Nucleobase analogue (NBA) drugs, such as 5-fluorouracil (5-FU), are effective chemotherapeutics, but their clinical use is limited by severe side effects. Compelling evidence suggests that the use of S-methyl-5'-thioadenosine (MTA) can selectively reduce NBA toxicity on normal tissues while maintaining the efficacy of NBAs on methylthioadenosine phosphorylase (MTAP)-deficient cancers. However, we found that MTA induced hypothermia at its effective dose, limiting its translational potential.
View Article and Find Full Text PDFAdult stem cell therapy holds great promise for treating decompensated liver cirrhosis on the basis of animal studies, despite uncertainty about its clinical therapeutic efficacy and unclear underlying mechanisms. Here, we investigated the role of follistatin-like 1 (FSTL1), a profibrotic and proinflammatory matricellular protein, in inflammation-related heterogeneity in stem cell therapy. Our results showed that a high level of circulating FSTL1 is significantly correlated with therapeutic response in patients with cirrhosis.
View Article and Find Full Text PDFHeterogeneous oxidation of SO by NO on aerosols has recently been found to be one of the major formation pathways of sulfate in the polluted troposphere, but the chemical mechanisms and kinetics remain uncertain. By combining lab experiments, theoretical chemistry calculations, and field measurements, here we show that the SO oxidation by NO is critically dependent on anions at the air-aerosol aqueous interface. The reaction rate of NO with (1.
View Article and Find Full Text PDFAim: To evaluate the relapse rate in children with tic disorders following medication withdrawal and to identify the risk factors associated with tic recurrence.
Methods: This prospective cohort study enrolled 387 children who had recently discontinued medication and had been tic-free for at least 3 months. Participants were followed monthly for 12 months to monitor tic relapse.
As important methane hydrate storage sites, cold seep areas are threatened by microplastics (MPs) contamination. To assess the environmental impact of MPs on microbial communities in cold seep sediments, an incubation experiment was conducted using cold seep sediment amended with different concentration of polyamide (PA), polyethylene (PE), polyethylene terephthalate (PET), and polypropylene (PP) microplastics. The results showed that the different type and concentration of MPs significantly altered the prokaryotic community structures.
View Article and Find Full Text PDFIschemic stroke (IS) continues to be a major public health concern and is characterized by significantly high mortality and disabling rates. Inhibiting nerve cells death and enhancing the repair of ischemic tissue are important treatment concepts for IS. Currently, the mainstream treatment strategies mainly focus on short-term care, which underscores the urgent need for novel therapeutic strategies for long-term care.
View Article and Find Full Text PDFArch Pharm (Weinheim)
February 2025
Cardiovascular diseases (CVDs), the leading cause of human death worldwide, are diseases that affect the heart and blood vessels and include arrhythmias, coronary atherosclerotic heart disease, hypertension, and so on. Resveratrol (RSV) is a natural nonflavonoid phenolic compound with antioxidant, anti-inflammatory, anticancer, and cardiovascular protection functions. RSV has shown significant protective effects against CVD.
View Article and Find Full Text PDFPlatelets, traditionally regarded as passive mediators of hemostasis, are now recognized as pivotal regulators in the tumor microenvironment, establishing metabolic feedback loops with tumor and immune cells. Tumor-derived signals trigger platelet activation, which induces rapid metabolic reprogramming, particularly glycolysis, to support activation-dependent functions such as granule secretion, morphological changes, and aggregation. Beyond self-regulation, platelets influence the metabolic processes of adjacent cells.
View Article and Find Full Text PDFFour previously undescribed cyclic peptides, reniochpeptins A-D (1-4), were isolated from the marine sponge Reniochalina sp. Their structures were elucidated through comprehensive spectroscopic analyses and a modified advanced Marfey's method. This method utilized ultra-high-performance liquid chromatography coupled with tandem multiple reaction monitoring mass spectrometry, employing a CORTECS T column to achieve simultaneous separation of derivatized -Leu, -Ile, -allo-Ile, -Leu, -Ile, and -allo-Ile within 25 min in a single analytical run.
View Article and Find Full Text PDF: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.
View Article and Find Full Text PDFThe massive production and widespread use of plastics have resulted in a growing marine plastic pollution problem. Cold seep ecosystems are maintained by microorganisms related to nitrogen and carbon cycling that occur in deep-sea areas, where cold hydrocarbon-rich water seeps from the ocean floor. Little is known about plastic pollution in this ecosystem.
View Article and Find Full Text PDFMethane leaking from the deep seabed is a primary source of carbon and energy for various microorganisms, sustaining the evolution and productivity of cold seep ecosystems. However, the dynamics of methane hydrate formation under methane seepage conditions and potential impacts on the evolution of cold seep ecosystems remain unclear. This study investigated the dynamic formation characteristics of gas hydrates within cold seep sediments by simulating the methane leakage process.
View Article and Find Full Text PDFThe research on the combination of starch and galactomannans (GM) with dry heat treatment (DHT) is currently insufficient, which hinders the starch application. In this study, the impacts of dry heat treatment and GM complex on the structural, gelatinization properties, and digestibility of pea starch (PS) were investigated. The gelatinization viscosity and gel hardness of dry heated-PS were decreased.
View Article and Find Full Text PDFBackground: The inflammatory response is associated with cardiac repair and ventricular remodeling after myocardial infarction (MI). The key inflammation regulatory factor thymic stromal lymphopoietin (TSLP) plays a critical role in various diseases. However, its role in cardiac repair after MI remains uncertain.
View Article and Find Full Text PDFThe deep hydrocarbon fluids discharged into the water column at cold seeps create diverse and heterogeneous habitats on the seafloor. Symbiosis is essential for the survival of marine life in extreme deep-sea environments. Although the symbiotic relationship between chemoautotrophic bacteria and invertebrates has been reported, our understanding of these host-microbe interactions under heterogeneous environment remains limited.
View Article and Find Full Text PDFCellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets.
View Article and Find Full Text PDFThe synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma (GBM) patients. The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein, facilitating tumor immune evasion. This study presents a pH-adapted excited state intramolecular proton transfer (ESIPT)-isomerized β-ketoamide-based covalent organic framework (COF) nanoplatform (denoted as OT@COF-RVG).
View Article and Find Full Text PDFMarine microplastics pose a significant threat to ecosystems, and deep-sea regions serve as critical sinks for these pollutants. Among these regions, cold seeps harbor relatively high concentrations of microplastics. However, research on the aging of microplastics under low-temperature, dark, methane-abundant, and high-pressure conditions remains limited.
View Article and Find Full Text PDFBackground: The occurrence and development of ST-segment elevation myocardial infarction (STEMI) are accompanied by coronary atherothrombosis and occlusion, and immune responses play prominent roles in their pathogeneses. However, the causes of atherothrombosis remain elusive, and a comprehensive study of T cell-mediated immune responses in coronary thrombi from STEMI patients is lacking.
Objectives: The aim of this study was to determine the heterogeneity and clonality of CD3 T lymphocytes in STEMI patients at the single-cell level.
Markov State Models (MSMs) have been widely applied to understand protein folding mechanisms by predicting long time scale dynamics from ensembles of short molecular simulations. Most MSM estimators enforce detailed balance, assuming that trajectory data are sampled at an equilibrium. This is rarely the case for ab initio folding studies, however, and as a result, MSMs can severely underestimate protein folding stabilities from such data.
View Article and Find Full Text PDFBackground: Traditional Chinese medicine (TCM) is used to treat pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment.
Method: We retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023.