BackgroundIn early 2020, during the COVID-19 pandemic, New Zealand implemented graduated, risk-informed national COVID-19 suppression measures aimed at disease elimination. We investigated their impacts on the epidemiology of the first wave of COVID-19 in the country and response performance measures. MethodsWe did a descriptive epidemiological study of all laboratory-confirmed and probable cases of COVID-19 and all patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New Zealand from Feb 2 to May 13, 2020, after which time community transmission ceased. We extracted data from the national notifiable diseases database and the national SARS-CoV-2 test results repository. Demographic features and disease outcomes, transmission patterns (source of infection, outbreaks, household transmission), time-to-event intervals, and testing coverage were described over five phases of the response, capturing different levels of non-pharmaceutical interventions. Risk factors for severe outcomes (hospitalisation or death) were examined with multivariable logistic regression and time-to-event intervals were analysed by fitting parametric distributions using maximum likelihood estimation. Findings 1503 cases were detected over the study period, including 95 (6•3%) hospital admissions and 22 (1•5%) COVID-19 deaths. The estimated case infection rate per million people per day peaked at 8•5 (95% CI 7•6-9•4) during the 10-day period of rapid response escalation, declining to 3•2 (2•8-3•7) in the start of lockdown and progressively thereafter. 1034 (69%) cases were imported or import related, tending to be younger adults, of European ethnicity, and of higher socioeconomic status. 702 (47%) cases were linked to 34 outbreaks. Severe outcomes were associated with locally acquired infection (crude odds ratio [OR] 2•32 [95% CI 1•40-3•82] compared with imported), older age (adjusted OR ranging from 2•72 [1•40-5•30] for 50-64 year olds to 8•25 [2•59-26•31] for people aged ≥80 years compared with 20-34 year olds), aged residential care residency (adjusted OR 3•86 [1•59-9•35]), and Pacific peoples (adjusted OR 2•76 [1•14-6•68]) and Asian (2•15 [1•10-4•20]) ethnicities relative to European or other. Times from illness onset to notification and isolation progressively decreased and testing increased over the study period, with few disparities and increasing coverage of females, Māori, Pacific peoples, and lower socioeconomic groups.Interpretation New Zealand's response resulted in low relative burden of disease, low levels of population disease disparities, and the initial achievement of COVID-19 elimination.

Background Emerging evidence indicates that tumor cells release a large amount of exosomes loaded with cargos during tumorigenesis. Exosome secretion is a multi-step process regulated by certain related molecules. Long non-coding RNAs (lncRNAs) play an important role in hepatocellular carcinoma (HCC) progression. However, the role of lncRNA HOTAIR in regulating exosome secretion in HCC cells remains unclear. Methods We analyzed the relationship between HOTAIR expression and exosome secretion-related genes using gene set enrichment analysis (GSEA). Nanoparticle tracking analysis was performed to validate the effect of HOTAIR on exosome secretion. The transport of multivesicular bodies (MVBs) after overexpression of HOTAIR was detected by transmission electron microscopy and confocal microscopy analysis of cluster determinant 63 (CD63) with synaptosome associated protein 23 (SNAP23). The mechanism of HOTAIR’s regulation of Ras-related protein Rab-35 (RAB35), vesicle associated membrane protein 3 (VAMP3), and SNAP23 was assessed using confocal co-localization analysis, phosphorylation assays, and rescue experiments. Results We found an enrichment of exosome secretion-related genes in the HOTAIR high expression group. HOTAIR promoted the release of exosomes by inducing MVB transport to the plasma membrane. HOTAIR regulated RAB35 expression and localization, which controlled the docking process. Moreover, HOTAIR facilitated the final step of fusion by influencing VAMP3 and SNAP23 colocalization. In addition, we validated that HOTAIR induced the phosphorylation of SNAP23 via mammalian target of rapamycin (mTOR) signaling. Conclusion Our study demonstrated a novel function of lncRNA HOTAIR in promoting exosome secretion from HCC cells and provided a new understanding of lncRNAs in tumor cell biology. Electronic supplementary material The online version of this article (10.1186/s12943-019-0990-6) contains supplementary material, which is available to authorized users.

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BackgroundHypoxia-inducible factor 1α (HIF-1α) is essential in hepatocellular carcinoma (HCC) glycolysis and progression. Yes-associated protein (YAP) is a powerful regulator and is overexpressed in many cancers, including HCC. The regulatory mechanism of YAP and HIF-1α in HCC glycolysis is unknown.MethodsWe detected YAP expression in 54 matched HCC tissues and the adjacent noncancerous tissues. The relationship between YAP mRNA expression and that of HIF-1α was analyzed using The Cancer Genome Atlas HCC tissue data. We cultured HepG2 and Huh7 HCC cells under normoxic (20% O2) and hypoxic (1% O2) conditions, and measured the lactate and glucose levels, migration and invasive capability, and the molecular mechanism of HCC cell glycolysis and progression.ResultsIn this study, we detected YAP expression in 54 matched HCC tissues and the adjacent noncancerous tissues. We observed that hypoxia-induced YAP activation is crucial for accelerating HCC cell glycolysis. Hypoxia inhibited the Hippo signaling pathway and promoted YAP nuclear localization, and decreased phosphorylated YAP expression in HCC cells. YAP knockdown inhibited HCC cell glycolysis under hypoxic. Mechanistically, hypoxic stress in the HCC cells promoted YAP binding to HIF-1α in the nucleus and sustained HIF-1α protein stability to bind to PKM2 gene and directly activates PKM2 transcription to accelerate glycolysis.ConclusionsOur findings describe a new regulatory mechanism of hypoxia-mediated HCC metabolism, and YAP might be a promising therapeutic target in HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0892-2) contains supplementary material, which is available to authorized users.