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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.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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

In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Preventing axon breakdown is key to treating neurodegeneration. Here, the authors show that after axotomy, DLK kinase drives apoptotic mitochondrial fission in axons. Blocking this reduces axon degeneration and neuron death in both human and mouse models.

Indoor air pollution from harmful and carcinogenic formaldehyde is a concern in developed countries. The authors present a sustainable solution using porous Metal-Organic Frameworks (MOFs) for efficient trapping of formaldehyde and regeneration.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

The burden of asthma varies between ancestries, but GWAS have so far focused on mainly European ancestry populations. Here, Daya et al. perform GWAS for asthma in 14,654 individuals of African ancestry and, besides confirming previously known loci, identify two potentially African ancestry-specific loci.

Diverse microbial trajectories in carbon and nitrogen cycle processes represent a positive feedback loop of deglaciation on climate warming.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

A recently discovered high-mass X-ray binary has an evolutionary history showing the neutron star component formed during an ultra-stripped supernova, and has orbital elements that should allow for forming a binary neutron star in the future.

A potential drug should specifically interact with its intended target in order to limit unwanted side effects. Here, the authors fabricate a biodegradable polymer nanoparticle with a fluorescent hepatic uptake transporter ligand to achieve targeted in vivosiRNA delivery and imaging of delivery.

Ataxia-telangiectasia mutated protein (ATM) phosphorylates CD98HC to promote neutral amino acid antiporter trafficking. Here the authors show that ATM loss impairs glutamate, cystine, and arginine transport, driving metabolic stress and ataxia telangiectasia–like phenotypes.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The complex equilibria of sulfur compounds at the liquid-vapor interface play key roles in atmospheric processes. Here, using X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular dynamics simulations the authors determining pKa values and tautomer ratios at the air-vapor interface in a liquid microjet.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

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.

Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

The application of all-perovskite tandem photovoltaics is limited by the poor operational stability of the solar cell. Here, the authors report a solar-assisted water-splitting system using an electrochemical flow cell and a tandem solar cell and achieve a solar-to-hydrogen efficiency of 17.8%.

Hypophysitis is a rare disease characterized by inflammation of the pituitary gland that can cause hypopituitarism-related symptoms, headaches and visual disturbances. This Review discusses the current understanding of the epidemiology, pathophysiology, diagnosis and clinical management of hypophysitis.

Whole-genome sequencing of an ancient male Egyptian revealed a mixture of North African Neolithic and eastern Fertile Crescent ancestry, suggesting human migration between Egypt and Mesopotamia by the Old Kingdom period.

Arabian killifish embryonic yolk sac microinjection of the emerging human fungal pathogen Candida auris and dual host-pathogen RNA-seq reveal an expanded and transcriptionally upregulated family of xenosiderophore transporter genes during infection.

Hydrous silicate melts atop the 410 km discontinuity have ultra-low viscosities, enabling rapid segregation. These melts form paired layers through continuous dehydration melting, which can merge under specific conditions, explaining seismically observed deep melt structures.

Using the Tara Oceans dataset, this study describes global patterns of diatom diversity, abundance and adaptation. The authors identify 25 distinct communities, with the Arctic as a hotspot, and highlight diatom transcriptional features. These insights aid understanding of the ecological roles of diatoms and their responses to global change.

Most individuals with primary familial brain calcification (PFBC) remain genetically unsolved. Here the authors show that NAA60 biallelic variants cause PFBC, likely via reduced N-terminal acetylation and SLC20A2 levels with impaired phosphate uptake.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.