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Sickle cell disease (SCD) is a monogenetic disease that results in the formation of hemoglobin S. Due to more rapid oxidation of hemoglobin S due to intracellular heme and adventitious iron in SCD, it has been thought that an inherent property of SCD red cells would be an imbalance in antioxidant defenses and oxidant production. Less deformable and fragile RBC in SCD results in intravascular hemolysis and release of free hemoglobin (PFHb) in the plasma, which might be expected to produce oxidative stress in the plasma. Thus, we aimed to characterize intracellular and vascular oxidative stress in whole blood and plasma samples from adult SCD patients and controls recruited into a large study of SCD at Children's Hospital of Los Angeles. We evaluated the cellular content of metHb and several components of the antioxidant system in RBC as well as oxidation of GSH and Prx-2 oxidation in RBC after challenge with hydroperoxides. Plasma markers included PFHb, low molecular weight protein bound heme (freed heme), hemopexin, isoprostanes, and protein carbonyls. While GSH was slightly lower in SCD RBC, protein carbonyls, NADH, NAD+ and total NADP+ + NADPH were not different. Furthermore, GSH or Prx-2 oxidation was not different after oxidative challenge in SCD vs. Control. Elevated freed heme and PFHb had a significant negative, non-linear association with hemopexin. There appeared to be a threshold effect for hemopexin (200 μg/ml), under which the freed heme rose acutely. Plasma F2-isoprostanes were not significantly elevated in SCD. Despite significant release of Hb and elevation of freed heme in SCD when hemopexin was apparently saturated, there was no clear indication of uncompensated vascular oxidative stress. This somewhat surprising result, suggests that oxidative stress is well compensated in RBCs and plasma during a period of relative health.

In this manuscript, phosphine-dependent [3 + 3] and [4 + 3] annulation reactions of allenoate with aziridines were disclosed. The alkyldiphenylphosphine-promoted [4 + 3] annulation of allenoate with aziridines has been achieved under mild conditions, providing biologically interesting functionalized tetrahydroazepines in moderate to excellent yield with moderate to excellent regioselectivity and diastereoselectivity.

Shallow coal mining in gully regions has resulted in significant subsidence hazards and increased the risk of surface water inflow into mining panels, compromising the sustainability of surface water management and underground resource exploitation. In this study, the chain disaster process caused by shallow coal seam mining and heavy rainfall is quantitatively analyzed. The findings reveal that shallow coal seam mining leads to the formation of caved and fractured zones in the vertical direction of the overlying rock. The fractured zone can be further classified into a compression subsidence zone and a shear subsidence zone in the horizontal direction. The shear subsidence zone is responsible for generating compression and shear deformations, intercepting rainfall runoff, and potentially triggering landslides, necessitating crack landfill treatments, which are critical for promoting sustainable mining practices. The HEC-RAS program was utilized to integrate annual maximum daily rainfall data across different frequencies, enabling the establishment of a dynamic risk assessment model for barrier lakes. Numerical simulations based on unsaturated seepage theory provide insights into the infiltration and seepage behavior of rainfall in the study area, indicating a significant increase in saturation within lower gully terrain. Precipitation infiltration was found to enhance the saturation of the shallow rock mass, reducing matric suction in unsaturated areas. Finally, the disaster chain is discussed, and recommendations for managing different stages of risk are proposed. This study offers a valuable reference for the prevention and control of surface water damage under coal mining conditions in gully regions. [ABSTRACT FROM AUTHOR]

With the development of unconventional natural gas resources, plunger gas lift technology has gained widespread application. Accurately predicting gas production from unconventional gas reservoirs is a crucial step in evaluating the effectiveness of plunger gas lift technology and optimizing its design. However, most existing prediction methods are mechanism-driven, incorporating numerous assumptions and simplifications that make it challenging to fully capture the complex physical processes involved in plunger gas lift technology, ultimately leading to significant errors in capacity prediction. Furthermore, engineering design factors and production system factors associated with plunger gas lift technology can contribute to substantial deviations in gas production forecasts. This study employs three powerful regression algorithms, XGBoost, Random Forest, and SVR, to predict gas production in plunger gas lift wells. This method comprehensively leverages various types of data, including collected engineering design, production system, and production data, directly extracting the underlying patterns within the data through machine learning algorithms to establish a prediction model for gas production in plunger gas lift wells. Among these, the XGBoost algorithm stands out due to its robustness and numerous advantages, such as high accuracy, ability to effectively handle outliers, and reduced risk of overfitting. The results indicate that the XGBoost algorithm exhibits impressive performance, achieving an R2 (coefficient of determination) value of 0.87 for six-fold cross-validation and 0.85 for the test set. Furthermore, to address the "black box" problem (the inability to know the internal working structure and workings of the model and to directly understand the decision-making process), which is commonly associated with conventional machine learning models, the SHAP (Shapley additive explanations) method was utilized to globally and locally interpret the established machine learning model, analyze the main factors (such as starting time of wells, gas–liquid ratio, catcher well inclination angle, etc.) influencing gas production, and enhance the credibility and transparency of the model. Taking plunger gas lift wells in southwest China as an example, the effectiveness and practicality of this method are demonstrated, providing reliable data support for shale gas production prediction, and offering valuable guidance for actual on-site production. [ABSTRACT FROM AUTHOR]

Objectives: Anti‐signal recognition particle (SRP) antibodies, markers of immune‐mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti‐SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti‐SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure–volume loop; cardiac histological changes were analysed using haematoxylin–eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti‐SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti‐SRP‐specific IgG, however, recovered normal mitochondrial metabolism after treatment with N‐acetylcysteine, an ROS scavenger. Moreover, patients positive for anti‐SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti‐SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti‐SRP antibody‐induced LVDD. [ABSTRACT FROM AUTHOR]

Background: CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. Methods: Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2'-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. Results: Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. Conclusions: Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC. [ABSTRACT FROM AUTHOR]

Objective Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. Methods Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyse the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. Results In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HCs). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine–cytokine receptor interaction, inflammatory response and regulation of mitogen-activated protein kinase cascade. Conclusion Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein–protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies. [ABSTRACT FROM AUTHOR]