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Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Experiments with human volunteers and macaques show that expectations produced by probabilistic cueing of future sensory inputs shape motor circuit dynamics in order to increase the efficiency of movement responses.

The authors show that the CD4 mimetic CJF-III-288 stabilizes HIV-1 Env in an asymmetric “open” State-3 conformation, guiding anti-CoRBS antibodies to boost ADCC against infected cells and delay viral rebound in vivo, underscoring therapeutic promise.

Characterizing quantum states is vital for quantum information or metrology tasks, but it remains challenging. Here, by a combination of weak and strong measurements, the authors directly measure the probability amplitudes of a pure state in the orbital angular momentum basis with dimensionality of 27.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

Antimony selenide is a promising photovoltaic material, but the presence of point defects degrades performance. Here, the authors use positron annihilation spectroscopy combined with theory to detect and identify vacancy-type point defects.

Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO₃ and 5d SrIrO₃due to the interplay of strong Coulomb and spin orbit interactions.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

Validating theoretical models against empirical data presents challenges. Here the authors present an assumption-light method to validate ecological models against time series data, along with a dedicated R package.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

A reassessment of soil radiocarbon profiles, which shows a strong influence of vertical transport processes, suggests that soil organic carbon is similarly responsive to environmental changes regardless of depth.

Electrochromic materials are widely explored in energy-saving smart windows, yet combining fast switching, neutral black coloration, and robust long-term durability remains challenging. Here the authors report a solution processed n-doped poly(benzodifurandione) affording an electrochromic black window that overcomes these limitations.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

 A bifunctional iminophosphorane-catalysed, stereo-controlled deconjugation for the synthesis of highly enantioenriched alkylidenecyclopropanes is described, alongside computational studies elucidating the mechanistic pathway and origins of diastereoselectivity and enantioselectivity.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

The study by Russo et al. demonstrates alterations in the presence of senescence hallmarks across cell types, inducers, and model systems. These findings spotlight TFAP4 as a key regulator of senescence phenotypes in aging and Parkinson’s Disease.

Fusion genes involving KMT2A rearrangements are frequent oncogenic drivers of acute myeloid leukaemia (KMT2A-r AML) but the cell of origin remains unclear. Here, using preclinical models of EVI1 positive KMT2A-r AML the authors investigate the cell of origin and find that the presence of exogenous factors influences AML initiation and the resulting phenotype.

HIV infection triggers transcriptomic remodelling and a quiescence programme via KLF2 and the p53 pathway leading to proviral silencing.

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.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

In this study, the authors present an fMRI‑based signature of corticospinal connections, which predicts individual pain sensitivity, generalizes to patient cohorts, and tracks changes after brain stimulation, suggesting a biomarker to guide personalized pain care.

The authors of this study map the human E3 ubiquitin ligome using a metric learning approach, revealing a unified classification framework that explains preserved patterns and functional segregation of E3 families, linking enzymes to substrates and drug interactions, and guiding strategies for targeted therapies.

During the present World Chess Championship in Iceland, Nature will publish a weekly commentary on the games by Dr Jonathan Penrose, British Chess Champion for 1958–63 and 1966–69. His first article appears below.

The authors demonstrate strong coupling in bound state in the continuum metasurfaces on nanostructured bulk WS₂ and exhibiting sharp resonances with tailored linewidths and controllable light-matter coupling strength.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

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.

Optically active semiconductor quantum dots have so far suffered from nuclear inhomogeneity limiting all dynamical decoupling measurements to a few microseconds. Lattice-matched GaAs–AlGaAs quantum dots now enable decoupling schemes to achieve a 0.11 ms spin coherence time.

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.

How chemotherapeutic nucleoside 6-thio-2’-deoxyguanosine (6-thiodG) targets telomerase to inhibit telomere maintenance in cancer cells and tumors was unclear. Here, the authors show that telomere length and telomerase status determine 6-thio-dG sensitivity and uncover the molecular mechanism by which 6-thio-dG selectively inhibits telomerase synthesis of telomeric DNA.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

The composition of lipid nanoparticles for the delivery of tumour-antigen-encoding mRNA can be optimized via a screening method to enhance antitumour activity via the modulation of the immune activity of helper T cells.

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.

Exotic six- and eight-particle excitonic complexes have recently been observed in 2D semiconductors. Here, the authors uncover a stable many-body exciton in WSe₂–comprising 20 interacting quasiparticles–that emerges when strong electrostatic doping fills the Q valley.

The factors governing mouse decision-making strategies in changing environments remain unclear. Here the authors use a 4-state input-driven model to show that past stimuli/choices drive switches in bias, while past rewards drive switches in engagement.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Regioselective functionalization of aliphatic carbon–hydrogen bonds is achieved using frustrated radical pairs generated from disilazide donors and an N-oxoammonium acceptor.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, but platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, the authors design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone, which exhibit the activity of both parent anticancer compounds and can overcome drug efflux effectively due to covalent binding to intracellular biomolecules.

Translation of evidence about dementia risk into effective public health policy is a challenge. In this Consensus Statement, Demnitz-King and colleagues present 56 policy recommendations for dementia prevention, providing policymakers with a foundation for designing and implementing evidence-based dementia prevention strategies, prioritizing clear communication, targeted intervention and sustained research investment.