Yuanyuan Fu

BACKGROUND: With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. METHODS: A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into 3 disease severity groups (nonsevere, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. RESULTS: Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age >65 years (P < .001), smoking (P = .001), critical disease status (P = .002), diabetes (P = .025), high hypersensitive troponin I (>0.04 pg/mL, P = .02), leukocytosis (>10 × 109/L, P < .001), and neutrophilia (>75 × 109/L, P < .001) predicted unfavorable clinical outcomes. In contrast, the administration of hypnotics was significantly associated with favorable outcomes (P < .001), which was confirmed by survival analysis. CONCLUSIONS: Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.

assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.

BACKGROUND/AIMS: It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs. METHODS: Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis. Platelets from healthy volunteers and mice were purified to obtain thrombin stimulated platelet-derived exosomes. Exosomes were isolated via differential ultracentrifugation, and western blotting and transmission electron microscopy were used for their identification. The total RNA was extracted, and quantitative real-time PCR was performed to determine the expression levels of miR-223, miR-339 and miR-21. DAVID Tools were used to analyze the pathways that were enriched among the miRNA target genes. Immuno-fluorescence staining was performed to identify the protein expression levels of platelet-derived exosome target genes in vascular smooth muscle cells (SMCs) in vitro and in vivo. RESULTS: The levels of miR-223, miR-339 and miR-21, which are associated with platelet activation, were elevated in pooled mouse plasma exosomes before thrombosis and enriched in thrombin-stimulated platelet-derived exosomes in vitro. Platelet-derived growth factor receptor-beta (PDGFRβ) was a target of these miRNAs, and PDGFRβ expression in vascular smooth muscle cells (SMCs) was inhibited following incubation with platelet-derived exosomes. Platelet-derived exosomes could also inhibit PDGF-stimulated SMC proliferation. Furthermore, a decrease in PDGFRβ expression was observed in vascular SMCs around thrombotic areas in vivo. CONCLUSIONS: Our data indicate that activated platelet-derived exosomes containing miR-223, miR-339 and miR-21 could be transferred into SMCs and inhibit PDGFRβ expression; these exosomal miRNAs may be a biomarker for predicting atherothrombosis.

Mei (Prunus mume) is an ornamental woody plant that has been domesticated in East Asia for thousands of years. High diversity in floral traits, along with its recent genome sequence, makes mei an ideal model system for studying the evolution of woody plants. Here, we investigate the genetic architecture of floral traits in mei and its domestication history by sampling and resequencing a total of 351 samples including 348 mei accessions and three other Prunus species at an average sequencing depth of 19.3×. Highly-admixed population structure and introgression from Prunus species are identified in mei accessions. Through a genome-wide association study (GWAS), we identify significant quantitative traits locus (QTLs) and genomic regions where several genes, such as MYB108, are positively associated with petal color, stigma color, calyx color, and bud color. Results from this study shed light on the genetic basis of domestication in flowering plants, particularly woody plants.

To investigate the biologic relevance and clinical implication of genes involved in multiple gene expression signatures for breast cancer prognosis, we identified 16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1. These genes appeared in 5 signatures and were involved in cell-cycle regulation. We analyzed the expression of these genes in relation to tumor features and disease outcomes. In vitro experiments were also performed in two breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration and invasion after knocking down the expression of these genes. High expression of these genes was found to be associated with aggressive tumors and poor disease-free survival of 203 breast cancer patients in our study, and the association with survival was confirmed in an online database consisting of 914 patients. In vitro experiments demonstrated that lowering the expression of these genes by siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our investigation suggests that MAD2L1 and BUB1 may play important roles in breast cancer progression, and measuring the expression of these genes may assist the prediction of breast cancer prognosis.