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Here, the authors conduct a metagenomic-based study of England’s rivers to show that biofilm bacteria are taxonomically and functionally diverse and are key to biogeochemical cycling, highlighting the importance of river biofilm bacteria in understanding and monitoring freshwater ecosystem health.

This study finds that cell segmentation errors affect numerous downstream applications of spatial transcriptomics data and provides a method to correct these errors by factorizing molecular neighborhoods.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Studies in zebra finches show that dopamine has a key role as a reinforcement signal in the trial-and-error process of learning that underlies complex natural behaviours.

In this work, the authors demonstrate nonlinearity-engineered dissipative quadratic solitons (DQS) for the first time. Moreover, they achieve an in-situ sign reversal of the effective nonlinearity, enabling a transition from bright DQS to platicon generation without requiring any dispersion engineering.

Nicholas and Mattar found that people use episodic memory to make decisions when it is unclear what will be needed in the future. These findings reveal how the rich representational capacity of episodic memory enables flexible decision-making.

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.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

With its attribution to Paranthropus, a 2.6-million-year-old partial mandible expands the range of the genus into the Afar region of Ethiopia and adds to our understanding of hominin evolution in eastern Africa.

The study by Russo et al. demonstrates alterations in the presence of senescence hallmarks across cell types, inducers, and model systems. These findings spotlight TFAP4 as a key regulator of senescence phenotypes in aging and Parkinson’s Disease.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.

Inversion of C3 stereochemistry of monoterpenoid indole alkaloids (MIAs) has to occur at some point during their biosynthesis; however, the mechanism has remained unresolved. Here, the authors report an oxidase–reductase enzyme pair encoded within a gene cluster and demonstrate their collaborative role in inverting MIA C3 stereochemistry.

Pan-expansion microscopy of tissue combines staining of proteins and lipids with immunolabeling.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Fusion genes involving KMT2A rearrangements are frequent oncogenic drivers of acute myeloid leukaemia (KMT2A-r AML) but the cell of origin remains unclear. Here, using preclinical models of EVI1 positive KMT2A-r AML the authors investigate the cell of origin and find that the presence of exogenous factors influences AML initiation and the resulting phenotype.

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.

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 authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.

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.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

Intramolecular coupling of extended biphen[n]arenes is developed to yield cycloparaphenylenes (CPPs). The modular nature of biphen[n]arenes makes it possible to customize CPP structures, which permits tuning of their photophysical properties. The syntheses are short and excellent yields are achieved. Moreover, postsynthetic functionalization is possible.

Authors use data from Togo to model onchocerciasis infection trends and elimination probabilities. Both ivermectin and vector control led to marked prevalence decline. Some areas may reach elimination by 2030 but others need alternative strategies.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

Fast panoramic rotational ultrasound tomography and photoacoustic tomography are integrated for hybrid rotational ultrasound and photoacoustic tomography, for three-dimensional dual-contrast imaging of soft tissue and vasculature across the human body.

Coagulase-negative staphylococci secrete natural products that prevent pathogen colonization. Here, the authors identify hominicin, a daptide bacteriocin produced by Staphylococcus hominis that has antimicrobial activity against a skin pathogen.

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.

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

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.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

The European Commission has set a regulatory benchmark for classifying green hydrogen in the European Union. New research finds that by regulating the power purchase for electrolysers, emission savings from green hydrogen production is ensured, but cost is also affected.

Exotic six- and eight-particle excitonic complexes have recently been observed in 2D semiconductors. Here, the authors uncover a stable many-body exciton in WSe₂–comprising 20 interacting quasiparticles–that emerges when strong electrostatic doping fills the Q valley.

High-dimensional immune profiling of a living recipient of a pig-to-human xenotransplant provides insight into the immune landscape of xenotransplantation and directions for improved immunosuppression strategies.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

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.

The authors present DNA-Diffusion, a generative AI framework that designs synthetic regulatory elements with tunable cell-type specificity. Experimental validation demonstrates their ability to reactivate AXIN2 expression, a leukemia-protective gene, in its native genomic context.

DNA data storage is an alternative to silicon-based data storage, but it demands advanced encryption and readout techniques. Here, the authors present an enhanced DNA origami cryptography protocol for data storage, using DNA-PAINT super-resolution imaging and unsupervised clustering to retrieve information in DNA cryptography.

Genome assemblies of 100 cultivated and seven semi-wild Gossypium hirsutum accessions provide insights into the evolutionary history of upland cotton and the genetic basis of fiber trait variation.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

In this work authors demonstrate how photocontrolled tag-targeted degradation enables precise, spatiotemporal control of protein expression in tumor cells and CAR T cells, offering an esapproach for regulating engineered proteins with light.

Uncertainty-aware machine learning models predict human toxicity for more than 100,000 chemicals, highlighting potency and uncertainty hotspots to guide safer use and to focus efforts to improve prediction confidence.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

How chemotherapeutic nucleoside 6-thio-2’-deoxyguanosine (6-thiodG) targets telomerase to inhibit telomere maintenance in cancer cells and tumors was unclear. Here, the authors show that telomere length and telomerase status determine 6-thio-dG sensitivity and uncover the molecular mechanism by which 6-thio-dG selectively inhibits telomerase synthesis of telomeric DNA.