A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans. The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic. www.eurosurveillance.org Methods Virus sampling and isolation Specimens as well as clinical and epidemiological information were collected from human cases. Environmental samples and avian samples were collected in the area where human cases identified. Virus isolation was conducted by Chinese National Influenza Center (CNIC) in a biosafety level 3 facility using nineday-old specific pathogen-free (SPF) embryonated chicken eggs and incubated at 37 °C for 48-72 hours. The allantoic fluid was harvested, aliquoted and stored at-80 ºC until use. RNA extraction and genome sequencing Viral RNA was extracted using QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany). Gene segments were amplified using the Qiagen OneStep RT-PCR Kit. A total of 48 primer pairs were used to generate PCR amplicons between 378 and 1,123 bp in length for full genome sequencing. Primer sequences are available from the authors on request. Amplified PCR products were purified using ExoSAP-IT reagent (USB, Cleveland, US). Complete genome sequencing was performed with an ABI 3730XL automatic DNA analyser (Applied Biosystems, Foster City, US) using the ABI BigDye Terminator v3.1 cycle sequencing kit (Applied Biosystems; Foster City, US). HA: haemagglutinin; NA: neuraminidase. Red dots represent the common ancestor of the novel H7N9 virus. A/Shanghai/5/2013 and A/Shanghai/1/2013 are highlighted in pink and green, respectively. Schematic unrooted trees of HA and NA genes are shown in lower left boxes. The authors gratefully acknowledge the originating and submitting laboratories who contributed sequences used in the phylogenetic analysis to GISAID, and recognise in ...
The Forkhead box M1 transcription factor (FoxM1) is essential for DNA replication and mitosis, and has important role in cell proliferation and apoptosis. To assess the role of FoxM1 in chemoresistance, we investigated FoxM1 protein expression and the correlation between FoxM1 expression, sensitivity to cisplatin-based therapy, and the survival of non-small cell lung cancer (NSCLC) patients. We generated a cisplatin-resistant lung cancer cell line (A549/CDDP) that showed elevated expression levels of FoxM1 protein and mRNA relative to those of the parental A549 cells. We investigated the effect of the knockdown or overexpression of FoxM1 on the sensitivity to cisplatin and the possible signaling transduction pathways in these cells. Our results revealed that the positive expression rate of FoxM1 in NSCLC was associated with chemosensitivity to cisplatin and a poor prognosis. When the expression of FoxM1 was inhibited by RNA interference, the sensitivity to cisplatin was enhanced. Inversely, in FoxM1-overexpressing cell models, we observed a reduced sensitivity to cisplatin. Moreover, we showed that the downregulation of FoxM1 enhanced cisplatin-induced A549/CDDP cell apoptosis through the activation of the c-Jun NH2-terminal kinase (JNK)/mitochondrial pathway. These results suggest that FoxM1 plays a critical role in chemoresistance to cisplatin and that FoxM1 depletion may be a promising approach to lung cancer therapy.
In this paper, the hazard factors of an optical enterprise were analyzed, and the appropriate prevention and control measures were discussed. The field investigation and detection of occupational health was applied. The on spot monitoring results showed that the over-standard rate of acetone in the workplace was 10.0%, the over-standard rate of trichloroethylene was 25.0%, the over-standard rate of dichloromethane was 50.0%, and the over-standard rate of noise was 23.8%. Acetone, trichloroethylene, dichloromethane and noise were the key points of prevention and control in this optical enterprise. It was suggested that the ventilation system of the cleaning workshop should been improved comprehensively, and the workers’ hearing protection measures should been increased to effectively protect their health.
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