To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019-nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and the USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood-mapping analyses of the genome sequences were performed. On the basis of the likelihood-mapping analysis, the increasing tree-like signals (from 0% to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019-nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019-nCoV strains. The estimated mean evolutionary rate for 2019-nCoV ranged from 1.7926 × 10^-3 to 1.8266 × 10^-3 substitutions per site per year. On the basis of our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019-nCOV transmission in real-time.

Although autophagy is most critical for survival of cancer cells, especially in fast-growing tumors, the mechanism remains to be fully characterized. Herein we report that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes. PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation. Subsequently, PSMD10 translocated into the nucleus and bound cooperatively with nuclear HSF1 (heat shock transcription factor 1) onto the ATG7 promoter, upregulated ATG7 expression in the advanced stage of starvation. Intriguingly, the type of PSMD10-mediated autophagy was independent of the proteasome system, although PSMD10 has been believed to be an indispensable chaperone for assembly of the 26S proteasome. A significant correlation between PSMD10 expression and ATG7 levels was detected in human HCC biopsies, and the combination of these 2 parameters is a powerful predictor of poor prognosis. The median survival of sorafenib-treated HCC patients with high expression of PSMD10 was much shorter than those with low expression of PSMD10. Furthermore, PSMD10 augmented autophagic flux to resist sorafenib or conventional chemotherapy, and inhibition of autophagy suppressed PSMD10-mediated resistance. We conclude that these results present a novel mechanism involving modulation of ATG7 by PSMD10 in sustaining autophagy, promoting HCC cell survival against starvation or chemotherapy. Targeting of PSMD10 might therefore be an attractive strategy in HCC treatment by suppressing autophagy and inducing HCC cell sensitivity to drugs.