Browse Articles

Comparative evaluation of neural networks and ensemble models for vegetation trend prediction in a semiarid mountain ecosystem, Saudi Arabia

Chloroplast genome editing of Rubisco boosts photosynthesis and plant growth

Comparison of incision and drainage procedure with drainage and ligation of the intersphincteric fistula tract in the treatment of deep perianal abscess

Memorization in large language models in medicine prevalence characteristics and implications

Timing of adverse childhood experiences shapes epigenetic ageing and life-history outcomes

Abstract Early-life adversity is widely linked to accelerated biological ageing, yet it remains unclear whether such associations reflect exposure during sensitive developmental periods, the cumulative burden of exposures, or temporal proximity to later outcomes. Here, we leverage life-history theory and a life course framework to nuance how the timing of adverse childhood experiences (ACEs) becomes biologically embedded through epigenetic ageing. Using longitudinal data from the Future of Families and Child Wellbeing Study (N=1,974), we apply statistical learning and structured life course modelling to test sensitive period, cumulative risk, and recency hypotheses across multiple domains of adversity (poverty, instability, deprivation, and maltreatment). We find that adversity exposure during specific developmental periods, rather than cumulative burden or recent exposure, are most strongly associated with epigenetic age acceleration in late childhood ( $$R^2_{pooled\ ACEs}$$ =0.003). Moreover, the timing and direction of these effects vary by adversity type. Epigenetic ageing is in turn associated with later health-related risks ( $$\beta _{bmi}$$ =0.29, SE=0.06; $$OR_{depression}$$ =1.62, SE=0.27) and demographic behaviour ( $$\beta _{no.\ births}$$ =0.21, SE=0.08; $$\beta _{no.\ pregnancies}$$ =0.22, SE=0.11), and further mediates the association between ACEs and outcomes in young adulthood, particularly for BMI ( $$\beta _{bmi}$$ =0.003, SE=0.002, $$prop.\ mediated$$ =11%). These findings demonstrate that childhood adversity may be linked to biological ageing in developmentally specific and domain-dependent ways, with certain developmental periods appearing more sensitive to adversity exposure than others.

Bidirectional reactant flux coupling in hollow hierarchical covalent organic framework enabling efficient uranium extraction from seawater

Distinct and common dynamics of central brain spontaneous neuronal activity across cell types during Drosophila pupal development

USP24 is a cross-reactive DUB targeting MOV10 to regulate IFN-I production

Evaluating 2D and 3D slope stability in a complex open-pit mine: a CAD-based numerical study

Replication origin firing capacity indicates ATR inhibitor sensitivity

Abstract Inhibitors of ATR, a central kinase controlling DNA replication origin firing and cellular checkpoints, are undergoing clinical trials, yet mechanisms underpinning sensitivity to ATR inhibitors (ATRi) and patient stratification biomarkers are lacking. Here, we perform in parallel, proteomics, transcriptomics and functional analyses and demonstrate that sensitive cancer cell lines have higher expression of DNA replication initiation factors, and exhibit higher origin firing, increased pan-nuclear γH2AX signals and cell death upon ATRi treatment. ATRi sensitivity is causally associated with origin firing rates, since we could modulate ATRi sensitivity by either up- or down-regulating origin firing capacity using CDC7 inhibition, CDK2 inhibition or CDC45 overexpression in both breast and colorectal cancer cells. High expression of replication initiation factors predicts ATRi sensitivity across cell lines from multiple cancer types and acute myeloid leukemia patient samples. This study reveals a contribution of lethal origin firing capacity to ATR sensitivity, providing key steps towards developing a multimodal clinically applicable biomarker.

Swin-SHARP: a novel approach to wheat disease classification using boosted MAML and weighted ensembling with deep learning classifiers

Mechanochemical disassembly pathways of self-assembled polymer-decorated PdnL2n supramolecular architectures

Abstract Supramolecular Pd n L 2n architectures are versatile molecular platforms with applications spanning catalysis, sensing, and therapeutic delivery. Whereas their thermodynamically driven assembly has been extensively studied, controlled strategies for disassembly remain scarce. Here, we show that ultrasound provides a powerful stimulus to trigger and probe disassembly pathways. Polymer-decorated ligands were synthesised to generate Pd n L 2n assemblies bearing appended polymer chains. Under ultrasound, shear forces transmitted through these chains apply mechanical stress to the square-planar palladium complexes, leading to ligand dissociation. Using Pd 2 L 4 cages, we explore the disassembly pathways and demonstrate ultrasound-triggered release of the anticancer drug cisplatin. Furthermore, we demonstrate that quantitative and entirely reversible activation can be achieved through solid-state ball milling. To illustrate the generality of this approach, we extend it to a Pd 12 L 24 nanosphere, one of the heaviest discrete self-assembled macromolecules reported (133 kDa), and achieve its controlled disassembly. Furthermore, ramped steered molecular dynamics simulations employing a tailored machine-learning interatomic potential reveal the force thresholds for Pd–N bond rupture and a stepwise disassembly pathway. This work establishes ultrasound as a broadly applicable strategy to access otherwise inaccessible kinetic pathways in supramolecular chemistry, with potential for applications in drug delivery and responsive materials.

Real-time yoga posture correction using deep learning for individuals with physical disabilities

In situ graphene-seq: spatial transcriptomics and chronic electrophysiological characterization of tissue microenvironments

Abstract Biological systems comprise diverse, interconnected cell types whose functional dynamics and molecular identities are tightly coupled, yet difficult to capture simultaneously at high spatiotemporal resolution. Electrophysiology provides real-time measurements of cellular activity but with limited molecular context, whereas transcriptomics profiles gene expression without dynamic physiological readouts. Here, we introduce in situ graphene-sequencing, a platform that integrates chronic electrophysiology with imaging-based, spatially resolved transcriptomics. The system combines stretchable mesh nanoelectronics for long-term, single-cell-level interfacing with transparent graphene/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate electrodes, enabling seamless integration of electrical recording and optical imaging. By coupling electrophysiology with high-throughput, imaging-based in situ sequencing, the platform enables multimodal analysis of heterogeneous tissue microenvironments. We demonstrate in situ graphene-sequencing by charting multimodal profiles of human-induced pluripotent stem cell-derived cardiomyocyte and endothelial cell co-cultures, examining how spatial heterogeneity is associated with electrophysiological activity and gene expression. This approach provides an integrative framework for studying how tissue microenvironments shape cell behavior and molecular states.

Ambiguous dietary behaviors of female school students: a qualitative content analysis via social cognitive theory

FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins

Therapist-guided virtual reality exposure therapy for fear of heights: evidence from a multiple-baseline single-case experimental design

Intercellular chemerin-cmklr1 couples epicardial mechanosensing to fibroblasts in pressure overload

Importance of the delivery route for the tolerability and efficacy of immunomodulatory agents for lung cancer

Abstract Although immune checkpoint inhibitors have revolutionized lung cancer treatment, their limited efficacy and significant toxicity highlight the need for improved therapeutic strategies. Immunomodulatory agents are known to enhance anti-tumor immune responses. In this study, we investigated how the route of administration affects the tolerability and immunological impact of these immunostimulants. We demonstrate that airway administration of poly I: C, CpG, and an anti-CD137 antibody in healthy mice results in significantly reduced liver toxicity and systemic inflammation compared with intravenous delivery. This was evidenced by lower AST levels, preserved body weight, and a reduced neutrophil-to-lymphocyte ratio. In addition, airway delivery of immunostimulant promoted dose-dependent recruitment of both myeloid and lymphoid cells as compared to intravenous administration. Using a syngeneic orthotopic mouse model of lung carcinoma, we further showed that local airway administration of anti-CD137 antibody resulted in increased pulmonary infiltration of CD4⁺, CD8⁺, and CD4⁺ TRM cells compared with intravenous injection. This enhanced immune infiltration correlated with improved tumor control. Overall, our findings indicate that local administration of immunostimulants enhances pulmonary adaptive immune responses and tumor suppression while limiting systemic toxicity.

Notch coordinates self-organization of germ layers and axial polarity in sea anemone gastruloids

Abstract Reaggregated early gastrula cells (“gastruloids”) of the sea anemone Nematostella vectensis are able to regenerate into whole polyps within a few days. However, the cellular and molecular mechanisms underlying restoration of body axis and germ layers remains largely unknown. Here, we show that mesodermal cells sort to the periphery of the gastruloid, where they form cell clusters with hitchhiking endodermal cells. One of these clusters immigrates at one pole, forming the future pharynx and inner layer. This morphogenetic behavior that enables the symmetry break of the organizer tissue, requires a Wnt-Notch signaling feedback loop. This highlights a hitherto unknown role of Notch signaling in self-organizing gastruloids. Conservation of Notch-mediated boundary formation between germ layers mirrors similar mechanisms in bilaterians. This demonstrates how adoption of ancestral regulatory networks enables a morphospace converging to similar body plans, thus contributing to evolutionary robustness.