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Compact Un1Cas12f1 enzyme suits AAV delivery but is limited by narrow PAMs and modest activity. Here, authors engineer evoCas12f to recognize broader NTNR/NYTR PAMs and boost editing efficiency up to 91%, enabling efficient multiplex editing, base editing, and gene activation in cells and mice.

Here, the authors show that residues N490 and M492 of Hepatitis E Virus capsid protein are pivotal, albeit not exclusive, host tropism determinants of hepatitis E virus (HEV) for swine infection, which enhance the understanding of HEV’s zoonotic transmission and host specificity.

Obesity impairs metabolic flexibility-the capacity to adapt to fluctuating energy demands. Here, authors show that PRMT3 mediates the post-translational adaptation of visceral fat to fasting regulates metabolic flexibility and could be a therapeutic target for obesity.

Here, Zhang et al. demonstrate that the microbial metabolite indole-3-propionic acid stimulates production of β-hydroxybutyrate in intestinal cells, in turn activating regenerative stem cells to promote mucosal healing in colitis.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Intracellular pathogens such as Mycobacterium tuberculosis can promote their survival within infected cells by preventing lysosomal acidification. Here, the authors show that M. tuberculosis secretes a protein that promotes phosphorylation of a subunit of the host vacuolar ATPase, thus inhibiting V-ATPase assembly and lysosomal acidification.

The direct coactivation of inert hydrocarbons and water typically requires high oxidation potentials. Here, the authors report that a Ni-activated tungsten-oxygen covalency anode is designed to steer the oxygen transfer from water to benzylic C(sp³)–H bonds via Ni-regulated interfacial water structure.

Neuromorphic photonic systems can incur significant energy for moving and converting data between digital and analog domains. This work shows that integrating analog memory into these processors can save 26 × power over conventional digital-to-analog architectures while keeping  > 90% inference accuracy.

The growing demand for rare earth elements (REEs) underscores the need for sustainable recovery methods and a reliable supply. Here the authors establish a platform using a yeast to produce bio-oxalic acid for REE recovery, achieving 99% REE recovery from low-grade ore.

The clinical adaptation of CRISPR assays is constrained by complexity and the absence of quality control. Here, authors report a thermally regulated asynchronous CRISPR-enhanced assay enabling direct, highly sensitive one-step detection of monkeypox virus and a human gene in clinical samples.

This study shows that acidification increases substrate affinity in ammonia-oxidizing microbes, partly offsetting reduced ammonia availability. Stronger responses in archaea than bacteria explain contrasting ecosystem reactions.

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.

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.

By modelling protein abundance as continuous spatial gradients, the study by Weiss et al., published in this issue of Nature Metabolism, reframes liver zonation as a quantitative variable, enabling protein-level comparisons across individuals, species and disease states.

Minerals in drinking water can influence gut health, especially during infection. This study finds that magnesium in drinking water worsens Salmonella-driven gut inflammation by boosting the pathogen’s competitiveness and disturbing the gut microbiome.

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.

In the phase 1/2 TRIDENT-1 trial, treatment of patients with NTRK fusion–positive advanced solid tumors with the tyrosine kinase inhibitor repotrectinib—selective for ROS1, TRKA−C and ALK—was safe and resulted in durable systemic and intracranial clinical response.

Battery electrode binders are hard to image but strongly affect battery performance. Here, authors use silver and bromine staining to reveal common cellulose- and rubber-based binders in graphite and Si negative electrodes and identify processing that reduces electrode resistance.

Mouse models demonstrate that vagal sensory neurons transmit signals from lung adenocarcinoma to the brain, increasing sympathetic efferent activity in the tumour microenvironment and thereby creating a immunologically permissive environment for tumour growth.

This study uncovers genetic links between plant roots and their microbiome in Brassica napus, identifying microbe-associated loci and a beneficial bacterium, Sphingopyxis, that promotes nitrogen uptake.

A large-twist-angle bilayer graphene platform exhibits a quantized ratio of displacement to magnetic field at Landau-level crossings, offering a route to high-resolution cryogenic magnetometry.

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.

This study applies generalized linear mixed models (GLMM) and advanced transcriptome wide association study (TWAS) methods to improve the discovery of colorectal cancer risk transcription factors and genes, including potential druggable targets.

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.

Zhang et al. found that histone deacetylase 1 (HDAC1) condensation is responsible for temozolomide resistance in glioblastoma by recruiting CCCTC-binding factor and remodeling chromatin in a deacetylase-independent manner. Disrupting the HDAC1 condensates with resminostat restores the sensitivity to temozolomide.

Highly pathogenic avian influenza H5N1 viruses are of global concern. This study shows that a low-dose H5N1 clade 2.3.4.4b Alum/CpG-adjuvanted vaccine elicits broad, durable antibody and T cell responses and protects female mice against lethal homologous and heterologous H5N1 challenges.

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

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Dinactin disrupts the proton motive force of the cell membrane of Mycobacterium tuberculosis by targeting the LCP family protein and thereby kills the Mycobacterium tuberculosis in vitro and in vivo.

This study shows that WDR5 remodels NANOG condensates to control transcriptional programs. Disrupting their interaction compromises stem cell identity and suppresses leukemia stem cell expansion.

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.

An amino-acid-encoded assembly strategy is developed for the synthesis of programmable chiral Solomon links, featuring tunable cavity dimensions and shapes. This template-free synthetic approach favours homochiral assembly over non-chiral or heterochiral pathways. The resulting interlocked molecules exhibit strong chiral amplification and exceptional enantioselective peptide recognition.

This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

Experimental realizations of discrete time crystals have mainly involved 1D models with Ising-like couplings. Here, the authors realize a 2D discrete time crystal with anisotropic Heisenberg coupling on a quantum simulator based on superconducting qubits, uncovering a rich phase diagram.

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.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

Using ancient DNA, isotopes and proteomics, this work reveals social inequality and mobility in Eastern Zhou China, showing female sacrifices, dietary disparities across classes, kinship networks among elites, and rare evidence of social mobility.

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.

There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.

An in situ multistep edge-contact process is developed for MoS₂ transistors, achieving quasi-non-volatile capacitorless two-transistor dynamic random-access memory with 5-bit accuracy and nanosecond write speeds.

DNA damage stalls RNA polymerase II and halts gene expression. Here, the authors reveal how cells clear stalled polymerase by two hierarchical pathways, in which CSB/CRL4^CSA -triggered ubiquitylation enables rapid TFIIH-driven removal, and with VCP-mediated extraction acting as a backup when this fails.