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This Review provides insights into nanosensor technologies for monitoring cellular biomarkers, proposing a spatial framework to clarify their distinct advantages, challenges and performance for high-resolution, dynamic profiling of cellular analytes.

The structure of a spontaneously activated immune protein is determined by cryo-electron microscopy. This reveals the passage of an entire domain through a transient opening. The authors investigate the mechanism by multiple biophysical approaches.

Khawaja et al. show sex-specific differences in neuronal-activity regulation by chaperone-mediated autophagy and that loss of chaperone-mediated autophagy leads to defective neuronal physiology and increased seizure susceptibility, linking chaperone-mediated autophagy to neuronal excitability.

Milling and grinding, long used to alter the chemical and physical properties of materials, have recently garnered interest as alternatives to traditional solution-based syntheses — but these reactions remain difficult to monitor. High-energy synchrotron X-ray radiation has now enabled the in situ observation, in real time, of solid-state transformations occurring during the mechanochemical syntheses of metal–organic frameworks.

The next major challenge for artificial intelligence in drug development lies in proving its value in real-world settings. A new technology not only supports the generation of novel chemical entities but also accelerates a range of real-world molecular design tasks.

Shigella sonnei is divided into five lineages and most infections are caused by Lineage 3. Here, the authors investigate factors contributing to the epidemiological success of Lineage 3 through comparative genomics and virulence analyses in a zebrafish infection model.

Adaptive optical vision Fourier transformer (AOViFT) is a machine learning-based framework for accurately inferring aberrations and restoring diffraction-limited performance in diverse biological specimens.

Here, authors provide a molecular view of a clustered saccharide patch on mucins as recognized by a bacterial binding module. This work provides insights into how microbes can remain attached to mucins in the mucus while grazing on their glycans.

SARS-CoV-2 seroprevalence surveys provide estimates of the extent of prior infection in a population. In this nationally representative survey from Mexico, the authors estimate seroprevalence after the first epidemic wave at ~25%, with variation by region, age, socioeconomic status, and education level.

Mesothelioma is a highly lethal cancer that remains challenging to diagnose. Here, the authors curate a histomorphological atlas of resected mesothelioma and map it using self-supervised AI endorsed by human pathological assessment, revealing patterns that generate highly interpretable predictions.

Community-based conservation efforts for ecosystems can have manifold effects beyond the direct areas being managed. This study finds that, deep in the Amazon, communities effectively protected an area 36 times larger than the area they were guarding, but also had to bear all of the costs.

To celebrate the journal’s 25th anniversary, we asked 13 researchers to offer a glimpse of what their research field might look like in 2050. They consider how technological breakthroughs — for example, artificial intelligence-powered virtual cells — could transform our understanding of how molecules, organelles and cells behave in different contexts, revolutionize therapies and enable the design of resilient crops.

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.

Higgins et al. present an AI tool that uses patient data to personalise treatment for Helicobacter pylori, the leading agent of gastric cancer, demonstrating improved eradication rates over prescribed therapies in retrospective clinical analysis.

Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 receptor in myeloid cells.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Matthieu Reymond and colleagues show that natural genetic variants at the SRF3 locus underlie genetic incompatibilities between European and central Asian accessions of Arabidopsis.

This paper explores how voltage-gated potassium channels can plug the pore to prevent the conductance of ions during inactivation.

Tactile sensing is essential for interacting with the environment. A bioinspired spiking neuronal network and large-area e-skin is presented, which enables unsupervised learning of touch localization and two-point discrimination.

Using passage and re-sequence experiments, this study revealed that the clonally reproducing fungal pathogen Fusarium oxysporum can rapidly adapt to new environments using transposons and accessory genomic regions as the main evolutionary drivers.

Intercellular mitochondria transfer has recently attracted substantial attention, both from a fundamental and therapeutic point of view. At the same time, the topic continues to be met with scepticism. In this Viewpoint, different experts in mitochondrial biology share their personal view on the topic.

Olfactomedin-2 is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis via the hypothalamus. The present findings functionally connect adipose-specific OLFM2 to obesity, and highlight its significance in maintaining adipocyte commitment to avoid metabolic disease.

A wristband combines continuous glucose monitoring with real-time detection of physiological signals to track glucose metabolism.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Single-cell RNA-seq facilitates the study of transcriptome diversity in individual cells. Here, authors introduce a tool for isoform quantification at the single-cell level using 3’ scRNA-seq data, contributing to the study of post-transcriptional gene regulation in individual cells.

This flagship study from the European Solve-Rare Diseases Consortium presents a diagnostic framework including bioinformatic analysis of clinical, pedigree and genomic data coupled with expert panel review, leading to 500 new diagnoses in a cohort of 6,000 families with suspected rare diseases.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Highly pathogenic avian influenza H5N1 virus has recently caused outbreaks in dairy cattle herds in the United States. Here, the authors describe the clinical features and associated economic impacts of an outbreak at a farm in Ohio between March and April 2024.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Cardiovascular function declines with age. In this study, the authors show that the BAT-derived lipokine 12,13-diHOME preserves cardiac function in aged mice by attenuating pathological CaMKII activity.

Achieving phosphorus circularity is a key challenge to realizing sustainable phosphorus use, and recycling is a major route to accomplish this goal. This Review explores global barriers to phosphorus recycling and discusses approaches to overcome the technical, economic and societal challenges in attaining sustainable phosphorus management.

Using cryo-electron microscopy and biochemistry, Zhang et al. reveal that the DNA helicase RECQL5 and the transcription-coupled DNA repair complex coordinate to regulate transcription elongation rates and maintain genome stability.

Materials that can generate physical unclonable functions (PUF) are needed for anti-counterfeiting applications. Here, self-assembly of liquid crystals with ionic liquids in a gelatin matrix is used to generate biodegradable optical PUF tags.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Visualizing dynamical changes in glassy systems is challenging because of the time and length scales involved. Now, atomic force microscopy is shown to be a viable method for obtaining a spatio-temporal description of the relaxation of a glass.

In this Q&A, we speak to Lakshmi Vijayakumar, a psychiatrist, researcher and founder of SNEHA, a suicide-prevention organization in India. Over the past four decades, her work — from tackling youth suicides to shaping laws and working with refugees — has saved countless lives, mainly because of her unshakeable belief in change. Here she speaks candidly about her journey, the challenges of changing minds, and the urgency of treating suicide as both a mental health and social issue.

Orsay virus establishes a latent infection in C. elegans, triggering age-dependent immunity and RNAi based cross-protection that limits secondary infections and reveals parallels to adaptive antiviral responses.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

IκBζ is a rather unknown transcriptional co-factor of NF-κB. Here, the authors show that constitutive IκBζ expression in a subgroup of patients with melanoma drives immunotherapy resistance and enhanced tumor growth.