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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.

A streamlined blood test using mass spectrometry improves measurement of amyloid-β for early Alzheimer’s disease diagnosis, requiring less sample volume and reagents while maintaining high accuracy, sensitivity and strong agreement with brain imaging.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

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.

There has been a recent interest in control of magnetism via ionic transport. The appeal of such magneto-ionic control lies in its extent, non-volatility and potential energy-efficiency, however, the number of systems showing such behaviour is limited. Here, Tan, Ma, and coauthors demonstrate magneto-ionic control through Carbon transport.

Psychedelics and their non-hallucinogenic analogues were compared, revealing that serotonin 2A receptor (5-HT_2AR)-mediated G_i signalling is essential for hallucinogenic effect, with the functional mechanisms underlying this providing insights for designing therapeutic drugs without hallucinogenic effects.

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.

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.

Amplification and optimal noise filtering in hyperpolarized noble-gas spins of observations from distributed intercity quantum sensors monitoring for unexpected transient rotations of polarized spins set parameter range constraints in the search for axion dark matter.

Aqueous two-phase systems have potential as biomimetic materials, but often lack stability and are prone to collapse. Here, the authors use interfacial assembly of chitin nanofibres and cellulose nanocrystals to prepare a biobased system with permeability and switchable motility.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

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.

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.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

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.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

An allosteric site on the E3 ligase adapter cereblon can be targeted to modulate the efficacy of cereblon in targeted protein degradation applications.

Micromitophagy is found to occur in plant male germline cells, mediated by ATG5–HSP90.2 signalling, and is evolutionarily conserved in angiosperms. This mechanism underpins paternal mitochondrial elimination and supports the zygote-to-embryo transition.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.

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.

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

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

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

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.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Dyskalemia is a dangerous potassium imbalance requiring rapid treatment. Here, the authors show, in a randomized trial of 14,989 patients, that real-time AI-ECG alerts increased hyperkalemia (69.1% vs. 41.6%, HR 2.23, 95% CI 1.44–3.46) but not hypokalemia treatment (HR 1.14, 95% CI 0.74–1.77).

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

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

Retinal prostheses aim to restore sight by stimulating residual retinal cells. Here, the authors develop a photoacoustic stimulation technology using a PDMS and carbon-based flexible film that activates retinal cells with near-infrared laser pulses, ex vivo and in vivo.

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.

Integrating computational analyses of T cell exhaustion and mitochondrial fitness atlases with in vivo CRISPR screens has identified KLHL6 as a dual-negative regulator of both exhaustion differentiation and mitochondrial dysfunction, highlighting its potential as a target to enhance anti-tumour immunity.

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.

Examples of materials with non-trivial band topology in the presence of strong electron correlations are rare. Now it is shown that quantum fluctuations near a quantum phase transition can promote topological phases in a heavy-fermion compound.

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.

Addressing how the nitrogen-induced changes in plant diversity differ from those in soil organisms is critical. This global meta-analysis suggests that nitrogen enrichment has stronger negative effects on plant diversity but modest to negligible effects on soil bacterial and fungal diversity.

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

Modelling suggests the carbon cost for nitrogen assimilation by plants will rise substantially under future climate change with further increase at higher latitudes, due partly to enhanced contributions of soil inorganic nitrogen.

Nanoparticles sensing glycosaminoglycan loss in osteoarthritis enable disease-severity-responsive delivery of ghrelin messenger RNA to cartilage lesions, reducing cartilage damage, bone thickening and pain in animal models.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

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.

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.

Stable adipocytes resist lipolysis in healthy states but are highly susceptible to a catecholamine-independent, neurosystemic pathway-driven catabolic state.

This work presents a global wind power simulation tool that uses high-resolution data and extensive validation to improve accuracy. It corrects wind speed biases and validates against real-world data, enhancing reliability for wind energy assessments across various scales and regions.