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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.

Granzyme B is an important factor in cytotoxic T lymphocytes anti-tumour immunity. Here, the authors report on a Pd-FTn granzyme B-mimicking nanozyme with a binuclear catalytic centre, delivered by functionalised nanovesicles to selectively trigger caspase-dependent apoptosis for a T cell-inspired cancer therapy.

The integration of high-κ dielectrics with low equivalent oxide thickness (EOT) is crucial for the development of 2D transistors. Here, the authors report the low-temperature fabrication of wafer-scale HfO₂ dielectric films with sub-5-Å EOT and their application for the realization of high-performance 2D MoS₂ transistors and circuits.

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.

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.

Limiting phosphate concentrations could be a strategy to protect and sequester carbon dioxide as fucoidan, a polysaccharide produced by marine algae.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

The existence of a long-lived, prethermal regime in many-body systems with tunable heating rates, driven by structured random protocols, is observed using a 78-qubit superconducting quantum processor.

Two-dimensional poly(arylene vinylene) frameworks are promising polymer semiconductors, yet obtaining highly crystalline materials is a major challenge. Now a series of 11 highly crystalline or single-crystalline 2D poly(arylene vinylene)s have been prepared—from 2D imine-linked covalent organic frameworks through a Mannich-elimination strategy—with diverse lattices, enhanced conjugation and specific surface areas up to 2,000 m² g⁻¹.

The properties of electronic transport through edge states of three-dimensional quantum Hall-like states are not yet resolved. Now, increasing the surface area of the edges is shown to produce increased conductance, suggesting that chiral surface states are present.

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.

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.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

AQP3 facilitates the transport of hydrogen peroxide. Here the authors report cryo-EM structures of AQP3 under different pH and in the presence of hydrogen peroxide. Along with molecular dynamics simulations, the study reveals how AQP3 maintains redox balance in endocrine pancreas.

Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves.

Nonconventional luminophores generally suffer from low solid-state quantum yields. Here, the authors report self-assembled cellulosic superstructures with high solid-state fluorescence quantum yields via oxygen cluster engineering and tailored non-covalent interactions.

Jaxley is a versatile platform for biophysical modeling in neuroscience. It allows efficiently simulating large-scale biophysical models on CPUs, GPUs and TPUs. Model parameters can be optimized with gradient descent via backpropagation of error.

Synthetic cells have huge potential in model systems. Here, the authors engineer synthetic–living hybrid tumoroids that replicate tumour-immune interactions in 3D, study synthetic cells integration, and demonstrate systematic studies of immune evasion and T cell engager therapies.

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.

Morphology control of two-dimensional metastable phase nanomaterials is a core issue for catalyst design. Here, two-dimensional metastable-phase Ni hexagonal nanosheets are synthesized via a one-pot method, exhibiting competitive catalytic performance in the electrocatalytic acetone hydrogenation.

This study reveals how the nature of optical excitation governs hot-carrier transport in transition metal oxides and directly visualizes distinct transport regimes via high spatiotemporal resolution imaging.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.

Reliability remains challenging for organic light-emitting diodes used in solid-state lighting. Here, the authors reduce the current density needed for a given brightness by fabricating devices on a high aspect ratio substrate with sub-mm texture, resulting in a 2.7x increase in operating lifetime.

β-thalassemia mutations show striking population differences, but their evolutionary origins are unclear. Here, the authors trace multiple independent origins of common β-thalassemia mutations in southern China, shaped by agricultural expansion, migration, and local selection.

The dysregulation of the inositol-requiring enzyme 1 alpha (IRE1α) has been associated with multiple human diseases, so IRE1α-targeting small molecules present great therapeutic potential. Here, the authors report a series of substituted indoles as IRE1α inhibitors of good potency and selectivity, and show that the inhibitor IA107 allosterically inhibits IRE1α RNase activity via binding to the IRE1α kinase domain but without inhibiting the IRE1α dimerization.

How a trait evolves depends on the shape of its fitness trade-off. Here, Huang et al. demonstrate evolution of trade-off shape in an experimental predator-prey system and develop a mathematical model of trait evolution when the underlying trade-off can also evolve.

When free electrons emit light, an entangled electron–photon state is created. Here measurements of the correlated multiparticle system have been used to produce non-classical photonic states.

The combination of plasmon-mediated electron enrichment and a continuous-flow reactor overcomes key challenges in selective methane oxidation, achieving a methanol production rate of over 6.5 mmol·g-1·h-1 with the selectivity of 100% and sustained stability over 100 h under ambient pressure.

Integrating an electronic device with a cavity can cause the electrons to couple to photons strongly enough to form hybrid modes. Now, the cavity effects induced by intrinsic graphite gates are shown to modify the low-energy properties of graphene.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

A large perturbation model that integrates diverse laboratory experiments is presented to predict biological responses to chemical or genetic perturbations and support various biological discovery tasks.

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

Reversible protonic ceramic cells face electrode interface degradation challenges. This study introduces an atomic trapping strategy to restructure heterointerfaces, improving power output and long-term stability while reducing precious metal usage.

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.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Penning trap mass spectrometry is used to measure the electronic transition energy from a long-lived metastable state to the ground state in highly charged rhenium ions with a precision of 10⁻¹¹.

The phosphoethanolamine modified cellulose in E. colibiofilms has revealed that polysaccharide functionalization alters the biofilm properties. Here, the authors show a model system to explore the role of phosphoethanolamine and other unnatural modifications on the properties of the biofilm-inspired assemblies.

The Verwey transition of magnetite is complex due to the coexistence of strong correlations and electron-phonon coupling. Here, the authors use resonant inelastic X-ray scattering to show evidence for magnetic polarons in magnetite and provide insight into the nature of the transition.

Genomic, transcriptomic and metabolomic analyses from a population of 295 diverse sweet-corn inbred lines provide insights into kernel quality formation mechanisms and the divergence of sweet corn and field corn.

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.

Inspired by the advance in protein structure prediction, CryoAtom builds protein models directly from cryogenic electron microscopy maps, producing more complete models, reducing the resolution requirement and accelerating modeling.