Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce.OBJECTIVE To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.

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The majority of plant viruses are transmitted by insect vectors between hosts, and transovarial transmission of viruses from vector parents to offspring has great significance to their epidemiology. Begomoviruses are transmitted by the whitefly Bemisia tabaci in a circulative manner and are maintained through a plantinsect-plant cycle. Other routes of begomovirus transmission are not clearly known. Here, we report that transovarial transmission from female whiteflies to offspring often happens for one begomovirus, Tomato yellow leaf curl virus (TYLCV), and may have contributed significantly to its global spread. We found that TYLCV entry of the reproductive organ of its vector mainly depended on the developmental stage of the whitefly ovary, and the transovarial transmission of TYLCV to offspring increased with whitefly adult age. The specific interaction between virus coat protein (CP) and whitefly vitellogenin (Vg) was vital for virus entry into whitefly ovary. When knocking down the expression of Vg, the entry of TYLCV into ovary was inhibited and the transovarial transmission efficiency decreased. In contrast, another begomovirus, Papaya leaf curl China virus (PaLCuCNV), CP did not interact with whitefly Vg, and PaLCuCNV could not be transovarially transmitted by whiteflies. We further showed that TYLCV could be maintained for at least two generations in the absence of virusinfected plants, and the adult progenies were able to infect healthy plants in both the laboratory and field. This study reports the transovarial transmission mechanism of begomoviruses, and it may help to explain the evolution and global spread of some begomoviruses.begomovirus | transovarial transmission | vector development | vitellogenin | whitefly

BackgroundMany applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA double strand breaks may be repaired preferentially by accurate NHEJ.ResultsIn the repair of two adjacent double strand breaks induced by paired Cas9-gRNAs at 71 genome sites, accurate NHEJ accounts for about 50% of NHEJ events. This paired Cas9-gRNA approach underestimates the level of accurate NHEJ due to frequent + 1 templated insertions, which can be avoided by the predefined Watson/Crick orientation of protospacer adjacent motifs (PAMs). The paired Cas9-gRNA strategy also provides a flexible, reporter-less approach for analyzing both accurate and mutagenic NHEJ in cells and in vivo, and it has been validated in cells deficient for XRCC4 and in mouse liver. Due to high frequencies of precise deletions of defined “3n”-, “3n + 1”-, or “3n + 2”-bp length, accurate NHEJ is used to improve the efficiency and homogeneity of gene knockouts and targeted in-frame deletions. Compared to “3n + 1”-bp, “3n + 2”-bp can overcome + 1 templated insertions to increase the frequency of out-of-frame mutations. By applying paired Cas9-gRNAs to edit MDC1 and key 53BP1 domains, we are able to generate predicted, precise deletions for functional analysis. Lastly, a Plk3 inhibitor promotes NHEJ with bias towards accurate NHEJ, providing a chemical approach to improve genome editing requiring precise deletions.ConclusionsNHEJ is inherently accurate in repair of Cas9-induced DNA double strand breaks and can be harnessed to improve CRISPR/Cas9 genome editing requiring precise deletion of a defined length.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1518-x) contains supplementary material, which is available to authorized users.

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BackgroundIn spite of progress in diagnostics and treatment of Hepatocellular Carcinoma (HCC), its prognosis remains poor, and improved treatment strategies for HCC require detailed understanding of the underlying mechanism. In this investigation we studied the role of Up-frameshift 1 (UPF1) in the tumorigenesis of HCC.MethodsWe determined the expression level of UPF1 in HCC tissues with quantitative real-time PCR and western blotting and then studied its clinical significance. Sodium bisulfite sequencing was used to investigate the regulation of UPF1. We explored the biological significance of UPF1 with gain-and-loss-of-function analyses both in vitro and in vivo. The relationship between UPF1 and SMAD7 was also investigated by western blotting and immunofluorescence.ResultsA great downregulation of UPF1 due to promoter hypermethylation was observed in tumor tissues compared to their adjacent normal tissues. Meanwhile, patients with low UPF1 expression have significantly poorer prognosis than those with high expression. Functionally, UPF1 regulated HCC tumorigenesis both in vitro and in vivo. Moreover, the decreased UPF1 level in HCC reduces NMD efficiency and leads to up-regulation of Smad7, then affects the TGF-β pathway.ConclusionOur findings revealed that UPF1 is a potential tumor suppressive gene and may be a potential therapeutic target for HCC.

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A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) metastasis is driven by lung cancer stem cell-like cells (LCSCs), but the underlying mechanisms remain unclear. Here, we aim to investigate biological function of CD44 in regulating metastatic trait of LCSCs and its underlying mechanisms. In this study, we found that CD133 CD44 cells which were derived from primary lung adenocarcinoma (LAC) possessed cancer stem cell-like features. Furthermore, CD44 was demonstrated functionally crucial to drive metastatic potential of CD133 CD44 LCSCs by in vitro and in vivo experiments. In patient cohorts, high level of CD44 predicted increased probability of metastasis. Significantly, microarray revealed that FoxM1 and key proteins of Wnt/β-catenin pathway were up-regulated in CD133 CD44 LCSCs compared with those in CD133 CD44 cells. Then, we demonstrated that CD44 promoted metastatic activity in CD133 CD44 LCSCs through Wnt/β-catenin pathway and FoxM1 was the downstream target of Wnt/β-catenin pathway. Meanwhile, our findings indicated that FoxM1 promoted metastatic activity in CD133 CD44 LCSCs by inducing EMT and Twist was a direct transcriptional target of FoxM1. Collectively, CD44, both a functional biomarker and therapeutic target, promoted CD133 CD44 LCSCs metastasis by Wnt/β-catenin-FoxM1-Twist signaling. This study provided support for the missing link between EMT and CSCs surface-marker and supplied a promising approach for elimination of LCSCs by targeting CD44-Wnt/β-catenin-FoxM1-Twist signaling. © 2015 Wiley Periodicals, Inc.