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Oestrogen receptor activation generates DNA breaks at regulatory elements that control gene expression. This study shows that APOBEC3B is required for these breaks, by deaminating cytosines within R-loops at oestrogen receptor-regulated enhancers.

The longevity of leaves determines the overall duration of photosynthesis for plants. This study suggests that climate change drives leaf longevity convergence toward intermediate ranges, which, by altering leaf traits and enhancing photosynthetic capacity, strengthens ecosystem stability and is closely linked to vegetation diversity.

Chen et al. developed a self-powered smart magnetoelastic stent for real-time hemodynamic monitoring and stenosis detection.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

In this randomized phase 3 trial, patients with treatment-naive stage III–IV nonsmall cell lung cancer who received sintilimab or pembrolizumab in combination with chemotherapy early in the day (before 15:00 h) experienced longer progression-free survival compared with those receiving late time-of-day infusions.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

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.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

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.

Induction of CD11b-positive regulatory B cells and low expression of CD40 in melanoma cells have been associated with resistance to agonist CD40 (aCD40) and immune checkpoint blockade (ICB). Here the authors show that the addition of RAS/MEK/PI3K inhibitors to aCD40 abrogates these effects and reverses ICB resistance in preclinical melanoma models.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Research in the tropics is unevenly distributed across regions and biomes. Here, the authors find that moist broadleaf forests account for 73% of all tropical citations but cover 29% of the land area, while drier, climate-vulnerable areas with fewer trees remain under-sampled and under-cited.

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuropathy.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

In this work, authors present their goal-directed subgroup identification (GD-SI) framework, reconciling biological heterogeneity with clinical actionability, and offering a scalable infrastructure for precision trial design and personalized sepsis management.

Prokaryotic pan-genome analysis is crucial for understanding microbial diversity, however current analytical methods often struggle to balance accuracy and computational efficiency. Here the authors present a more precise, robust and scalable toolkit for large-scale pan genome analysis.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Quantum simulation has the potential to enable experimentally studying problems which are not directly tractable in a laboratory or computationally. Here, the authors simulate the Majorana equation with a ytterbium ion, which requires them to simulate antiunitary and therefore unphysical operations.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Crop diversification is a promising strategy to enhance global food security, yet potential trade-offs between yields and nutritional outcomes remain unclear. This global synthesis reveals that transitioning from monoculture to crop rotation consistently boosts total yield, nutritional quality, and revenue by 14–27%, with win-win outcomes significantly outweighing trade-offs across major agricultural regions.

Here the authors report NiGa₂O_4–x(OH)_y for light-driven CO₂ hydrogenation to methanol. The surface Lewis acid–base pairs and -OH groups act as conduits for H^- /H⁺ transport to active sites, enhancing photocatalytic methanol production.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Resistance drift, also known as the temporal change in electrical resistance, hampers the application of phase-change materials for neuromorphic computing. Here an amorphous CrTe₃ thin film with no resistance drift in the working temperature from −200 °C to 165 °C is reported.

In vivo experiments and clinical cohort analyses show that hypoxia-inducible factor 2 (HIF2)-induced parathyroid hormone-related protein (PTHrP) expression contributes to cachexia in the context of renal cell carcinoma (RCC). The pathway can be targeted by HIF2 inhibitors, including belzutifan, which may reduce cachexia in patients with RCC.

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Electroreduction of CO₂ into C2 hydrocarbons and liquid fuels is a promising but challenging energy conversion technology, with copper exhibiting fair selectivity for these products. Here, the authors report that N-doped graphene quantum dots can also catalyze the electrochemical reduction of CO₂into multi-carbon hydrocarbons and oxygenates.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.