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KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Non-invasive strategies to detect and track activated myeloid cells will facilitate disease diagnosis and monitoring in patients affected by neuroinflammatory disorders. Here, the authors present 18F-FMD, a dendrimer-based PET tracer that detects and monitors activated myeloid cells at different stages (presymptomatic and symptomatic) of Experimental Autoimmune Encephalomyelitis (EAE) in mice and in response to disease-modifying therapies.

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.

Controlled dislocation self-assembly is demonstrated in discontinuous-columnar Bi(Fe,Mn)O₃ thin film. Guiding dislocations along grain boundaries tailors polarization homogeneity, revealing a microstructure-driven design principle for ferroelectrics.

China’s carbon neutrality and clean-air policies cause global warming from reduced aerosols that nearly offsets cooling from reduced CO2 before 2060, with warming emerging afterwards, calling for early carbon neutrality and more mitigation strategies.

Biological system for stable object manipulation is facilitated by a unified tactile memory system. Here, GenForce enables transferable force sensing across diverse tactile sensors using a unified representation, enhancing robot manipulation through cross-sensor transfer and multi-sensor coordination.

In Eastern Asia, vegetation greening, especially in perennial drylands, has increasingly reduced dust emissions since the early 2000s, with effects amplified over long timescales, underscoring the mitigating capacity of land-surface change for multi-decadal dust trends.

Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

Self-oscillators are critical in various natural and engineered systems, as they enable complex collective behaviors through interactions among individual units. This study demonstrates that populations of Quincke colloids-self-oscillators whose back-and-forth motion defines both a phase and a nematic oscillation axis-can achieve a form of collective order, termed synchronematic order, characterized by hydrodynamic interactions that synchronize their oscillation phases and align their orientations.

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.

Atomic force microscopy is used to investigate the adsorption and organization of ions on charged surfaces. Trivalent ions adopt complex networks, clusters and layers associated with overcharging, whereas divalent ions follow classical predictions.

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.

The authors create a room-temperature super relaxor critical state in a lead-free ceramic, delivering dual-high recoverable energy density and efficiency by residing at a crossover between dynamic and static/frozen polar states.

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.

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.

Developing hafnium dioxide-based high-κ dielectrics via morphotropic phase boundaries remains challenging. This study proposes a thermal-stable high-κ strategy via coherent interface design and elucidates the atomic-scale enhancement mechanism.

Accurately locating underground contaminations is a major hurdle for cleaning up groundwater. Here, the authors address this issue by designing a smart nano reporter that travels with groundwater and releases signals upon contact with even trace-level contamination, allowing precise mapping of the residual organic contaminants.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

There is a lack of effective therapies for patients with non-V600E BRAF mutant cancer. Here, the authors report limited response in a phase II trial investigating the combination of binimetinib (MEK inhibitor) and encorafenib (BRAF inhibitor) for the treatment of non-V600E BRAF mutant cancer and subsequently investigate resistance mechanisms and combination therapeutic strategies in patient-derived models.

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.

The authors report long-lived pump-induced conductivity suppression in metallic Ti₃C₂ MXenes using ultrafast terahertz and reflectance spectroscopy. The effect is attributed to strong photothermal heating and slow heat dissipation.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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

The study introduces radio interferometric multiplexed spectroscopy (RIMS), a method designed to efficiently monitor the radio emissions of massive samples of stars. Applying it to LOFAR data, the authors identify stellar bursts, offering clues to possible star–planet magnetic interactions.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.

An integrated optical parametric amplifier on thin-film lithium niobate achieves more than 17 dB gain with less than 200 mW input power.

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.

MultiSuSiE is an extension of the Sum of Single Effects fine-mapping model that allows causal effect sizes to vary across ancestries. Applying MultiSuSiE to quantitative traits in All of Us identifies fine-mapped variants not implicated by other methods.

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.

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

Man-made ammonia emissions have harmful effects on human health and ecosystems, yet global mitigation strategies remain underexploited. A study now finds that emissions could be halved cost-effectively by 2050 through targeted and prioritized measures, with benefits far outweighing costs.

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.

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.

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.

A van der Waals heterostructure made from atomic layers of ferroelectric CuCrP₂S₆ and ferromagnetic Fe₃GeTe₂ can offer reversible, non-volatile ferroelectric control of two-dimensional magnetism.

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.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

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.

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.