Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression, but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and rescued viral infection-induced mouse weight loss, but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.

ABSTRACT:The incomplete mass-balance of organic fluorine in human serum indicates the existence of unknown per-and polyfluoroalkyl substances (PFASs) with persistent and bioaccumulative properties. Here we characterized human exposure and elimination kinetics of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) in metal plating workers (n = 19), high fish consumers (n = 45), and background controls (n = 8). Cl-PFESAs were detected in >98% of the sampled individuals with serum concentrations ranging <0.019−5040 ng/mL. Statistically higher median serum levels were observed in high fish consumers (93.7 ng/mL) and metal plating workers (51.5 ng/mL) compared to the background control group (4.78 ng/mL) (Kruskal−Wallis rank sum test, p < 0.01). Cl-PFESAs could account for 0.269 to 93.3% of ∑PFASs in human serum indicating that this compound class may explain a substantial fraction of previously unidentified organic fluorine in the Chinese population. Estimated half-lives for renal clearance (median 280 years; range 7.1−4230 years) and total elimination (median 15.3 years; range 10.1−56.4 years) for the eight carbon Cl-PFESA suggest that this is the most biopersistent PFAS in humans reported to date. The apparent ubiquitous distribution and slow elimination kinetics in humans underscore the need for more research and regulatory actions on Cl-PFESAs and PFAS alternatives with similar chemical structures.

Following the global actions to phase out perfluoroctanesulfonic acid (PFOS) a large number of alternative per- and polyfluoroalkyl substances, with poorly defined hazard properties, are being used in increasing quantities. Here, we report on the first detection of the chlorinated polyfluoroalkyl ether sulfonic acid F-53B in biological samples and determine the tissue distribution and whole body bioaccumulation factors (BAFwhole body) in crucian carp (Carassius carassius). Analysis of fish samples from Xiaoqing River (XR) and Tangxun Lake (TL) demonstrated a similar level of F-53B contamination with median concentrations in blood of 41.9 and 20.9 ng/g, respectively. Tissue/blood ratios showed that distribution of F-53B primarily occurs to the kidney (TL: 0.48, XR: 0.54), gonad (TL: 0.36, XR: 0.54), liver (TL: 0.38, XR: 0.53), and heart (TL: 0.47, XR: 0.47). Median Log BAFwhole body values for F-53B (XR: 4.124, TL: 4.322) exceeded regulatory bioaccumulation criterion and were significantly higher than those of PFOS in the same data sets (XR: 3.430, TL: 3.279). On the basis of its apparent omnipresence and strong bioaccumulation propensity, it is hypothesized that F-53B could explain a significant fraction of previously unidentified organofluorine in biological samples from China, and regulatory actions for this compound are encouraged.

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