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This study found E. coli phylogenetic background shapes TEM-1 beta-lactamase expression and co-amoxiclav resistance. Phylogeny alone shifted isolates from susceptible to resistant, stressing a need for lineage-sensitive genotype-phenotype prediction.

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.

Prime editing is a CRISPR methodology whose efficiency declines with distance from the target sequence. Here the authors demonstrate prime editing with prolonged editing window, proPE, which extends the editing distance, enabling the use of prime editing for therapeutic interventions.

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

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).

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.

Researchers reveal widespread, newly formed seafloor seeps along Antarctica’s Ross Sea coast. Methane-rich flows alter local ecosystems and may influence warming. The drivers remain unknown, warranting coordinated study.

The authors developed a screen to find compounds that modulate intracellular Staphylococcus aureus metabolism and discovered KL1, which sensitizes persisters to antibiotics by reversing host-induced tolerance.

Engineered aminoacyl-tRNA synthetase (aaRS) mutants have been developed that facilitate ultrafast bioorthogonal noncanonical amino acid tagging (BONCAT) of newly synthesized proteins in diverse bacteria, including ESKAPE pathogens. The substrate polyspecificity of the aaRS mutants enables pulse-chase BONCAT and differential tagging of temporally distinct nascent proteomes in cells.

Sperry et al. used machine learning approaches to investigate profiles of mood instability and create a prediction model for clinical and functioning outcomes using data from the Prechter Longitudinal Study of Bipolar Disorder.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

ChatGPT provides a way of teaching people about climate change. This research reveals that conversations between climate sceptics and ChatGPT reduced climate scepticism, but these effects are modest, inconsistent across studies and prone to decay over time.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Iridoids are terpenoid metabolites found in thousands of plants. Using single-cell transcriptomics, the authors discovered an unexpected enzyme that has been neofunctionalized to catalyse the cyclization required to form the iridoid scaffold.

Advances have been made in thin-film piezoelectrics; however, the linearity of electric-field-induced strain with frequency and temperature still requires improvement. Here, by growing interlocked monoclinic and tetragonal polar nanoregions in (K,Na)NbO₃ thin films, highly linear strains of up to 1.1% are reported at frequencies up to 10⁵ Hz.

Despite being a virulence factor, candidalysin toxin is essential for Candida albicans to penetrate the oral epithelium to establish and maintain non-infectious colonization

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

A 12-month multicentre randomized clinical trial finds that replacing added sugar in foods and beverages with sweeteners and sweetness enhancers supports modest weight loss maintenance and alters gut microbiota composition, with no safety concerns identified.

Simulations show that the Solar System’s gas disk shaped how and where primitive bodies were implanted in the asteroid belt, revealing different arrival times for CM and CI parent bodies and identifying CM bodies as likely sources of Earth’s water.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

Nutrient-induced soil carbon gains in grasslands can persist for decades after fertilization stops as long as the soil remains untilled, according to a multidecadal field experiment on retired agricultural fields with sandy soils.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Observed 730 Myr after the Big Bang, a little red dot is found to anchor an overdensity of eight galaxies and seems to be embedded in a massive host dark matter halo.

Solid-state NMR reveals that lignin-carbohydrate contact patterns, rather than lignin amount, shape the structure and property of plant cell walls, highlighting distinct roles of lignin and carbohydrate units during wall formation.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

A combination of large-scale phylogenomic analysis, mouse lethality experiments and bacterial growth assays shows that gene loss in the putrescine utilization pathway has enhanced biofilm formation and transmission-related characteristics in the pandemic clone of a bacterial pathogen, Vibrio parahaemolyticus, promoting successive waves of global transmission events.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

The authors use 1,603 estimates of local extinctions from 1980 to 2021 to show that dragonfly species with wing ornamentation have disproportionately gone extinct and lost habitat because of climate change and wildfire. This highlights the important role of mating traits in species survival under change.

Repetitive head impacts from contact sports are associated with brain inflammation, vascular damage and neuron loss that are independent of hyperphosphorylated tau pathology.

Ricca et al discover a new family of tubular pili in Microcystis aeruginosa, a harmful algal bloom-forming cyanobacterium. These pili are crucial for buoyancy by forming cell micro-colonies, which increases drag and prevents sinking. The pili also enrich microcystin and co-localize with iron-enriched extracellular matrix components, suggesting a vital role in bloom proliferation.

A summary of CAR T-cell engineering approaches, including functional screening methods, gene editing and delivery advances, and optimization of metabolic fitness.

Meltwater ponding reduces Greenland Ice Sheet albedo, but this process is not included in models. This study uses drone imagery to show that small streams and ponds, often missed by satellites, considerably increase the energy available for melt.

Genetic factors affecting Aedes aegypti susceptibility to dengue virus infection aren’t well studied. Here the authors show that a cytochrome P450 gene, typically linked to cuticle structure and insecticide resistance, influences dengue infection in Aedes aegypti.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Intermediate-coverage long-read sequencing in 1,019 diverse humans from the 1000 Genomes Project, representing 26 populations, enables the generation of comprehensive population-scale structural variant catalogues comprising common and rare alleles.

The role of the tumour microenvironment in the response to immune checkpoint inhibitors in metastatic melanoma remains poorly understood. Here, single cell profiling of metastatic melanoma samples identifies associations of the mature dendritic enriched in immunoregulatory molecules subtype with immunotherapy response.

Online cognitive testing combined with the reach of a digital patient registry revealed a subtype of people with Multiple Sclerosis with significant cognitive impairment but no motor deficits. This hidden disability is often underestimated and left untreated.

pOXA-48 plasmids have emerged as key vectors of carbapenem resistance within Enterobacteriaceae. In this study, the authors use a transposon sequencing (Tn-seq) approach to identify genetic determinants critical for plasmid stability and conjugative transfer.

Using historical aerial photographs and new bed topography data, accelerating changes on Kennicott and Root Glaciers, Alaska since 1938 are documented. These observations inform projections showing 38–63% mass loss by 2100, depending on future climate.

Intratumoral hypoxia promotes cancer progression. Here, authors show that hypoxia upregulates RNA Polymerase I activity and ribosome biogenesis in breast cancer cells and targeting RNA Polymerase I with BMH-21 reduces tumor growth and metastasis in murine models.

Dormant liver stages of Plasmodium vivax complicate malaria elimination efforts by causing relapses that obscure the efficacy of antimalarial treatments. Here, the authors develop a high-throughput amplicon sequencing assay to reconstruct P. vivax lineages, demonstrating its capacity for geospatial infection tracking, and distinguishing recurrent malaria caused by new infections versus untreated dormant liver stages.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.