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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 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.

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.

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.

Drought, fires, and human activities have reversed the accumulation of live biomass carbon in the Northern Hemisphere, with total biomass shifting from a positive to a negative trend around 2016.

Spin transitions — metal ions changing from high- to low-spin states — can be triggered by a range of stimuli and have normally only been observed in octahedrally coordinated ions. Now, a four-coordinate, square-planar iron(II) compound, SrFeO₂, exhibits such a spin transition, accompanied by a transition from an antiferromagnetic insulator to a ferromagnetic half-metal.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole 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.

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.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Protein citrullination regulates the physiological function of proteins and is linked to various autoimmune disorders. Here, the authors report on the allosteric targeting of PAD1-4 leading to broad inhibition of protein citrullination in neutrophils.

In a quantum simulation of a (2+1)D lattice gauge theory using a superconducting quantum processor, the dynamics of strings reveal the transition from deconfined to confined excitations as the effective electric field is increased.

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.

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.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

This study uncovers how seasonal temperature variations influence organic carbon burial in lake sediments. The authors predict that a decline in temperature seasonality will significantly slow or reduce organic carbon burial in lake sediments, leading to carbon emissions and amplified global warming.

There is limited epidemiological data on PRRSV sublineage 8.7 in Asia. Using national PRRSV surveillance data, the authors compiled a genomic dataset showing a geographically centralized spread, the likely impact of human-related activities on PRRSV spread and regional variability in interlineage recombination likelihood.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Whistler-mode chorus waves have been observed in the tail region of the terrestrial magnetosphere, where the magnetic field is not dipolar so that chorus waves were not expected, and their generation mechanisms have been tested with state-of-the-art observations.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Systemic sclerosis (SSc) is an autoimmune disease causing skin fibrosis and organ inflammation. Here the authors generate and analyze SSc skin single cell RNA sequencing data to propose contributions from both myofibroblasts and endothelial-to-mesenchymal -transitioning cells (EndoMT) to skin fibrosis, and to implicate the involvement of Hippo signaling pathways.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

A novel covalent inhibitor, ISM3312, targets the main protease of multiple human coronaviruses, including drug-resistant strains, and shows broad antiviral activity. It offers a promising therapeutic strategy against current and future coronavirus threats.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Dawicki-McKenna and Felix et al comprehensively map binding and alternative splicing by PTBP2 in human brain and neurons, thus identifying splice switching therapeutic strategies for the neurodevelopmental disorder associated gene SYNGAP1.

The local variation of grain boundary atomic structure and chemistry caused by segregation of impurities influences the macroscopic properties of polycrystalline materials. Here, the effect of co-segregation of carbon and boron on the depletion of aluminum in a α − Fe grain boundary is shown.

Leishmania donovani is a protozoan parasite that can cause fatal infections in humans. Here the authors present a high resolution cryoEM structure of the L. donovani80S ribosome and compare it to its human counterpart to provide insight into the basis for drug selectivity towards this eukaryotic parasite.

A vanadium-based lithium-rich disordered rock salt oxide is shown to work as a low-potential anode with rapid intercalation kinetics for lithium-ion batteries.

While HER2-targeted therapies such as trastuzumab can be effective in patients with breast cancer, resistance often develops. Here, the authors demonstrate that the histone reader ZYMND8 promotes glycerophospholipid metabolic reprogramming via c-Myc and cPLA2α to increase secretion of IL-27, mediating resistance to HER2-targeted antibodies in preclinical models of breast cancer.

Changes in Psoriasis and other inflammatory skin diseases during severity stages can be investigated using single cell and spatial transcriptomics. Here the authors compare different inflammatory skin diseases to emphasise differences in immune cells and inflammatory markers particularly keratinocytes and fibroblasts.

As Nature Chemical Biology approaches its third decade we asked a collection of chemical biologists, “What do you think are the most exciting frontiers or the most needed developments in your main field of research?” — here is what they said.

This study reveals neuronal targets of Lac-Phe in the hypothalamus that mediate its suppression of food intake.

Yu et al. developed AIPatient, a virtual patient that uses a large language model-based AI in curating a medical knowledge base that holds realistic and personality-aware clinical conversations. The system shows high accuracy in answering questions and medical-term recognition, with readable, reliable, and consistent outputs for medical training.

Here, the authors built a non-redundant catalogue of nearly 1 billion putative small proteins from the global microbiome as a publicly-available resource, and highlight how some highly prevalent and evolutionarily conserved sequences lack functional annotation.

Heparin is a family of complex carbohydrates binding to proteins to modulate cell activities. Here the authors report the synthesis, and conformations simulations of S-linked hemi-A heparosan [GlcA-S-GlcNAc]_n, a thio-glycosidic uncleavable polysaccharide, and test it as human heparanase inhibitor.

Amid virus inoculation by hemipteran insects, vector infestation induces salicylic acid (SA)-mediated plant antiviral defense. Here it is found that the vector-borne plant virus circumvents this antiviral defense via disrupting the SA signaling pathway.

A hybrid analogue–digital quantum simulator is used to demonstrate beyond-classical performance in benchmarking experiments and to study thermalization phenomena in an XY quantum magnet, including the breakdown of Kibble–Zurek scaling predictions and signatures of the Kosterlitz–Thouless phase transition.

Exsolution enables the formation of active catalytic nanoparticles, but their thermal stability remains limited. Here, the authors use secondary-electron imaging at atomic resolution to directly visualize the coarsening of exsolved nanoparticles.

Increased late sodium current due to the disruption of voltage-gated sodium channel inactivation is a common pathogenic mechanism in different arrhythmogenic syndromes. Chakouri et al. show that fibroblast growth factor homologous factors (FHFs) modulate pathogenic late sodium current in an isoform-specific way, and leverage this observation to design and test a prototype of inhibitor peptide based on a protein domain from an inhibitory FHF isoform.