Metabolic-associated steatohepatitis (MASH) is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma. Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease. This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH, which benefit a broad spectrum of MASH patients, including those who have difficulty engaging in physical activity.

We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serine-cysteine transporter 2. Mice were fed a high-fat high-cholesterol diet and subjected to either short- or long-term exercise regimens. We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase (BCKDH) as well as branched-chain amino acid (BCAA) content in skeletal muscle following exercise.

Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight. It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation. Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice. In contrast, muscle-specific L-type amino acid transporter 1 knockdown, which suppresses BCAA uptake, markedly abolished these beneficial effects. Interestingly, BCKDH overexpression in muscle increased glutamine levels in both the blood and liver. Hepatic alanine-serine-cysteine transporter 2 knockdown, which inhibited glutamine uptake, lessened the protective effect of exercise on MASH. Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.

Short-term exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production, which circulates to the liver to improve redox balance and alleviate MASH.

Soft tissue cytopathology plays a vital role in the diagnosis and management of soft tissue neoplasms, necessitating a standardized classification system to improve diagnostic accuracy and guide clinical decision-making. This article provides a concise review of the World Health Organization (WHO) Reporting System for Soft Tissue Cytopathology and presents a practical diagnostic approach to soft tissue cytopathology.

The WHO Reporting System is reviewed in conjunction with relevant literature. The reporting system employs a six-category framework: non-diagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant. Each category is associated with a corresponding risk of malignancy and recommended clinical management guidelines. This classification aligns with the WHO Classification of Soft Tissue and Bone Tumours (5th edition) and incorporates cytomorphologic features, ancillary studies, and clinical correlation to enhance diagnostic reproducibility and communication among pathologists and clinicians.

The system supports a probabilistic approach to risk stratification, enabling more consistent diagnostic and therapeutic strategies.

As molecular diagnostics and immunocytochemistry continue to advance, this framework provides a robust foundation for the interpretation of soft tissue fine-needle aspiration biopsies and optimized patient care.

Chronic liver cirrhosis (LC) and acute-on-chronic liver failure (ACLF) are interconnected hepatic disorders associated with substantial morbidity and mortality. Despite their distinct clinical characteristics, both conditions share common pathogenic pathways that remain inadequately understood. This study aimed to identify shared gene signatures and elucidate underlying molecular mechanisms.

In this study, we employed Weighted Gene Co-Expression Network Analysis to explore transcriptomic data from the Gene Expression Omnibus for LC and ACLF.

Key co-expression modules enriched with genes involved in glycolysis and gluconeogenesis pathways were identified, implicating metabolic dysfunction as a central feature in both conditions. Furthermore, microRNA analysis revealed that hsa-miR-122 and hsa-miR-194 play pivotal roles in regulating these metabolic pathways, potentially contributing to immune dysregulation.

Our findings indicate that these shared molecular mechanisms are critical in the progression from LC to ACLF, providing novel insights into potential therapeutic targets for mitigating disease severity and improving clinical outcomes.

Metabolic dysfunction-associated fatty liver disease, representing a spectrum of liver disorders from simple steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, and cirrhosis, has emerged as one of the most prevalent chronic liver conditions globally, affecting an estimated approximately 30% of the world's population. Its pathogenesis is highly complex, involving intricate interactions between genetic predisposition, metabolic dysregulation, inflammation, and cellular stress responses. Within this complex landscape, orphan nuclear receptors (ONRs) have gained significant attention. Defined by the lack of identified endogenous ligands, ONRs function as master transcriptional regulators controlling diverse biological processes. Crucially, they play pivotal roles in the development and progression of numerous diseases, including metabolic disorders.This review specifically focuses on elucidating the critical contributions of various ONRs to the pathogenesis of metabolic dysfunction-associated fatty liver disease. We examined how these receptors modulate key pathological drivers: lipid metabolism, inflammation,and autophagy.

Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to efficiently deliver therapeutic cargo. These systems, primarily based on synthetic and natural polymers, offer significant advantages in terms of safety, controlled gene release, and targeted delivery. This review explores the design and synthesis of macromolecular carriers, focusing on their chemical and physical architectures, which play a key role in improving gene delivery. Catanionic polymers and their derivatives (comb, brush, and star polymers) have been extensively researched for their capacity to condense and protect genetic material. Furthermore, natural polymers like chitosan and hyaluronic acid have been modified to enhance gene delivery capabilities. These macromolecular carriers are engineered to boost circulation time, increase cellular uptake, and facilitate the controlled release of genetic material at the target site. Strategies such as incorporating targeting ligands, stimuli-responsive elements, and reducing cytotoxicity are being pursued to improve the overall efficiency and specificity of these systems. This review highlights the current state of macromolecular gene delivery systems, their applications, and the ongoing research aimed at overcoming existing challenges, paving the way for more effective non-viral gene therapies.