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The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

An ex vivo model and pre-clinical study in a brain-dead recipient provide enzyme-converted O organs to avoid hyperacute rejection in ABO-incompatible kidney transplant patients.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Using voltage imaging, the authors show that interneurons in the hippocampus sharpen memory-encoding-activity by increasing the signal-to-noise ratio of pyramidal neuron sensory representations during working memory in mice.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA-lipid nanoparticles while enabling high RNA expression.

The gH-associated tropism and entry (GATE) complex consists of glycoprotein H, UL116 and UL141. This complex is abundant on human cytomegalovirus virions and enables entry into human endothelial cells.

Transcriptome-scale maps of RNA secondary structure ensembles in living cells detect candidate RNA structural switches.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

Viral vector integration can affect the safety of gene and cell therapies. Here, authors introduce MELISSA, a regression-based statistical tool that quantifies integration site risks and clone growth effects, aiding the safety evaluation of therapies in both research and clinical settings.

Internucleosomal linker length alters the stability and dynamics of chromatin condensates by shifting the balance between inter- and intramolecular interactions. Further, by changing the linker lengths, a remodeler can induce or suppress chromatin phase separation.

Spatial relationships between clustered proteins within synapses shape neurotransmission. Here, NMDA receptors are shown to align with only a subset of presynaptic release sites, suggesting a structural mechanism controls NMDAR-mediated synaptic transmission.

Decisions are typically associated with a sense of confidence and can be followed by an impulse to change our minds. Here, the authors use intracranial recordings in humans to show that confidence and changes of mind derive from a cortical process called evidence accumulation.

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

What we eat, as well as where and how it is grown, impacts species extinction risks through agricultural land use. Using a new global biodiversity impact data product, this study estimates how many species extinctions may potentially be caused by the production and consumption of different food types on a country-by-country basis.

The authors showcase the capabilities of time-resolved momentum microscopy to image spin- and valley-resolved excitons in monolayer WS₂ with high energy resolution, revealing distinct long-lived, valley-polarized dark excitons that dominate at different timescales.

The enterococcal cytolysin is a two-component toxin that is responsible for a fatal form of alcoholic hepatitis. Here, authors used knowledge of the toxin’s biosynthesis to develop small molecule inhibitors of toxin production.

Here, the authors introduce carbon-to-carbon metal migration as a platform for dynamic association and show how such migrations, in combination with the incorporation of a simple hydrocarbon, can be harnessed to achieve autonomous directional translational motion of a metal centre along the length of a polyaromatic thread.

Multiple types of cell elongation have been described in bacteria, but little is known about how these strategies vary across species. Here, the authors use fluorescent D-amino acids to track the spatiotemporal dynamics of bacterial cell elongation, revealing unsuspected diversity of elongation modes among closely related species of the family Caulobacteraceae.

There are no vaccines or antivirals available against enterovirus D68. Here, the authors report Jun6504 as a 2C inhibitor and show that it provides broad-spectrum antiviral activity against EV-D68, EV-A71, and CVB3 and potent antiviral efficacy in a neonatal neurological mouse model of EV-D68 infection.

APC/C activity is transiently inhibited to generate a pulse of glycolysis that is required for mammalian cell cycle entry.

The structure-function relationships of a β-helix, a folding motif formed by parallel β-strands arranged in a helical repetitive pattern, remain poorly understood and underexploited. Here, the authors reconstitute a protein β-helix by design from an elementary sequence of 18 amino acids, which self-assembles into a self-contained multifunctional motif exhibiting a range of biological functions.

Copper (Cu) dysregulation contributes to aging and oxidative stress. Here the authors develop imaging probes to detect labile hepatic Cu, revealing age-related increases that deplete ALDH1A1 activity, and show that chelation therapy restores Cu homeostasis, offering a potential strategy to mitigate liver aging.

The shift in fluorescence lifetime of tumour tissue with respect to normal tissue after systemic injection of the near-infrared dye indocyanine green can be used to distinguish tumour tissue from normal tissue with high accuracy.

The authors show that ~100-kyr climate cycles over the past ~800 ka, and even since ~34 Ma, likely arose from a ~2.4-Myr eccentricity-modulated competition between low- and high-latitude continental carbon reservoirs for dominance in carbon cycles.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Cardiovascular function declines with age. In this study, the authors show that the BAT-derived lipokine 12,13-diHOME preserves cardiac function in aged mice by attenuating pathological CaMKII activity.

Current CO₂ capture strategies often suffer from high thermal regeneration costs. Now a photobase has been shown to reversibly capture and release CO₂ from ambient air using visible light, offering a sustainable, energy-efficient alternative.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

The fungus Sclerotinia sclerotiorum distributes its 16 chromosomes irregularly between two nuclei within single ascospore cells. Here, the authors show that chromosomal segregation and genetic recombination occur normally during meiosis in this fungus, despite the unusual chromosomal distribution.

This work uses differentiable simulations and reinforcement learning to design interpretable genetic networks, enabling simulated cells to self-organize into emergent developmental patterns by responding to local chemical and mechanical cues.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

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.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

Bacteriocins include antimicrobial peptides (AMPs) that often disrupt the cytoplasmic membrane. Here, the authors describe TMcin (transmembrane helix-containing bacteriocin), a class of AMPs that forms large, structured pores in the target membrane.

Here, the authors show that KDM2A regulates cell cycle progression, modulation of H3K36me2 and H3K27me3 chromatin states and gene repression which are critical for survival of differentiating spermatogonia. KDM2A regulates progression through meiosis as well.

In this work the authors develop a machine learning tool to classify spherical densities as ions and waters in provided x-ray crystallography and cryo-EM macromolecular structures. The method is validated on a variety of inputs and shows improved accuracy over existing techniques.

Wildfire risk in California’s WUI is rising. Analysis of past events shows home hardening and defensible space can reduce structure loss by up to 52%, but coordinated, community-scale action is essential to maximize impact.

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Lindlar catalysts are widely used for partial hydrogenation of alkynes, however they can be somewhat limited by toxicity of lead and low selectivity. Here, the authors report that the modification of palladium nanoparticles with boron atoms in the interstitial sites yields selective hydrogenation catalysts.

The authors introduce a new spectroscopic technique for studying Higgs modes in superconductors and apply it to a cuprate superconductor. The method involves a soft quench of the Mexican-Hat potential, populating Higgs modes of different symmetries, which are then probed by non equilibrium anti-Stokes Raman scattering.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Rare earth mineralisation at Maoniuping formed when its carrying carbonatite brine-melt reacted with surrounding siliceous rocks, forming an antiskarn. The melt lost its fluxing alkali elements, which led to deposition of coarse grained bastnäsite.

How Meckel-Gruber syndrome protein TMEM67 functions in ciliogenesis and Wnt signaling simultaneously is unknown. Here the authors show that TMEM67 is proteolytically cleaved by the matrix metalloproteinase ADAMTS9 generating two functional isoforms.

Aging leads to progressive loss of effective tissue regeneration, which has been linked to the accumulation of senescent cells. Here, the authors use machine learning to identify a stable nuclear morphometric phenotype that detects senescent cells across tissues and age, enabling their quantification and mapping in diverse environments.

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.