Modeling substrate efflux in human P-glycoprotein at the atomic level.

Human P-glycoprotein (hP-gp) is an ATP-binding cassette (ABC) exporter that actively extrudes a wide range of xenobiotics from the cell, thus limiting drug delivery and contributing to multidrug resistance (MDR) in cancers. Recent structural studies have provided insights into how hP-gp binds diverse compounds, but how they are translocated through the membrane remains poorly understood at the atomic level. In this work, we used steered molecular dynamics (SMD) simulations to investigate the molecular mechanism of how hP-gp expels structurally different compounds and which molecular features favor this efflux step.

Exosome tropism and various pathways in lung cancer metastasis.

Lung cancer, characterized by its high morbidity and mortality rates, has the capability to metastasize to various organs, thereby amplifying its detrimental impact and fatality. The metastasis of lung cancer is a complex biological phenomenon involving numerous physiological transformations. Exosomes, small membranous vesicles enriched with biologically active components, are pivotal in mediating intercellular communication and regulating physiological functions due to their specificity and stability.

Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.

The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in cancer treatment over recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone of tumor immunotherapy, have emerged as one of the most promising advancements in cancer treatment.

Inhibition of SLC3A2 Deletion-Mediated Ferroptosis by Bone Marrow Stromal Cells to Alleviate Inflammation and Fibrosis in Diabetic Kidney Disease.

Renal fibrosis and inflammatory infiltration are common pathological features of diabetic kidney disease (DKD). Bone marrow mesenchymal stem cells (BMSCs) are recognized for their anti-fibrotic and anti-inflammatory properties. The objective of this study was to assess the effects of BMSCs on DKD and elucidate their potential mechanisms of action.

Efficacy of sorafenib combined with transarterial chemoembolization in the treatment of advanced hepatocellular carcinoma: A meta-analysis.

Background: The combination of sorafenib with transarterial chemoembolization (TACE) is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma (HCC).

Aim: To evaluate the efficacy of this combined treatment strategy in enhancing overall survival (OS) and progression-free survival (PFS) compared to monotherapies.

Methods: A systematic review was conducted following the PRISMA guidelines.

Changes in body composition during acute exposure to high altitude is related to acute mountain sickness.

Background: Acute hypoxia exposure leads to a high incidence of acute mountain sickness (AMS) and changes in body composition, while the relationship between body composition and AMS remains unclear. We designed this study to detect the body composition and discern its relationship with AMS.

Methods: Eighty-one subjects were transported from the plain (300 m) to the plateau (3680 m).

Mixed fleet-based two-echelon vehicle routing optimization for cold chain logistics with diverse recharging strategies.

The expansion of cold chain logistics necessitates a substantial fleet of fuel-refrigerated trucks, which presents environmental challenges. Electric vehicles (EVs) offer an environmentally friendly solution for low-carbon development despite the issue of range anxiety. Diverging from the conventional two-echelon distribution structure, this paper explores alternative recharging strategies and introduces an innovative scheme: employing fuel vehicles in suburban areas and EVs in urban central zones.

Global Epidemiology of Early-Onset Aortic Aneurysm: Temporal Trends, Risk Factors, and Future Burden Projections.

Background: Aortic aneurysm has a subtle onset, high rupture mortality, rapid progression in younger individuals, and increasing annual mortality rates. Our study aimed to estimate the global burden and trends of early-onset aortic aneurysm from 1990 to 2021.

Methods: Participants aged 15-39 years from 204 countries and regions (Global Burdern of Disease, GBD) from 1990 to 2021.

Divergent MYB paralogs determine spatial distribution of linalool mediated by JA and DNA demethylation participating in aroma formation and cold tolerance of tea plants.

Linalool not only is one of characteristic flavour volatiles of tea, contributing to floral aroma, but also a kind of defensive compounds, playing essential roles in resistance against biotic/abiotic stresses. Although the linalool synthases have been identified, much is unknown about the regulation mechanism in tea plants. We identified two pairs of MYB paralogs as linalool biosynthesis activators, in which one pair (CsMYB148/CsMYB193) specifically expressed in flowers, and another (CsMYB68/CsMYB147) highly expressed in flowers, leaves, fruits and roots.

Minimally invasive lateral, posterior, and posterolateral sacroiliac joint fusion for low back pain: a systematic review and meta-analysis.

Objective: This study aimed to evaluate the therapeutic effects of minimally invasive lateral, posterior, and posterolateral sacroiliac joint fusion for low back pain through a meta-analysis.

Methods: The PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov databases were comprehensively searched for studies up to 31 August 2024.

Modulation of arterial wall remodeling by mechanical stress: Focus on abdominal aortic aneurysm.

The rupture of an abdominal aortic aneurysm (AAA) poses a significant threat, with a high mortality rate, and the mechanical stability of the arterial wall determines both its growth and potential for rupture. Owing to extracellular matrix (ECM) degradation, wall-resident cells are subjected to an aberrant mechanical stress environment. In response to stress, the cellular mechanical signaling pathway is activated, initiating the remodeling of the arterial wall to restore stability.

Therapeutic Effects of Natural Products in the Treatment of Chronic Diseases: The Role in Regulating KEAP1-NRF2 Pathway.

Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1-transcription factor NF-E2 p45-related factor 2 (KEAP1-NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1-NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer.

Identification of RAD51AP1 as a key gene in hepatitis B virus-associated hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a significant global health concern, with chronic hepatitis B virus (HBV) infection being a major contributor. Understanding the mechanisms of HBV-associated HCC is crucial to improving the prognosis and developing effective treatments.

Methods: HBV-associated HCC datasets (GSE19665, GSE121248, GSE55092, GSE94660, and TCGA-LIHC) acquired from public databases were mined to identify key driver genes by differentially expressed gene analysis, weighted gene co-expression network analysis (WGCNA), followed by protein-protein interaction network analysis, Lasso-Cox regression analysis, and randomforestSRC algorithm.

Crystalline, Porous Figure-Eight-Noded Covalent Organic Frameworks.

Figure-eight macrocycles represent a fascinating class of π-conjugated units characterized by unique aesthetics and non-contact molecular crossing at the center. Despite progress in synthesis over the past century, research into inorganic, organic, and polymeric figure-eight materials remains in its infancy. Here we report the first examples of figure-eight covalent organic frameworks by condensing figure-eight knots to create extended porous figure-eight π architectures.

Geriatric nursing competence of clinical nursing staff at different hospital levels in Chongqing, China: A cross-sectional study.

Objectives: This study aimed to survey the geriatric nursing competencies of clinical nursing staff in Chongqing City, China, and provide suggestions to enhance these competencies.

Methods: This study was conducted in 204 hospitals in Southwest China from December 24, 2022 to January 7, 2023. The "Geriatric Nursing Competence of Clinical Nurse Investigation Tool" was used to explore factors that influence geriatric nurses' competencies via stratified sampling.

The feasibility and short-term safety of single-site hysterectomy: a retrospective cohort study of a novel robotic platform.

Background: Robotic-assisted laparoscopic single-site hysterectomy is popular among patients and surgeons due to good cosmetic outcomes and fast recovery. However, questions remain such as loss of triangulation and instrument collision. Our aim is to test the feasibility and safety of a purpose-designed single-site robotic surgical platform mainly in hysterectomies.

New Insights into the Pathogenesis of Alcoholic Liver Disease Based on Global Research.

Background And Aims: Alcoholic liver disease (ALD) is the leading cause of death among alcohol-related diseases, yet its pathogenesis remains incompletely understood. This article employs data mining methods to conduct an indepth study of articles on ALD published in the past three decades, aiming to elucidate the pathogenesis of ALD.

Methods: Firstly, articles related to the pathogenesis of ALD were retrieved from the Web of Science (WOS) database.

Targeting lipid metabolism in regulatory T cells for enhancing cancer immunotherapy.

As immunosuppressive cells, Regulatory T cells (Tregs) exert their influence on tumor immune escape within the tumor microenvironment (TME) by effectively suppressing the activity of other immune cells, thereby significantly impeding the anti-tumor immune response. In recent years, the metabolic characteristics of Tregs have become a focus of research, especially the important role of lipid metabolism in maintaining the function of Tregs. Consequently, targeted interventions aimed at modulating lipid metabolism in Tregs have been recognized as an innovative and promising approach to enhance the effectiveness of tumor immunotherapy.

Inhibition of Abdominal Aortic Aneurysm Progression Through the CXCL12/CXCR4 Axis via MiR206-3p Sponge.

Notably, the C-X-C Motif Chemokine Ligand 12/C-X-C Chemokine Receptor Type 4 (CXCL12/CXCR4) signalling pathway's activation is markedly increased in a mouse model of abdominal aortic aneurysms (AAA). Nonetheless, the precise contribution of this pathway to AAA development remains to be elucidated. The AAA mouse model was induced by local incubation with elastase and oral administration of β-aminopropionitrile.