Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.

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.

Development of a predictive model for lung metastasis in hepatocellular carcinoma patients: insights from SEER database analysis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with lung metastasis significantly impacting patient prognosis. Identifying predictors of lung metastasis is crucial for improving patient outcomes. This study utilizes data from the Surveillance Epidemiology and End Results (SEER) database, focusing on a cohort of 13,441 HCC patients.

Triadic Electrophilic Centers Specifically Bind to SMO Transmembrane Domain to Inhibit the Hedgehog Pathway.

Designing drugs to target overexpressed membrane protein smoothened (SMO) to selectively inhibit the Hedgehog signaling pathway represents a promising approach to achieving effective chemotherapy. Currently, only three organic small molecular inhibitors of SMO have been approved for clinically targeted therapy. Herein, we demonstrate a novel strategy to anchor SMO by designing metallodrugs (RuSe, OsSe, RuIP, OsIP) containing triadic electrophilic centers (─N(δ)─X(δ)─N(δ)─).

Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression.

Introduction: The mechanisms of estrogen in glucose metabolism are well established; however, the role of this hormone in glucose absorption remains unclear. In this study, we investigated the effects of estrogen on glucose absorption in humans, mice, and the human intestinal epithelium cell line SCBN.

Research Design And Methods: The ovariectomized (OVX) animal model was established.

Synaptic Density in Multiple Sclerosis: An In Vivo Study Using [C]UCB-J-PET Imaging.

Background And Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease coupled with neurodegenerative processes affecting both the white matter and gray matter (GM) in the CNS. Several histopathologic studies have reported a reduction in synaptic density in various areas of the brain. However, this pathologic feature is yet an unexplored entity among people with MS (pwMS).

Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease.

Introduction: Positron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF).

Methods: Twenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [C]UCB-J PET.

A Feedback Loop Between Fatty Acid Metabolism and Epigenetics in Clear Cell Renal Carcinoma.

Lipid storage and epigenetic dysregulation are key features for clear cell renal carcinoma (ccRCC). However, the interplay between fatty acid metabolism and epigenetics in ccRCC remains to be further demonstrated. Here, the landscape of active enhancers is profiled in paired ccRCC samples and identifies 10171 gain variant enhancer loci (VELs) in the tumor tissues.

A prospective study on enhanced recovery of Mycobacterium tuberculosis from children's stool using novel power ultrasound decontamination.

Stool specimen is commonly used for mycobacterial culture to provide critical microbiological evidence for diagnosing tuberculosis (TB) in pediatric patients, especially when obtaining sputum specimens is challenging. However, the utilization of stool specimens for mycobacterial culture continues to face significant challenges in clinical practice, mainly owing to the relatively low diagnostic sensitivity and the frequent contamination by intestinal flora during specimen processing. This study evaluated the effectiveness of power ultrasound (PU) method in improving the recovery of Mycobacterium tuberculosis (M.

Fluorescent probes in autoimmune disease research: current status and future prospects.

Autoimmune diseases (AD) present substantial challenges for early diagnosis and precise treatment due to their intricate pathogenesis and varied clinical manifestations. While existing diagnostic methods and treatment strategies have advanced, their sensitivity, specificity, and real-time applicability in clinical settings continue to exhibit significant limitations. In recent years, fluorescent probes have emerged as highly sensitive and specific biological imaging tools, demonstrating substantial potential in AD research.

Development and validation of a pathological model predicting the efficacy of neoadjuvant therapy for breast cancer based on RCB scoring.

Introduction: Breast cancer has become the most prevalent malignant tumor among women globally, posing a serious threat to women's life and health. Neoadjuvant therapy (NAT) has emerged as one of the standard treatment approaches for breast cancer patients. However, due to varying responses to NAT among different patients, significant differences in treatment effectiveness occur, impacting the timely alteration of treatment strategies for patients.

Progress of IL-10 and liver metastasis.

Liver metastasis can occur in a wide range of cancers and have a significant impact on patient survival and prognosis. Once liver metastasis occurs, patients often lose the opportunity for surgery, and although a small percentage of patients can undergo hepatic resection to prolong survival, the benefit is not great. There were also many factors affecting liver metastasis, including reprogramming of the primary tumor metabolism, disturbances in the immune microenvironment and immune cells, alterations in the gut microbiota, and epigenetic changes.

The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.

Solute carrier (SLC) family transporters are crucial transmembrane proteins responsible for transporting various molecules, including amino acids, electrolytes, fatty acids, and nucleotides. To date, more than fifty SLC transporter subfamilies have been identified, many of which are linked to the progression of hepatic steatosis and fibrosis. These conditions are often caused by factors such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, which are major contributors to the global liver disease burden.

Causal Effects of Sleep Traits on Angina Pectoris: Mediation by Cardiovascular Risk Factors.

Purpose: Angina pectoris (AP) is a major factor in heightened risk of cardiac arrest and has been previously linked to sleep patterns. It remains unclear if sleep traits play a role in the onset of AP. Our study aims to declare the causality of sleep traits on AP by Mendelian randomization (MR) analyses.

Identification of IL-34 and Slc7al as potential key regulators in MASLD progression through epigenomic profiling.

Objective: Epigenetic alterations are critical regulators in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the dynamic epigenomic landscapes are not well defined. Our previous study found that H3K27ac and H3K9me3 play important roles in regulating lipid metabolic pathways in the early stages of MASLD. However, the epigenomic status in the inflammation stages still needs to be determined.

Selenium Electrophilic Center Responsive to Biological Electron Donors for Efficient Chemotherapy.

Designing drugs to intelligently respond to different ratio of biological electron donors/receptors in cancer cells and normal cells is a promising strategy to achieve highly effective and less toxic chemotherapy. Herein by employing metal center to active the selenium-containing electrophilic center drug Ru(phtpy-NO)(phenSe)Cl (RuSe) with strongly polarization characteristics are synthesized which can efficiently shuttle electrons from biological electron donors to convert to oxidative stress. The rate of electron transfer at the selenium electrophilic center is 1.

Effectiveness of Low-Volume Versus High-Volume Ropivacaine for Ultrasound-Guided Maxillary Nerve Block in Double-Jaw Surgery: A Randomized Non-inferiority Trial.

Background: Ultrasound-guided maxillary nerve block (UGMNB) is applied in oral and maxillofacial surgery to improve perioperative analgesia, decrease the risk of postoperative nausea and vomiting, and enhance recovery. However, the optimum volume of ropivacaine used for UGMNB is undetermined. Thus, it was hypothesized that in patients undergoing double-jaw surgery, low- and high-volume ropivacaine reduces perioperative pain with similar efficacy.

The Effect of Computer-Aided Device on Adenoma Detection Rate in Different Implement Scenarios: A Real-World Study.

Background: Several recent studies have found that the efficacy of computer-aided polyp detection (CADe) on the adenoma detection rate (ADR) diminished in real-world settings. The role of unmeasured factors in AI-human interaction, such as monitor approaches, remains unknown. This study aimed to validate the effectiveness of CADe in the real world and assess the impact of monitor approaches.

Timing of endoscopy in cirrhotic patients with acute variceal bleeding: protocol of a multicenter randomized controlled trial.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB.

CD8+ T cell associated scoring model helps prognostic diagnosis and immunotherapy selection in patients with colon adenocarcinoma.

Objective: T cell-mediated immunity plays a crucial role in the immune response against tumors, with CD 8+ T cells playing a leading role in the eradication of cancer cells.

Material And Methods: A total of 5 datasets were included in this study. Single cell transcriptome data were used to discover CD8 T cell marker genes, and Bulk transcriptome data from TCGA and GEO were jointly analyzed to screen candidate prognostic genes.

Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [C]UCB-J PET.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [C]UCB-J PET. Participants included 31 older adults with AD and 16 with normal cognition.

Human umbilical cord mesenchymal stem cell-derived exosomes mitigate diabetic nephropathy via enhancing M2 macrophages polarization.

Background And Objectives: Exosomes, which are small nanoscale vesicles capable of secretion, have garnered significant attention in recent years because of their therapeutic potential, particularly in the context of kidney diseases. Notably, human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) are emerging as promising targeted therapies for renal conditions. The aim of this study was to investigate the therapeutic effects of hucMSC-Exos on diabetic kidney disease (DKD) both in vivo and in vitro.

Chirality-driven strong thioredoxin reductase inhibition.

Overexpression of thioredoxin reductase (TXNRD) plays crucial role in tumorigenesis. Therefore, designing TXNRD inhibitors is a promising strategy for targeted anticancer drug development. However, poor selectivity has always been a challenge, resulting in unavoidable toxicity in clinic.

The Role of Interferon Regulatory Factors in Liver Diseases.

The interferon regulatory factors (IRFs) family comprises 11 members that are involved in various biological processes such as antiviral defense, cell proliferation regulation, differentiation, and apoptosis. Recent studies have highlighted the roles of IRF1-9 in a range of liver diseases, including hepatic ischemia-reperfusion injury (IRI), alcohol-induced liver injury, Con A-induced liver injury, nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). IRF1 is involved in the progression of hepatic IRI through signaling pathways such as PIAS1/NFATc1/HDAC1/IRF1/p38 MAPK and IRF1/JNK.