miR-21 regulates autophagy and apoptosis of ectopic endometrial stromal cells of adenomyosis via PI3K/ AKT/ mTOR pathway.

Adenomyosis (AM) is a common and challenging disease in gynecological clinics, which adversely affects women's physical and mental health. Despite the growing number of studies, the mechanisms associated with the growth of the lesion are poorly understood. Studies show that abnormal proliferation, apoptosis, and migration in ectopic endometrial stromal cells (EESc) of AM may contribute to the development and progression of AM.

A Serial MRI-based Deep Learning Model to Predict Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose To develop and evaluate a deep learning-based prognostic model for predicting survival in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) using serial MRI before and after induction chemotherapy (IC). Materials and Methods This multicenter retrospective study included 1039 patients with LA-NPC (779 male and 260 female patients; mean age, 44 years ± 11 [SD]) diagnosed between December 2011 and January 2016. A radiomics-clinical prognostic model (model RC) was developed using pre- and post-IC MRI acquisitions and other clinical factors using graph convolutional neural networks.

Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.

Background: Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.

Comparative Effectiveness of Cell-Based Versus Egg-Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-2023 Season Among Adults 18-64 Years.

This retrospective cohort study evaluated the comparative vaccine effectiveness (cVE) of licensed standard-dose cell-based versus egg-based influenza vaccines in preventing influenza hospitalization among adults 18-64 years during the 2022-2023 season. The cohort included eligible Kaiser Permanente Southern California members who received ≥ 1 dose of influenza vaccine (n = 848,334). The adjusted cVE against influenza hospitalization was -10.

ATP2A3 in Primary Aldosteronism: Machine Learning-Based Discovery and Functional Validation.

Background: Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism that can lead to cardiovascular complications if left untreated. Machine learning-based bioinformatics approaches have emerged as powerful tools for identifying potential disease markers, gaining widespread recognition in biomedical research. We aimed to use machine learning to discover novel biomarkers of APAs to identify new pathophysiological mechanisms.

A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.

is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

Pathophysiology of carotid atherosclerosis: Calcification, intraplaque haemorrhage and pulse pressure as key players.

Purpose: Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH.

Methods: We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

Background: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions.

Methods: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods.

Forming, Enzyme-Responsive Peptoid-Peptide Hydrogels: An Advanced Long-Acting Injectable Drug Delivery System.

Long-acting drug delivery systems are promising platforms to improve patient adherence to medication by delivering drugs over sustained periods and removing the need for patients to comply with oral regimens. This research paper provides a proof-of-concept for the development of a new optimized forming injectable depot based on a tetrabenzylamine-tetraglycine-d-lysine-O-phospho-d-tyrosine peptoid-D-peptide formulation ((Phe)GGGGk(AZT)y(p)-OH). The chemical versatility of the peptoid-peptide motif allows low-molecular-weight drugs to be precisely and covalently conjugated.

Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K-AKT signaling in rheumatoid arthritis.

Background: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA).

Methods: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University.

Matrine inhibits invasion and migration of gallbladder cancer via regulating the PI3K/AKT signaling pathway.

Gallbladder cancer (GBC) is a common malignant cancer in the biliary system, which poses a serious threat to human health. It is urgent to explore ideal drugs for the treatment of GBC. Matrine is the main active ingredient of Sophora flavescentis, with a wide range of biological activities encompassing anti-inflammatory, antiviral, immunomodulatory, and anti-tumor.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.

Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).

TXNIP Regulates NLRP3 Inflammasome-Induced Pyroptosis Related to Aging via cAMP/PKA and PI3K/Akt Signaling Pathways.

Aging is an inevitable natural process with time-dependent dysfunction and the occurrence of various diseases, which impose heavy burdens on individuals, families, and society. It has been reported that NLRP3 inflammasome-induced pyroptosis contributes significantly to age-related diseases and aging, while TXNIP is suggested to be involved in regulating pyroptosis mediated by NLRP3. However, the mechanism between TXNIP and NLRP3 inflammasome is still unclear.

CTA-Based Radiomics and Area Change Rate Predict Infrarenal Abdominal Aortic Aneurysms Patients Events: A Multicenter Study.

Rationale And Objectives: Clinical assessment of abdominal aortic aneurysm (AAA) intervention and rupture risk relies primarily on maximum diameter, but studies have shown that sole dependence on diameter has limitations. CTA-based radiomics, aneurysm and lumen area change rates (AACR, LACR) are measured to predict potential AAA events.

Materials And Methods: Between January 2017 and November 2022, 260 AAA patients from four centers who underwent two preoperative CTA examinations were included in this retrospective study.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear.

Short peptides derived from pigment epithelium-derived factor attenuate retinal ischemia reperfusion injury through inhibition of apoptosis and inflammatory response in rats.

Pigment epithelium-derived factor (PEDF) is widely recognized as a neuroprotective factor expressed in the retina and has shown therapeutic potential in several retinal diseases. Our study aimed to identify the neuroprotective fragment in PEDF and investigate its protective activity in retinas under ischemia-reperfusion (IR) condition. We synthesized a series of shorter synthetic peptides, 6-mer (Ser93-Gln98) and its d-form variant (6 dS) derived from the 44-mer (Val78-Thr121; a PEDF neurotrophic fragment), to determine their cytoprotective activity in IR injury, which was induced in rat retinas by injection of saline into the anterior chamber to increase the intraocular pressure (IOP) followed by reperfusion.

Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Objective: We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes.

Research Design And Methods: Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0-10.