DNA Origami Scaffold-Based Peptide-Major Histocompatibility Complex Multimers for Spatial Imaging of T Cells.

Visualizing the spatial distribution of antigen-specific T cells is essential for understanding immune responses and improving therapeutic strategies. However, detecting low-affinity antigen-specific T cells and enhancing signals from low-abundance populations remain challenging due to limitations in sensitivity. Here, we report DNA origami scaffold-based peptide-major histocompatibility complex multimers (DOS-pMHCs) with precise spatial organization of pMHC and signaling molecules on the nanoscale for enhanced in situ visualization of antigen-specific T cells.

Cell-type deconvolution for bulk RNA-seq data using single-cell reference: a comparative analysis and recommendation guideline.

The accurate estimation of cell type proportions in tissues is crucial for various downstream analyses. With the increasing availability of single-cell sequencing data, numerous deconvolution methods that use single-cell RNA sequencing data as a reference have been developed. However, a unified understanding of how these deconvolution approaches perform in practical applications is still lacking.

Completely conserved VP2 residue K140 of KREMEN1-dependent enteroviruses is critical for virus-receptor interactions and viral infection.

Unlabelled: The KREMEN1 (KRM1) protein is a cellular receptor for multiple enteroviruses that cause hand, foot, and mouth disease (HFMD), including coxsackievirus CVA2, CVA3, CVA4, CVA5, CVA6, CVA10, and CVA12. The molecular basis for the broad recognition of these viruses by the KRM1 receptor remains unclear. Here, we report the indispensable role of the completely conserved VP2 capsid protein residue K140 (designated K2140) in mediating receptor recognition and infection by CVA10 and other KRM1-dependent enteroviruses.

Belt conveyor idler fault detection algorithm based on improved YOLOv5.

The rapid expansion of the coal mining industry has introduced significant safety risks, particularly within the harsh environments of open-pit coal mines. The safe and stable operation of belt conveyor idlers is crucial not only for ensuring efficient coal production but also for safeguarding the lives of coal mine workers. Therefore, this paper proposes a method based on deep learning for real-time detection of conveyor idler faults.

Incidence, mortality, and global burden of retinoblastoma in 204 countries worldwide from 1990 to 2021: Data and systematic analysis from the Global Burden of Disease Study 2021.

Background: Retinoblastoma (Rb), the primary intraocular malignancy in children, poses significant risks, yet its overall burden remains inadequately assessed. This study aims to analyze global Rb trends using Global Burden of Disease, Injuries, and Risk Factors study (GBD) 2021 data.

Methods: GBD 2021 data was analyzed to assess Rb incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021.

MobiChIP: a compatible library construction method of single-cell ChIP-seq based droplets.

To illustrate epigenetic heterogeneity, versatile tools of single-cell ChIP-seq (scChIP-seq) are essential for both convenience and accuracy. We developed MobiChIP, a compatible ChIP-seq library construction method based on current sequencing platforms for single-cell applications. MobiChIP efficiently captures fragments from tagmented nuclei across various species and allows sample mixing from different tissues or species.

Creating a bacterium that forms eukaryotic nucleosome core particles.

The nucleosome is one of the hallmarks of eukaryotes, a dynamic platform that supports many critical functions in eukaryotic cells. Here, we engineer the in vivo assembly of the nucleosome core in the model bacterium Escherichia coli. We show that bacterial chromosome DNA and eukaryotic histones can assemble in vivo to form nucleosome complexes with many features resembling those found in eukaryotes.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

Background And Aim: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF.

Causal associations between severe COVID-19 and diseases of seven organs: a proteome-wide mendelian randomization study.

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous threat to public health worldwide. Many retrospective studies and case reports to date have shown associations between severe COVID-19 and diseases of multi-organs. However, the research on the causal mechanisms behind this phenomenon is neither extensive nor comprehensive.

Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.

Objectives: Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis.

Revealing Differential RNA Editing Specificity of Human ADAR1 and ADAR2 in .

Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional modification mediated by the adenosine deaminases acting on RNA (ADAR) family of enzymes, expanding the transcriptome by altering selected nucleotides A to I in RNA molecules. Recently, A-to-I editing has been explored for correcting disease-causing mutations in RNA using therapeutic guide oligonucleotides to direct ADAR editing at specific sites. Humans have two active ADARs whose preferences and specificities are not well understood.

Designer cellular spheroids with DNA origami for drug screening.

Current in vitro models struggle to balance the complexity of human diseases with suitability for large-scale drug tests. While 3D cultures simulate human tissues, they lack cellular intricacy, and integrating these models with high-throughput drug screening remains a challenge. Here, we introduce a method that uses self-assembling nucleic acid nanostructures decorated living cells, termed NACs, to create spheroids with a customizable 3D layout.

Encoding signal propagation on topology-programmed DNA origami.

Biological systems often rely on topological transformation to reconfigure connectivity between nodes to guide the flux of molecular information. Here we develop a topology-programmed DNA origami system that encodes signal propagation at the nanoscale, analogous to topologically efficient information processing in cellular systems. We present a systematic molecular implementation of topological operations involving 'glue-cut' processes that can prompt global conformational change of DNA origami structures, with demonstrated major topological properties including genus, number of boundary components and orientability.

Antidiabetic Close Loop Based on Wearable DNA-Hydrogel Glucometer and Implantable Optogenetic Cells.

Diabetes mellitus and its associated secondary complications have become a pressing global healthcare issue. The current integrated theranostic plan involves a glucometer-tandem pump. However, external condition-responsive insulin delivery systems utilizing rigid glucose sensors pose challenges in on-demand, long-term insulin administration.

Immunological profile of lactylation-related genes in Crohn's disease: a comprehensive analysis based on bulk and single-cell RNA sequencing data.

Background: Crohn's disease (CD) is a disease characterized by intestinal immune dysfunction, often accompanied by metabolic abnormalities. Disturbances in lactate metabolism have been found in the intestine of patients with CD, but studies on the role of lactate and related Lactylation in the pathogenesis of CD are still unknown.

Methods: We identified the core genes associated with Lactylation by downloading and merging three CD-related datasets (GSE16879, GSE75214, and GSE112366) from the GEO database, and analyzed the functions associated with the hub genes and the correlation between their expression levels and immune infiltration through comprehensive analysis.

MoS-Based Sensor Array for Accurate Identification of Cancer Cells with Ensemble-Modified Aptamers.

In this work, we present an array-based chemical nose sensor that utilizes a set of ensemble-modified aptamer (EMAmer) probes to sense subtle physicochemical changes on the cell surface for cancer cell identification. The EMAmer probes are engineered by domain-selective incorporation of different types and/or copies of positively charged functional groups into DNA scaffolds, and their differential interactions with cancer cells can be transduced through competitive adsorption of fluorophore-labeled EMAmer probes loaded on MoS nanosheets. We demonstrate that this MoS-EMAmer-based sensor array enables rapid and effective discrimination among six types of cancer cells and their mixtures with a concentration of 10 cells within 60 min, achieving a 94.

meHOLMES: A CRISPR-cas12a-based method for rapid detection of DNA methylation in a sequence-independent manner.

Aberrant DNA methylation is closely associated with various diseases, particularly cancer, and its precise detection plays an essential role in disease diagnosis and monitoring. In this study, we present a novel DNA methylation detection method (namely meHOLMES), which integrates both the TET2/APOBEC-mediated cytosine deamination step and the CRISPR-Cas12a-based signal readout step. TET2/APOBEC efficiently converts unmethylated cytosine to uracil, which is subsequently changed to thymine after PCR amplification.

Shaping immune landscape of colorectal cancer by cholesterol metabolites.

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC.

RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3- and FADD-mediated cell death.

Regulatory T (T) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying T homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for T cell survival and homeostasis.