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Here they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

Grain chalkiness is an undesirable trait that severely compromises rice quality. Here, the authors report the cloning of an E3 ubiquitin ligase encoding gene Chalk9 and reveal its crucial role in regulating grain chalkiness through mediating the ubiquitination-dependent degradation of OsEBP89.

Tumor pericytes are located surrounding blood vessels, and can regulate tumor vascular structure. Here, the authors discover that a subpopulation of NKX2-3 high tumor pericytes modulates vasodilation and hemodynamics to promote metastasis.

Natural variation in hecw-1 encoding an E3 ubiquitin ligase influences the avoidance of pathogenic bacteria by Caenorhabditis elegans and forms a molecular basis for behavioural variation.

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.

Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.

The genetic basis underlying resistance to Sclerotinia stem rot (SSR) in oilseed rape remains elusive. Here, the authors identify BnaA07.MKK9 as a pivotal regulator of SSR resistance in oilseed rape by GWAS, providing new insights into plant defense mechanisms against necrotrophic pathogens.

Contributions of vehicular and structural proton transport are quantified in phosphoric acid electrolytes, with linking structural diffusion to hydrogen bonds. The derived conductivity model guides electrolyte-conductivity trends and identifies 5.8 M for low-temperature batteries.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

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.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

Biomolecular condensates are made of multiple components but current techniques cannot capture their complex composition quantitatively. Now it has been shown that the dense-phase binodal point defining the composition of multicomponent condensates can be inferred precisely from the intersection of a spectrometrically determined tie-line with an isorefractive line obtained from quantitative phase imaging.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

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.

Neoadjuvant immunochemotherapy against NSCLC has been tested in clinical trials. Here, the authors follow up longer-term survival and measure immune cell phenotype changes in a single-arm phase II clinical trial of neoadjuvant immunochemotherapy, indicating association of intratumoural TCR diversity and CD8 T cell positioning.

The authors develop a molecular dopant to avoid the dimerization of the electron-selective material phenyl-C₆₁-butyric acid methyl ester, resulting in enhanced stability and efficiency in inverted perovskite solar cells.

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.

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.

Mulholland et al. identify progenitor exhausted T cells, expressing intermediate levels of PD-1 (PD-1^int), as a prominent source of pro-inflammatory cytokines in the murine atherosclerotic aorta and potential cellular targets driving checkpoint inhibition-elicited pro-atherosclerotic immune responses. They further demonstrate elevated levels of circulating PD-1-expressing T cells in individuals with subclinical cardiovascular disease.

The authors provide a comprehensive characterization of how glutamine uptake and utilization regulate macrophage function in atherosclerosis.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

Aging is a risk factor for neurodegenerative diseases associated with protein aggregation. Here the authors identify age-related hyperactivation of EPS8/RAC signaling in C. elegans as a driver of pathological protein aggregation, highlighting EPS8 and its regulators as potential therapeutic targets.

Surgery is currently the only treatment option for cataract. Here, the authors report on ocular delivery of lipid nanoparticles-formulated mRNA encoding lanosterol synthase as a potential anti-cataract therapy, which ameliorates cataract development in two rat cataract models.

Modern communication networks must balance efficiency with user privacy. Here, authors develop a privacy-preserving interpretable Bayesian framework that enables network optimization using only aggregated data, without compromising individual user information.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Embryonic stem cells for chicken and seven other avian species are derived.

The taurine–taurine transporter axis is a critical dependency of aggressive myeloid leukaemias.

In a small trial of patients with severe systemic lupus erythematosus and nephritis, treatment with allogeneic T cells with a CD19 chimeric antigen receptor inserted into the T cell receptor locus and deletion of the PD-1 (PDCD1) gene were safe and associated with reduced disease activity.

Blanpain and colleagues delineate lineage reprogramming following PTEN deletion in different prostate cancer-originating cells, demonstrating that in basal cells the NF-κB pathway and innate immunity control stem cell plasticity and tumor initiation.

Clonal hematopoiesis is associated with an increased risk of hematologic and a range of inflammation-related diseases. Here, Yang et al. demonstrate a critical role for aberrant thrombopoietin receptor signaling in TET2-mutation driven clonal hematopoiesis.

Bhandoola and colleagues describe the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice, and which may be conserved in humans.

The growth of wafer-scale single-crystalline 2D semiconductors on sapphire is important for their electronic applications, but the underlying mechanisms are not yet fully understood. Here, the authors study the influence of air-induced sapphire surface hydrolysis on the growth process of 2D WS₂ and propose an ultraviolet light healing method to repair the degraded substrates.

This study introduces a label-free imaging and machine learning platform that predicts hematopoietic stem cell function based on their dynamic behaviors, offering new insights into stem cell diversity and potential clinical applications.

Cellular exhaustion can limit the ability of immune cells to control tumors. Here the authors show that expression of the transcription factor Irf4 marks NK cell percursors that will go on to become exhausted mature NK cells and identify targets to interfere with this trajectory to enhance control over melanoma metastasis.

Giotto Suite provides a comprehensive, flexible and scalable platform for technology-agnostic spatial omics analysis using R.

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.

High IL1RL1 correlates with poor survival in acute myeloid leukemia. A stress-driven IL-33/IL1RL1 loop induces leukemogenesis and a tolerogenic immune environment. Targeting this axis with bispecific antibodies offers a promising treatment.

Multiple energy system models are used under jointly adopted deep decarbonisation scenarios to conclude that the direct penetration of electricity and hydrogen in final energy consumption may rise to shares of, respectively, 60% and 6%, in Europe by 2050.

Xu et al. reveal that a bottom-up neural circuit from the medial septum to the subfornical organ prevents overhydration in mice by integrating oral and gastrointestinal signals before osmolality changes, demonstrating precise drinking control mechanisms.

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.