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Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Rearrangement of the B cell receptor is sequential, and pairing of the successfully assembled heavy chain with the surrogate light chain proteins VpreB and λ5 to form the pre-B cell receptor is an important checkpoint signal for continued B cell development. Here, the authors show that λ5 plays a key role in the multi-step assembly process involving association-induced folding reactions.

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

Nanomechanical resonators behave as resonant filters for driving forces. Here, the authors employ a few-layer graphene nanomechanical resonator as a filter for multifrequency forces modulated by a video signal. They demonstrate that the modulated vibrations encode an accurate copy of the video.

Taking advantage of the abundant renewable energy sources along seashores, this work describes a three-chamber electrolyser that combines electrolysis and desalination to produce both freshwater and green hydrogen.

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

When senescent cells accumulate during adulthood they negatively influence lifespan and promote age-dependent changes in several organs; clearance of these cells delayed tumorigenesis in mice and attenuated age-related deterioration of several organs without overt side effects, suggesting that the therapeutic removal of senescent cells may be able to extend healthy lifespan.

The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

Transition of superfluid to insulator is observed in the layer-imbalanced regime of bilayer magnetoexcitons.

Using Argo profile data with a mixing estimation method, this work reveals ocean subsurface mixing acting as pivotal positive feedback on the central Pacific ENSO and suggests ENSO diabatic positive feedback mechanism.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

A model trained to generate spatial proteomics profiles and predict the expression of 40 biomarkers directly from histopathology slides is shown to improve survival and treatment response prediction in patients with lung cancer.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

Cell segmentation remains a great challenge in high-resolution spatial-omics data. Here, the authors introduce a graph-based deep learning model that exploits transcript colocalization patterns to jointly perform noise-aware cell segmentation and annotation in spatial transcriptomics data.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Advances have been made in thin-film piezoelectrics; however, the linearity of electric-field-induced strain with frequency and temperature still requires improvement. Here, by growing interlocked monoclinic and tetragonal polar nanoregions in (K,Na)NbO₃ thin films, highly linear strains of up to 1.1% are reported at frequencies up to 10⁵ Hz.

A neuromorphic sensing system combining a flexible piezoelectric sensor array, event-triggered circuitry and a memristive chip enables energy-efficient, low-latency edge processing of event-based data through analogue in-memory computing.

Previous efforts to study the circadian clock using scRNA-seq have relied on time course designs that treat cell collection time as a proxy for circadian time. Here, the authors introduce a statistical method to infer circadian timing directly from expression, enabling researchers to study circadian phase heterogeneity.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Rare earth Nickelates, (RENiO₃) host a bond disproportionation phase transition where oxygen 2p holes form at one of the Ni sites. This process results in a spin-disproportionation state where a singlet state is formed by the spin of the nickel and the spin of the oxygen hole at every other site. Here, Li et al find evidence of this spin-disproportionated state in a rareearth nickelate.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Oriented growth is an important pathway for crystal growth. Here, the authors show that gibbsite nanoplates form mesocrystals through directed sliding and staggered stacking, as demonstrated by in situ microscopy and molecular simulations.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.