Yan Liu

The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short β-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificity. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.

Abstract We examined how external stakeholder pressure and ethical leadership independently and interactively influence the implementation of corporate social responsibility. Based on data collected from 292 employees from 53 companies (Study 1) and from 224 middle-level managers from 40 companies (Study 2) in mainland China, we found that both ethical leadership and external stakeholder pressure have significant and positive impacts on corporate social responsibility implementation and the positive effect of external stakeholder pressure on corporate social responsibility weakens under a higher level of ethical leadership and strengthens under a low level of ethical leadership. The theoretical and practical implications of these findings are discussed.

Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively correlates with RA disease severity as does lipid hyperoxidation of focal monocyte/macrophages. Further study reveals high susceptibility to iron induced ferroptosis of the anti-inflammatory macrophages M2, while pro-inflammatory M1 are less affected. Distinct glutathione peroxidase 4 (GPX4) degradation depending on p62/SQSTM1 in the two cell types make great contribution mechanically. Of note, ferroptosis inhibitor liproxstatin-1 (LPX-1) can alleviate the progression of K/BxN serum-transfer induced arthritis (STIA) mice accompanied with increasing M2 macrophages proportion. We thus propose that the heterogeneous ferroptosis susceptibility of macrophage subtypes as well as consequent inflammation and immune disorders are potential biomarkers and therapeutic targets in RA.

iNOS plays an important role in mediating inflammation. In this study, we found that iNOS-derived NO was increased 2.4-fold in the serum samples of 101 patients infected with influenza A virus in comparison with samples of 105 healthy individuals. In A549 human lung epithelial cells, infection with influenza A virus or stimulation with poly(I:C)+IFN-gamma resulted in increased mRNA and protein levels of both IL-32 and iNOS, with subsequent release of NO. Over-expression of IL-32 resulted in upregulated iNOS expression with subsequent NO production. Knock down of IL-32 by IL-32-specific siRNA resulted in the inhibition of dsRNA-induced expression of iNOS and NO release, indicating that IL-32 is an upstream regulatory factor of dsRNA-triggered iNOS production. Surprisingly, over-expression of iNOS resulted in the reduction of IL-32 expression, and suppression of iNOS by the selective iNOS inhibitor S-methylisothiourea sulfate stimulated IL-32 expression, indicating that a negative feedback mechanism operates between the iNOS/NO and IL-32 systems. These findings suggest that influenza A virus infection activates IL-32 and iNOS expression by a heretofore unrecognized complex mechanism, in which the two pro-inflammatory factors regulate each other, involving positive and negative feedback regulatory loops.