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).

IC2Bert: masked gene expression pretraining and supervised fine tuning for robust immune checkpoint blockade (ICB) response prediction.

Bulk RNA-seq-based prediction of immune checkpoint blockade (ICB) responses has been extensively studied to distinguish responders from non-responders. However, cohort heterogeneity remains a major challenge, hindering the robustness and generalizability of predictive models across diverse RNA-seq datasets. In this study, we present IC2Bert, a novel model that employs masked gene expression pretraining combined with domain-specific supervised fine-tuning to enhance predictive robustness across heterogeneous ICB response cohorts.

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.

Assessment of diversity indices and ecological quality status using multiple biotic indices in the subtidal zone of Cheonsu Bay, Korea.

This study assessed the biodiversity and ecological quality status of Cheonsu Bay in 1993, 2010, and 2020 to evaluate the ecological impacts of dike construction and identify the most suitable biotic indices. Although various biotic indices have been developed to evaluate ecological quality, each reflects a limited aspect of ecosystem status. Hence, utilizing multiple indices is likely to provide a more comprehensive understanding of overall environmental conditions.

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.

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.

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.

Whole-genome sequencing analysis of soybean diversity across different countries and selection signature of Korean soybean accession.

Soybean is an important agricultural crop known for its high protein and oil content, contributing to essential nutritional and health benefits for humans. Domesticated in China over 5,000 years ago, soybean has since adapted to diverse environments and spread worldwide. This study aimed to investigate the genomic characteristics and population structures of 2,317 publicly available soybean whole-genome sequences from diverse geographical regions, including China, Korea, Japan, Europe, North America, and South America.

CILP2 is a potential biomarker for the prediction and therapeutic target of peritoneal metastases in colorectal cancer.

Peritoneal metastases (PM) in colorectal cancer (CRC) is associated with a dismal prognosis. Identifying and exploiting new biomarkers, signatures, and molecular targets for personalised interventions in the treatment of PM in CRC is imperative. We conducted transcriptomic profiling using RNA-seq data generated from the primary tissues of 19 CRC patients with PM.

Transcriptomic characteristics according to tumor size and SUV in papillary thyroid cancer patients.

The SUV is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship between SUV and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUV and tumor size.

Neutrophil diversity is associated with T-cell immunity and clinical relevance in patients with thyroid cancer.

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n = 10) by transcriptomic data and cytometry.

Small RNA-modulated anaerobic respiration allows bacteria to survive under antibiotic stress conditions.

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics.

Systematic identification of a synthetic lethal interaction in brain-metastatic lung adenocarcinoma.

Metastatic lung adenocarcinoma (LuAC) presents a significant clinical challenge due to the short latency and the lack of efficient treatment options. Therefore, identification of molecular vulnerabilities in metastatic LuAC holds great importance in the development of therapeutic drugs against this disease. In this study, we performed a genome-wide siRNA screening using poorly and highly brain-metastatic LuAC cell lines.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features.

Hypoxia stabilizes SETDB1 to maintain genome stability.

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target.

Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis.

Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation.

Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging.

The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy.

The EDN1/EDNRA/β‑arrestin axis promotes colorectal cancer progression by regulating STAT3 phosphorylation.

Endothelin receptor A (EDNRA) has been reported to play various crucial physiological roles and has been shown to be associated with the pathology of several diseases, including colorectal cancer (CRC). However, the molecular mechanisms of EDNRA in the development of human CRC have not been fully elucidated to date. In this context, the present study was performed to investigate biological functions and novel downstream signaling pathways affected by EDNRA, during CRC progression.

Utility of a Molecular Signature for Predicting Recurrence and Progression in Non-Muscle-Invasive Bladder Cancer Patients: Comparison with the EORTC, CUETO and 2021 EAU Risk Groups.

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed.