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Using two-photon intravital imaging, the authors show that mechanical stress in skin triggers fluid-filled “stress vesicles” in epidermal cells, altering Piezo1-dependent calcium signals to drive stem cell differentiation and protect tissue integrity.

Symmetry breaking is key to tissue formation. Now it is shown that symmetry breaking of epithelial spheroids is controlled by an interplay of collective migration with curvature and matrix remodelling.

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.

Hexim regulates transcription by sequestering kinase P-TEFb in the 7SK RNP. Here, the authors show that Hexim autoinhibition dictates its specificity for 7SK RNA and safeguards against premature P-TEFb inactivation, coupling transcriptional control to RNP assembly.

The protospacer-adjacent motif specificity of several Cas enzymes is customized using protein language models.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

In this Viewpoint, actor, author, and broadcaster Stephen Fry describes his prostate cancer journey alongside the same story from his surgeon, Ben Challacombe, enabling us to consider “both sides of the scalpel”.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

RNAi therapy has huge potential but effective delivery to target location is a major issue. Here, the authors report on the delivery of RNAi to tumors using self-agglomerating nanohydrogels that can overcome the different delivery barriers and supply multiple RNAi payloads.

Plant Augmin cryo-EM structures reveal a 40-nm hetero-octameric fork with coiled-coil interfaces, dual CH domains at V-junction switch for microtubule binding and NEDD1 β-propeller binding to the V-junction boosts anti-parallel Augmin dimerization, recruiting γ-TuRC for branch nucleation.

The article reviews benefit-sharing efforts in South African genomics research, highlighting lessons from varied community settings and urging flexible, sustainable models that prioritize engagement, representation, and strong benefit management.

VRACs are ubiquitously expressed osmosensitive ion channels assembled from LRRC8A-E subunits. Here, the authors determine the structures of a LRRC8A:D VRAC using cryo-EM and identified that these channels are gated by lipids inside the channel pore.

The J2 antibody is widely used for detecting double-stranded RNAs. Here, Bou-Nader et al. define its nucleic acid specificity and recognition mechanism by solving its co-crystal structure bound to dsRNA, establishing a framework for its reliable use in RNA detection.

Many clinically relevant pathogens enter the body through mucosal surfaces, yet conventional parenteral immunization is insufficient to elicit robust mucosal immunity. This Review examines the unique anatomical and immunological features of the mucosal surfaces of the body and how this knowledge can be used to develop protective mucosal vaccines.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

S receiver function data reveal distinctive mantle gradients at 75-km and 180-km depths near the Rocky Mountains, suggesting a dual-lithosphere architecture in which the Cordillera is underthrust by Precambrian craton core.

In coordination and organometallic chemistry, back-bonding between an electron-rich, typically mid- or low-oxidation-state d-block metal centre and a ligand with accepting π* orbitals is widespread. Now, such an interaction has been observed between unlikely partners—high-oxidation-state uranium(v) 5f¹ ion and the poor π-acceptor ligand dinitrogen—in a U(v)–bis(imido)–N₂ complex stabilized by a lithium counterion.

In one earthquake, an oceanic transform fault ruptured in one direction and then backwards at a speed exceeding that of shear-wave propagation, according to an analysis of data recorded by nearby seafloor and global seismometers.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Premenopausal women aged <40 years diagnosed with oestrogen receptor-positive early-stage breast cancer have disproportionately poorer outcomes relative to older women. The authors of this Review propose a biology-driven approach to challenge the conventional sequencing of chemotherapy and endocrine therapy in this population.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

ANKLE1 senses DNA tension and negative supercoiling, enhancing cleavage of stretched, supercoiled DNA to resolve chromatin bridges, highlighting its unique mechanosensitive role in maintaining genome stability during cell division.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Myotonic dystrophy type 1 affects both muscle and neuronal function, but its synaptic pathology is poorly understood. Here, the authors show that upregulation of FasII (NCAM1) in both pre- and postsynaptic cells synergistically drives neuropathological and behavioral DM1 phenotypes, which can be rescued by FasII knockdown or specific isoform modulation.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Organic tandem solar cells combining solution- and vapour-deposited layers are difficult to fabricate due to the degradation of the underlying subcell during the deposition of the next subcell. Here, Che et al. design a charge recombination layer that protects the underlying cell and leads to 15% average PCE for 2 mm² devices and 11.5% PCE for 1 cm² devices.

Particle fusion is a promising process for constructing nanomaterials, but challenging to control in synthetic systems. Here, the authors report a method for kinetically regulated particle fusion controlled by variation in polymer chain length.

Bacterial resistance to polymyxin antibiotics is conferred by enzymes such as phosphoethanolamine transferases, which add positively charged phosphoethanolamine to lipid A. Here, the authors present the structure of one such enzyme in its liganded form, and propose an enzymatic mechanism that may be generally applicable to other phosphoform transferases.

During filamentous growth in the human fungal pathogen Candida albicans, a reduction in ribosome concentration leads to a decrease in macromolecular crowding. Inhibition of ribosome biogenesis can trigger filamentous growth in this pathogen.