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Eukaryotic Fanzor proteins are compact and advantageous for delivery, but their activity remains limited. Here, the authors engineer an improved Fanzor2 system (evoMmeFz2) using structure-guided and AI-assisted strategies to enable efficient exon skipping in a Duchenne muscular dystrophy model.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

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.

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.

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.

Florets of indica rice open earlier than japonica rice, hindering utilization of the cross subspecies heterosis. Here, the authors show that an OsMYB8-OsJAR1 module regulates diurnal floret opening time divergences between the two subspecies.

A soft robotic probe enables continuous in utero monitoring of fetal physiological parameters, including heart rate, blood oxygen saturation, temperature and electrocardiogram data, during open or fetoscopic surgery to provide real-time information on fetal condition and distress.

STING–type-I interferon pathway regulates the immunogenicity of several cancer types, including head and neck squamous cell carcinoma. Here the authors describe that glutamine metabolism in the tumour microenvironment dampens the STING–type-I interferon pathway by epigenetically silencing the expression of BATF2, which functions as a tumour suppressor.

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.

The role of protein UFMylation in cancer remains to be understood. Here, the authors show that UFM1-specific ligase 1 and AKT positively regulate each other through UFMylation and phosphorylation, facilitating lipid synthesis and breast tumor growth.

In a trial involving 2,069 patients and 111 clinicians across 24 disciplines, patients performing a preconsultation session with an LLM-powered chatbot had a significantly lower consultation time and both patients and clinicians reported improved communication and satisfaction.

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.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

pH is a critical regulator of (bio)chemical processes and therefore tightly regulated in nature. Now, proteins have been shown to possess the functionality to drive pH gradients without requiring energy input or membrane enclosure but through condensation. Protein condensates can drive unique pH gradients that modulate biochemical activity in both living and artificial systems.

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

Fabrication of fully stretchable organic light-emitting diodes incorporating an intrinsically stretchable exciplex-assisted phosphorescent layer along with MXene-contact stretchable electrodes is described, demonstrating high efficiency and mechanical compliance for applications in next-generation wearable and deformable displays.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Therapeutic suppressor tRNAs are engineered to broaden their target range in vivo.

Here, authors experimentally demonstrate broadband far-field phonon coupling in a valley metamaterial integrated with a Dirac-strip, achieving coupling at a five-wavelength distance.

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.

Detection of hot intracluster gas in SPT2349−56 with the Atacama Large Millimeter/submillimeter Array provides new insights into early cluster formation.

The structure and functioning of soil food webs between biomes remains unknown. Here, tropical soil food webs are shown to have higher energy flux, predation and herbivory than temperate soil food webs which are based on litter and microbial biomass.

Fracto-mechanoluminescence is the emission of light from fracturing solids. Here, the authors show that this emission in Mn halides arises from elastic stiffness, electromechanical coupling, and trap states that activate Mn²⁺ d−d transitions.

The presence of EGFR mutations and de novo MET aberrations limited response to EGFR inhibitors in patients with advance non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 randomised clinical trial investigating first-line osimertinib (EGFR inhibitor) plus savolitinib (c-MET inhibitor) in patients with MET-aberrant, EGFR-mutant advanced NSCLC.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

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.

Wu and colleagues present the efficacy and safety results from the phase 3 SCORES trial evaluating suvemcitug plus chemotherapy in persons with platinum-refractory or resistant recurrent ovarian cancer.

This study reveals how Tau pathology in spinal neurons contributes to early tactile deficits in Alzheimer’s disease, linking sensory dysfunction to cognitive decline. It highlights potential peripheral biomarkers and new therapeutic targets beyond the brain.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

A three-dimensional (3D) nanofabrication platform based on metalens-generated focal spot arrays is introduced to parallelize two-photon lithography beyond centimetre-scale write field areas, revealing the potential of 3D nanolithography towards wafer-scale production.

Biomimetic artificial nanochannels have potential applications in signal regulation and subcellular biosensing. Here authors present artificial nanochannels based on DNA-functionalized glass nanopipettes, which when targeted to mitochondria can be used to evaluate and manipulate the interaction network between mitochondria and other organelles.

Skeletal muscle is central to whole-body energy balance. Here, Yang et al. show that MLL4-dependent enhancer activation is a key regulatory node for the governance of muscle metabolic efficiency and systemic metabolism via the control of muscle AMPK.

Elgendi and Markov et al. systematically review 26 studies on wearable devices that use physiological signals such as heart activity, breathing, skin responses, and blood flow to detect anxiety. They find that combining multiple signals improves accuracy over single-signal methods, highlighting the potential of wearables for anxiety detection.

The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.

The genetic mechanisms of why polyploid plants exhibit adaptive advantages over diploids are unclear. Here, the authors assemble the autotetraploid alfalfa genome, incorporate it into a pangenome analysis, and reveal the trade-off between adaptive advantages and evolutionary constraints mediated by tetra-copy core genes.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

DNA methylation and copy number variant analyses across a large number of genetic mouse models of pediatric brain tumors reveal subtype-specific molecular alterations shared with the corresponding human diseases.

MATTERIX, a multiscale graphics processing unit-accelerated framework for high-fidelity digital twins and workflows of chemistry laboratories, is presented, simulating robot and device operation, fluids and powders, and processes such as heat transfer and chemical kinetics.

By twisting bilayer conductive layers with engineered diffusivity, the authors realize moiré-driven thermal localization without nonlinearity, enabling commensurate and quasi-crystalline thermal patterns for programmable transport control.

Here, the authors show that brain dynamics mature from childhood to adulthood with increased hierarchical propagation and reduced visual-somatomotor dynamics. Top-down hierarchical flow strengthens throughout this developmental period.

The evolutionary mechanisms leading to symbiont replacement in insects are not well understood. Zhou et al. show that genome degradation results in nested symbiosis and endosymbiont replacement in cicadas, offering insight into the endosymbiotic origins of cellular organelles.

A cell surface reporter that binds to a fluorine-18-labelled radioligand enables the monitoring of CAR T cells and gene therapy vectors in preclinical models using PET imaging.

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.

Combining multiomic datasets from adolescent and middle-aged-to-older population cohorts with a purposefully devised analytical framework, we revealed substantial heterogeneity in brain-chronotype-behavior patterns and their complex interactions with everyday life.