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Multi-phase field model reveals internal dissipation is crucial for spontaneous hole formation in cell monolayers
Abstract Although cell monolayers typically remain confluent, they can spontaneously develop persistent holes as a result of collective cellular motion. Recent studies on MDCK monolayers cultured on soft substrates have revealed that cells can align to create regions of local nematic order, and topological defects that generate localised mechanical stresses which can spontaneously trigger hole formation. To investigate this process, we develop a continuum multi-phase field model that incorporates internal dissipation and active dipolar forces that drive cell shape anisotropy. Our simulations show that reducing substrate friction enhances cell-cell velocity correlations. In the low-friction regime, topological defects generate spiral flow patterns that concentrate stress and can trigger hole formation. By contrast, in the high-friction regime, holes do not nucleate. We further demonstrate that the number and stability of the holes—whether they close or persist—depends on both substrate friction and cellular activity, through a non-dimensional friction number. These findings highlight the importance of internal dissipation in modelling collective cell motion and the critical role of collective dynamics in maintaining tissue integrity.
Oral microbiome modulation mitigates hyperglycemia exacerbation in gestational diabetes mellitus
ER sensing of lipid metabolism drives PRA family-dependent regulation of COPII vesicle transport
Critical slowing down of semiarid vegetation resilience is amplified by intensifying heatwaves
Direct extraction of bromine from seawater through an electrolysis-driven styrene enrichment process
Lipid metabolism of hepatocyte-like cells supports intestinal tumor growth in Drosophila
Abstract Tumors reprogram lipid metabolism in distant tissues to support their growth. In adult Drosophila , gut tumors secrete the PDGF/VEGF-like factor Pvf1, which activates the TORC1-Hnf4 pathway in hepatocyte-like oenocytes. This drives production of very long-chain fatty acids and wax esters essential for tracheal growth around the tumor. Blocking Hnf4 or the elongase mElo in oenocytes strongly suppresses tracheogenesis, tumor progression, and cachexia-like organ wasting, while extending host lifespan. The same pathway also controls tracheal development in healthy flies. Lipoprotein receptor LpR2 depletion in oenocytes rescues the observed tumor induced tracheal tracheal remodeling. This tumor-host interaction is conserved: VEGF-A induces lipid metabolism genes in human hepatocytes, and lung tumor-bearing mice show elevated hepatic Hnf4 and Elovl7 . Altogether, this study reveals a non-autonomous role of the TORC1-Hnf4 axis in lipid-mediated tumor progression and identifies potential therapeutic targets for cancer-associated metabolic dysfunction.
Pangenome-based structural variant imputation enables large-scale genotype-phenotype studies in dairy cattle
Abstract Pangenomes of several species have been assembled recently, facilitating the detection and genotyping of structural variants. As part of the FarmGTEx Project, we previously constructed a Holstein pangenome (H20D) based on 40 phased haploid assemblies. Here, we use this breed specific pangenome to genotype 93,059 structural variants from whole-genome sequences of 1,571 cattle. We then develop a Holstein pangenome variation imputation reference panel we name HolPIP. Leveraging HolPIP, we impute 86.65% (68,354/78,886) of structural variants for 50,299 bulls with Beagle R² ≥ 0.8. Using these imputed structural variants and phenotypes for 43 complex traits, we conduct GWAS, identifying 1,225 structural variant-trait associations. We next use fine-mapping to prioritize 32 high-confidence candidate structural variants, including a 75-bp deletion in ANKRD11 linked to dairy form, rump width, and stature, as well as an insertion in DHX32 associated with RNA metabolism. Compared to SNPs across various functional annotations, structural variants show a stronger genome-wide enrichment across most complex traits in cattle, suggesting that structural variants may have an important contribution to the genetic basis of dairy traits.
Vasculature segmentation in 3D hierarchical phase-contrast tomography images of human kidneys
Abstract Efficient algorithms are needed to segment vasculature in new 3D medical imaging datasets at scale for research and clinical applications. Manual segmentation of vessels in images is time-consuming and expensive whereas computational approaches have limited accuracy. We organize a global machine learning competition, engaging 1,401 participants, to promote development of deep learning methods for 3D blood vessel segmentation in Hierarchical Phase-Contrast Tomography (HiP-CT) datasets. This paper presents a meta-analysis of the top-performing solutions, focusing on segmentation accuracy and morphological analysis. The competition and subsequent analysis reveal convergent methodological innovations: pseudo-labeling approaches that exploit data distributions, metrics and loss functions that optimize for vessel surface and topology, and multi-scale approaches that handle data heterogeneity. Additionally, the paper presents techniques for building deep learning models for the defined task, metrics to assess and compare algorithm performance, and a dataset with manually annotated and curated gold standard segmentations for future studies in blood vessel segmentation within HiP-CT imaging.
Daily briefing: How cooperation built the world
Open- and Closed-Shell Roles of Sensitizer and Annihilator in Pseudo-Single Component Mixtures for Upconversion
Distinct sensory and autonomic involvement in hypermobile Ehlers–Danlos syndrome compared with idiopathic small fiber neuropathy: a multimodal study
A CYP11B2 variant (rs7831617) is associated with lower blood pressure and a reduced risk of incident hypertension
A metal sieve-linked double-syringe sugaring-out liquid–liquid microextraction as a new analytical system for the accurate and sensitive determination of pyrimethanil in GC-MS
Untargeted metabolomics and network pharmacology unveil AKT1 inhibition by Kanchanara Guggulu in triple-negative breast cancer
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptors. This study investigates the anticancer potential and underlying molecular mechanisms of the traditional ayurvedic formulation Kanchanara guggulu in TNBC cells. The cytotoxic, anti-migratory, and membrane integrity-modulating effects of Kanchanara guggulu on MDA-MB-231 cells were assessed using MTT, wound-healing, and Live/Dead assays. Untargeted LC–MS/MS metabolomics identified over 1,019 metabolites, of which 237 met drug-likeness and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) criteria. Network pharmacology revealed 50 shared targets with TNBC-associated proteins, highlighting enrichment in PI3K/AKT/mTOR, HIF-1, AGE–RAGE, calcium signaling, and microRNA-related pathways. Molecular docking (LibDock and CDOCKER) identified top bioactive candidates with strong binding affinity towards AKT1, supported by density functional theory (DFT) showing favorable electronic stability. Experimental validation demonstrated significant dose-dependent cytotoxicity (IC₅₀ = 45 µg/mL), inhibition of migration, and increased cell death. Western blot analysis confirmed downregulation of phospho-AKT and mTOR, indicating suppression of PI3K/AKT/mTOR signaling. Overall, TNBC cells showed reduced proliferative and migratory potential upon treatment, suggesting that Kanchanara guggulu extract exerts anticancer effects and provides promising lead compounds for TNBC therapy development.
Integrating DNA methylation biomarkers for breast cancer risk prediction using artificial intelligence
Abstract Breast cancer remains a major cause of morbidity and mortality among women worldwide, highlighting the necessity for predictive tools to identify at-risk individuals prior to the manifestation of symptoms. Standard imaging, like mammography, has limited sensitivity in dense breasts and relies on visible morphological changes. In contrast, circulating DNA methylation biomarkers provide a minimally invasive, stable alternative that detects systemic epigenetic changes before tumors develop. This study analyzes DNA methylation profiles from the GSE51032 EPIC-Italy cohort (Illumina HumanMethylation450K platform), involving 845 participants, including only 658 cancer-free and breast cancer samples. After quality control (QC), 224 pre-diagnostic breast cancer cases and 418 controls are included, totaling 642 samples across 483,848 CpG sites. Differential methylation analysis identifies 4621 CpG sites with significant methylation differences (FDR < 0.1, |Δβ| >= 0.03). These features are subsequently utilized to train and evaluate a variety of machine learning (ML) and deep learning (DL) classifiers. Among these, the random forest demonstrated the highest overall performance, attaining an area under the curve (AUC) of 0.849 and an accuracy of 0.798. These findings highlight the potential of integrating high-dimensional epigenomic biomarkers with artificial intelligence (AI) to enable early prediction of breast cancer risk, thereby promoting minimally invasive screening and personalized prevention strategies.
Enabling extended tool manipulation through redundancy-driven contact exploitation
Abstract Extended tool manipulation poses significant challenges for torque-limited robotic manipulators, as interaction forces acting at a distance amplify joint torques through the lever-arm effect and can compromise dynamic feasibility even when tasks are kinematically admissible. This paper presents a control methodology that enables extended-tool tasks by systematically inducing environmental support contact through redundancy resolution. The proposed framework integrates motion and force control in task space with secondary objectives in the null space that promote support contact without explicitly modeling the environment. Rather than predefining contact, the manipulator adapts its configuration under force feedback to establish and maintain support that counteracts lever-arm-induced loading. The methodological contribution lies in formalizing redundancy-driven support contact as a mechanism for extending torque feasibility in extended-tool manipulation. The approach is validated through a comparative experimental study of three null-space formulations on a seven-degree-of-freedom robotic manipulator performing a moderate-force wall-painting task with a 1.4 m tool. The results show how different null-space strategies influence contact consistency, load redistribution, and coupled motion–force interaction during sustained support. These findings demonstrate the feasibility of redundancy-driven support exploitation in moderate-force extended-tool manipulation and motivate future extensions toward higher operational loads and more complex contact conditions.
Application of the Multi Theory Model to improve self reported determinants of appropriate antibiotic prescribing among veterinary students
Microbial contamination of donor corneas and post-keratoplasty endophthalmitis: a comparison between Japanese and U.S. eye banks using cold storage
Abstract This study evaluated the prevalence and microbial spectrum of positive corneoscleral donor rim cultures and the associated risk factors for post-keratoplasty infection in Japan. We retrospectively included consecutive corneal transplantations performed by a single surgeon between April 2015 and September 2021. Donor corneas were obtained from eye banks in Japan ( n = 134) or the United States ( n = 365) and preserved using cold storage. Donor corneoscleral rim cultures were obtained during surgery. Culture positivity and microbial profiles were analyzed. Risk factors for contamination were evaluated using logistic regression. Overall, 78 (15.6%) were culture-positive. Domestic grafts had significantly higher microbial contamination rates than overseas grafts (30.6% vs. 10.1%, P < 0.001), whereas fungal contamination rates did not differ between groups (1.5% vs. 1.9%, P = 1.000). In the multivariate analysis, overseas eye bank origin was independently associated with a lower risk of microbial contamination (OR 0.259, 95% CI, 0.139–0.486; P < 0.001). Post-keratoplasty endophthalmitis occurred in three cases (0.6%), all of which were associated with positive fungal cultures. Therefore, fungal pathogens may play a key role in increasing clinically significant postoperative endophthalmitis risk after keratoplasty, highlighting the importance of targeted donor tissue screening and postoperative management.