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KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

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.

Wearable devices generate vast streams of health data, but making sense of these measurements requires complex numerical reasoning beyond the reach of conventional language models. This study introduces a large language model agent that interprets wearable data to deliver accurate, personalized health insights.

Offshore wind-powered green methanol could achieve cost parity with conventional marine fuels by 2030−2035 under EU regulations, enabling sustainable shipping through scalable technology and policy incentives.

SmartEM is a ‘smart’ pipeline for electron microscopy-based data acquisition for connectomics. In order to efficiently image large datasets, the approach involves imaging at short pixel dwell times and identifying problematic regions that are then imaged with longer dwell times and therefore higher quality.

It is challenging to analyse chromosomal rearrangements in heterogeneous solid cancers. Here the authors present HiDENSEC, a method to jointly infer absolute copy number, ploidy, tumor purity and large-scale rearrangements from Hi-C data. The increased statistical power afforded by joint inference enables novel insights into cancer genome evolution.

Infective endocarditis (IE) is an understudied biofilm-associated infection. Here, analyses of preclinical and clinical data reveal that the Fsr quorum sensing (QS) system of Enterococcus faecalis is a negative regulator of IE pathogenesis.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Water and ion ingress are challenging to quantify, especially in miniaturized microsystems. Here, Mariello et al. report a wireless and battery-free flexible water-permeation sensing platform, using backscatter communication and Mg-based microsensors for in-situ monitoring of implantable bioelectronics.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

The study combines bulk, single-cell, and spatial transcriptomics of human carotid plaques. It identifies immune– stromal cell diversity, spatial macrophage gradients, smooth muscle cell heterogeneity, and morphology-defined plaque subtypes.

A randomized field study in rural western Kenya, a region most vulnerable to the health impacts of climate change, found that modifying houses with cool-roofs and vector proofing most effectively reduced indoor heat, improved thermal comfort and lowered malaria mosquito density.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

A new approach to determine nitrogen fixation rates in the world's oceans is used; it involves interpreting nutrient distributions in the context of an ocean circulation model.

Trends in global H₂ sources and sinks are analysed from 1990 to 2020, and a comprehensive budget for the decade 2010–2020 is presented.

Royer and colleagues find a principal dimension of neural dynamic similarity dissociating unimodal and association cortices. Systematic variations in local and macroscale constraints across the cortex also followed this pattern.

Mapping brain connections is critical for decoding brain functions. Here, the authors present an integrated resource of awake resting-state fMRI and neuronal tracing data of marmosets to understand structural-functional relationships of brain connections.

The interplay between neuronal activity and tumor progression is well-established. Here, the authors demonstrate that blockade of β-adrenergic signaling via administration of propranolol suppresses lung metastasis in multiple mouse tumor models by enhancing the accumulation of cytotoxic CD4 T cells while reducing CCR2+ monocytes, highlighting the re-purposing of β-blockers as a valid therapeutic approach for cancer treatment.

Long-range interactions are challenging for machine learning interatomic potentials (MLIPs). Here, authors show that, by just learning from energies and forces, MLIPs can accurately capture electrostatics and predict atomic charges.

Diffusion models are reframed by developing a generative blood cell classifier that performs reliably in low-data regimes, adapts to domain shifts, detects anomalies with robustness and provides uncertainty estimates that surpass clinical expert benchmarks.

Studies of high-acuity foveal neurons in the retina have been limited by an inability to accurately track eye position. Here, McFarland et al. present a method that accurately estimates eye position, allowing for detailed analyses of foveal and parafoveal stimulus processing.

Synapse dysfunction contributes to cognitive decline with age. Here, the authors show that aging-related changes in microglia and the extracellular matrix are associated with synapse abundance, extracellular matrix buildup, and cognitive deficits in aging mice.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Here the authors perform a gene knockout screen in myeloid cells, identifying 295 genes regulating interleukin-1β production, of which 57 lie in regions associated with inflammatory disease risk. The study sheds light on genetic control of interleukin-1β in inflammation, beyond previously known factors.

This protocol describes the synthesis, purification and assembly of stable branched 4-way junction (4WJ) RNA nanoparticles conjugated with multiple hydrophobic chemotherapeutic drug molecules to target specific tumors with minimal side effects.

Data from 42 chronosequence sites show a geater abundance of legumes in seasonally dry forests than in wet forests, particularly during early secondary succession, probably owing to legumes’ nitrogen-fixing ability and reduced leaflet size.

This study explores the use of quantum computing to address multi-objective optimization challenges. By using a low-depth quantum approximate optimization algorithm to approximate the optimal Pareto front of multi-objective weighted max-cut problems, the authors demonstrate promising results—both in simulation and on IBM Quantum hardware—surpassing classical approaches.

Fusobacterium nucleatum promotes colorectal cancer via its adhesin Fap2. Here, Schöpf et al. show the molecular basis for Fap2 interaction with its receptors TIGIT on immune cells and Gal-GalNAc on tumor cells using cryo-EM and integrative modeling.

Mulholland et al. identify progenitor exhausted T cells, expressing intermediate levels of PD-1 (PD-1^int), as a prominent source of pro-inflammatory cytokines in the murine atherosclerotic aorta and potential cellular targets driving checkpoint inhibition-elicited pro-atherosclerotic immune responses. They further demonstrate elevated levels of circulating PD-1-expressing T cells in individuals with subclinical cardiovascular disease.

CD123 expression on leukemic stem and progenitor cells (LSPCs) and leukemic blasts representing a promising therapeutic target. However previous CD123-targeting approaches had limited efficacy and safety concerns. The authors here evaluate the bispecific CD123/CD16A innate cell engager AFM28 and manifest its efficacy both in vitro and in vivo, which is mediated by NK cells.

Reducing rotational dephasing is a major challenge in ultracold molecules. Here, the authors demonstrate coherent control of three rotational states in ultracold molecules trapped in magic-wavelength optical tweezers, opening prospects towards quantum applications with higher-dimensional systems.

In this study, the authors analysed a large genomic dataset to trace how jumping genes shaped the global spread of a major wheat pathogen and reveal bursts of activity over decades that drove adaptation to antifungals and crops, highlighting the power of big genomic data to track evolution.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

How the environment regulates neuronal maturation during brain development is poorly understood. Here, Kreysing et al. identify brain stiffness as a key factor and determine a mechanotransduction pathway linking tissue mechanics to neuronal maturation.

Eusociality evolved independently in Hymenoptera and in termites. Here, the authors sequence genomes of the German cockroach and a drywood termite and provide insights into the evolutionary signatures of termite eusociality.

Hole spin qubits benefit from large spin-orbit interaction for efficient manipulation, but this can result in qubit variability. Here the authors study anisotropies in microwave-driven singlet-triplet qubits in planar germanium, revealing two distinct operating regimes due to different quantization axes alignments.

External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

Tumor microenvironment elements can influence tumor state, including in skin basal cell carcinomas. Here the authors show that spatially organized and self-propagating TREM2+ tumor associated macrophages promote Ly6D- tumor cell proliferation via secretion of oncostatin M.

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

A doped quantum antiferromagnet is obtained by using a Rydberg tweezer array comprising three levels encoding spins and holes to implement a tunable model that allows the study of previously inaccessible parameter regimes.