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The DNA methylation landscape of primary triple-negative breast cancer
Abstract Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcriptional patterns are correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Further subdivision of the Basal and non-Basal subtypes identifies subgroups transcending genetic and proposed TNBC mRNA subtypes, demonstrating widely differing immunological microenvironments, putative epigenetically-mediated immune evasion strategies, and a specific metabolic gene network in older patients that may be epigenetically regulated. Our study attempts to target the epigenetic backbone of TNBC, an approach that may inform future studies regarding tumor origins and the role of the microenvironment in shaping the cancer epigenome.
Author Correction: Deep learning based decision-making and outcome prediction for adolescent idiopathic scoliosis patients with posterior surgery
Magnetotransport evidence for the coexistence of two-dimensional superconductivity and ferromagnetism at (111)-oriented a-CaZrO3/KTaO3 interfaces
Impact of host switching at different larval instars on the performance of the polyphagous pest Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)
Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction
Assessing the accuracy of multi-model approaches for downscaling land surface temperature across diverse agroclimatic zones
Advanced enzyme-assembled hydrogels for the remediation of contaminated water
Exploring the effects of olfactory VR on visuospatial memory and cognitive processing in older adults
Abstract This study examined the effects of Olfactory Virtual Reality (VR) Gaming on cognitive performance in older adults. A VR game environment (“Interactive Smellscape”) was created to enable this, and 30 participants aged 63–90 years completed both VR gaming sessions and cognitive assessments, conducted with a 6-day interval between the two sessions. Significant improvements were observed in spatial tasks of Japanese characters and words, with notable enhancements specifically in visuospatial rotation performance and word-location recall accuracy. However, no significant changes were detected in olfactory identification or other general cognitive tasks. These findings suggest potential cognitive benefits of incorporating VR and olfactory stimuli into interventions for older populations, particularly for tasks requiring attention and spatial processing. The results further underscore the importance of task-specific designs to maximize the utility of multisensory VR systems for cognitive rehabilitation.
Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes
Effects of climate-related disasters on loneliness, social support, social functioning, and social contacts: longitudinal analyses of impact and recovery
Beyond surface tension-dominated water surface jumping
Abstract Water surface jumping motions of semi-aquatic insects are primarily rely on surface tension-dominated jumping mechanism to achieve impressive jumping performance. However, this mechanism faces an inherent physical constraint: the propulsion force must remain below the threshold required to break the water surface, limiting efficient momentum acquisition. Herein, we present a water surface jumping strategy that addresses the limitations of surface tension-dominated mechanism. Our approach allows the engineered jumper to achieve a record-breaking jumping height of 18 body lengths (63 cm) and take-off velocity of 100.6 body length/s (3.52 m/s). This strategy is built on three key design principles: (I) superhydrophobic body for floating on water surface, (II) light-weight, high-power actuation module capable of providing significant propulsion force within an ultrashort time, (III) well-engineered momentum transmission system for efficient kinetic energy transfer. The developed soft jumper based on these design principles advances the development of water environment related robotics.
Publisher Correction: A hybrid fused-KNN based intelligent model to access melanoma disease risk using indoor positioning system
Uncertainty estimation with prediction-error circuits
Abstract Neural circuits continuously integrate noisy sensory stimuli with predictions that often do not perfectly match, requiring the brain to combine these conflicting feedforward and feedback inputs according to their uncertainties. However, how the brain tracks both stimulus and prediction uncertainty remains unclear. Here, we show that a hierarchical prediction-error network can estimate both the sensory and prediction uncertainty with positive and negative prediction-error neurons. Consistent with prior hypotheses, we demonstrate that neural circuits rely more on predictions when sensory inputs are noisy and the environment is stable. By perturbing inhibitory interneurons within the prediction-error circuit, we reveal their role in uncertainty estimation and input weighting. Finally, we link our model to biased perception, showing how stimulus and prediction uncertainty contribute to the contraction bias.
Unveiling sources, contamination, and eco-human health implications of potentially toxic metals from urban road dust
Sensing flow gradients is necessary for learning autonomous underwater navigation
Duchenne muscular dystrophy gene product expression is associated with survival in head and neck squamous cell carcinoma
Abstract Mutation of the Duchenne muscular dystrophy (DMD) gene causes neuromuscular disorders, but increasing evidence has implicated DMD in the development and progression of several major cancer types. This study investigates the prognostic and biological significance of DMD expression in head and neck squamous cell carcinoma (HNSCC). Analysis of The Cancer Genome Atlas (TCGA) data revealed that high DMD expression correlates with improved overall (median survival difference: 22 months, p = 0.0083) and progression-free (p = 0.0237) survival. The Dp71ab transcript is most strongly associated with better outcomes (median overall survival: 42 months, p = 0.0007). Notably, DMD expression levels stratify HPV-positive patients, identifying a DMD low/HPV-positive subgroup with poor outcomes. Immunohistochemical analysis of 50 HNSCC tissue cases confirmed dystrophin localisation in the nucleus and cytoplasm, with high nuclear expression linked to longer overall survival (mean difference: 31 months, p = 0.0497). Functional assays in HNSCC cells showed that Dp71ab overexpression disrupts nuclear morphology and reduces proliferation. Differential gene expression analysis additionally identified 388 upregulated and 30 downregulated genes, with pathways linked to muscle processes, ribosome biogenesis and non-coding RNA regulation. These findings highlight DMD as a potential biomarker and/or therapeutic target in HNSCC, warranting further mechanistic studies of Dp71 isoforms.
Structural visualization of small molecule recognition by CXCR3 uncovers dual-agonism in the CXCR3-CXCR7 system
Abstract Chemokine receptors are critically involved in multiple physiological and pathophysiological processes related to immune response mechanisms. Most chemokine receptors are prototypical GPCRs although some also exhibit naturally-encoded signaling-bias toward β-arrestins (βarrs). C-X-C type chemokine receptors, namely CXCR3 and CXCR7, constitute a pair wherein the former is a prototypical GPCR while the latter exhibits selective coupling to βarrs despite sharing a common natural agonist: CXCL11. Moreover, CXCR3 and CXCR7 also recognize small molecule agonists suggesting a modular orthosteric ligand binding pocket. Here, we determine cryo-EM structures of CXCR3 in an Apo-state and in complex with small molecule agonists biased toward G-proteins or βarrs. These structural snapshots uncover an allosteric network bridging the ligand-binding pocket to intracellular side, driving the transducer-coupling bias at this receptor. Furthermore, structural topology of the orthosteric binding pocket also allows us to discover and validate that selected small molecule agonists of CXCR3 display robust agonism at CXCR7. Collectively, our study offers molecular insights into signaling-bias and dual agonism in the CXCR3-CXCR7 system with therapeutic implications.
A novel broadband reflectarray antenna employing equivalent magnetic dipole elements
Nature-inspired hierarchical building materials with low CO2 emission and superior performance
Abstract Conventional cement-based materials are faced with significant challenges, including large carbon emissions, high density, and quasi-brittleness. Here, inspired by hierarchical porous structures existing in nature, we develop a low carbon, lightweight, strong and tough cement-based material (LLST), which is obtained by a rapid gelation of hydrogel as skeleton and subsequent deposition of cement hydrates as a skin. As a result, the LLST exhibits hierarchical structure consisting of sponge-like micropores (1 ~ 50 μm) and nanopores (5 ~ 100 nm), without detrimental macropores that compromise light weight, strength, and toughness. Compared with the normal cement paste, LLST displays a 54% reduction in density, 145% and 1365% improvement in specific compressive strength and fracture energy, with only 51% carbon emission. These properties are further investigated with machine learning force field molecular dynamics along with well-tempered metadynamics simulations, indicating that strong chemical bonding is generated at the atomic level between functional groups in the hydrogel and Ca ion released from cement hydration. These findings not only demonstrate a strategy for developing lightweight building materials with low-carbon emission and remarkable mechanical properties, but also provide valuable insights for realizing the coexistence of light weight, strength and toughness by tailoring the hierarchical pore structure.