Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses.Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments.Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry.Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.

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Background and purpose: Synaptic deficiency is generally accepted to be involved in major depression, and accordingly classic antidepressants exert their effects through enhancing synaptic efficiency. Hypericin is one of the major active constituents of extracts of St. John's Wort (Hypericum perforatum L.) with antidepressive actions, but little is known about its therapeutic mechanisms. Our aim was to explore whether hypericin has a modulatory effect on neuronal action potential (AP) duration by acting on voltage-gated ion channels. Experimental approach: We used voltage-clamp and current-clamp techniques in a whole-cell configuration to study primary cultures of neonatal rat hippocampal neurones. We measured the effects of extracellularly applied hypericin on AP duration as well as on voltage-gated Na + , IA and IK currents. Key results: Extracellularly applied hypericin dose-dependently increased AP duration but barely affected its amplitude. Further analysis revealed that hypericin inhibited both transient IA and delayed rectifier IK potassium currents. In contrast, hypericin exerted no significant effect on both Na + peak current and its decay kinetics. Conclusions and implications:Extracellularly applied hypericin increased AP duration, which might be ascribed to its effect on IA and IK currents. As a small increase in AP duration could lead to a dramatic increase in synaptic efficiency, our results imply that hypericin might exert its antidepressant effects by enhancing presynaptic efficiency.

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AbstractObjectiveShigellosis has been a heavy burden in China. However, its relative transmissibility in male and female individuals remains unclear.MethodA sex-based Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to explore the dataset of reported shigellosis cases built by Hubei Province from 2005 to 2017. Two indicators, secondary attack rate (SAR) and relative ratio of SAR between males and females, were developed to assess the relative transmissibility in males and females.ResultsThe number of cases and reported incidences in males and females demonstrated a significant decreasing trend (Male trend: χ2 = 11.268, P = 0.001, Female trend: χ2 = 11.144, P = 0.001). SEIAR model had a great fitting effect with the data of shigellosis (P < 0.001). Our simulation revealed that, when parameter βfm = 0, the greatest decrease in cases were obtained for different genders. The median value for SARmm was 2.3225 × 10−8 (Range: 1.7574 × 10−8 – 3.8565 × 10−8), SARmf was 2.5729 × 10−8 (Range: 1.3772 × 10−8 – 3.2773 × 10−8), SARfm was 2.7630 × 10−8 (Range: 1.8387 × 10−8 – 4.2638 × 10−8) and SARff was 2.1061 × 10−8 (Range: 1.0201 × 10−8 – 3.2140 × 10−8). The median value of relative ratio calculated by SAR in mm versus (vs) mf was 0.93 (Range: 0.75 – 1.47), mm vs fm was 0.90 (Range: 0.41 – 1.81), mm vs ff was 1.07 (Range: 0.55 – 2.93), mf vs fm was 0.99 (Range: 0.32 – 1.25), mf vs ff was 1.17 (Range: 0.43 – 3.21) and ff vs fm was 0.75 (Range: 0.35 – 1.06).ConclusionTransmissibility of shigellosis is different among male and female individuals. Shigellosis seems to be more transmissible in males than in females.Author summaryShigellosis, also known as bacillary dysentery, is an infectious disease caused by the genus Shigella spp. Developing countries have high disease burden of shigellosis. However, its relative transmissibility in male and female individuals remains unclear. In this study, we employed a mathematical model to explore the dataset of reported shigellosis cases built by Hubei Province, China from 2005 to 2017. Two indicators, secondary attack rate (SAR) and relative ratio of SAR between males and females, were developed to assess the relative transmissibility in males and females. We found that shigellosis has medium transmissibility among male and female individuals. The disease seems to be more transmissible in males than in females.