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Background: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. Methods: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. Results: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. Conclusions: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance. [ABSTRACT FROM AUTHOR]

Abstract: Uniaxial ratcheting and low-cycle fatigue failure behaviors of the hot-rolled AZ31B magnesium alloy are studied by uniaxial asymmetrical cyclic stress-controlled experiments at room temperature. The effects of mean stress, stress amplitude and stress rate on the uniaxial ratcheting response and ratcheting life of the studied magnesium alloy are analyzed. The microscopic observations near fracture surface are carried out. In addition, a fatigue parameter is introduced to describe the ratcheting damage and fatigue damage processes, and a new model is established to describe the relationship between the linear density of twins and the fatigue parameter. Results show that (1) the mean stress and stress amplitude has a great influence on the ratcheting strain and fatigue failure life. When the mean stress or stress amplitude is increased, the ratcheting strain and its rate rapidly increase. So, the fatigue failure life is reduced. (2) The increase of mean stress and stress amplitude can accelerate the generation of twins, which decreases the fatigue resistance and increases the ratcheting strain. However, the stress rate has little effect on the twinning. So, the effects of stress rate on ratcheting and low-cycle fatigue failure behaviors are not obvious under the tested conditions. This is because the studied magnesium alloy shows highly rate-independent property at room temperature within the tested strain rate range. (3) The established model can accurately describe the relationship between the linear density of twins and the fatigue parameter. Furthermore, the threshold fatigue parameter for twinning is found. [Copyright &y& Elsevier]

Background: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. Objective: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. Methods: A prospective, diagnostic case‐control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug‐naïve patients with PD, and 185 non‐PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. Results: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%–96%), 95% (95% CI: 93%–97%), and 19.16 (95% CI: 13.52–27.16) and 0.10 (95% CI: 0.05–0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug‐naïve were 89% (95% CI: 75%–96%), 86% (95% CI: 81%–91%), and 6.6 (95% CI: 4.51–9.66) and 0.13 (95% CI: 0.05–0.32), respectively. Conclusions: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost‐effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Abstract: The uniaxial low-cycle fatigue behavior of hot-rolled AZ91 magnesium alloy was investigated by asymmetric cyclic stress-controlled experiments at room temperature. The effects of the sampling direction, peak stress and stress ratio on the fatigue life were discussed. The fatigue life increases with increasing the stress ratio or decreasing the peak stress. Due to the anisotropic property, the specimen in transverse direction shows superior fatigue resistance. Considering the effects of mean stress on the fatigue strength coefficient and fatigue strength exponent, a modified Basquin model was proposed and validated to evaluate the fatigue life of AZ91 magnesium alloy. [Copyright &y& Elsevier]