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The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Nuzum et al. used cross-sectional data from the UK PROTECT study to evaluate the relationship between high autistic traits and suicidality in older adults.

Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.

Alkenes are essential functional groups in organic chemistry, featuring well-defined geometries and bond orders of 2. In this study, cubene and 1,7-quadricyclene are calculated to possess unusual hyperpyramidalized geometries and low alkene bond orders near 1.5. Their resultant high reactivities ultimately permit access to intricate scaffolds and new chemical space.

Demand-side food policies show small average effects, with effectiveness varying across intervention types. Targeted strategies and a better understanding of how context and population influence outcomes can advance food system sustainability.

Pre-treatment dual immune checkpoint blockade in cervical cancer remains understudied. In this trial, the authors show that neoadjuvant immune checkpoint blockade enhances immune activation and correlates with improved response to subsequent chemoradiation in patients with cervical carcinoma.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

Effective substrates are key to probing and harnessing protease activity. This work presents CleaveNet, an AI tool that generates efficient, selective substrates, revealing known and distinct cleavage motifs and tuning designs to target activity profiles.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Genetic variants of TREX1, a negative regulator of type I interferon responses, have been linked previously to non-monogenic systemic lupus erythematosus (SLE). Here the authors analyze UK Biobank multi-omics data to show that, while a derived oligoprotein interferon signature associates with increased SLE risk, TREX1 variants do not.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

Early vertebrates, particularly myllokunmingids, possessed four camera-type eyes (a pair of lateral eyes and pineal and parapineal organs), which indicates that these structures functioned in image formation, in support of the hypothesis that the four camera-type eyes represent an ancestral vertebrate trait.

Species homogenisation driven by land-use intensification is threatening many taxa globally. Here, the authors find that for arthropod communities in Central Europe, managed grasslands are the most affected land-use type, while there is a strong distance–decay relationship in settlements and arable fields, meaning that these support heterogeneous communities between locations.

The structure and functioning of soil food webs between biomes remains unknown. Here, tropical soil food webs are shown to have higher energy flux, predation and herbivory than temperate soil food webs which are based on litter and microbial biomass.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Disease course and pathology an infection may cause can change owing to the structural and functional physiological changes that accumulate with age, but therapy can be tailored accordingly; disease tolerance genes show antagonistic pleiotropy.

High-pressure measurements of the electrical conductivity of (Mg,Fe)O, used as an analogue for basal magma ocean material, indicate that the conductivity is high enough to produce a dynamo much stronger than a core-driven dynamo for super-Earths larger than 3–6 Earth masses.

Neutrophils infiltrate glioblastomas with the capacity to engage pro/anti tumoural responses. Here the authors developed proteomic workflows to stratify neutrophil heterogeneity by function. This work provides a platform to study neutrophil proteomes with single cell resolution in glioblastoma.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Tropical forests regulate Earth’s carbon cycle, but what governs carbon sequestration following land use remains unclear. Here Tang et al find a shift from strong nitrogen limitation to no nutrient limitation over tropical forest secondary succession.

ABC toxins are bacterial insecticides with biotechnological potential. Here, Low et al. have deciphered soluble and membrane-inserted structures of YenTc that highlight structural and mechanistic diversity in the ABC toxin family and provide insights into their evolution.

The HIV-1 RNA-binding protein rev facilitates nuclear export of viral RNA. Here, the authors use native mass spectrometry to study the interactions between rev-derived peptides and rev response elements of HIV-1 RNA, providing mechanistic insights into rev recognition and recruitment.

Analyses of liver biopsies from a child with spinal muscular atrophy treated with adeno-associated virus gene therapy who developed hepatitis reveal contaminating manufacturing plasmids and disrupted vector genomes, possibly resulting from recombination events.

New hominin fossils from the Grotte à Hominidés at Thomas Quarry I (ThI-GH) in Casablanca, Morocco, dated to around 773 thousand years ago are similar in age to Homo antecessor, yet are morphologically distinct.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Covalent KRAS inhibitors show initial responses but resistance limits durability. Here drug-induced hapten peptides are identified and characterized, enabling production of high affinity, cross-HLA T cell engagers that stabilize low density hapten peptide MHCs to drive tumor-specific killing.

Nucleoside triphosphates (NTPs) are important building blocks that underpin emerging enzymatic approaches to RNA therapeutics manufacturing. Here, authors develop a biocatalytic strategy to convert nucleosides into NTPs containing clinically relevant modifications, using simple phosphate donors.

Trace fossils from the end Ordovician of South Africa suggest a low-diversity meiofaunal benthic community fed by episodic concentrations of phytoplankton (marine snow).

Central charge, a key quantity in conformal field theories, is crucial in the study of critical phenomena, yet its measurement has remained elusive. Here, the authors extract the central charge of several quantum critical models by accurately preparing their ground states on a superconducting quantum processor.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

Accurate projections of heating and cooling needs are vital for planning energy use and achieving the sustainable development goals. A global dataset now maps global heating and cooling degree days, finding future hotspots, rising cooling demand and early shifts in energy needs with major global impacts.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

The impact of tumour heterogeneity on metastatic potential in prostate cancer remains poorly understood. Here, the analysis of single nuclei RNA sequencing and whole-genome sequencing from samples from five patients suggests an interplay between clonal evolution and cellular plasticity driving metastatic seeding.

Replication-dependent histone mRNA decay involves the RNA helicase UPF1, the histone stem-loop binding protein SLBP and the exoribonuclease 3’hExo. Here, the authors present evidence for assembly of a degradosome-like complex involving the three proteins and delineate the mechanism that drives their concerted action to achieve histone mRNA decay.