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Wong et al. uncover a nutritional dependency for acute lymphoblastic leukemia cells that spread to the central nervous system and propose using copper restriction to impair leukemia progression by disrupting nucleotide synthesis through the inhibition of electron transport chain activity.

How embryonic hematopoietic stem and progenitor cells proliferate while maintaining multipotency remains unclear. Here they show that Bnip3lb-regulated mitophagy reduces ROS levels, enabling sustained HSPC proliferation.

A single-cell spatial atlas identifies a B cell-predominant microenvironment within the profibrotic tubular niche that marks a subset of patients with diabetic kidney disease with rapid progression.

An early event after lung injury is extracellular matrix remodelling. Here, the authors show that thrombospondin-1 (TSP1) from megakaryocytes/platelets protects the lung’s extracellular matrix, particularly basement protein COL6. Mice without TSP1 had greater lung damage and neutrophil activity, showing TSP1 reduces injury severity.

Cue–reward learning rate scales proportionally with the time between rewards. Consequently, learning over a fixed duration is independent of the number of trials. This challenges trial-based dopamine learning models but supports retrospective learning.

Porous materials are actively researched for iodine adsorption, but the pore characteristics of frameworks required for efficient iodine capture in water are not well understood. Here, the authors construct a series of covalent organic frameworks with triangular pores and different local polarities for efficient iodine capture from aqueous solution.

QuantUMS implements uncertainty estimation for protein quantification in mass spectrometry.

This paper identifies the ‘master regulators’ that maintain cell transcriptional states in diffuse midline gliomas and shows that targeting them in combination could represent a promising therapeutic avenue for the disease.

Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

Mouse demyelination models are widely used to study myelin loss and repair in the central nervous system. Here, the authors use single-cell RNA sequencing to compare glial responses across mouse models and human multiple sclerosis lesions.

Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

Microglia, the brain’s immune cells, are important for neuronal phagocytosis during brain development. Here the authors show that microglial lysosomal protease cathepsin B is required for efficient neuronal efferocytosis during brain development.

Immune-remodeling mRNAs delivered in lipid nanoparticles boost antitumor immunity.

Studies explaining the secondary Igk recombination mechanism are described and Cer/Sis deletion and/or displacement is implicated as a developmental switch converting the rearrangement mechanisms from two-loop-based diffusional primary Igk into one-loop-based linear scanning secondary mechanisms.

The two species of African elephants are facing severe declines. Here, authors assess their continent-wide genomic diversity, identifying differences in their evolutionary histories and highlighting the formative role of gene flow.

Intracranial recordings in children revealed neural signals predicting attentional lapses. Closed-loop stimulation rescued performance and scalp EEG enabled noninvasive modulation, identifying a reproducible marker of attentional control.

Profiling of pleural mesothelioma samples from 91 patients identifies four DNA methylation subtypes that correlate with response to immune checkpoint inhibition and survival

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

Comprehensive, multinational validation of the PREVENT and SCORE2 cardiovascular risk scores, used in the United States and Europe, respectively, in 44 observational studies and 18 randomized trials, shows similar performance for the two risk scores and generally good performance across geographical regions.

In the hippocampus, complex processing of sensory stimuli occurs even in the unconscious state.

The mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

Foamy microglia are associated with multiple sclerosis progression, linking phagocytosis, altered lipid metabolism (oxylipins) and lysosomal stress to nonclassical neuroinflammation and disease severity, highlighting potential therapeutic targets.

Parkinson’s disease is managed through co-treatment with levodopa and tolcapone, with tolcapone altering the microbiome to increase its capacity to metabolize levodopa, implicating the gut microbiome in drug–drug interaction.

Researchers developed ultralow-density rigid-network hydrogels for stable solar desalination under intense sunlight. They reach an evaporation rate of 25.57 kg m⁻² h⁻¹ at 10 suns and deliver water production of 138 L m⁻² day⁻¹ in low-cost modules.

The efficiency of horizontal gene transfer between different bacterial lineages is often unclear. Here, Figueroa et al. show that lateral transduction is the primary driver of gene exchange between Staphylococcus aureus lineages, and immune-deficient mutants enable the spread of new genetic trait

The role of cortical PV neurons in the regulation of sleep architecture and homeostatic sleep rebound is not fully understood. Here, the authors show that CaMKII-mediated control of cortical parvalbumin-neuron activity regulates the homeostatic sleep rebound in mice.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implications for how these orally delivered weight-loss drugs engage brain reward circuits.

An analysis of the responses of 15 diverse human gut bacteria in more than 100 pairwise co-cultures reveals extensive remodelling of the bacterial proteome and metabolome in response to the presence of other species.

Developmental programs are frequently co-opted in glioblastoma. Here, the authors show the role of transcription factors Olig1/2 in fate specification of tri-potential intermediate progenitor cells and their connection with gliomagenesis in mouse models; they also show that Olig1/2 deletion can reprogram such stem cell differentiation and inhibit tumour growth.

In this work, authors report a mechanism for how phage can promote the spread of costly antibiotic resistance. They show that faster-growing sensitive cells dominate the biomass periphery where they encounter more phage, allowing for slower growing resistant cells to persist.

A pan-haematologic cancer approach, involving analysis of data from 256 patients across 5 cancer types and 13 clinical trials, revealed predictive biomarkers for understanding the response or non-response of patients to CAR-T therapy.

The transition from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is associated with poorer patient prognosis. Here, the authors investigate NUMB loss as a driver of the NMIBC-to-MIBC transition and identify a RHOA/ROCK/YAP signaling pathway as a therapeutic vulnerability.

This study reveals that the malaria parasite Plasmodium uses a unique Aurora kinase complex to control cell division. This divergent machinery regulates spindle formation and is essential for parasite transmission.

The management of ulcerative colitis (UC) remains challenging due to the complexity of its etiology. Here, the authors establish that argininosuccinate synthetase 1 (ASS1) and its metabolite arginine are pivotal inducers of UC, through the triggering of mTOR and iNOS activation, and the induction of gut microbiota dysbiosis by metabolomics and proteomics. Inhibition of ASS1 by C-01 provides a viable strategy for the treatment of UC.

Salmonella-invaded intestinal stem cells activate an inflammasome-driven differentiation program toward antimicrobial Paneth cells, revealing a protective stem cell defense mechanism that helps restrict pathogen spread.

In this study, Flickinger et al. uncover the essential role of cytosolic NADK and why the relative importance of this role further depends on folate availability.

Cells reduce the S–S bond in cystine to obtain cysteine. A robust alternative pathway, initiating with enzymatic cleavage of a cystine C–S bond followed by nonenzymatic reactions, is here shown to support survival of reductase-deficient cells.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Neural crest cells differentiate into skeletogenic mesenchyme and neuro-glial lineages, thereby contributing to craniofacial formation. Here, single-cell analysis of cranial neural crest shows that specific rRNA modification and ribosome assembly factors contribute to skeletogenic fate. Their disruption causes craniofacial defects, while high levels in neuroblastoma predict poor survival.

The impact of phage predation on spreading antimicrobial resistance is unclear in the context of its effects on microbial community spatial organization. Here, the authors show that phage predation can promote the spread of plasmid-encoded antibiotic resistance by increasing microbial spatial intermixing.

During evolution, how adaptive walks cross fitness valleys remains unclear. This integrative study on monkeyflowers reveals that convergence in large steps (floral color and gene expression) drives a shift in pollinator attraction despite non-optimal fit, paving paths to reproductive isolation.

Escherichia coli is widespread in healthy breastfed infants, yet its ecological role is unclear. Here, the authors provide insights into the mechanisms supporting its persistence and co-existence with dominant Bifidobacterium, including potential cross-feeding of human milk oligosaccharides.

This study develops a platform that enables simultaneous, multiplexed tracing of 30 nitrogen isotope-labelled metabolites, uncovering differences in pyrimidine synthesis pathway choice between primitive and differentiated cells.

Cancer-associated somatic mutations can change RNA structures. Here, the authors develop a method to detect interactions between RNA and small molecules, showing that such mutations can affect small molecule binding by changing the RNA’s G quadruplex structures.

ATRX mutations are associated with developmental disorders and cancer, but how they affect gene regulation is unclear. Here, the authors report that ATRX loss can perturb alpha-globin gene expression by promoting G4- and R-loop-associated DNA damage via a G-rich repeat.

Here, the authors develop a shape-based approach to identify DNA sequence from cryoEM density maps. Integrating sequence identification with quantitative analysis of base-pair step deformability, their work reveals that gyrase engages DNA regions with specific mechanical properties.

A large-scale proteomics analysis of the dark proteome by the TransCODE Consortium reveals many translated non-canonical open reading frames to encode microproteins and peptideins.