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Metal-free plano-convex lens-based optical probes for high-sensitivity and chemically resistant refractive index sensing
Airqtl dissects cell state-specific causal gene regulatory networks with efficient single-cell eQTL mapping
Abstract Single-cell expression quantitative trait loci (sceQTL) mapping offers a powerful approach for understanding gene regulation and its heterogeneity across cell types and states. It has profound applications in genetics and genomics, particularly causal gene regulatory network (cGRN) inference to unravel the molecular circuits governing cell identity and function. However, computational scalability remains a critical bottleneck for sceQTL mapping, prohibiting thorough benchmarking and optimization of statistical accuracy. We present airqtl, an efficient method to overcome these challenges through algorithmic advances and efficient implementations of linear mixed models. Airqtl achieves superior time complexity and over 10 8 times of acceleration, enabling objective method benchmarking and optimization. Airqtl offers de novo inference of robust, experimentally validated cell state-specific cGRNs that reflect perturbation outcomes. Our results dissect the drivers of cGRN heterogeneity and underscore the value of natural genetic variations in primary human cell types for biologically relevant single-cell cGRN inference.
Quantitative LFQ-DIA proteomics reveals FTH1-MCM5/WNT axis mediated osteoblastic dysfunction via ferroptosis drives diabetic osteoporosis
Magnetic reconnection in the plasma disk at 23 Jupiter radii
N6-methyladenosine (m6A) of LINC01315 promotes hepatocellular carcinoma progression by activating β-Catentin/WNT pathway
Reading the immune clock: a machine learning model predicts mouse immune age from cellular patterns
An experimental study of the effect of electric field enhancement on the adsorption characteristics of coalbed methane
Cross-spatial scale processing of hierarchical auditory sequences in human brains revealed using 7 T magnetic resonance imaging
Health risk assessment and morpho-physiological, biochemical response of rice (Oryza sativa L.) to foliar application of lead oxide nanoparticles
IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats
Abstract Mutant mRNA of the fragile X messenger ribonucleoprotein 1 gene ( FMR1 ) containing expanded CGG repeats in its 5’UTR is a primary cause of fragile X premutation associated conditions. It serves as a template for the biosynthesis of the major open reading frame encoding canonical protein and the downstream open reading frame containing expanded CGG repeats encoding toxic FMRpolyG protein that comprise a long polyglycine stretch, produced via repeat-associated non-AUG initiated translation. Here, we show that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) binds directly to the 5’UTR of FMR1 RNA, and the sequence in the vicinity of near-cognate start codons of non-AUG translation is pivotal for IGF2BP3 binding. Upon IGF2BP3’s knockdown, FMRpolyG biosynthesis and cell toxicity evoked by FMRpolyG, significantly decreased in cells expressing mutant FMR1 with expanded CGG repeats. Disruption of IGF2BP ortholog in novel fragile X premutation associated conditions C. elegans model rescues the disease phenotype induced by expression of a human FMR1 RNA fragment containing expanded CGG repeats. Our results suggest that IGF2BP3 positively regulates the noncanonical translation of expanded CGG repeats and may be a promising target for clinical applications.
A sex-adjusted 7-biomarker clinical aging clock for translational preventative medicine
Abstract Biological aging clocks capture heterogeneous rates of aging in individuals and transform current medical practice toward translational preventive medicine. Here, we developed a clinical aging clock based on routine blood biochemistry markers from 59,741 healthy samples in a Southeast Asian cohort. We established a novel correction method to address the systematic skew in predictions from first-generation clocks. This correction improved the accuracy of age-acceleration predictions for disease risks and enhanced interpretability for disease-driven and organ-specific aging processes without relying on mortality data. Based on only seven biomarkers, our clock accurately predicts both self-reported and physician-annotated ICD health data, indicating an increased hazard ratio. Importantly, the clock is robust even in the presence of acute infections or transient immune activation. To demonstrate the multi-ethnic generalizability of our biological age clock, we validated our approach using data from both the NHANES and UK Biobank cohorts. Our approach demonstrates the feasibility of a simple, robust, and interpretable clinical aging clock with potential for real-world implementation in personalized health monitoring and preventive care.
RoCK and ROI: single-cell transcriptomics with multiplexed enrichment of selected transcripts and region-specific sequencing
Abstract Single-cell profiling technologies allow exploring molecular mechanisms that drive development, health, and disease. However, current methods still fall short of profiling single cell transcriptomes comprehensively, with one major challenge being high non-detection rates of specific transcripts and transcript regions. Such information is often crucial to understanding the biology of cells. Here, we introduce RoCK and ROI (Robust Capture of Key transcripts and Regions Of Interest), a scRNA-seq workflow encompassing two techniques. RoCKseq uses targeted capture to enrich for key transcripts, thereby supporting the detection and identification of cell types and complex phenotypes in scRNA-seq experiments. ROIseq directs a subset of reads to a specific region of interest via selective priming. Importantly, RoCK and ROI enables retrieval of specific sequence information without compromising overall single cell transcriptome information. We validate RoCK and ROI across diverse biological systems highlighting the versatility and showing the power of the method to retrieve critical transcriptomic features.
Rheological performance and strength on two component backfilling grout in shield TBM
Seed amplification of MSA alpha-synuclein aggregates preserves the biological and structural properties of brain-derived aggregates
Dynamics of kink solitons under additive white noise in the power-law nonlinear Schrödinger equation
Information advantage in sensing revealed by Fano-resonant Fourier scatterometry
Abstract Fano resonances in nanophotonic structures are attractive for sensing due to their ultanarrow resonant linewidths and high local fields. Conventional read out schemes rely on measuring a frequency shift in Fano scattering spectra as function of perturbation. We experimentally demonstrate that angle-resolved analysis of the scattering of a Fano resonant structure is quantitatively more informative than measuring spectral shifts. We theoretically discuss how a perturbation affects fundamental nanophotonic properties of a Fano resonant metasystem, and how these are transduced to an observable far field response. We perform a rigorous experimental study in which we characterize deeply subwavelength perturbations in a Fano resonant dielectric metasurface using a conventional spectral approach, and a Fourier scatterometry based approach, and show that perturbations can lead to marked directional scattering in Fourier space. We finally quantitatively compare these two sensing methods in terms of their inherent Fisher information content, and show that an information advantage is obtained when the signal is resolved in Fourier space.
A rapid detection method for coal dust thickness in heavy-haul railway ballast based on time and frequency domain response characteristics from GPR signal
Self-assembly of hybrid 3D cultures by integrating living and synthetic cells
Abstract Self-assembly is a fundamental property of living matter that drives the three-dimensional organization of cell collectives such as tissues and organs. Here, the co-assembly of synthetic and natural cells is leveraged to create hybrid living 3D cancer cultures. We screen a range of synthetic cell models for their ability to form augmented tumoroids with artificial but controllable micro-environments, and show that the balance of inter- and extracellular adhesion and synthetic cell surface tension are key material properties driving integrated co-assembly. We demonstrate that synthetic cells based on droplet-supported lipid bilayers can establish artificial tumor immune microenvironments (ART-TIMEs), mimicking immunogenic signals within tumoroids and eliminating the need to integrate complex living immune cells. Using the ART-TIME approach, we identify a AhR-ARNT-mediated co-signaling mechanism between PD-1 and CD2 as a driver in immune evasion of pancreatic ductal adenocarcinoma. Our study advances the field of hybrid organoid engineering, offers opportunities for the construction and modelling of artificial tumour environments, and marks a step towards the design of functional living/non-living cytomimetic materials.