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This work describes three people living with HIV-1 who maintain long-term immune-mediated control of HIV-1 after pausing antiretroviral therapy. Autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4⁺ and CD8⁺ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. This serves as a model of ART-free control of HIV-1 and informs new HIV-1 cure strategies.

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.

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.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Leveraging long-read RNA sequencing and multiomics analyses, Cheon and Alvstad et al. systematically map transposable element (TE)-derived isoforms across species and cell states, revealing RNA quality control mechanisms regulating TE–gene chimeras that shape transcriptome plasticity.

Genome-wide analyses identify 418 independent associations with autoimmune hypothyroidism and classify risk loci into distinct groupings related to systemic autoimmunity and thyroid-specific dysfunction.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Many thermophiles that are abundant in geothermal systems have never been cultivated and are poorly understood. Here, Lai et al. describe the cultivation of one such organism, a deeply branching member of the archaeal phylum Thermoproteota, and provide evidence that it has evolved to specialize in branched-chain amino acid metabolism.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

Energetically charged particles affect polar ozone levels and have been linked to surface climate variability. This study discusses the pathway that explains the rapid connection from high altitude mesospheric ozone to surface regional climate.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

The role of the innate immune system in pancreatic cancer is largely unexplored. Here, the authors reveal a targetable cancer cell-intrinsic axis in pancreatic cancer comprising ASC inflammasome complexes that link innate immunity with mitochondrial function and metabolism.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Disaster response often suffers from delays and inconsistent assessments. Here, the authors develop DisasTeller, a multi-agent LVLM system that interprets disaster images, generates alerts and plans, and provides rapid, standardised support for post-disaster decision-making.

Quinuclidine-pyridone and sulfonamide-pyridone ligands enable transannular γ-methylene C–H arylation of cycloalkane carboxylic acids with a range of ring sizes, bringing us closer to molecular editing of saturated carbocycles.

Current vaccines induce broadly cross-reactive cellular immunity against SARS-CoV-2 variants, including Omicron, and provide protection against severe disease despite a substantially reduced neutralizing antibody response.

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.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

“This randomized controlled trial in adults with central obesity found that high-intensity interval training, performed once or thrice weekly, reduced body fat mass compared with control, highlighting the benefits of “weekend warrior” interventions.”

Two out of 15 dogs from households with confirmed human cases of COVID-19 were asymptomatically infected with SARS-CoV-2 and showed antibody responses to the virus.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Ligand detection is an essential component of pre-clinical drug development. Here, the authors develop an assay directly coupling protein ligand binding to the luminescence intensity of NanoLuc luciferase; enabling a compound discovery strategy for a broad spectrum of potential drug targets.

A universal design strategy for nanograined metals aimed at utilizing oxygen nanoclustering to achieve the highly desired combination of high strength and large deformability that evades inverse Hall-Petch softening.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

The impact of land-use and cover-change (LUCC) on ecosystem carbon stock in China is poorly known due to large biases in existing databases. Here the authors develop a new LUCC database with corrected false signals and reveal that forest expansion is the dominant driver of China’s recent carbon sink.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Heart failure can be caused by cardiac fibroblasts replacing myocytes. Here, the authors use functional genomic data from fibroblasts, genetic signals enriched in people with heart disease, and gene perturbation analyses to link disease-associated regulatory elements to protein-coding genes.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Weyl semimetals are interesting because they are characterized by topological invariants, but specific examples discovered to date tend to have complicated band structures with many Weyl points. Here, the authors show that TaIrTe₄ has only four Weyl points, the minimal number required by time-reversal symmetry.

This scoping review examines previous experience in performing silent evaluations of clinical AI applications, collecting evidence from 75 studies on implementation features and the sociotechnical context.

Observing and tuning the Kondo effect in graphene is experimentally challenging. Here, the authors identify the spectroscopic signature of Kondo screening in graphene, along with a quantum phase transition between screened and unscreened phases of vacancy magnetic moments.

High spatial resolution is essential for resolving cellular and subcellular organization in tissues. Here, authors present Seq-Scope-X, which integrates tissue expansion with Seq-Scope to achieve an order-of-magnitude improvement in resolution of spatial transcriptomics and proteomics.

Optical frequency combs in the mid-infrared are required for molecular gas detection applications but their realization in compact microresonator-based platforms is challenging. Here, Griffith et al. demonstrate on-chip broadband comb generation on a silicon microresonator spanning from 2.1 to 3.5 μm.