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Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

Kinetics for a multi-cleavage reaction of polyproteins and the viral protease from four human coronaviruses reveals that processing speed and order are not conserved. Moreover, full processing is not always a requirement for complex formation.

Resistance mutations in BCL-2 reduce the clinical efficacy of venetoclax. DeAngelo et al. show stapled BAD BH3 peptides can retain and even enhance binding to these mutants, offering a structurally informed strategy to overcome this mechanism of cancer drug resistance.

Here, the authors found that human NAT16 acetylates histidine in vitro and in vivo. Biochemical and structural characterisation uncovered a double-GNAT fold with distinct active site architecture that is conserved across species.

Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

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.

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.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

The diversity of perovskite compositions has led to ambiguity in their representation and impose challenges for data mining and machine learning applications. Here, the authors propose a set of guidelines and a JSON schema for standardized description and reporting of perovskite compositions.

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.

Aqueous two-phase systems have potential as biomimetic materials, but often lack stability and are prone to collapse. Here, the authors use interfacial assembly of chitin nanofibres and cellulose nanocrystals to prepare a biobased system with permeability and switchable motility.

Kidney shortages limit treatment options for patients with end-stage kidney disease, prompting exploration of xenotransplantation. Here, the authors show that a genetically modified pig kidney sustained essential functions in a living human for 51 days, informing future clinical strategies.

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.

Spin-enhanced lateral flow tests use nanodiamonds for the sensitive, robust detection of disease biomarkers. Here, authors report a clinical evaluation of a test for SARS-CoV-2 antigen, finding 95.1% sensitivity (Ct ≤ 30) and 100% specificity, with detection 2.0 days earlier than conventional tests.

Nuclear architecture depends on proper regulation of lamin A/C modifications. Here, the authors show that TAF4A and NF-Y control Kansl2 expression in muscle stem cells, preserving genome stability and supporting muscle regeneration.

In this study, the authors determine the structure of a Type I-A retron from E. coli FORC82 and reveal the functional interplay between Reverse Transcriptases (RTs) and Structural Maintenance of Chromosomes (SMC) ATPases.’

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

This study demonstrates how to combine molecular dynamics computer simulations with experimental biophysical data to determine accurate atomic-resolution ensembles of intrinsically disordered proteins.

Previous research has suggested that pDCs are required for an effective antiviral immune response, but direct experimental evidence to support this is lacking. Here Ngo et al. develop a pDC knockin mouse model and find that pDCs are dispensable for an antiviral immune response to mouse cytomegalovirus and may be detrimental during influenza or SARS-CoV-2 infection.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

The authors studied mice with targeted deletion of OPA1, a mitochondrial fusion protein, in intervertebral disc and knee articular cartilage, and showed that maintenance of mitochondrial dynamics is critical for the health of these hypoxic tissues

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Graphene systems have the potential to host Wigner crystal states at zero magnetic field. Here, the authors report transport signatures consistent with Wigner crystallization in AB-stacked bilayer graphene at both zero and finite magnetic fields.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

How translation of M-phase promoting factors is blocked in immature oocytes is poorly understood. Here, the authors show 4E-T suppresses cyclin-B and c-Mos translation, preventing oocytes from maturing spontaneously without hormonal stimulation.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Conventional Dendritic cells (cDCs) continually migrate from peripheral tissues in homeostasis. Here, the authors analyse the homeostatic turnover of cDC subsets in the intestine from tissue entry to migration to the draining lymph nodes, noting a dynamic life cycle with changes in transcriptome and proliferation rates.

NMR spectroscopy is a powerful tool for studying chemical reactions, but short-lived intermediates are hard to capture. The authors present a system combining LED and rapid-injection NMR for in situ monitoring of photochemical processes, advancing the study of reactive species and kinetics.

Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

Despite the efficacy of artemisinin against Plasmodium falciparum, young intraerythrocytic ring stage parasites may survive and persist in a dormant state. In this study, Yu et al elucidate the epigenetic regulatory mechanism of artemisinin resistance in P. falciparum ring-stage survival.

Targeted in situ sequencing directly maps editing rates at single-cell resolution in postmortem tissues to visualize base and prime editor delivery.

The authors present a multicenter database to investigate the neural correlates of dreaming, including physiological, behavioral and experiential data. This database could boost the research on the mechanisms of dreaming in humans and the signatures of consciousness.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Sea-ice expansion around Antarctica, and related surface cooling, is shown to be linked to natural long-term variability of Southern Ocean convection. Model simulations reproduce the observed trends, if they start from an active phase of convection.

The PhenoSphere is a unique plant cultivation facility in which field-like environments can be simulated. Here, the authors find that a single season simulation is superior to an averaged season and to a climatized glasshouse cultivation to elicit field-like phenotypes evaluated in 11 maize lines.

Machine-learning meta-analysis reveals ethylene as a central component of the molecular core in abiotic stress responses in Arabidopsis.

Incorporation of the far-red light adaptation of cyanobacteria into crops has been suggested as a potential strategy to increase photosynthesis and yields, but the magnitude of this benefits has not been estimated. Here, via 3D canopy model of soybean, the authors show that it could increase CO₂ assimilation up to 26%.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

Indonesian cattle are unique due to their history of admixture involving both zebu and banteng. Here, Wang et al. identify ~3.5 million novel introgressed SNP variants and provide a genomic map of banteng introgression within and across many cattle breeds, each with unique introgression histories.

The authors model regional electricity grid coordination, which enables access to geographically dispersed resources. Results suggest grid integration can reduce planning uncertainty region-wide but may impact individual countries differently.

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.

A scalable pipeline MARQO resolves the multiparametric cellular and spatial data in responders to immune checkpoint blockade therapy relative to non-responders.

Ecosystems that provide fresh water for cities also impact sediment flows, flood mitigation and hydropower provision. This Article looks at over 300 cities globally to gauge the interactions of natural ecosystems with built infrastructure.

Predictive coding is a popular theory of brain function, but it remains unclear if and how it may be implemented in the brain. The authors present a spiking neural network model that offers a fresh perspective on predictive coding and reproduces many observations from visual cortex.

Genetic factors affecting Aedes aegypti susceptibility to dengue virus infection aren’t well studied. Here the authors show that a cytochrome P450 gene, typically linked to cuticle structure and insecticide resistance, influences dengue infection in Aedes aegypti.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

This study maps chromatin accessibility at single-cell resolution in rice and related grasses, revealing how regulatory DNA elements evolve across cell types and species and identifying potential silencers that control gene expression.