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The study employed the random forest (RF) and artificial neural network (ANN) methods based on the quantitative structure–activity relationship (QSAR) techniques to analyze NSAIDs-Se derivatives and their antioxidant abilities. The best predictive models by the RF method yielded a coefficient of determination (R2) value of 0.868 for the training set, and the root mean square error (RMSE) of the test set was only 0.053. For the QSAR-ANN, the best predictive models resulted in an R2 value of 0.935, and the RMSE of the test set was 0.068. Based on the best models, the steric, electrostatic, and enthalpy descriptors are found to be related to antioxidant prediction. Thus, to extend the predictive ability of the obtained QSAR-ML models, an external set was collected from a later publication of NSAIDs-Se derivatives with experimental antioxidant abilities. The efficacy of two QSAR models in forecasting the antioxidant abilities of an external set of NSAIDs-Se derivatives was evaluated. The QSAR with machine learning models demonstrated high efficiency in predicting the antioxidant abilities of the external NSAIDs-Se set with an RMSE of the external set in the range of 0.074–0.087. Therefore, the results suggest that fine-tuning machine learning-based QSAR studies can aid in the design of novel NSAIDs-Se derivatives with highly efficient antioxidant prediction. [ABSTRACT FROM AUTHOR]

Context Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown. Objective This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM. Methods In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy. Results Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway. Conclusion In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM. [ABSTRACT FROM AUTHOR]

The quantitative structure–electrochemistry relationship (QSER) method was applied to a series of transition-metal-coordinated porphyrins to relate their structural properties to their electrochemical CO2 reduction activity. Since the reactions mainly occur within the core of the metalloporphyrin catalysts, the cluster model was used to calculate their structural and electronic properties using density functional theory with the M06L exchange–correlation functional. Three dependent variables were employed in this work: the Gibbs free energies of H*, C*OOH, and O*CHO. QSER, with the genetic algorithm combined with multiple linear regression (GA–MLR), was used to manipulate the mathematical models of all three Gibbs free energies. The obtained statistical values resulted in a good predictive ability (R2 value) greater than 0.945. Based on our QSER models, both the electronic properties (charges of the metal and porphyrin) and the structural properties (bond lengths between the metal center and the nitrogen atoms of the porphyrin) play a significant role in the three Gibbs free energies. This finding was further applied to estimate the CO2 reduction activities of the metal–monoamino–porphyrins, which will prove beneficial in further experimental developments. [ABSTRACT FROM AUTHOR]

The land use information extraction technology for the high-resolution remote sensing images of the Gaofen No. 1 satellite was constructed . According to the spectral, band, texture and shape attributes, land use types were divided, and the changing laws of land use types were analyzed. Afterwards, according to the Table of Grading Standard of Soil Erosion Intensity (SL190-96), as well as vegetation coverage index NDVI and slope, the risks of soil and water loss were assessed. Meanwhile, the level, scale, location and scope of changes in the risks of soil and water loss were monitored by using spatial visualization and spatial statistical techniques. The results showed that the area of areas without soil erosion and moderate soil erosion areas decreased obviously from 2015 to 2017, and the decreases were up to 22.929 3 and 13.626 3 km2 respectively. The area of mild soil erosion areas increased fast, and the increase reached 31.140 0 km². The area of extremely strong soil erosion areas increased by 7.267 4 km2. In the city, moderate and strong soil erosion areas reduced, while extremely strong soil erosion patches increased fast, which was mainly related to road construction and construction and development of orchards. The extremely strong soil erosion areas were distributed in the shape of a banded loop, surrounded the suburbs of the city, and shrank towards the center of Ruijin City. The constructed technology to monitor the changes in land use and soil and water loss, as well as the changing laws of land use and soil and water loss provide the theoretical basis and planning basis of soil and water conservation for urban planning departments and soil and water conservation departments. [ABSTRACT FROM AUTHOR]

Phencyclidine (PCP) is a frequently abused dissociative agent. It causes confusion, increased tendencies toward violence, and concentration-dependent cytotoxicity after entry into the body. The parent nucleus of phencyclidine-type substances is arylcyclohexylamine, which is easy to modify; therefore, abusers and dealers can readily synthesize substitutes beyond the drug control catalog. An urgent need exists to establish screening methods for phencyclidine-type substances to provide technical support for abuse monitoring. In this study, 20 mg of hair was pulverized in 500 mL of methanol containing 0.5 ng/mL PCP-d 5. After ultrasonication, centrifugation, and filtration, the supernatant was analyzed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) operating in the multiple reaction monitoring mode. Phencyclidine-type substances were separated in 13 min on a biphenyl column using a mobile phase gradient composed of A (water, formic acid 0.1%, acetonitrile 5%, 20 mmol/L ammonium acetate) and B (acetonitrile). The developed and validated method showed good selectivity, sensitivity (limit of detection: 0.25–2 pg/mg and lower limit of quantitation: 0.5–4 pg/mg), linearity (R2 > 0.994), accuracy, and precision (< 20%), and a dilution effect. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of phencyclidine-type substances in hair from 87 authentic forensic cases. Nine analytes were detected: ketamine (10.3–26211.3 pg/mg), 2-F-2-oxo-PCE (11.5–4034.9 pg/mg), 2-FDCK (14.0–43290.2 pg/mg), 2-BrDCK (10.6–21170.0 pg/mg), nor2-FDCK (10.1–16767.4 pg/mg), tiletamine (10.1–3250.8 pg/mg), O-PCE (43.3–166.1 pg/mg), DCK (10.2–90.4 pg/mg), and norDCK (24.9–103.0 pg/mg). • A systematic screening method for 36 phencyclidine-type substances was established. • Excellent sensitivity compatible with hair analysis, LOD: 0.25–2 pg/mg. • Seven groups of isomers were effectively separated. • Applied to forensic toxicology analysis and detected 87 positive samples. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N 2 O), also known as laughing gas, has a euphoric effect and is becoming increasingly popular as a recreational inhalant drug. Deaths caused by recreational nitrous oxide abuse are rare, but may still occur. Although some methods for the quantification of N 2 O by GC-MS have been reported, elimination of carbon dioxide interference and the choice of a suitable internal standard remain current limitations to accurate N 2 O quantification. Here, a validated method using headspace-gas chromatography–mass spectrometry (HS-GC–MS) is described that allows the quantification of N 2 O in human blood samples: sodium hydroxide is used to remove carbon dioxide, and n-pentane is chosen as a suitable internal standard. Collectively, the validation results show a good linear relationship of N 2 O in blood within the concentration range of 0.02 ∼ 0.5 mL/mL and an LOD of 0.005 mL/mL. Subsequent application of the validated method to two real mortality cases due to N 2 O intoxication provided reference values for blood concentrations in forensic cases. Other biological specimens (gaseous samples and tissues) of the deceased were also analyzed to demonstrate that the deaths were caused by asphyxia due to the inhalation of N 2 O. [Display omitted] • A method for the determination of N 2 O in biological matrices. • Removing possible interference from CO 2 in the detection of N 2 O. • Detection of N 2 O in blood of two decedents from acute N 2 O poisoning. [ABSTRACT FROM AUTHOR]

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Ren, Xie, Chen, Liang, Jiang, Wang and Zheng.)

Context: Excessive insulin resistance, inadequate insulin compensation, or both could result in gestational diabetes mellitus (GDM). Levels of pigment epithelium-derived factor (PEDF), a novel adipokine that could induce insulin resistance, are high in patients with obesity and diabetes. However, the impact of PEDF in pregnancy remains unknown., Objective: This study aimed to elucidate the role of PEDF on insulin resistance and compensatory elevation of insulin levels during normal pregnancy and in patients with GDM., Methods: In this population-based and cohort study, logistic regression analysis was performed to determine the association of PEDF/adiponectin/leptin levels with the risk of developing GDM and to predict postpartum prediabetes. PEDF protein, PEDF transgenic mice, PEDF knockout mice, and PEDF-neutralized antibodies were used to observe changes in insulin resistance and insulin levels with pregnancy., Results: Plasma PEDF levels were increased in normal pregnancy and higher in GDM women. Higher PEDF levels were associated with the increased risk of developing GDM and emerged as a significant independent determinant of postpartum prediabetes in GDM women. Mechanistically, in vivo and in vitro experiments revealed that PEDF induced insulin resistance by inhibiting the insulin signaling pathway., Conclusion: In addition to insulin resistance and upregulated insulin levels in normal pregnancy and GDM, aberrant PEDF levels can serve as a "fingerprint" of metabolic abnormalities during pregnancy. Thus, PEDF is a valuable biomarker but could interfere with the time course for early diagnosis and prognosis of GDM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)