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Imaging of large, cleared samples in diverse media is achieved using a mirror objective.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

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.

Dierl, Hinsen et al. investigate long term pulmonary toxicity in pediatric cancer survivors by the use of Free-breathing phase-resolved functional lung (PREFUL) MRI on a low-field system. Subclinical and time-dependent reduction in pulmonary ventilation and perfusion is revealed.

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.

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.

Here, the authors present genome-wide aDNA from 138 Early Bronze Age individuals from Lower Austria. Their findings point to a patrilocal society with non-strict female exogamic practices and long-distance genetic connections across Central Europe.

Nonlinear interactions such as parametric down-conversion and four-wave mixing are limited by transverse and longitudinal walk-off effects. Here, Pérez et al. demonstrate bright, tunable, diffraction-limited twin-beam radiation by ensuring that signal or idler pulse propagates in the direction or velocity of the pump.

High-harmonic generation (HHG) in organic molecular crystals was previously demonstrated only in the non-perturbative regime. Here, the authors demonstrate HHG up to the 17th order in pentacene crystals, with a strong orientational dependence caused by the neighbouring molecules.

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.

Eggplants are important vegetables worldwide. Here, the authors report 40 genome assemblies of Solanum melongena, its progenitor S. insanum and the allied species S. incanum to construct two pangenomes, and identify loci associated with multiple traits via pangenome-wide association analysis.

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.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Marine sponges host bacteria that produce diverse bioactive compounds. Here, the authors conduct a large-scale metagenomic, single-bacterial and biochemical study to reveal the untapped biosynthetic potential of ‘Entotheonella’ symbionts, a talented producer taxon from microbial dark matter.

Monod fits biophysically motivated models to single-cell transcriptomics data, empowering multifaceted and integrative insights of gene expression dynamics, stochasticity and regulation.

Naturally mummified cheetah remains in a Saudi Arabian cave system with radiocarbon-calibrated ages between about 4,200 and 100 years cluster with Asian as well as West-African sub-species, with implications for rewilding efforts, suggests a genomic analysis of the remains.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Intermittent fasting is investigated as an alternative to caloric restriction as a treatment modality for weight loss and improvement of cardiometabolic risk factors. Here the authors report the secondary and exploratory outcomes of a randomized controlled cross-over trial showing that six months of intermittent fasting reduced body weight and improved lipid profiles, which associated with altered GLP−1–related enteroendocrine signaling and B-cell pathways based on colon transcriptomics and plasma metabolimics.

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.

Riverine systems help transfer mismanaged waste into the ocean, but riverine litter data are scarce. Using a database of riverine floating macrolitter across Europe, this study estimates that 307–925 million litter items—82% of which is plastic—are transferred annually from Europe into the ocean.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

CETP inhibitors are being developed for treatment of coronary heart disease. Here, the authors show that the anticipated beneficial effects of lower plasma levels of CETP are shared among individuals of European and East Asian ancestry.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Mecp2 deficiency underlies Rett syndrome, a genetic disorder presenting with chronic low-grade inflammation of unknown origin. Here, the authors show that Mecp2 is a central regulator of the onset, breadth and nature of nucleic acid immunity.

High-dimensional quantum entanglement is generated via a singly filtered biphoton frequency comb, with energy-time entanglement witnessed for both between time bins and frequency bins. Entanglement distribution of such high dimensional entangled state is verified with high quality and provides a testbed for high-dimensional quantum key distribution.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

High near-surface nitrogen-fixation rates that promoted the recent growth of the Great Atlantic Sargassum Belt were tied to greater upwelling of phosphorus from the equatorial Atlantic, according to coral-bound nitrogen isotope records from the Caribbean.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

The role of astrocytes in Alzheimer’s disease pathology remains insufficiently characterized. Here, the authors show that aggravated astrocyte response to Aβ causes brain inflammation, and amyloid and tau co-morbidity, driven by aberrant induction of δ secretase.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Greda et al. show that sortilin and apolipoprotein E3 mediate import and utilization of long-chain fatty acids as a metabolic fuel in neurons after glucose restriction.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Bai and colleagues present MapDiff, a discrete diffusion-based framework for generating amino acid sequences conditioned on a target protein structure, with strong performance in predicting uncertain regions and achieving high in silico foldability.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

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.

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.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.