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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.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

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.

Guided by density functional theory, a commercially viable refractory alloy is developed, which exhibits excellent room-temperature ductility and strength, and high strength at elevated temperatures.

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.

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

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Achieving high resolution with optical neural interfaces is challenging. Here, the authors developed and chronically implanted 100-pixel microLED arrays on the surface of the mouse auditory cortex for optogenetic behavioural experiements.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

An Earth system model estimates that natural halogens, of marine biotic and abiotic origin, remove about 13% of present-day global tropospheric O₃. Projections suggest this ratio is stable through 2100, with high spatial heterogeneity, despite increasing natural halogens.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Plasmodium sporozoites must invade mosquito salivary glands to facilitate malaria transmission, yet the effects of this invasion are not well understood. Here, the authors use high-resolution proteomics and show that malaria parasite invasion damages mosquito salivary glands, alters saliva protein composition, and attracts immune cells, potentially increasing parasite transmission.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Myeloid derived suppressor cells (MDSC) use different metabolic mechanisms to adapt to the tumour microenvironment. Here the authors show that 6-phosphogluconate dehydrogenase (6PGD) is important for MSDC function and that blockade of 6PGD impaired MDSC function and suppresses tumour growth leading to metabolic and functional changes in the MDSC and a more pro-inflammatory phenotype.

Iron–sulfur minerals play critical roles in regulating nitrogen cycling under anoxic conditions. This study shows that pyrrhotite with abundant iron vacancies promotes electron transfer and microbial nitrate reduction to dinitrogen.

Active galactic nuclei are surrounded by a dusty and molecular disk that fuels supermassive black holes and connects them to their host galaxies. Here, the authors show with JWST interferometric observations that most of the dust in the Circinus galaxies lies in a compact disk, while only a tiny fraction traces hot outflowing material.

Schmidt et al. develop sentence-level datasets for Crohn’s phenotypes and compare rule-based NLP with GPT-4 to extract disease behavior and age at diagnosis from EHR notes. Both methods achieve high recall on notes; GPT-4 perfectly identifies age at diagnosis and simple ensembles improve precision and enable chart-review prioritization.

This study shows that long-term climate change systematically alters small-scale wind variability and its vertical velocity, influencing cloud microphysics and the Earth’s radiative balance.

This study introduces P3T-Net, a pseudo-3D deep learning model that enables accurate and efficient cross-domain transfer of large 3D material images, improving image quality and ensuring image consistency across diverse imaging conditions.

H5N1 avian influenza viruses caused an outbreak in dairy cattle. We show that the potential for avian viruses to replicate in cow cells varies across H5N1 evolution, suggesting that the risk of spillover into mammals differs between variants.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

Here the authors reveal how replication stress in BRCA2-deficient cells triggers a mutagenic cycle of APOBEC3B upregulation, uracil accumulation at stalled forks, and DNA damage, uncovering a self-reinforcing loop that fuels genomic instability.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

Achieving tight Cas9 regulation without sacrificing activity remains difficult. Here, the authors design multi-level circuits combining anti-CRISPRs, splice sites, chemical induction, and degron control to enable ultra-high dynamic range and precise, on-demand genome editing across contexts.

The cool sub-Neptune LP 791-18 c, with an equilibrium temperature of 355 K, was found to host a hazy atmosphere, distinct from any other temperate sub-Neptune studied so far. The discovery demonstrates the intrinsic diversity of these worlds.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

An approach combining BONCAT, stable isotope probing and metaproteomics showcases the hidden metabolic interconnectivity of microorganisms within an anaerobic digestion community.

Chimeric antigen receptor T (CAR-T) cell therapy uses engineered donor T cells to recognize and eliminate cancer cells through cognate antigen-dependent activation. Here authors develop an alternative to bead-based or cancer-cell-induced CAR-T cell activation by presenting the antigen on the surface of engineered yeast cells, which allows precise regulation of antigen density.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

In a prior edition of this journal, Ryan and colleagues conducted an experiment to examine the role of AI on physician decision making. They observed that 67% of physicians who initially recommended against treatment, but later viewed AI output recommending treatment, changed their decision. This is an important study because it shows how AI can have a dramatic influence on doctors. Medico-legal consequences are considered.

Here authors demonstrate how opposing trajectories of dopamine transmission underlie changes in drug seeking and taking over chronic drug use. Increased dopamine to drug cues elevates craving, whereas decreased dopamine produces escalation of drug consumption.

This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.

Dysregulated protein levels can cause disease. The authors present a scalable platform capable of identifying small molecules that alter disease-linked target protein levels, and report >40 that increase SynGAP protein abundance, with SR1815 restoring neuronal function in Syngap1 deficient neurons.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.