The triglyceride-glucose (TyG) index, a readily accessible surrogate biomarker for insulin resistance and metabolic health, has been extensively investigated across various ethnic populations. The critical role of physical activity (PA) in enhancing insulin sensitivity has been corroborated by numerous studies. Nonetheless, the relationship between different patterns of PA and the TyG index remains ambiguous.
View Article and Find Full Text PDFThe structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohn's disease (CD) model (Tnf ), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host's immune susceptibility to drive region-specific disease. We identified , an intracellular bacterium and murine counterpart to the human sexually transmitted , as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD.
View Article and Find Full Text PDFProtein arginine methyltransferase 5 (PRMT5), which catalyzes the symmetric dimethylation of arginine residues on target proteins, plays a critical role in gene expression regulation, RNA processing, and signal transduction. Aberrant PRMT5 activity has been implicated in cancers and other diseases, making it a potential therapeutic target. Here, we report the discovery of a methylthioadenosine (MTA) cooperative PRMT5 inhibitor.
View Article and Find Full Text PDFImmune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury.
View Article and Find Full Text PDFIntervertebral disc (IVD) degeneration represents a significant cause of chronic back pain and disability, with a substantial impact on the quality of life. Conventional therapeutic modalities frequently address the symptoms rather than the underlying etiology, underscoring the necessity for regenerative therapies that restore disc function. Polysaccharide-based materials, such as hyaluronic acid, alginate, chitosan, and chondroitin sulfate, have emerged as promising candidates for intervertebral disc degeneration (IVDD) therapy due to their biocompatibility, biodegradability, and ability to mimic the native extracellular matrix (ECM) of the nucleus pulposus (NP).
View Article and Find Full Text PDFDespite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal-organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnO/(A/R)TiO (MTO) in situ from MIL-125-NH (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation.
View Article and Find Full Text PDFThe role of oxidative stress metabolism during hepatocellular carcinoma (HCC) formation potentially allows for positron emission tomography (PET) imaging of oxidative stress activity for early and precise HCC detection. However, there is currently limited data available on oxidative-stress-related PET imaging for longitudinal monitoring of the pathophysiological changes during HCC formation. This work aimed to explore PET-based longitudinal monitoring of oxidative stress metabolism and determine the sensitivity of [18F]-5-fluoroaminosuberic acid ([18F]FASu) for assessing pathophysiological processes in diethylnitrosamine (DEN) induced rat HCC.
View Article and Find Full Text PDFAstrocytes are abundant glial cells in the central nervous system (CNS) that play important roles in brain injury following cardiac arrest (CA). Following brain ischemia, astrocytes trigger endogenous neuroprotective mechanisms, such as fatty acid transport. Lipid droplets (LDs) are cellular structures involved in neutral lipid storage and play essential roles in many biological processes.
View Article and Find Full Text PDFGlioblastoma (GBM) is a lethal disease with a poor prognosis due to its strong infiltration, which makes it difficult to remove completely. In this study, an implantable, modulus-tunable, and ultrasound-powered MXene/PVA hydrogel-based tumor treatment device (UP-MPH-TTD), which generates specific electromagnetic alternating fields that disrupt the mitosis of cancer cells without adversely affecting normal neurons is developed. The MXene/PVA hydrogel is used to form a tumor treatment field due to its high biocompatibility, excellent flexibility, and high conductivity, which improves ultrasonic electrical conversion efficiency and significantly reduces the size of the equipment.
View Article and Find Full Text PDFTissue factor (TF) initiates local blood clotting and infiltration of tumor-associated macrophages, leading to tumor recurrence post-local ablation. Our study addressed inefficient cancer cell killing and immunosuppressive macrophage infiltration after percutaneous ethanol injection (PEI) in hepatocellular carcinoma (HCC). We evaluated the feasibility of F-radiolabeled polypeptide TF-targeted radioligand (tTF) as a PET tracer for assessing tumor response.
View Article and Find Full Text PDFHypoxia and reactive oxygen species (ROS) overaccumulation cause persistent oxidative stress and impair intrinsic regenerative potential upon tissue injury. For local tissue injury with hypoxia, such as bone fracture and defects, a localized-sufficient oxygen supply is highly desirable but remains challenging. Therefore, to explore a strategy and its intrinsic mechanism for supplying oxygen locally and remodeling the regenerative microenvironment, an innovative oxygenating hydrogel microsphere system with sustained oxygenation and antioxidant properties is introduced by loading CaO@SiO@PDA (CSP) nanoparticles.
View Article and Find Full Text PDFIron is an essential element for plants. Iron uptake by plants is highly regulated, but the underlying mechanism is poorly understood. Using a truncated fragment of the iron deficiency-responsive bHLH100 gene promoter, we screened the Arabidopsis transcription factor yeast one-hybrid (Y1H) library and identified the DOF family protein, OBP3, as a crucial component of the iron deficiency-signaling pathway.
View Article and Find Full Text PDFTemporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Undifferentiated intestinal stem cells (ISCs) are crucial for maintaining homeostasis and resolving injury. Lgr5+ cells in the crypt base constantly divide, pushing daughter cells upward along the crypt axis where they differentiate into specialized cell types. Coordinated execution of complex transcriptional programs is necessary to allow for the maintenance of undifferentiated stem cells while permitting differentiation of the wide array of intestinal cells necessary for homeostasis.
View Article and Find Full Text PDFThe retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes.
View Article and Find Full Text PDFAlthough lipid metabolism in fetal livers under intrauterine growth restriction (IUGR) conditions has been widely studied, the implications of maternal undernutrition on fetal hepatic lipid metabolism, lipotoxic injury, and abnormal development remain largely unknown. Therefore, this study investigated the effects of maternal undernutrition on disordered hepatic lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses using transcriptome analysis. Seventeen singleton ewes were randomly divided into three groups on day 90 of pregnancy: a control group (CG; 0.
View Article and Find Full Text PDFFloating photovoltaics (FPV) are an emerging renewable energy technology. Although they have received extensive attention in recent years, understanding of their environmental impacts is limited. To address this knowledge gap, we measured water temperature and meteorological parameters for six months under FPV arrays and in the control open water site and constructed a numerical model reflecting the water energy balance.
View Article and Find Full Text PDF