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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.

A consumption-based carbon accounting method that takes into account how national policy changes affect emissions redraws the global emissions map.

Cullin-RING ligases are regulated by the COP9 signalosome (CSN) through deneddylation. Here, authors report high-resolution cryo-EM structures that capture catalytic and dissociation intermediates, identify CSNAP within the complex, and reveal a stepwise pathway for CSN disengagement.

A large-twist-angle bilayer graphene platform exhibits a quantized ratio of displacement to magnetic field at Landau-level crossings, offering a route to high-resolution cryogenic magnetometry.

SleepGPT is a time-frequency foundation model for sleep decoding, built on a generative pretrained transformer, achieving superior performance in various downstream tasks across datasets.

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.

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

Nuzum et al. used cross-sectional data from the UK PROTECT study to evaluate the relationship between high autistic traits and suicidality in older adults.

Rapid immune activation requires tight control of mRNA stability in CD8⁺ T cells. Here, the authors show that a compositive RNA motif – m⁶A sites positioned next to AU-rich elements - marks mRNAs for rapid decay during activation, revealing a coordinated mechanism that shapes T-cell immunity.

Respiratory virus genomic surveillance output is unevenly distributed globally. Here, the authors show that addressing this imbalance could substantially reduce the time to first detection of novel (variant) viruses, enhancing surveillance effectiveness and efficiency.

A large, multicenter, double-blind RCT in 150 children and adolescents found that external trigeminal nerve stimulation, although safe and well tolerated, did not produce significant short-term or long-term clinical benefits for ADHD compared to sham treatment.

A hierarchical cross-entropy loss is presented, which incorporates ontology structure into training and improves the out-of-distribution performance of large-scale single-cell annotation models without additional computational cost.

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

This study introduces a sediment-based method to reconstruct Antarctic fast-ice change during the late Holocene, revealing cyclic patterns linked to solar variability and offering insight into long-term cryosphere climate dynamics.

NiPS₃ is a van der Waals antiferromagnetic semiconductor where the exciton formation is strongly influenced by the magnetic ordering. Previous studies have been limited to magneto-optical approaches, but here, Lebedev, Gish and coauthors succeed in making field effect transistors that operate below the Néel temperature and observe an ultranarrow electroluminescence with a high degree of linear polarization.

Cancer immunotherapy benefits from antibody-lectin chimeras that block glyco-immune checkpoints.

Inconsistent diagnostic criteria and treatment approaches may hinder medical care and research for lipedema. Here the authors report a multi-phase Delphi study proposing consensus-based definition and management of lipedema.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

Effective substrates are key to probing and harnessing protease activity. This work presents CleaveNet, an AI tool that generates efficient, selective substrates, revealing known and distinct cleavage motifs and tuning designs to target activity profiles.

Yashinskie, Zhu and colleagues show that p53 activation triggers increased synthesis and accumulation of phospholipids, with enhanced activation of autophagy and lysosomal catabolism programmes and increased reliance on lipid headgroup recycling.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

The inability of intrinsically photosensitive retinal ganglion cells to shift the circadian clock in the suprachiasmatic nucleus during daytime is caused by light-dependent depolarization block of these cells.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

Albumin selectively inhibits Mucorales growth through the release of bound free fatty acids.

GluFormer, a generative foundation model, uses continuous glucose monitoring data to accurately forecast glycaemia-related health responses, particularly for long-term outcomes.

Disease course and pathology an infection may cause can change owing to the structural and functional physiological changes that accumulate with age, but therapy can be tailored accordingly; disease tolerance genes show antagonistic pleiotropy.

Hammerhead is a compact high-voltage vacuum bushing designed, simulated, and tested to 330 kV. It significantly increases voltage holdoff per volume compared to other designs and operates stably at 300 kV with leakage current below 10 μA without requiring ultra-high vacuum or polishing.

Radiation reaction (RR) on particles in strong fields is the subject of intense experimental research, but previous efforts lacked statistical significance due to the extreme regimes required. Here, the authors report a 5σ observation of RR and obtain strong, quantitative evidence favouring quantum models over classical, using an all-optical setup where electrons are accelerated by a laser in a gas jet before colliding with a second, intense pulse.

Qian and colleagues show that IL-17REL functions as a decoy receptor to suppress the effects of IL-17 family cytokines and reduce intestinal inflammation.

Using ancient DNA, isotopes and proteomics, this work reveals social inequality and mobility in Eastern Zhou China, showing female sacrifices, dietary disparities across classes, kinship networks among elites, and rare evidence of social mobility.

New results indicate that rhabdodontids and the previously described Ajkaceratops are actually distinctive European ceratopsians, a group better known from Asia and North America.

In this two-nation administrative register study (~5 million individuals), mental health conditions were linked to subsequent unintentional, self-harm and assault injuries. These results highlight the need for targeted injury prevention strategies.

CELSR1 is a core component of the tissue/planar cell polarity pathway. Here, the authors report a CELSR1-related disorder featuring brain malformations, neurodevelopmental delay and epilepsy, and use mice to explore the pathophysiological mechanisms.

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

Glitches in video calls can have a negative effect on the judgement of the people involved and correspond to worse outcomes in major areas of life such as job interviews and parole hearings.

Tropical forests regulate Earth’s carbon cycle, but what governs carbon sequestration following land use remains unclear. Here Tang et al find a shift from strong nitrogen limitation to no nutrient limitation over tropical forest secondary succession.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Accurate IC₅₀ prediction of small molecules is crucial for advancing anticancer drug development, however, the effectiveness of deep learning methods for predicting IC₅₀ values remains underexplored. Here, the authors benchmark five deep learning models against a mean-based baseline, revealing that while DeepCDR, DrugCell, and tCNN slightly outperform others, all models struggle with unseen compounds, underscoring the need for improved predictive accuracy.

The bacterial helicase-like transcription factor HelD associates with the RNA polymerase (RNAP) and recycles stalled transcription complexes. Here, the authors present the cryo-EM structures of three Mycobacterium smegmatis HelD bound RNAP complexes and further show that HelD can prevent the binding of the RNAP core to non-specific DNA and also actively removes RNAP from stalled elongation complexes.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

Over the past decade, funding for cancer research by the US government—and others—has stagnated, while the demand for investment has grown because of the increasing cancer incidence worldwide. We discuss how National Cancer Institute funding efforts have developed during this period, and the contemporary and future impact of these measures on cancer research in the USA.

Host antibodies can alter the glycan binding of adhesin proteins from infectious bacteria, but the antibodies’ mechanisms of action remain unclear. Here, the authors define four mechanisms of modulation, including ligand mimicry and multiple modes of allosteric interference.

There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.