The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1+TIM-3+ T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3+ cytotoxic CD8 T cells and immunosuppressive regulatory T cells (Treg cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes Treg cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.

The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.

Discovering new functional genes, designing perfect crystal structures, and developing high‐performance materials are the goals being pursued by scientists. Herein, the first antimony pyrophosphate, K2Sb(P2O7)F, possessing an optimal layered structure, is reported, where the perfect structural arrangement induces excellent optical properties. K2Sb(P2O7)F not only displays a sharply enhanced birefringence (0.157@546 nm) compared to the existing phosphate optical materials, but also exhibits a strong second‐harmonic generation response (4.0×KDP). Remarkably, a new bifunctional gene, the square‐pyramidal SbO4F group, was discovered, and a unique two‐dimensional arrangement of Cairo pentagonal tiling units was observed in inorganic compounds for the first time.

This paper presents both experimental and theoretical investigations of the sensing capabilities of graphite based magnetorheological elastomers (MREs). In this study, eight MRE samples with varying graphite weight fractions were fabricated and their resistance under different magnetic fields and external loadings were measured with a multi-meter. With an increment of graphite weight fraction, the resistance of MRE sample decreases steadily. Higher magnetic fields result in a resistance increase. Based on an ideal assumption of a perfect chain structure, a mathematical model was developed to investigate the relationship between the MRE resistance with external loading. In this model, the current flowing through the chain structure consists of both a tunnel current and a conductivity current, both of which depend on external loadings. The modelling parameters have been identified and reconstructed from comparison with experimental results. The comparison indicates that both experimental results and modelling predictions agree favourably well.