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Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

The extrusion-based three-dimensional printing of polymers, metals, and composites requires elevated temperatures and may lead to diverse undesirable defects on printed parts. Here, the authors develop a vapor-induced phase separation printing technique to construct polymeric, metallic, and composite parts by using a polymer as a binder.

Virus-like particles are engineered to edit human hematopoietic cells in vivo.

Direct observation of G-quadruplexes (G4s) in live cells is challenging. Here the authors report a method to identify G4s within the nuclei of live and fixed cells using a fluorescent probe combined with fluorescence lifetime imaging microscopy.

The lack of tumour-specific antigens and control over T-cell activity limits the development of CAR-T cell therapies for solid tumours. Here the authors present an avidity-controlled CAR platform with inducible logic control functions.

In this biomarker cohort analysis of CheckMate 153, analyses of genomic alterations and neoepitope immunogenicity in tumor tissue samples from patients with non-small cell lung cancer treated with nivolumab show the evolution of neoantigens during nivolumab-induced selection pressure and how it associates with clinical response.

CD16a triggers antibody-dependent cellular cytotoxicity but CD16a shedding dampens its anti-tumor activity. Here the authors develop a monoclonal antibody (F9H4) that prevents CD16a shedding, which synergizes with a tumor cell opsonizing antibody (cetuximab) to elicit natural killer cell-driven immunity.

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.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

Electrotherapy requires electronic powered devices, set-up, and accessories. Here the authors, developed an integrated single-use platform for wearable electrotherapy as simple as a band-aid

A neutralizing nanobody specific to the prefusion conformation of herpes simplex virus glycoprotein B has cross-species activity and offers insights into virus neutralization, possible immunogens and an attractive avenue for antiviral interventions.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely applicable to small protein targets.

A large resource of shared tumor neoepitopes aims to accelerate cancer immunotherapy.

In the nematode C. elegans, cohesin creates specifically at active enhancers chromatin 3D structures named fountains. Cohesin artificial cleavage disrupts fountains and changes neuronal gene expression, function and animal behavior.

Accurate prediction of immunogenic CD8⁺ T cell epitopes would greatly accelerate T cell vaccine development. A new deep learning model, MUNIS, can rapidly identify HLA-binding, immunogenic and immunodominant peptides in foreign pathogens.

Covalent KRAS inhibitors show initial responses but resistance limits durability. Here drug-induced hapten peptides are identified and characterized, enabling production of high affinity, cross-HLA T cell engagers that stabilize low density hapten peptide MHCs to drive tumor-specific killing.

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

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.

Researchers use a chimeric approach to reveal the first near-atomic resolution structures the yellow fever virion, showing key differences between vaccine and virulent strains that affect how antibodies recognise and neutralise the virus.

High levels of histone acetylation at rhabdomyosarcoma SEs, including SOX8, are detrimental to transcription via exclusion of RNA Pol II, but not BRD4, from phase condensates.

Detailed analysis of the structure–activity relationship for cyclin K degraders reveals diverse compounds that acquire glue activity through simultaneous binding to the CDK12 kinase pocket and engagement of several key DDB1 interfacial residues.

A dynamic interconversion of three nickel states in lithium nickel oxide is demonstrated using evidence from x-ray spectroscopic data and first-principles calculations, which explains many physical properties of this and similar materials.

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.

The theory-guided synthesis of a tungsten-based W₂TiC₂T_x MXene from a non-MAX nanolaminated ternary carbide (W,Ti)₄C_4−y is reported. The tungsten-rich basal plane of the W₂TiC₂T_x MXene is then examined for the electrocatalytic hydrogen evolution reaction using a combined experimental and theoretical approach.

Current proteolysis-targeting chimeras can promote the ubiquitination and subsequent degradation of both target and off-target proteins by inducing their respective proximity with the cereblon ubiquitin ligase. Now, by developing and deploying an off-target profiling platform, ‘bumped proteolysis-targeting chimeras’ can maintain on-target degradation efficacy with reduced off-targets.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

We present genome-wide data from 64 subadults interred in Chichén Itzá around ad 500–900 that gives insight into burial rituals, and shows that their genomic legacy is still present and has adapted to immune challenges post-1492.

In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked long-lived persistence of neoantigen-specific CD8⁺ T cell clones, which correlated with prolonged recurrence-free survival at a 3.2-year follow-up.

This study of immunological memory diversity in the human upper airway provides new understanding of immune memory at a major mucosal barrier tissue in humans.

Epithelial organoids are grown without Matrigel using a single-chain antibody.

Although single-cell RNA sequencing analysis now allows simultaneous examination of transcriptome and T cell receptor repertoire sequences, integrating these two modalities remains a challenge. Here, the authors develop mvTCR, a generative deep learning model that integrates transcriptome and T cell receptor data into a joint representation capturing cell functions and phenotypes.

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.

Wiita and colleagues use cross-linking mass spectrometry and glycoprotein surface capture to identify an activated conformation of integrin β₂ present on AML cells and develop CAR T cells that target this conformation antigen in preclinical models.

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.

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.

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.

Quantitative multi-omics profiling of HDAC inhibitor responses in non-isogenic cancer cell lines reveals shared and divergent molecular remodeling. Responses highlight cell-type-dependent and -independent epigenetic drug mechanisms of action.

An integrated experimental and deep learning pipeline reveals cell-level targeting of nanocarriers in whole bodies.

This study identifies a fundamental link between slow-moving ions inside grains and fast-moving ions along grain boundaries in metal halide perovskites that governs their environmental stability and current–voltage responses.

Developing inhibitors that target specific protein-protein interactions (PPIs) is challenging. Here, the authors show that target selectivity and PPI blocking can be achieved simultaneously with PPI inhibitors that contain two functional modules, and create a paralog-selective PSD-95 inhibitor as proof-of-concept.

As presented at the ESMO Congress 2025, in the single-arm phase 2 IKF/AIO PHERFLOT trial, the perioperative combination of FLOT chemotherapy with anti-PD-1 and anti-HER2 monoclonal antibodies led to a pathological complete response rate of 48.4% in patients with resectable HER2+ esophagogastric adenocarcinoma, meeting the prespecified co-primary endpoint.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Alternating-current electroluminescent fibres hold promise as light sources for smart textiles and soft machines, yet they suffer from low durability and stability. Here, the authors report a bright, durable electroluminescent fibre that recovers from severing damage and remains stable for months, with omnidirectional magnetic actuation.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

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.