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Background: Genome-wide association studies (GWAS) provide a powerful method for identifying the loci and genes that contribute to disease. However, in many cases, the specific cell types and states that confer disease risk through these genes remain unknown. Determining this relationship is crucial for identifying pathogenic processes and developing therapeutic strategies. Methods: In this study, we utilized the sc-linker framework developed by Jagadeesh, which is an integrated framework that combines single-cell RNA sequencing (scRNA-seq), epigenomic single nucleotide polymorphism (SNP)-to-gene mapping, and GWAS summary statistics to infer potential cell types and diseases affected by genetic variations. Results: Using normal cell type programs in the sc-linker, we identified type 2 alveolar cells in normal lung tissues that are closely associated with non-small cell lung cancer (NSCLC). Additionally, we identified cancer-associated fibroblasts (CAFs) associated with lung cancer using disease-dependent programs. By integrating extensive single-cell data from NSCLC, we discerned heterogeneity among CAFs subgroups. Finally, using MAGMA, we identified RAB31 as a driver gene in disease-related fibroblasts. Proteins from the RAB family are involved in the dynamic regulation of cell membrane compartments and are dysregulated in various tumor types, potentially altering biological properties such as the proliferation, migration, and invasion of cancer cells. We found that the Ras-related protein Rab-31 (RAB31) was significantly overexpressed in tumor-associated fibroblasts compared to that in normal fibroblasts and was closely associated with poor prognosis in patients with NSCLC. Conclusions: By integrating scRNA-seq, epigenomic, and GWAS datasets, we found that ACT2 and CAFs have specific disease heritability in lung cancer and identified the driver gene RAB31 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis. However, recent evidence suggests that sepsis-related opportunistic pathogens can directly induce organ failure by promoting PCD in parenchymal cells of each affected organ. This study provides an overview of PCD in damaged organ and the induction of PCD in host parenchymal cells by opportunistic pathogens, proposing innovative strategies for preventing organ failure in sepsis., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose of Review: Recent advancements in molecular biomarkers and therapeutic options for Alzheimer's disease have brought into focus the need for greater progress in the second most common cause of dementia, vascular cognitive impairment and dementia (VCID). We examine how the study of monogenic causes of VCID has contributed to the understanding of its pathophysiology and potential biomarker and treatment research., Recent Findings: It is widely accepted that conditions which disrupt the cerebral small vessels contribute to vascular pathologies including stroke and cerebral microbleeds, ultimately leading to vascular cognitive impairment and dementia. Among these conditions are a range of monogenic small vessel diseases (SVDs) such as CADASIL, CARASIL, Fabry disease and COL4A-related disorders., Summary: This review indicates the importance of furthering research into monogenic SVDs in order to gain insight into the pathomechanisms of VCID more broadly. Monogenic conditions are easier to model than sporadic VCID and can serve as a guide for identifying biomarkers for diagnosis, monitoring and intervention outcomes., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Staphylococcus aureus is a multi-host pathogen that can colonize and infect both humans and livestock in a tissue-specific manner. This amazing feature of the pathogen is mainly facilitated by the surplus virulence agents produced upon necessity and favorable environmental factors. These factors are adept at damaging cellular barriers, manipulating host immune factors, and circumventing the host complement system. The delicate balance between the timely release of virulent factors and the regulation of their production underscores the significance of the exoenzyme network. Moreover, the intricate relationship between the pathogen and host tissue highlights the importance of understanding tissue-specific phenotypes for effective therapeutic strategies. Here, we provide a review on the diverse role played by the extracellular enzymes of S. aureus in tissue-specific infection and systemic colonization leading to distinctive diseased conditions. The article highlights the need to study the role of staphylococcal exoenzymes in various systemic invasions, their impact on the deterioration of host tissue, and the regulation of S. aureus virulence factors., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)