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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.

Wafer bonding has allowed the synthesis of twisted interfaces which support polar discontinuities in ferroelectric lithium niobate. Two-dimensional sheet conductivity arises but is suppressed when twist angles lead to interfacial lattice aperiodicity.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Laser flash melting experiments have rendered cryo-EM fast enough to observe the microsecond motions of proteins. The authors extend the observation window of this emerging technique tenfold, to hundreds of microseconds, by sealing cryo-EM samples in ultrathin liquid cells.

This paper reports the excess mortality estimated during the evolving consecutive waves of COVID-19 in countries participating in the European Mortality Monitoring Network (EuroMOMO) in 2020-2023 and how they compare to recent influenza seasons.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

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.

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.

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.

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.

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.

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.

Arctic ground squirrels recycle microbially-liberated urea-nitrogen into anabolic amino acids during subzero hibernation, potentially supporting protein and nitrogen balance during prolonged fasting.

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).

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.

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

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.

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.

Multiscale and multiway brain network interactions during the first six months of life reveal rapid developmental changes. High-order triadic interactions provide insights beyond pairwise functional network connectivity by capturing nonlinear dynamics and yielding more reliable biomarkers of developmental trajectories.

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.

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.

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.

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.

Achieving charge separation with minimal energy loss remains a key challenge in photocatalysis, but traditional approaches often suffer from rapid charge recombination or inefficient energy utilization. Now it has been shown that symmetry-breaking charge separation within organic crystalline nanoparticles can generate long-lived charge-separated states, enabling efficient photocatalytic hydrogen production.

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.

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.

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.

Wegner et al. apply machine learning to video recordings of walking tasks in people with ataxia and healthy controls using sensor-free motion capture. Their models replicate clinical ratings and detect subtle longitudinal gait changes that are challenging to capture in standard assessments, supporting improved monitoring of disease progression.

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.

In this study, Kennedy et al. combine crystallography, biophysical measurements and biochemical assays to define a structural cycle for Werner syndrome helicase (WRN) and reveal how nucleotide binding and ssDNA engagement lead to conformational transitions.

Cryo-EM structures of yeast complex II in active and inhibitor-bound states reveal fungi-specific features governing enzyme stability and fungicide binding, paving the way for structure-guided design of improved inhibitors for agriculture and health.

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.

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.

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.

A safety engineer feels abandoned by their principal investigator. How should they find support?

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

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.

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.

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.