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Background: Doxorubicin (DOX) is a chemotherapeutic drug that induces cardiotoxicity known as doxorubicin -induced cardiomyopathy(DIC). Studies have confirmed that DOX can cause cardiac damage via ferroptosis. High uric acid (HUA), as a pro-oxidant, participates in the pathophysiology of cardiovascular disease. Epidemiological studies suggest elevated uric acid levels can have detrimentaleffects on cardiovascular disease. However, the effect of hyperuricemia in a specific type of cardiomyopathy, DIC, is unclear. It is unknown if HUA exacerbates DIC and if the tumor patients with hyperuricemia will aggravate the cardiac side effects of DOX. Methods: In uricase knockout (Uox-/-) mice, we explored the effect of HUA on DOX-induced cardiotoxicity, including cardiac function, pathomorphology, and its mechanism. Results: We demonstrated that Uox-KO mice accelerated the development of DIC, causing significantly impaired cardiac function and myocardial fibrosis. Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with DOX treatment. Benzbromarone, a UA-lowering drug, decreases myocardial fibrosis and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterwards, we demonstrated that HUA can promote oxidative stress in DOX, characterised by increased mitochondrial ROS, and down-regulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-L-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression. Conclusions: Our data suggested that HUA promotes the DIC. And HUA promotes DOX-induced ferroptosis by increasing oxidative stress and down-regulating GPX4. It is implied that tumor patients with hyperuricemia may increase cardiac side effects when taking DOX during chemotherapy treatment.

The positioning accuracy is a key index to measure the performance of the robot. This paper studies the positioning accuracy of the main pouring mechanism of the hybrid truss pouring robot and analyzes that the main error sources affecting the positioning accuracy are machining error, assembly error, and thermal deformation error. Error transfer matrix is constructed to describe the influence of machining errors and assembly errors on the position and pose of the terminal, and the error parameters have physical significance. The probability distribution of sensitive errors is discussed. A joint regression prediction model based on sensitive error sets is established to determine the thermal deformation error on the basis of fully considering the contribution rate of component error. The results show that the position error has a wide range of influences on the end pose, but the angle error is more sensitive, and the probability distribution of the sensitive error is concentrated. The reliable data can be obtained without reorganizing the measurement in the calibration process. The joint regression model considering the contribution rate of component error can effectively eliminate the collinearity problem in the prediction of thermal deformation from a single heat source. Compared with the single regression model, it has better prediction accuracy and effect.

Acute rupture or erosion of unstable atherosclerotic plaques is a major cause of adverse consequences of atherosclerotic cardiovascular disease, often leading to myocardial infarction or stroke. High uric acid (HUA) is associated with the increasing risk of cardiovascular events and death. However, the mechanism by which HUA promotes atherosclerosis and whether HUA affects plaque stability are still unclear.We constructed an atherosclerotic Apoe-/- mouse model with HUA. The progression of atherosclerosis and plaques was determined by Oil Red O staining, hematoxylin and eosin (HE) staining, and Masson staining. TdT-mediated dUTP nick-end labeling assay and immunohistochemistry were used to observe the changes of apoptosis and autophagy in plaques, respectively. Then, we validated the in vivo results with RAW 264.7 cell line.HUA promoted atherosclerosis and exacerbated plaque vulnerability, including significantly increased macrophage infiltration, lipid accumulation, enlarged necrotic cores, and decreased collagen fibers. HUA increased cell apoptosis and inhibited autophagy in plaques. In vitro results showed that HUA decreased cell viability and increased cell apoptosis in foam cells macrophages treated with oxidized low-density lipoprotein. An activator of autophagy, rapamycin, can partially reverse the increasing apoptosis.HUA promoted atherosclerosis and exacerbated plaque vulnerability, and HUA facilitates foam cell apoptosis by inhibiting autophagy.

Uric acid (UA), the end-product of purine metabolism, is closely related to hepatic insulin resistance (IR). Autophagy is a conserved intracellular degradation process maintaining cellular homeostasis. Autophagy plays a protective role in obesity-related hepatic IR, but whether it occurs in high uric acid (HUA)-induced hepatic IR is unclear. In this study, spontaneously elevated UA level induced hepatic IR and facilitated hepatic autophagy degradation in uricase knockout (Uox