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This study presents ECloudGen, which uses latent diffusion to generate electron clouds from protein pockets and decodes them into molecules. The adopted two-stage training expands the chemical space accessible to generative drug design.

Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

The origin of water is one biggest unknowns in the field of star and planet formation: is it inherited or created in situ? Through the detection of heavy water (D₂O) in a protoplanetary disk, it is shown that this water must be older than the central star.

Biomolecular condensates of Eps15 recruit and assemble clathrin. In turn, clathrin assembly restricts condensate growth while imposing the preferred curvature of the clathrin lattice.

This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T_H17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms.

FUGAsseM predicts protein function in microbiomes using coexpression patterns from metatranscriptomes and diverse community-wide data.

cfDNA fragmentomics is a potential clinically applicable method for identifying cancer. Here, the authors assess fragmentomics analysis methods and their application to commercial targeted sequencing panels.

Engineering motif-specific 'hot spots' into an antibody scaffold yields antibodies with high affinity to targets containing phosphoserine, phosphothreonine or phosphotyrosine.

Interactions between qubits and defect-related two-level systems in superconducting qubit devices are a major source of noise fluctuations that hinder error-mitigation performance. Here, the authors experimentally show that modulating this interaction can reduce noise fluctuation and improve error mitigation performance.

Achieving deep blue emission and high practical efficiency in organic light-emitting devices remains a considerable challenge. Here, the authors report late-stage double borylation of boron/nitrogen based multi-resonance frameworks, achieving maximum efficiency of over 32% in stable devices.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Neural mechanisms underlying flexible learning and decision-making are not fully understood. Using single-cell calcium imaging, authors here found that neurons in orbitofrontal and secondary motor cortex exhibit complementary roles in reward learning, with neurons in the former exerting a sustained role in conditions of uncertainty.

This work reveals how a regulatory domain in O-GlcNAc hydrolase (OGA) shapes enzyme flexibility and activity, uncovering mechanisms that help maintain O-GlcNAc balance in cells.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Membrane budding plays pivotal roles in cellular processes, but a fully artificial system mimicking natural budding processes remains elusive. Here, the authors report a DNA origami-based membrane budding system that recapitulates key aspects of clathrin-mediated endocytosis without relying on components of cellular budding machineries.

RNA base editing represents an exciting modality in precision genetic medicine. Here the authors develop short, metabolically stable RNA oligonucleotides (RESTORE 2.0) that enable precise and efficient RNA base editing, demonstrating successful in-vivo correction of a disease-causing human mutation.

Whether paternal pre-conceptual SARS-CoV-2 infection impacts sperm RNA content, or effects offspring phenotypes, has not been previously investigated. Here authors report changes in sperm noncoding RNAs in SARS-CoV-2 infected sires and increased anxiety-like behaviors in offspring.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Several computational tools have now been developed to identify copy number variations (CNVs) from scRNA-seq data. Here authors benchmark these methods, showing that performance is affected by dataset quality, CNV type and reference dataset, with methods including allelic information being more robust in large datasets.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

The release of triplet or singlet oxygen is governed by individual Marcus normal and inverted region behaviour.

Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) is important for invasion of reticulocytes and PvRBP2b antibodies correlate with protection. Here, Chan et al. isolate and characterize anti-PvRBP2b human monoclonal antibodies and describe mechanisms by which these antibodies inhibit invasion.

The authors report the implementation of a Transformer-based model on the same architecture used in Large Language Models in a 14nm analog AI accelerator with 35 million Phase Change Memory devices, which achieves near iso-accuracy despite hardware imperfections and noise.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

The Panoptes antiphage system defends bacteria by detecting phage-encoded counter-defences that sequester cyclic nucleotide signals, triggering membrane disruption and highlighting a broader strategy of sensing immune evasion through second-messenger surveillance.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

Lekkos et al. show that a metabolic switch toward oxidative phosphorylation is required for cardiomyocyte re-differentiation and heart regeneration after injury in fish.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

The underlying physics of the strange metal phase observed in many strongly correlated materials is not well understood. Now, evidence emerges that antiferromagnetic spin fluctuations play an important role.

The gut microbiota can influence the severity of pneumonia through the production of metabolites. In this translational study, the authors investigate the effects of tryptophan metabolites, specifically indole-3-acetic acid (IAA), on pneumonia.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Observations of the shape, topography, crustal thickness and surface composition of the South Pole–Aitken impact basin on the Moon suggest a southward impact trajectory and the excavation of a discontinuous remnant magma ocean from beneath the crust.

Asteroid 1998 KY26 is the target of Hayabusa2 extended space mission. Here, authors show that it is smaller and rotates faster than known.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.