Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic abstract
Objective Emerging evidence has indicated that excessive reactive oxygen species (ROS) have detrimental effects on osteoarthritis (OA). This study aimed to elucidate the effects of melatonin (MT), an antioxidant indolamine secreted from the pineal gland, on chondrocyte senescence and cartilage degeneration, thereby clarifying the underlying mechanisms of ROS-induced OA pathogenesis. Design Hydrogen peroxide (H2O2) was used to induce oxidative stress in rat chondrocytes. ROS levels were evaluated using cytometry and immunofluorescence. Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay. Western blotting and qPCR (Quantiative Real-Time Polymerase Chain Reaction) were used to examine apoptosis and autophagy. For in vivo experiments, male Sprague-Dawley rats were randomly divided into a sham-operated group, DMM (destabilization of the medial meniscus) surgery group, and surgery groups that received melatonin. Knee joints were collected and stained for histological analysis. Results The data demonstrated that melatonin treatment significantly suppressed H2O2-induced matrix degradation and apoptosis, and maintained mitochondrial redox homeostasis. In addition, an enhancement of autophagic flux was observed through western blotting. These findings corresponded with activation of the AMPK/Foxo3 signaling pathways upon melatonin treatment. Histological staining and transmission electron microscopy (TEM) micrographs also demonstrated that melatonin alleviated cartilage ossification and chondrocyte hypertrophy in vivo. Conclusions Our results indicated that melatonin protected chondrocytes via mitochondrial redox homeostasis and autophagy. The effects of melatonin on senescence may apply to other age-related diseases. Thus, melatonin may have multiple potential therapeutic applications.
Spoolable reinforced plastic line pipes (RTPs), exhibiting a series of advantages such as good flexibility, few joints, long single length, light weight, easy installation, etc., have been widely used in the onshore oil and gas industry such as oil and gas gathering and transportation, high pressure alcohol injection, water injection, sewage treatment, and other fields. However, due to the lack of clear standard specificationof the limit operating properties for RTPs, three typical failure modes, i.e., tensile, flexure, and torsion, frequently occur in terrain changes,construction operation, and subsequent application, which seriously affects the promotion and use of RTPs. In this paper, the stress distribution of a non-bonded polyester fiber reinforced high-density polyethylene (HDPE) pipe (DN 150, PN 2.5 MPa) was systematically studied by the finite element method (FEM),and then the limit operating values under the axial tensile, coiled bending, and torsion load were determined.The corresponding experiments were conducted to validate the reliability and accuracy of the FEM model. The FEM results showed that the critical strain for axial tensile was 3%, the minimum respooling bend radius was 1016.286 mm, and the limit torsion angle of this RTP was 58.77°, which are very close to the experimental results. These limit values will be useful to establish normative guidelines for field construction and failure prevention of onshore RTP.
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