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The synthesis of benzocyclobutenes is reported through Pd(II)-catalysed γ,δ-methylene C(sp³)–H bond activation and [2 + 2] annulation between aliphatic carboxylic acids and dihaloarenes, using bidentate carboxyl-pyridone ligands. Regiocontrol is achieved in benzocyclobutene formation through the differentiation of reactivity between the aryl iodide and bromide sites.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Little is known about the mean free path spectra of lattice vibrations—known as phonons—that carry heat in non-metallic solids. Regner et al. demonstrate a technique that enables measurement of these spectra over an unprecedented range, enabling a more complete picture of heat flow in non-metals.

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.

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.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Spin torques generated via the spin-Hall effect in CoFeB/W/MgO are found to stabilize magnetization in a high-energy anti-parallel state relative to an applied magnetic field. This observation serves as a platform for studying far-from-equilibrium spin dynamics and holds promise for realizing unconventional computing paradigms.

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.

This study uses a multi-model intercomparison framework and a large-scale observational constraint based on a volcanic eruption and shows that climate models strongly underestimate how cloud cover responds to aerosols, leading to major uncertainties in climate projections.

Using ARPES, this work identifies dice-lattice flat bands in the electride material YCl. The authors show that anionic electrons act as lattice sites to create this rare electronic structure.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

The early postnatal roles of dendrite-targeting interneurons in primary visual cortex (V1) remain elusive. Here, the authors find that somatostatin interneurons in mouse V1 exhibit a uniquely delayed developmental trajectory for innervation and sensory responses, highlighting a window for the emergence of a key mechanism for normalization in cortical circuits.

A modular platform for engineering immunogenic lipid nanoparticle mRNA vaccines is used to display antigens from a variety of pathogens to induce antigen responses.

Tubulin conservation presents a challenge to understanding microtubules’ diverse functions in eukaryotes. Here, the authors characterize the structures of P. falciparum microtubules to show how evolutionary adaptation of tubulin modulates the material properties of the cytoskeleton.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

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.

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.

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.

An on-chip tunable laser operates by harnessing nanomechanical resonances at the radio frequency, achieving ultralow tuning power consumption.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

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.

A large language model (LLM)-powered systematic review of over 1,000 studies revealed that, despite the growth of medical research involving LLMs, a majority of studies do not involve real-world clinical data.

Breast cancer cells interact with neighbouring adipocytes, but the mechanisms are not fully understood. Here, the authors show that triple-negative breast cancer (TNBC) cells transfer cAMP through gap junctions, activating lipolysis in tumour-associated adipocytes to promote TNBC growth.

Mass spectrometry (MS)-based proteomics is increasingly central to systems biology. Here, the authors present a high-throughput, multi-organ workflow that profiles 11,472 proteins in 507 mouse samples, enabling rapid, system-level evaluation of drug efficacy and toxicity.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

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.

Despite high morbidity and mortality, there are currently no approved vaccines for protection against Middle East respiratory syndrome (MERS) coronavirus. Here the authors develop a ferritin nanoparticle-based MERS-CoV vaccine that elicits high levels of neutralizing antibodies in mice, non-human primates, and alpacas and prevents infection in an alpaca challenge model.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

Epigenetic clocks are promising biomarkers of biological aging but require longitudinal evaluation. In this longitudinal study, the authors evaluated whether temporal acceleration of multiple epigenetic clocks was associated with mortality, and report that faster increases in several clocks were linked to higher risk of death, independent of baseline epigenetic age and other confounders.

Spondyloarthropathies are characterized by a distinct pattern of inflammation at distinct anatomical sites and are associated with elevated expression of interleukin 23 (IL-23). Daniel Cua and his colleagues identify an IL-23–responsive CD4⁻CD8⁻ T cell population located within entheses. Systemic overexpression of IL-23 activates these cells and recapitulates aspects of the human disease in mice, and neutralization of IL-17 and IL-22 decreases pathology, suggesting new therapeutic targets for these disorders.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

The authors identify feeblin, an inhibitory compound of the proinflammatory TLR7/8/9-IRF5 pathway with therapeutic potential, which acts by binding SLC15A4 via an allosteric mechanism mediating degradation of its signaling partner TASL.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

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.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

A comprehensive phylogeny and taxonomy for the medically and ecologically important genus Artemisia remain unavailable. Here, the authors combine genomic data with morphological analyses to reconstruct the most comprehensive phylogeny and taxonomy of global Artemisia.

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.