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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Respiratory complex I is pivotal for cellular energy conversion. Here, the authors present the structure of complex I from the α-proteobacterium Paracoccus denitrificans, revealing the elements that stabilise the closed state and completing P. denitrificans complex I as a unified platform for combining structure, function and genetics in mechanistic studies.

Adoptive regulatory T cell (Treg) therapy holds promise for the treatment of a range of immunopathological conditions. Here the authors explore the HLA engineering of allogenic Treg products that avoid T cell and NK cell attack and maintain immunomodulatory function in a human skin-xenograft model.

In this work, authors tracked a pneumococcal serotype 3 strain persisting for a year in a healthy adult, revealing limited genetic change but stable multidrug resistance and features linked to vaccine escape.

Large-area two-dimensional materials can be transferred at low temperatures and without solvents using conformable tapes whose adhesive force varies with ultraviolet illumination, allowing transfer to various planar and non-planar substrates.

Mehl and colleagues present a protocol for selecting aminoacyl-tRNA synthetase (RS)/tRNA pairs from a publicly available MaPylRS active site mutant library for specific and efficient incorporation of noncanonical amino acids into proteins.

Large language models hold significant potential in healthcare settings. This study exposes their vulnerability in medical applications and demonstrates the inadequacy of existing safeguards, highlighting the need for future studies to develop reliable methods for detecting and mitigating these risks.

Recurring deep ocean oxygen minimum events occur in the Pacific Southern Ocean during the warm climate interval Marine Isotope Stage 11. They are linked with perturbed Antarctic Bottom Water formation caused by West Antarctic Ice Sheet retreat.

A significant challenge in modern drug development is the comprehensive profiling of covalent inhibitors. Here, the authors develop COOKIE-Pro, an unbiased method for quantifying the binding kinetics of irreversible covalent inhibitors on a proteome-wide scale.

Loretan and colleagues present a low-cost smartphone-based microscope capable of detecting single-molecule fluorescence. This approach opens doors to personalised and widely distributed applications in diagnostics, biosensing, and science education.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Some mafic rocks have a ⁴⁰K/³⁹K ratio lower than all other terrestrial samples, according to isotopic composition analyses, suggesting parts of Earth’s mantle have retained their composition prior to the Moon-forming impact to the present day.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

In a randomized, placebo-controlled, stepwise dose-escalation phase 1 trial evaluating a conjugate vaccine against both typhoid and invasive non-typhoidal Salmonella infections, the vaccine was found to be safe and immunogenic in healthy adults.

2D semiconductors hold promise for solution-processed circuits requiring low-cost components and manufacturing scalability. Here, the authors investigate the criteria for the electrochemical exfoliation of high aspect-ratio nanosheets from 28 different layered materials, identifying the most promising candidates and key bottlenecks for solution-processed complementary electronics and functional circuits.

CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

Lekkos et al. show that a metabolic switch toward oxidative phosphorylation is required for cardiomyocyte re-differentiation and heart regeneration after injury in fish.

Excessive apoptotic cell death and defective efferocytosis drive loss of tolerance and autoimmunity; however, a direct role for macrophage-specific defects in autoimmunity is underexplored. Here, the authors identify macrophage WDFY3 as a negative regulator of autoimmunity by enhancing efferocytosis and reducing MHC-II-mediated antigen presentation, T cell activation, and cytokine dysregulation.

Mass spectrometry-based lipidomics and metabolomics generate large, complex datasets requiring effective analysis. Here, authors review key statistical and visualization methods alongside widely used R and Python tools, and provide a GitBook with step-by-step code for accessible, reproducible data analysis.

Broad-spectrum vaccines have been proposed as a tool for rapid response to emerging infectious disease threats and are in pre-clinical development. Here, the authors use mathematical modelling to assess the potential impacts of broadly protective sarbecovirus vaccines for a hypothetical “SARS-X” outbreak.

The GPS Pipeline enables accessible and scalable genomic surveillance of Streptococcus pneumoniae. It performs quality control and in silico typing of sequencing reads with high accuracy using a single simple command, without requiring the internet.

Our understanding of chromosome organization and dynamics in spherical bacteria, such as Staphylococcus aureus, remains limited. Here, the authors show that chromosome replication and cell division cycles are not synchronized in S. aureus, with cells exhibiting two segregated origins of replication at the start of the cell cycle.

How the brain creates compositional cognitive maps that support both flexible and efficient planning remains poorly understood. Here, authors propose a biologically-realistic computational model addressing this question, which reproduces response fields across cells in the medial entorhinal cortex.

Here the authors show that REST/NRSF represses non-muscle lineage genes in muscle stem cells and progenitors, preserving their identity and differentiation capacity. Loss of REST disrupts gene silencing, impairs muscle regeneration, and leads to stem cell pool depletion.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

In this randomized controlled trial, Baudouin et al. find that both pedagogical activities and a chatbot improve ninth graders’ attitudes and knowledge about vaccination, offering scalable ways to counter vaccine hesitancy in adolescents.

This Perspective discusses challenges associated with sharing annotated image datasets and offers specific guidance to improve the reuse of bioimages and annotations for AI applications.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

Prenatal stress triggers molecular dysregulations in fetal neuroimmune circuits, leading to altered mast cell and sensory neuron function, which predisposes offspring to develop eczema in response to otherwise harmless mechanical friction after birth.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

Loss and damage funds are intended to support low-income regions experiencing impacts of human-caused climate change. Currently, event attribution should only play a limited role in determining loss and damage spending, but this role could grow as the field advances.

Access to green space has been a critical, and contentious, issue for neighbourhood inequality and health outcomes. This Analysis looks at how the COVID-19 pandemic interacts with availability of nature for urban residents.

Analysis of circulating tumour DNA (ctDNA) is commonly used for molecular profiling in patients with advanced-stage non-small-cell lung cancer (NSCLC). The authors of this Review summarize the available evidence on the potential utility of incorporating ctDNA in the management of those with early stage and locally advanced NSCLC and propose interventional studies to provide the necessary additional evidence.

A free-living trial in people with overweight or obesity found that minimally processed diets led to greater weight loss and cardiometabolic improvements than ultraprocessed diets following UK healthy eating guidelines at 8 weeks.

The finding that a thin sheet of fibrous tissue under the skin contains a prefabricated, movable cellular sealant that can heal deep wounds might have implications for the treatment of scars and ulcers.

Miyoshi and colleagues propose STELLA-SPIM microscopy to visualise single MYO7A molecules in live murine inner ear hair cells. Their data suggest that MYO7A traffics as a dimer within stereocilia to assemble the mechanoelectrical transduction machinery.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

The CO dehydrogenase–acetyl-coenzyme A synthase complex produces acetyl-coenzyme A from CO₂, but its structural dynamics during catalysis remain unresolved. Now cryo-EM maps of six intermediate states reveal how ligand binding to a Ni–Fe cluster orchestrates the conformational changes of the complex during catalysis.

Salt substitutes hold great potential for the control of blood pressure and prevention of chronic disease, but the evidence base remains inadequate. Data from a community-based trial in Peru add to this evidence base and support the conduct of large-scale trials to drive the global uptake of salt substitution.

Pawel Mieszczanek and colleagues design a machine learning-based approach to improve 3D printing processes based on melt electrowriting. They present a closed-loop control framework that is based on data-driven models and enables them to monitor the melt electrowriting operations in real time in order to improve reproducibility.

This Review explores in detail the complexity of NK cell biology in humans and highlights the role of these cells in cancer immunity.