Graphical Abstract Highlights d Pangolin-CoV is 91.02% identical to SARS-CoV-2 at the whole-genome level d Pangolin-CoV is the second closest relative of SARS-CoV-2 behind RaTG13 d Five key amino acids in the RBD are consistent between Pangolin-CoV and SARS-CoV-2 d Only SARS-CoV-2 contains a potential cleavage site for furin proteases SUMMARY An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1].We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the wholegenome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.

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SUMMARY Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate γδT (γδT17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.

BackgroundBacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944.ResultsWe hypothesized that persisters are dormant cells with a low level of translation, and used this to physically sort dim E. coli cells which do not contain sufficient amounts of unstable GFP expressed from a promoter whose activity depends on the growth rate. The dim cells were tolerant to antibiotics and exhibited a gene expression profile distinctly different from those observed for cells in exponential or stationary phases. Genes coding for toxin-antitoxin module proteins were expressed in persisters and are likely contributors to this condition.ConclusionWe report a method for persister isolation and conclude that these cells represent a distinct state of bacterial physiology.