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Here the authors use genetic mutations to alter TCR signal strength and clonal selection of exhausted CD8⁺ T cells. They implicate CARD11 signaling as a sensor of this TCR signal strength and as a regulator of antitumor function in exhausted T cells that might be targeted to enhance cancer immunotherapies.

Structures of the yeast replisome associated with the FACT complex and an evicted histone hexamer offer insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.

Seahorses may have required adaptations to avoid immunological rejection of allogenic embryos by males. The authors show that a single substitution in tlx1 is associated with loss of the spleen in seahorses, and that across the clade, degree of male pregnancy is negatively correlated with immune gene repertoire complexity.

It is shown that long-lived reactive oxygen intermediates are formed in heterogeneous reactions of ozone with aerosol particles, resolving apparent discrepancies between earlier quantum mechanical calculations and kinetic experiments. These intermediates play a key role in the chemical transformations and adverse health effects of toxic and allergenic air particulates.

The heterodimer of METTL1-WDR4 is responsible for adding methylation group to the N7 atom of guanine (m7G) in tRNA molecules. Here the authors show how the tRNA m7G modification mediates tRNA stability to control proteostasis by maintaining efficient protein synthesis, which is important for preventing premature senescence and aging.

Lymphocyte subsets remain inadequately understood in jawless vertebrates, relative to jawed vertebrates. In this study, the authors combine single-cell RNA and whole-transcriptome sequencing to demonstrate that the lamprey, Lampreta morii, harbours specialised T-like cells that are distinct from those found in jawed vertebrates.

An organic regulator that can tune the crystallization sequence of active layer components has been described, achieving a certified efficiency of over 20% in single-junction organic solar cells, demonstrating remarkable tolerance for active layer thickness of 100–400 nm.

The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G₀–G₁ phase, thus suppressing proliferation in human hepatocellular carcinoma cells.

Transition fibres (TFs) and the transition zone (TZ) are basal ciliary structures thought to act as a gate to regulate protein transport. Here the authors show that the C. elegansorthologue of hydrolethalus protein 1, HYLS-1, disrupts both structures and compromises the trafficking of cargo through the ciliary gate.

Both cartilaginous and bony fishes have adaptive immune cells, but the evolutionary features of these diverse cell populations remain understudied. Here the authors report single-cell RNA sequencing atlas of both species to define these features and to find reduced evolutionary diversification of immune cells in cartilaginous fishes.

Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.

High-resolution structures of phosphatidylinositol 3-kinase (PI3K) type IIa unravel a coincident mechanism of lipid-induced enzyme activation and enable the development of inhibitors of class II PI3K function with applications in biomedicine.

How stresses result in cellular senescence is not fully understood. Here, the authors show that cell stress induces the assembly of a polyglutamylated microtubule array connecting nucleus and cilium, which aids in transporting a senescence-inducing protein.

TMEM63s are mechanosensitive ion channels activated by hypo-osmolality. Here, the authors determine the cryo-EM structure of mouse TMEM63C confirming its predominant monomeric state and the significance of TM0-TM6 coupling in channel activity.

The authors demonstrate a significant influence of canopy structure on autumn phenology in temperate forests, mediated by microclimate regulation. Incorporating this relationship into autumn phenology models enhances their prediction accuracy and reduces previously projected delays in autumn phenology.

Exposure to irreparable stresses induces transient ciliogenesis, enabling communication with PML-NBs via a FBF1 pathway to trigger senescence in mammalian cells. Fbf1 ablation reduces senescence and associated health decline in mice, highlighting cilia as a promising senotherapy target.

This study shows that intermittent fasting (IF) protects against Alzheimer’s disease in a transgenic mouse model. The authors demonstrate that altered metabolism through remodeling of the gut microbiota mediates the beneficial effects of IF regimen.

Pentameric ligand-gated ion channels (pLGICs) are key players in neurotransmission and have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. Here, the authors report structures of the pLGIC 5-HT_3A serotonin receptor reconstituted into lipid bilayer discs and reveal lipid–protein interactions as well as asymmetric activation of the homopentameric receptor.

Combining cryo-electron tomography with subtomogram averaging (StA) allows the in situ structure determination of proteins and protein complexes. Here, the authors present the hybrid StA (hStA) workflow that combines the advantages of single particle cryo-EM and StA and consists of a tomographic data collection scheme and a data processing workflow and they demonstrate how hStA can improve the resolution using two examples: the ion channel RyR1 and tobacco mosaic virus.

The role of DNA methylation in early embryo development has been difficult to determine due to the functional redundancy of DNA methyltransferases. Here they develop an efficient base editing system that enables one-step generation of Dnmt-null embryos and show that DNA methylation-related miRNA suppression may be involved in gastrulation.

CRISPR-Cas9 is widely used for genome engineering but structural data for the DNA cleavage step are still incomplete. Here, the authors present the cryo-EM structure of a ternary Cas9-sgRNA-target DNA complex, perform MD simulations and discuss implications for the Cas9 DNA cleavage mechanism.

Metal oxide nanocrystals can be grown with different facets exposed to give variations in reactivity, but the chemical state of these surfaces is not clear. Here, the authors make use of a phosphine probe molecule allowing the differences in surface chemistry to be mapped by NMR spectroscopy.

The Automatic Emesis Detection (AED) tool uses deep learning to quantify emesis in Suncus murinus with high accuracy, reducing human error and enhancing efficiency, offering potential for preclinical research and drug development.