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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.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

The omentum is the main metastatic site for ovarian cancer. Here, the authors present a human cell atlas of both benign and omentum metastatic ovarian cancer, providing insights into established metastatic sites but also of the omentum pre-metastatic niche.

Activity-based protein profiling identifies covalent small molecules that potentiate the activity of the METTL5:TRMT112 complex through binding to a complexoform-restricted allosteric pocket absent in other TRMT112:methyltransferase complexes

A survey of the reconstructed gene set of the last eukaryotic common ancestor shows a consistent link between Asgard archaea and the origin of numerous, functionally diverse eukaryotic genes, demonstrating the dominant Asgard contribution to eukaryogenesis.

Break-induced replication (BIR) repairs broken DNA but can also destabilize genomes. The authors identify 33 new genes controlling BIR completion, showing that spindle assembly and spindle positioning checkpoints coordinate repair, and that nuclear pore proteins regulate BIR at multiple steps.

Qudits can encode a richer class of topologically ordered states, which are promising for quantum information, but experimental realizations have been limited to qubits. Here, the authors report a study of a qutrit toric code on a trapped-ion quantum computer.

Distinct endocannabinoids signal to either astrocytes or neurons, evoking contrasting regulation of synaptic function. This works reveals the high degree of complexity of neuronal and astrocytic signaling in brain function.

LEVA is a label-free immobilization method for studying surface-bound extracellular vesicles.

Inhibitors of the protein kinase Wee1 are promising drugs for cancer therapy. Here, the authors show that these drugs activate the integrated stress response via GCN2, synergising with mRNA translation defects. They suggest strategies such as PROTACs or ISR inhibitors to improve WEE1 mediated toxicity.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Diamonds provide a window into deep Earth processes and can be used to understand the deep carbon cycle. Here, Jacob et al. show that diamond precipitation can be triggered by the oxidation of pyrrhotite to magnetite at the base of a cratonic lithosphere, providing insight into diamond formation.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

In this work, researchers show how laser annealing is used to create complex 2D gradients in magnetic properties, which can steer spin waves and domain walls. This fast, maskless method enables the development of next-generation computing devices.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

To what extent regeneration recapitulates embryonic development is a longstanding question. Here, they show that embryonic gene modules are re-used, rewired, and interconnected to specific injury-induced down-stream targets during regeneration.

Jonaitis et al demonstrate that serotonin differentially modulates feedforward inhibitory neurons in the olfactory system of Drosophila which likely reflects odor categorization in higher order brain regions.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Yakut communities, with Trans-Baikal admixture during the Mongol expansion, preserved genomic diversity and oral microbiomes despite the Russian conquest, which introduced cereals, pathogens and Christianity, whereas marital practices preserved low consanguinity except in one late case of traditional shamanism.

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.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

The mechanism(s) controlling CD8+ virtual memory T cell (TVM) development are still under investigation. Here, using uninfected or IAV-challenged Ikzf3-deficient mice, the authors identify the transcription factor Aiolos as a negative regulator of TVM cell development by repressing Eomes and IL-15/STAT5 signaling.

Mendelian genetics posits equal transmission of alleles, but selfish alleles can bias the transmission of large genomic regions or entire chromosomes. This study reveals the evolution of large amplicons as a distinct genetic feature of chromosomes with selfish alleles.

Tau misfolds in Alzheimer’s disease, but how the link between tau filament structure and pathogenicity is unclear. This study shows that both filament core structure and phosphorylation in the fuzzy coat are required for full seeding capacity.

The cell death effector Gasdermin A is only known to be activated by Streptococcus pyogenes. This work discovers a mechanism for its activation by Staphylococcus aureus, and shows a conserved role in immunity against invasive skin pathogens

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.

Genome-wide analysis in individuals of African ancestry identifies a nonsense variant in CD36 associated with increased risk of dilated cardiomyopathy (DCM), partly accounting for the higher incidence of DCM in African-ancestry populations.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, but platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, the authors design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone, which exhibit the activity of both parent anticancer compounds and can overcome drug efflux effectively due to covalent binding to intracellular biomolecules.

High-resolution imaging mass cytometry attains subcellular resolution through a combination of oversampling and deconvolution and enables highly multiplex imaging of subcellular structures such as nuclear foci and mitochondrial networks.

Sequencing of 144 ancient genomes from Shimao city and its satellites presents pedigrees among tomb owners spanning up to four generations showing predominantly patrilineal descent structure across Shimao communities, and possibly sex-specific sacrificial rituals.

Post-acute sequelae of SARS-CoV-2 (PASC) have been linked to brain alterations, but association with cognitive problems are not well understood. Here, the authors analyze blood proteins and brain MRI data one year after mild COVID-19, revealing distinct neurodegenerative processes in PASC patients with cognitive problems, such as cortical thinning, brain iron deposition, enlarged choroid plexus, and increased blood neuronal/glial injury markers, compared to other-PASC.

Using multiple visualization and profiling methods, Gigi et al. characterize the microbiome diversity of 322 brain tumors including brain metastases and glioblastomas.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

Streptococcal S protein activates a peptidoglycan cell wall repair and modification complex to promote resistance of Streptococcus pneumoniae to lysozyme and LL-37, and increase virulence during infection.

Intercellular calcium waves drive numerous biological processes. Here light-activated molecular machines that—via nanomechanical action—stimulate ICW are reported, opening up avenues for the modulation of downstream biological processes using molecular-scale devices.

Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

Josephson junctions are used for SQUIDs, voltage standards, and superconducting qubits. These applications are located at one corner of the device parameter space. Here, the authors shed light on the other corner and show the quantized current of Josephson junctions — dual to the quantized voltage.

Duan and Kaushik et al. reveal the structural basis of how Escherichia coli and Thermus thermophilus RNA polymerases initiate transcription from Np₄A alarmones producing Np₄-capped transcripts. The caps form various interactions with a polymerase during initial steps, influencing capping efficiency.

Understanding of the immune microenvironment in pediatric acute T cell lymphoblastic leukemia is limited. By analyzing single-cell transcriptome, surface protein expression and immune repertoire data, the authors here identify non-malignant CD4^-CD8^- TCRαβ T cells that are present in a subset of patients with Rap1 signaling in leukemia cells and are associated with adverse clinical outcome in patients with low minimal residual disease.