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Many vascular‑disease risk loci lack defined causal genes. Here, the authors integrate functional genomics and CRISPR screens to identify genes influencing smooth muscle cell behaviour, validating roles for FES, BCAR1, CARF and SMARCA4, with Fes loss promoting atherosclerosis and hypertension.

ASXL1 is often mutated in myeloid cancers. Here, the authors describe the molecular and structural mechanism by which ASXL1 associates with the transcriptional coactivator BRD4, helping to explain their high correlation in cancers.

Nicotinamide adenine dinucleotide (NAD) biosynthetic enzymes have been reported to be oncogenic. Here, the authors show that NAPRT, a key enzyme in the deamidated NAD biosynthesis pathway, functions as a suppressor of colon inflammation and tumorigenesis by maintaining DNA repair capability.

Over the past 40 years, 42% of tropical and subtropical ecosystems have experienced an increase in plant reliance on past precipitation, consistent with greening during the late growing season in drylands and drying during the wet-to-dry period in non-drylands.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

Conventional slurry electrodes limit high-energy lithium batteries. This work shows that dry-processed electrodes with molecularly coupled carbon–binder networks enable high mass and active material loading, supporting stable high-voltage operation and enhancing battery energy density.

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.

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.

Diatoms are critical for carbon fixation and have strong biotechnology potential. Here, the authors optimized DNA and protein delivery methods for the model diatom Phaeodactylum tricornutum, also showing that DNA pieces can be stitched together directly in algal cells.

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.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Quantum range finding struggles in bright background and at long distance. Here, the authors demonstrate a quantum-inspired, energy-time correlated classical rangefinder. It preserves quantum noise suppression, works at low power, and enables robust daylight remote ranging in real-world environments

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Chen et al. developed a self-powered smart magnetoelastic stent for real-time hemodynamic monitoring and stenosis detection.

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.

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 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.

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

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.

Biodegradable enzymatic microbubble robots self-propel in urea, are magnetically or chemotactically guided, provide ultrasound imaging and enhance intratumoural drug delivery with focused ultrasound.

In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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.

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.

A cortical premotor network in HVC, once initiated, can sustain and regulate the sequential production of zebra finch song syllables without major extrinsic inputs.

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.

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.

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.

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.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

Bright electron bunches power particle physics and photon science. Here, reproducible bunches were generated in a plasma with simultaneous high charge per unit energy and low emittance, advancing a scheme to produce ultra-bright bunches in future.

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.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

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.

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.

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.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

Nagahata, Kato and Yamada et al. provide cryo-electron microscopy structures of four phylogenetically diverse RNA-guided nucleases—HfmIscB, TbaIscB, YnpsCas9 and NbaCas9—each in complex with its guide RNA and target DNA, providing insights into CRISPR–Cas9 evolution.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

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.

ADGRL4 is a cancer-implicated adhesion GPCR whose ability to couple to G proteins had been unclear. Here, authors show that ADGRL4 weakly engages Gq and determine its 3.1 Å active-state structure, revealing its mechanism of activation.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.