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The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

The GIAB genomic stratification resource defines challenging regions in three commonly used human genome references, including the first complete human genome (CHM13). These help understand strengths and weaknesses of sequencing and analysis methods.

Conventional PROTACs have limited capacity for misfolded proteins. Here, authors develop a BioPROTAC containing an scFv specifically targeting misfolded SOD1, fused to an E3 ligase, and demonstrate a strategy for reducing misfolded SOD1 accumulation.

In this 4-year unblinded follow-up study, the authors evaluate 63% of the participants of a double-blind randomised control trial that assessed the effects of faecal microbiota transplantation (FMT) on adolescents with obesity.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

The heteromeric insect TRPV channel, Nanchung-Inactive, is a previously structurally uncharacterized insecticide target. Here, Fedor et al. provide insights into how an insecticide and a natural agonist modulate channel behavior, paving the way for future insecticide development.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

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.

Despite evidence for an ice-rich outer shell, little water ice has been observed on the surface of Ceres. Lobate morphologies observed on Ceres that are increasingly prevalent towards the dwarf planet’s poles are consistent with ice-rich flows.

MERS-CoV ORF4b antagonizes host innate immune response, partially via blocking nuclear import adapter IMPα activity and preventing nuclear translocation of NF-κB. Here, Munasinghe and Edwards et al. biochemically and structurally define the interaction between ORF4b and IMPα-family members and find a non-canonical interaction between ORF4b NLS and IMPα2 and IMPα3.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

Diversity in medical fields is beneficial to both clinicians and patients, and Nature Reviews Urology is committed to improving the diversity of our specialty and supporting Black and under-represented minority urologists. In this Viewpoint, 12 medical students who are embarking on a career in urology describe their reasons for choosing the specialty, explain what they think can be done to increase the number of Black urologists, and describe what has led them to apply to specific programmes.

The disruption of the rhomboid protease gene glpG in E. coli leads to defects in bacterial colonization. Here, the authors show that GlpG is essential for the assembly of type 1 pili, a virulence factor required for colonization of bacteria in eukaryotic cells.

Analysis of the pivotal phase 3 ZUMA-7 trial identifies tumor gene expression signatures that are uniquely predictive of anti-CD19 CAR T cell response and event-free survival in second-line treatment for patients with relapsed or refractory large B cell lymphoma.

Invariant natural killer T (iNKT) cells recognize abnormal cells, but their T cell receptor is not variable and kill cancerous or infected target cells without MHC I restriction. Here, the authors show that in a clinical trial, donor-unrestricted allogeneic iNKT cells could be safely administered to human COVID-19 patients suffering from acute respiratory distress syndrome and trigger an anti-inflammatory response.

Ghatbale et al. adapted a co-evolutionary technique to develop Klebsiella pneumoniae phages to be highly active longitudinally against K. pneumoniae clinical isolates, including drug resistant isolates.

Tree longevity is thought to increase in harsh environments, but global evidence of drivers is lacking. Here, the authors find two different pathways for tree longevity: slow growth in resource limited environments and increasing tree stature and/or slow growth in competitive environments.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Genomic deletions in poxviruses are not well understood, the authors found large deletions in >2% of Mpox virus genomes during routine surveillance, highlighting their role in poxvirus evolution and potential impact on diagnostics and therapeutics.

Meeting the Kunming–Montreal Global Biodiversity Framework goals in Africa relies on scaling up genomics research and digital sequence information infrastructure across the continent. This Roadmap presents the African BioGenome Project’s theory of change, which identifies challenges and makes recommendations for actions to improve genomics research while meeting global biodiversity goals.

Multiplexed editing in primary human T cells generates enhanced immune cell therapies.

In an ongoing phase 1 trial, the combination of two new immunotherapies targeting CTLA-4 and PD-1 was overall well tolerated and elicited encouraging clinical responses in patients with relapsed/refractory microsatellite stable colorectal cancer, a tumor type typically unresponsive to immune checkpoint blockade.

Electronic health records are a rich source of clinical data but identifying associations with outcomes is complex. Here, the authors propose a modelling framework ‘InfEHR’ that identifies patient trajectories in electronic health records and generates a likelihood for clinical phenotypes.

To investigate the link between the gut microbiome and ovarian health, here the authors transplant gut microbiota from estropausal female mice to young adult female mice. Microbial transplantation improves ovarian hormone profiles, follicle metrics and fertility-related outcomes, highlighting a causal role for the aging gut microbiome in regulating ovarian function.

LRRC15-positive cancer-associated fibroblasts constitute a pivotal axis in tumorigenesis and are potential therapeutic targets to improve responses to immune checkpoint blockade.

Justin Crocker, Garth Ilsley and David Stern use engineered transcription factors to regulate enhancers in a quantitatively predictable manner in Drosophila embryos. Their models of enhancer function provide a framework for the quantitative control of enhancers in vivo.

Access to safe, affordable and accessible drinking water is influenced by various socioeconomic factors. A survey of a large number of California water systems shows how different levels of enfranchisement are linked to uneven access to drinking water in terms of affordability and accessibility.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

Genomic coupling theory predicts that speciation progress involves the buildup of genomic associations that manifest in aggregate barriers to gene flow. This study develops approaches to quantify genomic coupling and applies them to a rattlesnake hybrid zone.

The authors discovered cluster of regulatory sequences that controls HOXA over large genomic distances and across topological domains. This cluster is required for normal craniofacial development in both humans and mice.

An analysis of T cell responses in people with amyotrophic lateral sclerosis shows that the C9orf72 antigen is a key target of autoimmune responses in the disease, and identifies C9orf72 epitopes that are recognized.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

The bacterial anti-phage defense systems known as ‘Zorya’ consist of a membrane protein complex (ZorAB) and soluble components of unclear function. Here, the authors solve cryo-EM structures of the ZorAB complex and show that the soluble component ZorE displays nickase activity and acts as an effector module.

A truth-set catalog of human tandem repeats allows benchmarking of variant analysis tools.

Detection of hot intracluster gas in SPT2349−56 with the Atacama Large Millimeter/submillimeter Array provides new insights into early cluster formation.

Meehan and colleagues study access to running water in large US cities since 1970, finding that the 2008 financial crisis worsened household ‘plumbing poverty’ in many cities. This disproportionately impacted households of color and generally squeezed lower-income households into more precarious living situations.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

The origin of the nematic state in the kagome metal CsTi₃Bi₅ remains unclear. Here, using polarization-dependent angle-resolved photoelectron spectroscopy and ab initio based field theoretical methods, the authors propose a d-wave nematic order driven by electronic correlations via an orbital-selective mechanism.

Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined.

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.

Dysregulated protein levels can cause disease. The authors present a scalable platform capable of identifying small molecules that alter disease-linked target protein levels, and report >40 that increase SynGAP protein abundance, with SR1815 restoring neuronal function in Syngap1 deficient neurons.

Genetic diversity between clinical and environmental fungal isolates of Aspergillus flavus is poorly studied. Here, the authors analysed genomic data from a global set of clinical and environmental A. flavus isolates and report that clinical prevalence is associated with population structure.

Fragile X syndrome is a neurodevelopmental disorder caused by inactivating the RNA-binding protein FMRP. Here, the authors show that FMRP acutely regulates structural plasticity in mature adult pacemaker neurons in the Drosophila central brain.

Structural analyses of antibody-virus complexes offer critical insights into immune recognition mechanisms. In this report, we present how a patient-derived IgG recognizes a quaternary epitope on EEEV particles through strictly bivalent interactions.