COVER Researchers have developed deep-learning methods to predict the structures of proteins in complex with small molecules, nucleic acids, and other nonprotein components and to design proteins to bind to small molecules. The illustration shows a background cloud of amino acids and short peptides coming together to form the central blue protein around a target ligand, heme, shown in orange. See eadl2528.

Image: C. Bickel/Science. Data: R. Krishna et al., Science 384, eadl2528 (2024).

ONLINE COVER An artistic depiction showing the delivery of DNA molecules via acousto-thermal transfection into a human cell. This technique uses acoustic waves and localized heating to enhance the permeability of cell membranes. Previous methods faced difficult tradeoffs between efficiency and cell viability. Liu et al. propose an acoustothermal transfection approach combining acoustic and thermal effects on cells to realize the efficient delivery of multiple large plasmids while maintaining cell viability and easy scalability. This approach may become a powerful tool for future cellular and gene therapies.

ONLINE COVER Cultivating Memory B Cell Responses to a Plant-Based Vaccine. CoVLP (coronavirus virus-like particle) is a promising COVID-19 vaccine produced in the weed Nicotiana benthamiana. A squalene-based adjuvant, AS03, can enhance immune responses to CoVLP vaccination, but how AS03 affects memory B cell responses to CoVLP is unknown. Grigoryan et al. studied immune responses in healthy individuals who received two doses of CoVLP with or without AS03. They found that AS03 promoted the progressive maturation of memory B cell responses over time, leading to enhanced neutralization of SARS-CoV-2 and increased memory B cell breadth. This month’s cover illustration depicts a syringe containing a plant-based SARS-CoV-2 vaccine.

ONLINE COVER Special Issue on Legged Robots. Developing legged robots capable of complex motor skills is a major challenge for roboticists. Haarnoja et al. used deep reinforcement learning to train miniature humanoid robots, Robotis OP3, to play a game of one-versus-one soccer. The robots were capable of exhibiting not only agile movements, such as walking, kicking the ball, and rapid recovery from falls, but also emergent behaviors to adapt to the game scenario, such as subtle defensive moves and dynamic footwork in response to the opponent. This month’s cover is an image of the miniature humanoid robot kicking a ball.

ONLINE COVER This week, Mews et al. explore the subcellular protein dynamics in nucleus accumbens (NAc) tissues from mouse models of cocaine use disorder. Their findings may reveal clues as to what drives cocaine addiction and relapse. The image is a diagram of the brain’s reward circuit that is implicated in addiction, highlighting the NAc.

ONLINE COVER Taking Senescence to Heart. The cover shows immunofluorescence of cytokeratin-7 (red), a trophoblast marker, in the placenta from a patient with preeclampsia. Nuclei are stained with DAPI (blue). Peripartum cardiomyopathy is a form of maternal heart failure associated with preeclampsia. Roh et al. used serum proteomics to discover that the senescence associated secretory phenotype, an indicator of cellular stress and biological aging, was increased in individuals with peripartum cardiomyopathy or preeclampsia and was associated with heart failure severity. In a mouse model of peripartum cardiomyopathy, treatment with Fisetin, a compound that depletes senescent cells, improved heart function. Cellular senescence may therefore be important to our understanding of pregnancy-induced cardiovascular diseases.