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EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Metals shortage threatens climate goals by affecting adoption of key technologies for the energy transition. Optimizing technology mixes is now shown to limit the supply-constrained energy transition metals to only copper, lithium, and vanadium, though economy-wide resource sobriety remains urgent.

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.

This study reveals how temporally restricted enhancers control gene expression over time, highlighting their role in transcription dynamics and enhancer–promoter interactions during mouse limb development.

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.

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.

Efficient Kr/Xe separation is crucial for high-tech industries, defense, and aerospace applications. While conventional adsorbents typically capture Xe, their application is hindered by high energy costs during desorption. Here authors present a MOF with synergistic structural dynamics and local flexibility that reverses conventional selectivity, enabling preferential adsorption of Kr at room temperature.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

Tree buds integrate cold and warm cues to control dormancy release. Extended warm periods block plasmodesmata opening by repressing Flowering Locus T and GA pathways in buds. This mechanism ensures robust temporal regulation of dormancy release.

Glaciers in New Zealand retreated at about the same time as mid-latitude glaciers in the Northern Hemisphere during Heinrich Stadials, indicating strong global teleconnections during the last glacial period, according to a marine sediment record.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

Laser shock experiments on an iron-water phase reveal its density, melting, and electronic changes under extreme pressures. The results suggest dense deep magma oceans and show that iron-water reactions can greatly shrink and densify super-Earths.

Exposure to twelve widely used preservative food additives are associated with a higher incidence of type 2 diabetes in the French NutriNet-Santé cohort of 108,723 adults, supporting recommendations to favour fresh and minimally processed foods

Phototoxicity can distort live-cell microscopy results, yet tools to measure it are limited. Here, the authors present PhotoFiTT, a machine learning–based framework that quantifies light-induced stress on cells, helping researchers optimise imaging protocols while protecting sample health.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

This study reveals the role of boron and carbon in protecting critical interfaces sensitive to hydrogen: the tailored segregation critically reduces the hydrogen ingress, leading to an unprecedented resistance against hydrogen embrittlement.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

PET-MAD is a fast and lightweight universal machine-learning potential, trained on a small but diverse dataset, that delivers near-quantum accuracy in atomistic simulations for both organic and inorganic bulk materials, surfaces, and molecules.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

Fluidic force microscopy combines atomic force microscopy with microfluidic probes to enable measurement and manipulation of materials at sub-micrometre resolution. In this Primer, Zambelli et al. discuss the principles of fluidic force microscopy and applications in biological research and nanotechnology.

Drainage of two surface lakes on Greenland’s fastest ice stream caused a pulse of faster flow to propagate downstream and triggered a long calving episode, suggesting the entire stream is strongly coupled, according to geophysical field observations.

By mapping the photocycles of reversibly switching fluorescent proteins, the authors show that tuned activation and red/NIR co-illumination lead to increased signal and reduced photobleaching, prolonging live-cell imaging across super-resolution and multiplexing modalities.

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) is found to enhance mitochondrial fatty acid and amino acid oxidation in CD4⁺ T cells. In mice, IPA-mediated metabolic reprogramming of CD4⁺ T cells exerts anti-inflammatory effects and protects against colitis.

The role of mosquito saliva proteins in viral infection remains incompletely understood. Here, the authors show that sialokinin facilitates viral dissemination while suppressing immune response and inflammation in chikungunya virus-infected mice.

This study reveals that plant proteins MAIL1, MAIN and MAIL2 function as anti-silencing factors that maintain active gene expression. They bind specific DNA motifs to prevent Polycomb-mediated repression, which is crucial for normal development.

Adrenocortical carcinomas (ACC) are aggressive and often resistant to therapy. Here, the authors provide a single-nucleus transcriptomic atlas of ACCs and normal adrenal glands, finding ecotypes in steroid and microenvironment cells that are associated with clinical outcomes.

In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

Little Red Dots (LRDs) are a high-redshift galaxy population with unclear nature. Here, authors show CANUCS-LRD-z8.6, a spectroscopically confirmed LRD, hosting an active galactic nucleus, and its properties provide insights for early black hole and galaxy formation.

Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is conserved in multicellular animals, suggesting that the mechanism of bidirectional actin filament nucleation is conserved.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Knots reduce the tensile strength of macroscopic threads and fibres. Now it has been shown that the presence of a well-defined overhand knot in a polymer chain can substantially increase the rate of scission of the polymer under tension, as deformation of the polymer backbone induced by the tightening knot activates otherwise unreactive covalent bonds.

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.

A survey of 10,000 members of the public across European Union countries in which there are large carnivores finds strong support for carnivore recovery but simultaneous, and somewhat paradoxical, opposition to both population growth and hunting.

The complex collisional history of shocked L chondrites is reconstructed by combining high-pressure mineralogy, geochemistry, geochronology and orbital data. The results show that those meteorites arrive on Earth from over three distinct asteroid families.

While classical approaches rely on the study of individual ferroelectric domain wall movement on long time scales, the authors consider collective movements of domain walls during short time scales, characterized by discrete jumps, as indicators of avalanches on a broad range of scales.

Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.

Extensive oxidative potential measurements from across Europe analysed with the two most common assays, dithiothreitol and ascorbic acid, using a standardized protocol show the strong influence of site type and suggest pathways for mitigation strategies.

This study demonstrates 3D printing of hierarchically ordered, porous transition metal oxides and nitrides directed by block copolymer self-assembly, with record surface areas and nanoconfinement-induced critical fields in the nitride superconductors

A rotaxane-based mechanochemical system enables force-controlled release of multiple cargo molecules that are appended to its molecular axle.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Dissipative quantum phase transitions in open quantum systems have been extensively studied, but experiments have been mostly limited to first-order transitions. Here, the authors report the observation of first- and second-order dissipative quantum phase transitions in a superconducting Kerr resonator under two-photon pumping.

Cells change gene expression in response to stress to promote survival. Here, the authors map the transcriptional dynamics of osmoadaptation in yeast, showing that isogenic populations respond to stress using different transcriptional strategies.

By analyzing bulk and single-cell RNA-sequencing datasets generated from left atrial appendages of individuals with atrial fibrillation and non-affected controls, Leblanc and Yiu identify cell-type-specific genes and transcriptomic programs implicated in atrial fibrillation, a cardiomyocyte-specific androgen receptor signaling signature and an anti-fibrotic effect of NR4A1 inhibition in atrial cardiofibroblasts.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.