COVER An alpine newt (Ichthyosaura alpestris) walks to a breeding pond in the Alps, France. Many amphibians have a cryptic upper side but a normally concealed, conspicuous underside. These hidden signals have evolved for several reasons, including as a warning display to would-be predators. A phylogenetic analysis reveals that species with hidden colors represent an important intermediate step in the evolution of species with permanently displayed warning signals. See page 1136.

Photo: Cyril Ruoso/NPL/Minden Pictures

ONLINE COVER Tears reveal more than just emotion. Tears' extracellular vesicles (EVs) allow us to see molecular-level signs of different diseases or actions of other organs inside our bodies. Hu et al. found that tear EVs act as immune effectors, maintain retinal homeostasis, and regulate inflammation. The rich bioinformation that tears carry offer value beyond the ocular system.

ONLINE COVER Glycoengineering the Tip of the Spear. This month’s cover depicts cellular soldiers (blue myeloid cells at the left and green T cells at the right) rushing to battle cancer cells. Leading the charge is an Fc-enhanced form of an anti–PD-L1 checkpoint blockade antibody. Using mice humanized to express human Fcγ receptors (FcγRs), Saban et al. found that the in vivo antitumor activity of anti–PD-L1 antibodies was enhanced by removing fucose residues from glycans on the human IgG1 Fc region to promote binding to activating FcγRs on myeloid cells. Treatment with afucosylated anti–PD-L1 enabled depletion of immunosuppressive PD-L1⁺ cells in the tumor microenvironment and blocked inhibitory signaling in PD-1⁺ T cells. These findings suggest that modifications in the Fc scaffold of currently used anti–PD-L1 immunotherapy drugs could yield a boost in their antitumor activity.

ONLINE COVER Robust robots. The ability of robots to endure severe damage, as well as offer the possibility for repair, can enable their deployment in challenging settings. Kim et al. have developed aerial robots that can endure several punctures while sustaining controlled flight. The dielectric elastomer actuators on the robots were also designed to be repairable by using laser ablation to isolate the defects and recover their performance. This month’s cover is a photograph of the aerial robot showing one dielectric elastomer actuator pierced with fiberglass needles.

ONLINE COVER This week, Wang et al. show that SUMOylation of interleukin-33 in the nucleus of hepatocellular carcinoma (HCC) cells disrupts its ability to regulate a transcription factor, leading to the production of immunomodulatory proteins that suppress the antitumor functions of macrophages and T cells. The image is a colored transmission electron micrograph featuring the nucleus and fat droplets within an HCC cell.

ONLINE COVER Navigating Nephritis. Shown is a confocal micrograph of kidney tissue from a mouse treated with a matrix metalloproteinase 12 (MMP12) inhibitor for glomerulonephritis. Fibrin and fibrinogen are shown in green, collagen IV in blue, major histocompatibility complex class II in red, and DNA in white. Paust et al. characterized pathological immune cells in patients with glomerulonephritis as well as in mouse models. The authors identified a CD4⁺ T cell–granulocyte-macrophage colony-stimulating factor (GM-CSF)–monocyte-derived cell–MMP12 axis that drove disease in mice. Targeting GM-CSF signaling or MMP12 reduced glomerulonephritis severity in the murine model, suggesting that similar inhibition of this pathway could be beneficial for patients with this disease.