Hydrogen decreases susceptibility to AngII-induced atrial fibrillation and atrial fibrosis via the NOX4/ROS/NLRP3 and TGF-β1/Smad2/3 signaling pathways.

Atrial fibrillation (AF) represents the commonly occurring cardiac arrhythmia and the main factor leading to stroke and heart failure. Hydrogen (H2) is a gaseous signaling molecule that has the effects of anti-inflammation and antioxidation. Our study provides evidence that hydrogen decreases susceptibility to AngII-mediated AF together with atrial fibrosis.

PEAR1 Promotes Myoblast Proliferation Through Notch Signaling Pathway.

PEAR1, also known as platelet endothelial aggregation receptor 1, is known to play a crucial role in the migration and differentiation of muscle satellite cells (MuSCs). However, its specific effects on skeletal muscle development and regeneration require further exploration. In this study, the expression of PEAR1; the proliferation marker proteins of Pax7, CCNB1, and PCNA; and the key molecules of N1-ICD, N2-ICD, and Hes1 were all increased gradually during the process of C2C12 cell proliferation.

Efficacy and Safety of SHR8554 on Postoperative Pain in Subjects with Moderate to Severe Acute Pain Following Orthopedic Surgery: A Multicenter, Randomized, Double-blind, Dose-explored, Active-controlled, Phase II/III Clinical Trial.

Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine.

Integration of metabolomics methodologies for the development of predictive models for mortality risk in elderly patients with severe COVID-19.

Background: The rapid evolution of the COVID-19 pandemic and subsequent global immunization efforts have rendered early metabolomics studies potentially outdated, as they primarily involved non-exposed, non-vaccinated populations. This paper presents a predictive model developed from up-to-date metabolomics data integrated with clinical data to estimate early mortality risk in critically ill COVID-19 patients. Our study addresses the critical gap in current research by utilizing current patient samples, providing fresh insights into the pathophysiology of the disease in a partially immunized global population.

hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination.

Hypoxic-ischemic brain injury (HIBD) is a major cause of neonatal mortality and long-term neurological deficits, with limited treatment options. Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) have shown promise in neuroprotection, but the mechanisms remain unclear. This study explores how hUC-MSC-EVs protect neonatal rats from HIBD.

LncRNA TMC3-AS1 silence alleviates lipopolysaccharide-induced acute kidney injury by suppressing Wnt5a-mediated autophagy and pyroptosis pathway.

Long non-coding RNA TMC3-AS1 is identified to be upregulated by lipopolysaccharide (LPS) in inflammatory disease, but its role in acute kidney injury (AKI) is almost unknown. The study investigated the involvement of TMC3-AS1 in LPS-induced AKI and its downstream molecular regulatory mechanism. Our data suggested that knocking down TMC3-AS1 significantly reduced renal dysfunction, tissue inflammation and tissue damage in LPS-induced mice, and promoted cell viability, inhibited inflammation, apoptosis and necrosis in LPS-stimulated human renal tubular epithelial cells HK2.

HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis.

Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2) foamy macrophages.

Brg1 and RUNX1 synergy in regulating TRPM4 channel in mouse cardiomyocytes.

Background: Transient Receptor Potential Melastatin 4 (TRPM4), a non-selective cation channel, plays a critical role in cardiac conduction abnormalities. Brg1, an ATP-dependent chromatin remodeler, is essential for regulating gene expression in both heart development and disease. Our previous studies demonstrated Brg1 impacted on cardiac sodium/potassium channels and electrophysiological stability, its influence on TRPM4 expression and function remained unexplored.

Finite element analysis of a novel patellar fracture fixation method.

Background: Patellar fractures present challenges in treatment, with traditional methods often leading to complications such as loss of reduction and implant failure. This study aimed to compare a novel suture fixation technique with the traditional tension band method using finite element analysis.

Methods: CT images of a healthy 35-year-old male were used to construct 3D patellar models.

Platelet-mimicking nanoparticles loaded with diallyl trisulfide for Mitigating Myocardial Ischemia-Reperfusion Injury in rats.

Hydrogen sulfide (HS) shows promise in treating myocardial ischemia-reperfusion injury (MIRI), but the challenge of controlled and sustained release hinders its clinical utility. In this study, we developed a platelet membrane-encapsulated mesoporous silica nanoparticle loaded with the HS donor diallyl trisulfide (PM-MSN-DATS). PM-MSN-DATS demonstrated optimal encapsulation efficiency and drug-loading content.

Enhancing medical education with chatbots: a randomized controlled trial on standardized patients for colorectal cancer.

Introduction: Combination of Standardized Patient (SP) and Case Based Learning (CBL) is a common method in medical education, but traditional SP (TSP) may not be conducive to students' mastery of basic medical knowledge and the cultivation of clinical thinking. Therefore, it is necessary to innovate SP to optimize SP combined with CBL teaching method.

Objective: This study aims to explore the effectiveness of a chatbot utilizing standardized patients based on CBL (CSP-CBL) for colorectal cancer education.

ASPH dysregulates cell death and induces chemoresistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is resistant to multiple conventional drugs including sorafenib, leading to poor prognosis. Inducing cell death has been inextricably pursued in therapeutics, although targeted therapy and immunotherapy have made very limited progress. ASPH (Aspartate β-hydroxylase) can be breakthrough in meeting this unmet clinical need.

Involvement of CXCL12/CXCR4 in CB2 receptor agonist-attenuated morphine tolerance in Walker 256 tumor-bearing rats with cancer pain.

While low-dose cannabinoid 2 (CB2) receptor agonists attenuate morphine tolerance in cancer pain models, chemokine ligand 12 (CXCL12)/chemokine receptor 4 (CXCR4) expression induces morphine tolerance. Whether CB2 receptor agonists attenuate morphine tolerance by modulating CXCL12/CXCR4 signaling or whether CXCL12/CXCR4 signaling affects the mu opioid receptor (MOR) in the development of morphine tolerance in cancer pain remains unclear. In this study, we investigated the attenuation of morphine tolerance by a non-analgesic dose of the CB2 receptor agonist AM1241, focusing specifically on the modulation of CXCL12/CXCR4 signaling and its effect on the MOR.

Integrating bioinformatics and machine learning to uncover lncRNA LINC00269 as a key regulator in Parkinson's disease via pyroptosis pathways.

Background: Pyroptosis, a specific type of programmed cell death, which has become a significant factor to Parkinson's disease (PD). Concurrently, long non-coding RNAs (lncRNAs) have garnered attention for their regulatory roles in neurodegenerative disorders. This study was designed to ascertain the key lncRNAs in pyroptosis pathways of PD and elucidate their regulatory mechanisms.

Impact of Treatment Strategies on Survival and Within Multivariate Predictive Model for Renal Cell Carcinoma Based on the SEER Database: A Retrospective Cohort Study.

Background: This project aims to shed light on how various treatment approaches affect RCC patients' chances of survival and create a prediction model for them.

Methods: Data from the Surveillance, Epidemiology, and End Results database were used in this investigation. OS and RCSS after radiation, chemotherapy, and surgery were investigated using the Kaplan-Meier approach.

Changes in the Structure, Function, and Fat Content of the Heart in Patients with Obesity After Bariatric Surgery-A Prospective Magnetic Resonance Imaging Study.

Background: Changes in myocardial fat in addition to changes in cardiac structure and function have not been accurately evaluated in obese patients following surgery.

Materials And Methods: Forty-four obese patients who underwent sleeve gastrectomy and completed preoperative and postoperative cardiac magnetic resonance imaging (CMR) before surgery and at 1, 3, and 6 months after surgery were enrolled, and their clinical and laboratory data were collected. The differences and correlations between clinical, laboratory, and CMR parameters between the preoperative and postoperative groups were analysed.

A biweekly DPP-4 inhibitor cofrogliptin monotherapy in Chinese patients with impaired glucose tolerance: A phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.

Aims: To assess the efficacy and safety of cofrogliptin for impaired glucose tolerance (IGT).

Methods: In this multicenter, double-blind, placebo-controlled phase 2 trial, IGT patients were randomized 1:1:1 to receive cofrogliptin 10 mg, cofrogliptin 25 mg or placebo once biweekly. The primary endpoint was the change from baseline in glucose total AUC during meal tolerance test (MTT) at week 12.

The High-Quality Genome Sequencing and Analysis of Red Raspberry ( L.).

Red raspberry ( L.), which is an important nutritional source for human health, belongs to fruit crops of the Rosaceae family. Here, we used Pacific Biosciences single-molecule real-time (SMRT) sequencing and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to assemble genomes and reported a high-quality L.

Exploring factors influencing the quality of life in diabetes: a network analysis-based study.

Objective: The purpose of this study was to explore the key pathways leading to low quality of life in type 2 diabetes patients by means of network analysis, so as to provide the possibility of effective interventions.

Methods: The study involved 1,011 adult type 2 diabetes patients from a tertiary hospital in Harbin. Data was collected through questionnaires, and network analysis was performed using R software to assess the centrality and predictability of each node.

Exploratory study on the enhancement of O-RADS application effectiveness for novice ultrasonographers via deep learning.

Purpose: The study aimed to create a deep convolutional neural network (DCNN) model based on ConvNeXt-Tiny to identify classic benign lesions (CBL) from other lesions (OL) within the Ovarian-Adnexal Reporting and Data System (O-RADS), enhancing the system's utility for novice ultrasonographers.

Methods: Two sets of sonographic images of pathologically confirmed adnexal lesions were retrospectively collected [development dataset (DD) and independent test dataset (ITD)]. The ConvNeXt-Tiny model, optimized through transfer learning, was trained on the DD using the original images directly and after automatic lesion segmentation by a U-Net model.

Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice.

Understanding the intricate cellular interactions involved in bone restoration is crucial for developing effective strategies to promote bone healing and mitigate conditions such as osteoporosis and fractures. Here, we provide compelling evidence supporting the anabolic effects of a pharmacological Pyk2 inhibitor (Pyk2-Inh) in promoting bone restoration. In vitro, Pyk2 signaling inhibition markedly enhances alkaline phosphatase (ALP) activity, a hallmark of osteoblast differentiation, through activation of canonical Wnt/β-catenin signaling.

Identification of Macrophage-Associated Novel Drug Targets in Atherosclerosis Based on Integrated Transcriptome Features.

Background: This study explores the pathological mechanisms of atherosclerosis (AS), focusing on the role of macrophages in its formation and development, and potential therapeutic targets.

Methods: The heterogeneity of the AS single-cell data set GSE131778 was analyzed using Seurat. Tissue sequencing data GSE28829 and GSE43292 were analyzed for immune cell abundance using CIBERSORT.

Micropapillary structure: A natural tumor collective invasion model with enhanced stem-like properties.

Cancer stem cells aggregate to form clusters, which have enhanced stem-like properties and metastasis potential. However, the molecular mechanisms underlying the formation of cancer stem cell cluster-like structures with acquisition of stronger invasion and metastasis abilities remain unclear. Micropapillary carcinoma (MPC) is a subpopulation of small, merulioid, inverted, nonfibrous vascular clusters floating in the stroma present in a range of solid malignant tumors and characterized by frequent vascular/lymphatic vessel invasion and lymph node metastasis.