Circular RNA IARS modulates the progression and ferroptosis of osteosarcoma via sponging miR-188-5p from RAB14.

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.

Quantitative Evaluation of the Lumbar Multifidus Muscle by Shear Wave Dispersion in Healthy Adults: A Preliminary Study.

OBJECTIVES: To investigate the application value of shear wave dispersion (SWD) in healthy adults with the lumbar multifidus muscle (LMM), to determine the range of normal reference values, and to analyze the influences of factors on the parameter. METHODS: Ninety-five healthy volunteers participated in the study, from whom 2-dimensional, shear wave elastography (SWE), and SWD images of the bilateral LMM were acquired in three positions (prone, standing, and anterior flexion). Subcutaneous fat thickness (SFH), SWE velocity, and SWD slope were measured accordingly for analyses. RESULTS: The mean SWD slope of the bilateral LMM in the prone position was as follows: left: 14.8 ± 3.1 (m/second)/kHz (female) and 13.0 ± 2.5 (m/second)/kHz (male); right: 14.8 ± 3.7 (m/second)/kHz (female) and 14.2 ± 3.4 (m/second)/kHz (male). In the prone position, there was a weak negative correlation between the bilateral LMM SWD slope of activity level 2 and level 1 (ß = -1.5 (2 versus 1, left), -1.9 (2 versus 1, right), all P < .05), and between the left SWD slope of activity level 3 and level 1 (ß = -2.3 [3 versus 1, left], P < .05). The correlation between SWE velocity and SWD slope value changed with the position: there was a weak positive correlation in the prone position (r = 0.3 [left], 0.37 [right], both P < .05), and a moderate positive correlation in the standing and anterior flexed positions (r = 0.49-0.74, both P < .001). SFH was moderately negatively correlated with bilateral SWD slope values in the anterior flexion (left: r = -0.4, P = .01; right: r = -0.7, P < .01). CONCLUSIONS: SWD imaging can be used as an adjunct tool to aid in the assessment of viscosity in LMM. Further, activity level, and position are influencing factors that should be considered in clinical practice.

One-Stop Automated Diagnostic System for Carpal Tunnel Syndrome in Ultrasound Images Using Deep Learning.

OBJECTIVE: Ultrasound (US) examination has unique advantages in diagnosing carpal tunnel syndrome (CTS), although identification of the median nerve (MN) and diagnosis of CTS depend heavily on the expertise of examiners. In the aim of alleviating this problem, we developed a one-stop automated CTS diagnosis system (OSA-CTSD) and evaluated its effectiveness as a computer-aided diagnostic tool. METHODS: We combined real-time MN delineation, accurate biometric measurements and explainable CTS diagnosis into a unified framework, called OSA-CTSD. We then collected a total of 32,301 static images from US videos of 90 normal wrists and 40 CTS wrists for evaluation using a simplified scanning protocol. RESULTS: The proposed model exhibited better segmentation and measurement performance than competing methods, with a Hausdorff distance (95th percentile) score of 7.21 px, average symmetric surface distance score of 2.64 px, Dice score of 85.78% and intersection over union score of 76.00%. In the reader study, it exhibited performance comparable to the average performance of experienced radiologists in classifying CTS and outperformed inexperienced radiologists in terms of classification metrics (e.g., accuracy score 3.59% higher and F1 score 5.85% higher). CONCLUSION: Diagnostic performance of the OSA-CTSD was promising, with the advantages of real-time delineation, automation and clinical interpretability. The application of such a tool not only reduces reliance on the expertise of examiners but also can help to promote future standardization of the CTS diagnostic process, benefiting both patients and radiologists.

Endothelial ELABELA improves post-ischemic angiogenesis by upregulating VEGFR2 expression.

BACKGROUND: Post-ischemic angiogenesis is critical for perfusion recovery and tissue repair. ELABELA (ELA) plays an essential role in embryonic heart development and vasculogenesis. However, the mechanism of ELA on post-ischemic angiogenesis is poorly characterized. METHODS: We first assessed ELA expression after hind limb ischemia (HLI) in mice. We then established a HLI model in tamoxifen-inducible endothelial-ELA-specific knockout mice (ELAECKO) and assessed the rate of perfusion recovery, capillary density, and VEGFR2 pathway. Knockdown of ELA with lentivirus or siRNA and exogenous addition of ELA peptides were employed to analyze the effects of ELA on angiogenic capacity and VEGFR2 pathway in endothelial cells in vitro. The serum levels of ELA in healthy people and patients with type 2 diabetes mellitus (T2DM) and diabetic foot ulcer (DFU) were detected by a commercial ELISA kit. RESULTS: In murine HLI models, ELA was significantly up-regulated in the ischemic hindlimb. Endothelial-specific deletion of ELA impaired perfusion recovery and angiogenesis. In physiologic conditions, no significant difference in VEGFR2 expression was found between ELAECKO mice and ELAWT mice. After ischemia, the expression of VEGFR2, p-VEGFR2, and p-AKT was significantly lower in ELAECKO mice than in ELAWT mice. In cellular experiments, the knockdown of ELA inhibited endothelial cell proliferation and tube formation, and the addition of ELA peptides promoted proliferation and tube formation. Mechanistically, ELA upregulated the expression of VEGFR2, p-VEGFR2, and p-AKT in endothelial cells under hypoxic conditions. In clinical investigations, DFU patients had significantly lower serum levels of ELA compared to T2DM patients. CONCLUSION: Our results indicated that endothelial ELA is a positive regulator of post-ischemic angiogenesis via upregulating VEGFR2 expression. Targeting ELA may be a potential therapeutic option for peripheral arterial diseases.

The storm runoff management strategy based on agricultural ditch nutrient loss characteristics in Erhai Lake, China.

Initial flush management is an effective measure to control non-point source pollution (NPSP) in storm runoff. However, determining the parameter of the initial flush in different areas may pose challenges in storm runoff management strategies. To address this issue, Erhai Lake in China, Yunnan-Guizhou Plateau, was selected as an example for the study. Erhai Lake is a typical mesotrophic lake with the profound influence of NPSP. The NPSP control strategy in this area will provide a valuable reference for other lakes. In 2021, 289 storm events and 190 ditchwater samples were detected around Erhai Lake. The average flow in the ditches ranged from 0.004 to 0.147 m3/s, the instant total nitrogen (TN) concentration ranged from 0.28 to 91.43 mg/L, and the instant total phosphorus (TP) concentration ranged from 0.26 to 7.35 mg/L in the storm events. It was found that the concentration of pollutants was lower than expected in the initial flush period. Instead, the event mean concentrations of TN and TP were 9.3 and 2.1 times higher than in the wet seasons, showing high nutrient concentration levels throughout the entire rainfall period. To manage storm runoff effectively, a flow-processes-division method was proposed to analyze the inflow condition and pollutant removal rate in different runoff periods. The peak flow interception strategy was recommended as the optimal stormwater management plan, as it showed the highest inflow conditions and 50% pollutant removal rate. Considering the need to reduce the constant flush of stormwater runoff, it is essential to establish a healthy water cycle system to alleviate NPSP and raise the Erhai water level. The storm runoff management method can serve as a practical tool for lake areas that do not exhibit initial flush characteristics.

Comprehensive effects of salinity, dissolved organic carbon and copper on mortality, osmotic regulation and bioaccumulation of copper in Oryzias melastigma.

Cu, as an essential and toxic element, has gained widespread attention. Both salinity and dissolved organic carbon (DOC) are known to influence Cu toxicity in marine organisms. However, the intricate interplay between these factors and their specific influence on Cu toxicity remains ambiguous. So, this study conducted toxicity tests of Cu on Oryzias melastigma. The experiments involved three salinity levels (10, 20, and 30 ppt) and three DOC levels (0, 1, and 5 mg/L) to comprehensively investigate the underlying mechanisms of toxicity. The complex toxic effects were analyzed by mortality, NKA activity, net Na+ flux and Cu bioaccumulation in O. melastigma. The results indicate that Cu toxicity is notably influenced by both DOC and salinity. Interestingly, the discernible variation in Cu toxicity across different DOC levels diminishes as salinity levels increase. The presence of DOC enhances the impact of salinity on Cu toxicity, especially at higher Cu concentrations. Additionally, Visual MINTEQ was utilized to elucidate the chemical composition of Cu, revealing that DOC had a significant impact on Cu forms. Furthermore, we observed that fluctuations in salinity lead to the inhibition of Na+/K+-ATPase (NKA) activity, subsequently hindering the inflow of Na+. The effects of salinity and DOC on the bioaccumulation of copper were not significant. The influence of salinity on Cu toxicity is mainly through its effect on the osmotic regulation and biophysiology of O. melastigma. Additionally, DOC plays a crucial role in the different forms of Cu. Moreover, DOC-Cu complexes can be utilized by organisms. This study contributes to understanding the mechanism of copper's biological toxicity in intricate marine environments and serves as a valuable reference for developing marine water quality criteria for Cu.