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Targeted ablation of prostaglandin E₂ (PGE₂) signalling in CAR T cells enhances their activity in PGE₂-rich solid tumours, with demonstrations of efficacy in vitro, in mouse xenografts and in patient-derived organotypic tumour spheroids.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that FAM118A/B processing of NAD involves head-to-tail filament formation and a partnership between the two paralogs.

Using satellite ocean-color data, this study reveals a 20-year decline in plankton biomass in a major nitrogen-fixation hotspot, suggesting reduced nitrogen inputs and potential implications for global biogeochemical cycles and climate regulation.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Multi-omics profiling of diverse cancer cachexia models uncovers a multi-tissue metabolite-coordinated response associated with disease progression and links multi-tissue one-carbon metabolism to wasting.

SARS-CoV-2 spike protein mediates viral entry into host cells. Shi et al. report a cryoEM structure of a proteolytically processed spike, possibly representing a functional intermediate state, with important implications for intervention strategies.

Here, the authors report that combining Army Liposome Formulation with QS21 saponin (ALFQ) and Alum to formulate the ΔV1gp120 boost decreases the risk of simian immunodeficiency virus (SIV) mac251 acquisition in female macaques.

Biocatalytic strategies typically transform only one alkene isomer into products, limiting the yield. Now a biocatalyst is reported to convert both isomeric silyl enol ethers into chiral α-branched ketones with high efficiency and excellent selectivity.

Here they show that specialized filopodia are essential for steroid hormone secretion in fruit flies, highlighting a vesicle-mediated mechanism adjusted by filopodia dynamics that challenges a simple secretory diffusion model.

Here, Hachfi et al show how spores of the enteropathogenic Bacillus cereus bacteria escape host innate immune responses in the intestine to favour bacterial persistence.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

HTLV-1 type-C causes more severe disease than type-A, but the underlying reason is unclear. Here the authors show in a macaque model how type-C orf-I affects lung pathogenesis and the immune response to HTLV-1, providing a model to test viral targets for disease prevention.

The cytosolic innate immune sensor NLRP10 interacts with NLRP3 and mediates the cleavage of oxidized mitochondrial DNA

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Although IFN-γ is known to regulate T cell function and expansion during virus-specific responses, its impact on T cells with varying avidity for antigen remains unclear. Here, the authors demonstrate that IFN-γ promotes the expansion of low-avidity CD8⁺ T cells during the effector phase, but favours those with high avidity in the memory pool.

We show the evolution of a case of EGFR mutant lung cancer treated with a combination of erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine targeting somatic mutations, including EGFR exon 19 deletion.

The extracellular matrix provides a critical scaffold for the epidermal layers of the skin. Here, He and Boraas et al. discover that the foundation for resilient skin healing in embryos lies in the supportive matrix beneath stem cells.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Here the authors demonstrate that the SARS-CoV-2 main protease (Mpro) is subject to redox regulation in vitro, reversibly switching between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues.

Interactions with the extracellular matrix (ECM) control tumor proliferation, invasion and metastasis. Here, authors provide spatial information on ECM organization and how it influences tumor cell invasive and metastasis properties through induction of cytoskeletal and transcriptional memory.

Direct stereoselective amination of tertiary C–H bonds without the assistance of directing groups is a challenging task in synthetic organic chemistry. Now a nitrene transferase is engineered to aminate tertiary C–H bonds with high enantioselectivity, providing direct access to valuable chiral α-tertiary primary amines.

Through a functional CRISPR/Cas9 screening, Pretto et al. identify Elovl1 as a target to improve antitumour immunity by remodelling T cell lipid metabolism.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Amyloid self-assembly is linked to type 2 diabetes and Alzheimer’s disease. Here the authors designed constrained peptides which are nanomolar amyloid inhibitors of the key polypeptides IAPP and Aβ42 and act via supramolecular nanofiber co-assembly.

HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14⁺ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.

The role of viral Fc-gamma receptors in rhesus cytomegalovirus (RhCMV) infection is unclear. Here, the authors characterized RhCMV vFcγRs and report that their deletion did not affect virus replication, tropism or superinfection in rhesus macaques but increased susceptibility of the virus to antibody control.

This study reports the development and preclinical evaluation of a humanized citrullinated histone H3 (CitH3) monoclonal antibody that mitigates inflammation, restores macrophage function, and protects against sepsis-induced pulmonary injury.

GC-biased gene conversion has many implications for evolutionary genetics, but its prevalence is unknown. Here, direct sequencing of tetrads in four species shows large differences in gene-conversion rate but no evidence of overall GC bias.

Advances in bionanotechnology demand an increased portfolio of assemblies beyond those currently available. Here, the authors design a crystallographically characterized super-helical sequence composed of single heptad repeats which, through derivatisation, offers vast potential applications.

Species coexistence can be explained by the competition–colonization trade-off theory. Here, Livingston et al. illustrate this theory in a metacommunity experiment using two bacterial strains, finding a negative correlation between diversity and productivity when scaled to full metacommunities.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Current proteolysis-targeting chimeras can promote the ubiquitination and subsequent degradation of both target and off-target proteins by inducing their respective proximity with the cereblon ubiquitin ligase. Now, by developing and deploying an off-target profiling platform, ‘bumped proteolysis-targeting chimeras’ can maintain on-target degradation efficacy with reduced off-targets.

CaST is a Ca²⁺-activated version of split-TurboID. The tool allows labeling active neurons quickly, simply by administration of exogenous biotin, thus enabling the study of behaviors that would be impaired by hardware required for the use of other, light-dependent tools.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Mutations in glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher’s disease and are the most common risk factor for Parkinson’s disease. Using a fusion protein comprising GCase and a transferrin receptor antibody fragment, the authors show that the transferrin receptor pathway can be therapeutically exploited to both pass the blood-brain barrier and efficiently target lysosomal GCase deficiency.

Defective insulin secretion is observed early in the development of diabetes. Here the authors report that β cell-specific deficiency of the insulin prohormone convertase 1/3 (PC1/3) leads not only to hyperglycemia, but also to hyperphagic obesity in mice.

In mice, a strong aversive experience drives offline ensemble reactivation of not only the recent aversive memory but also a neutral memory formed 2 days before, linking fear of the recent aversive memory to the previous neutral memory.

The fibupeptide lugdunin has shown activity against antibiotic-resistant bacteria. Here, authors disclose its mechanism of action in lipid membranes and demonstrate that it assembles into nanotubes facilitating the translocation of monovalent cations.

Structural and single-molecule analyses show the CTPase, KorB, is a sliding DNA clamp that interacts with a clamp-locking protein KorA to inhibit gene expression over distances of more than 1 kb in the multi-drug resistance RK2 plasmid.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Single-cell Proliferation Rate Inference in Non-homogeneous Tumors through Evolutionary Routes (SPRINTER) allows users to infer proliferation rates of individual clones within a tumor from single-cell DNA sequencing data. Applying SPRINTER to human tumor datasets highlighted a link between proliferation and metastatic potential.

BilR is identified as a bilirubin reductase encoded by gut bacteria, which reduces bilirubin to urobilinogen.

Poeck and colleagues identify a microbiome signature in patients receiving allogenic stem cell transplantation, which is associated with protective immune-modulatory metabolites, improved survival and less transplant-related mortality.

Metabolism of oxidized sugars during inflammation has been implicated as a pathogen colonization factor. Here, the authors characterize oxidized sugar utilization pathways in commensal bacteria, identifying genes essential for oxidized sugar utilization in the commensal E. clostridioformis, where GarABC and GudL can functionally replace GudP and GarL in pathogenic E. coli.

In patients with Crohn’s disease, CD4⁺ T cells with cytotoxic T_H1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.

The mycobacterial ABC transporter IrtAB functions as a siderophore importer despite exhibiting an exporter fold in its structure, and contains a siderophore interaction domain capable of siderophore reduction and iron release inside the cell.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.