Deep learning-driven whole-slide image analysis predicts chemo-resistance and motility subtypes in muscle-invasive bladder cancer.

Background: Muscle-invasive bladder cancer (MIBC) is a clinically aggressive and heterogeneous disease with variable treatment responses. Transcriptome-based classifications, such as the Chemoresistance-Motility (CrM) signature, are valuable for understanding therapeutic resistance, but their clinical use is often hindered by high cost and tissue requirements. This study explores an alternative, scalable approach using deep learning analysis of whole slide images (WSIs).

Prognostic and therapeutic value of a 23-gene risk score tailored to the molecular characteristics of mucinous colorectal cancer.

Background: Mucinous adenocarcinoma (MuC), a colorectal cancer (CRC) subtype, exhibits distinct molecular features and poorer response to chemoradiotherapy than non-mucinous adenocarcinoma (NMuC). Conventional treatments often fail to address CRC heterogeneity, particularly in stage II disease. Therefore, improved biomarkers for risk stratification and personalised treatment are needed.

Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS), an extremely rare progressive genetic disorder, is caused by a point mutation in LMNA that induces progerin production, which disrupts cellular function and triggers premature aging and mortality. Despite extensive efforts, HPGS remains incurable. We successfully implemented a strategy using RfxCas13d to selectively target progerin mRNA at specific junction regions, without unintended cleavage and reduce its expression.

Genome-wide DNA methylome profiling to differentiate monozygotic twins.

In the current forensic environment, short tandem repeat (STR) profiling originating from genomic differences is highly accurate and widely used to identify individuals. However, if the person of interest is a monozygotic (MZ) twin, his or her DNA profile is identical to that of his or her twin; thus, STR profiling cannot discriminate between them. Therefore, DNA methylation, which is known to have different patterns even in MZ twins, has attracted attention as a promising marker to differentiate MZ twins.

Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer.

Individuals with retinal degenerative diseases struggle to restore vision due to the inability to regenerate retinal cells. Unlike cold-blooded vertebrates, mammals lack Müller glia (MG)-mediated retinal regeneration, indicating the limited regenerative capacity of mammalian MG. Here, we identify prospero-related homeobox 1 (Prox1) as a key factor restricting this process.

Protective Effect of Ganjang, a Traditional Fermented Soy Sauce, on Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is one of the most prevalent causes of cancer-related fatalities globally, and its development is closely associated with dietary and microbial factors. The aim of this study was to investigate the potential of ganjang, a traditional fermented soy sauce, in alleviating colitis-associated colorectal cancer (CAC) in a mouse model induced by azoxymethane/dextran sulfate sodium (AOM/DSS). The bacterial composition of ganjang samples from different regions primarily included spp.

Immune landscape and novel therapeutic targets of epidermal growth factor receptor and anaplastic lymphoma kinase wild type never-smoker lung adenocarcinoma.

Background: Never-smoker lung adenocarcinoma (NSLA) exhibits distinct immunosuppressive profiles and a lower tumor mutation burden compared with lung adenocarcinoma in smokers. These correlate with poor responses to immune checkpoint inhibitors. In this study, we aimed to elucidate the tumor-immune microenvironment of NSLA without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations and identify novel therapeutic targets.

The immune sensitivity caused by DUSP11, an RNA 5'-end maturation phosphatase, is adjusted by a human non-coding RNA, nc886.

All cellular transcripts initially have a tri-phosphate (PPP) group at the 5'-end, recognized as a pathogen-associated molecular pattern (PAMP) by a cell's innate immune system. The removal of 5'-PPP occurs to varying extents, causing immune imbalance. However, how cells manage this situation has not yet been documented.

Molecular characterization of Pseudomyxoma peritonei with single-cell and bulk RNA sequencing.

Pseudomyxoma peritonei (PMP), a rare condition characterized by mucinous ascites in the peritoneal cavity, often leads to a poor prognosis. However, omics profiling of this disease remains significantly underexplored. Here, we present single-cell transcriptomic profiling of five PMP cases to identify cell type-specific gene features associated with PMP pathogenesis.

Liver X Receptor-Growth Differentiation Factor 15 Activation Drives Profibrotic Changes in the Aqueous Outflow Tract of Uveitic Glaucoma.

Cytomegalovirus (CMV)-induced anterior uveitis is linked to increased intraocular pressure, suggesting profibrotic changes in the eye's drainage system. Previous studies on the aqueous humor (AH) of patients with CMV uveitic glaucoma (UG) highlighted the activation of the liver X receptor (LXR) pathway, yet a potential that it has a role in increased intraocular pressure remained unelucidated. Herein, the LXR pathway's role in AH outflow in UG was explored.

Mechanisms of uropathogenic mucosal association in the gastrointestinal tract.

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic (UPEC) strains that can be found in patient intestines. Seeding of the urinary tract from this intestinal reservoir likely contributes to UTI recurrence (rUTI) rates. Thus, understanding the factors that promote UPEC intestinal colonization is of critical importance to designing therapeutics to reduce rUTI incidence.

The Role of Knowledge and Personal Experience in Shaping Stigma Associated With COVID-19 and Mental Illness.

Objective: Stigma influences perceptions of mental illness and novel diseases like coronavirus disease-2019 (COVID-19), often impeding healthcare access despite advancements in medical treatment. This study compares the stigma associated with COVID-19 and mental illness to identify factors that could help reduce stigma.

Methods: An online survey was conducted in May 2023 among 1,500 participants aged 19 to 65 in South Korea, using a panel from Embrain, an online survey service.

Probiotic Potential and Enhanced Adhesion of Fermented Foods-Isolated Lactic Acid Bacteria to Intestinal Epithelial Caco-2 and HT-29 Cells.

This study evaluated the probiotic potential of lactic acid bacteria (LAB) isolated from fermented milk and soymilk products purchased from local markets. The LAB strains were assessed for acid and bile resistance, antibiotic resistance, and adhesion to human intestinal epithelial models. (JAMI_LB_02) and (JAMI_LB_05) showed the highest survival rates in artificial gastric and bile juices, at 87.

Highly accurate Korean draft genomes reveal structural variation highlighting human telomere evolution.

Given the presence of highly repetitive genomic regions such as subtelomeric regions, understanding human genomic evolution remains challenging. Recently, long-read sequencing technology has facilitated the identification of complex genetic variants, including structural variants (SVs), at the single-nucleotide level. Here, we resolved SVs and their underlying DNA damage-repair mechanisms in subtelomeric regions, which are among the most uncharted genomic regions.

Physiological activation of liver X receptor provides protection against ocular inflammation in uveitic glaucoma.

Virus-induced trabeculitis is considered a significant cause of uveitic glaucoma, being marked by a sudden increase in intraocular pressure and relatively mild inflammation in the anterior chamber of the eye. In previous proteome analyses of aqueous humor (AH) derived from Cytomegalovirus (CMV) uveitic glaucoma patients, we observed the liver X receptor (LXR) pathway to be among the most prominently activated canonical pathways. In the present study, we explored the role of the LXR pathway in the etiology of glaucoma in association with ocular inflammation.

Hair Growth Effect and the Mechanisms of Extract in DHT-Induced Alopecia Mice Model.

is a medicinal plant known for its potential anti-inflammatory, antioxidant, anti-cancer, and antimicrobial benefits. The pharmacological effects of extract on hair loss have not yet been documented. This research sought to assess the inhibitory effects and mechanisms of action of water extract (RWE) in a mouse model of dihydrotestosterone (DHT)-induced alopecia.

The DMPTool NIH DMSP Templates Project.

The DMPTool NIH Data Management and Sharing Plan (DMSP) Templates Project was launched in response to the 2023 NIH Data Management and Sharing (DMS) Policy. This new policy introduced a more structured framework for DMS Plans, featuring six key elements, a departure from the 2003 NIH DMS policy. The project aimed to simplify the process for data librarians, research administrators, and researchers by providing a template with curated guidance, eliminating the need to navigate various policies and guidelines.

Cu-Electrocatalysis Enables Vicinal Bis(difluoromethylation) of Alkenes: Unraveling Dichotomous Role of Zn(CFH)(DMPU) as Both Radical and Anion Source.

The difluoromethyl group (CFH) serves as an essential bioisostere in drug discovery campaigns according to Lipinski's Rule of 5 due to its advantageous combination of lipophilicity and hydrogen bonding ability, thereby improving the ADME properties. However, despite the high prevalence and importance of vicinal hydrogen bond donors in pharmaceutical agents, a general synthetic method for doubly difluoromethylated compounds in the vicinal position is absent. Here we describe a copper-electrocatalyzed strategy that enables the vicinal bis(difluoromethylation) of alkenes.

Metabolic Profiling Changes Induced by Fermented Blackberries in High-Fat-Diet-Fed Mice Utilizing Gas Chromatography-Mass Spectrometry Analysis.

The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by , and high-fat diet with blackberry fermented by . After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with showed the most pronounced reduction in liver weight.

N-terminal acetylation of Set1-COMPASS fine-tunes H3K4 methylation patterns.

H3K4 methylation by Set1-COMPASS (complex of proteins associated with Set1) is a conserved histone modification. Although it is critical for gene regulation, the posttranslational modifications of this complex that affect its function are largely unexplored. This study showed that N-terminal acetylation of Set1-COMPASS proteins by N-terminal acetyltransferases (NATs) can modulate H3K4 methylation patterns.

Anti-Inflammatory Effect of Korean Soybean Sauce (Ganjang) on Mice with Induced Colitis.

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gut, is caused by several factors. Among these factors, microbial factors are correlated with the gut microbiota, which produces short-chain fatty acids (SCFAs) via anaerobic fermentation. Fermented foods are known to regulate the gut microbiota composition.

Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks.

Mortalin (encoded by HSPA9) is a mitochondrial chaperone often overexpressed in cancer through as-yet-unknown mechanisms. By searching different RNA-sequencing datasets, we found that ESRRA is a transcription factor highly correlated with HSPA9 in thyroid cancer, especially in follicular, but not C cell-originated, tumors. Consistent with this correlation, ESRRA depletion decreased mortalin expression only in follicular thyroid tumor cells.