR in long-term mortality in patients with acute myocardial infarction (AMI) has not yet been evaluated. Methods: In this retrospective cohort study, the patients were recruited from the Medical Information Mart for Intensive Care III (MIMIC III) database and categorized into two groups by a cutoff value of BAR. Kaplan–Meier (K-M) analysis and Cox proportional hazard model were performed to determine the predictive value of BAR in long-term mortality following AMI. In order to adjust the baseline differences, a 1:1 propensity score matching (PSM) was carried out and the results were further validated. Results: A total of 1827 eligible patients were enrolled. The optimal cutoff value of BAR for four-year mortality was 7.83 mg/g. Patients in the high BAR group tended to have a longer intensive care unit (ICU) stay and a higher rate of one-, two-, three- and four-year mortality (all p< 0.001) compared with those in the low BAR group. K-M curves indicated a significant difference in four-year survival (p< 0.001) between low and high BAR groups. The Cox proportional hazards model showed that higher BAR (> 7.83) was independently associated with increased four-year mortality in the entire cohort, with a hazard ratio (HR) of 1.478 [95% CI (1.254– 1.740), p< 0.001]. After PSM, the baseline characteristics of 312 pairs of patients in the high and low BAR groups were well balanced, and similar results were observed in K-M curve (p=0.003). Conclusion: A higher BAR (> 7.83) was associated with four-year mortality in patients with AMI. As an easily available biomarker, BAR can predict the long-term mortality in AMI patients independently.

Red blood cells (RBCs) generated ex vivo have the potential to be used for transfusion. Human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) possess unlimited self‐renewal capacity and are the preferred cell sources to be used for ex vivo RBC generation. However, their applications are hindered by the facts that the expansion of ES/iPS‐derived erythroid cells is limited and the enucleation of ES/iPS‐derived erythroblasts is low compared to that derived from cord blood (CB) or peripheral blood (PB). To address this, we sought to investigate the underlying mechanisms by comparing the in vitro erythropoiesis profiles of CB CD34⁺ and ES CD34⁺ cells. We found that the limited expansion of ES CD34⁺ cell‐derived erythroid cells was associated with defective cell cycle of erythroid progenitors. In exploring the cellular and molecular mechanisms for the impaired enucleation of ES CD34⁺ cell‐derived orthochromatic erythroblasts (ES‐ortho), we found the chromatin of ES‐ortho was less condensed than that of CB CD34⁺ cell‐derived orthochromatic erythroblasts (CB‐ortho). At the molecular level, both RNA‐seq and ATAC‐seq analyses revealed that pathways involved in chromatin modification were down‐regulated in ES‐ortho. Additionally, the expression levels of molecules known to play important role in chromatin condensation or/and enucleation were significantly lower in ES‐ortho compared to that in CB‐ortho. Together, our findings have uncovered mechanisms for the limited expansion and impaired enucleation of ES CD34⁺ cell‐derived erythroid cells and may help to improve ex vivo RBC production from stem cells.

Alzheimer's disease (AD) is the most common neurodegenerative disease and is manifested by memory loss and spatial disorientation. There is currently no effective treatment for AD. Abnormalities of the chromosome 9 open reading frame 72 (C9orf72) gene have been associated with various neurodegenerative diseases. However, its intrinsic roles in AD remain to be elucidated. Here we found that A beta(25-35) increased the expression of C9orf72 in PC12 cells at both mRNA and protein levels. In A beta(25-35)-treated PC12 cells, C9orf72 overexpression induced an abnormally condensed and fragmented nucleus and apoptosis, as well as significantly enhanced reactive oxygen species (ROS) levels. Mechanistically, an A beta(25-35)-induced decrease of superoxide dismutase activity was augmented by C9orf72 overexpression, which in contrast increased malondialdehyde content. Consistently, further apoptotic analysis revealed significant downregulation of Bcl-2 and Bcl-xL expression and enhanced cleavage of caspase-3 with A beta(25-35) treatment, all of which were exacerbated by C9orf72 overexpression. In addition, tau phosphorylation, another hallmark of AD pathology, was induced by A beta(25-35) and was remarkably enhanced by C9orf72 overexpression. Our data indicate that C9orf72 plays important roles in intracellular ROS signaling and A beta(25-35)-induced neuronal apoptosis in AD. These findings provide insights into C9orf72 function in the pathogenesis of many related neurodegenerative diseases and provide a basis for potential therapeutic interventions.