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PurposeThis study retrospectively investigated the clinical utility of 2-deoxy-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) in the diagnosis and prognosis of treatment-naive patients with non-small-cell lung cancer (NSCLC).MethodsThe blood samples of treatment-naive patients with NSCLC were collected for CTCs detection, and the tumor metabolic parameters of 18F-FDG PET/CT, including maximum standard uptake value (SUVmax), metabolic tumor volume of primary lesion (MTV-P) and combination of primary lesion and metastases (MTV-C), and total lesion glycolysis of primary lesion (TLG-P) and combination of primary lesion and metastases (TLG-C), were analyzed. Age, sex, smoking, serum tumor markers, tumor size, location, TNM stage, and genetic mutations were also reviewed. Moreover, progression-free survival (PFS) and overall survival (OS) of these patients were analyzed.ResultsA total of 309 patients with NSCLC (200 men, 109 women; mean age: 61 ± 9 years) were enrolled in this study, including 217 patients with adenocarcinoma and 92 with squamous cell carcinoma. Of the 309 cases, 11 were misdiagnosed with benign diseases by 18F-FDG PET/CT. CTCs positivity was detected in 234 cases. The sensitivity of 18F-FDG PET/CT and CTCs in NSCLC were 96.4% and 75.7%, respectively. SUVmax, MTV-P, TLG-P, MTV-C, TLG-C, tumor size, and serum CYFRA211 levels were significantly higher in CTCs positive group than negative group; and advanced TNM stage, squamous cell carcinoma, and EGFR wild type presented higher CTCs positivity. Multivariate logistic regression analysis revealed that SUVmax was significantly associated with CTCs positivity. Multivariate cox regression analysis showed that TLG-P, TLG-C, and CTCs were independent predictors of PFS in patients with NSCLC, and TLG-C and CTCs were independent predictors of OS.Conclusions18F-FDG PET/CT was superior to CTCs in the diagnosis of treatment-naive patients with NSCLC. The levels of CTCs in the peripheral blood were associated with tumor glucose metabolism in NSCLC. Metabolic parameters of 18F-FDG PET/CT and CTCs could separately predict the outcomes of treatment-naive patients with NSCLC.

Objective We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p  = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

Background: Inhibition of intestinal α-glucosidase is a key strategy for controlling postprandial hyperglycemia in diabetes. Astragali Radix (AR), a traditional medicinal and dietary herb widely consumed in China, is rich in flavonoids that are believed to exhibit hypoglycemic properties. Methods: A total of 29 AR-related flavonoids, including both original constituents and metabolites, were screened for α-glucosidase inhibitory activity using in vitro enzymatic assays. Mechanistic investigations were conducted through enzyme kinetics, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), and molecular docking. The in vivo hypoglycemic effects were assessed using a postprandial hyperglycemic mouse model. Additionally, potential mixture effects of flavonoid combinations were evaluated. Results: Of the 29 flavonoids, 16 demonstrated significant α-glucosidase inhibitory activity, with five (C3, C17, C19, C28, and C29) identified as novel inhibitors. Structure–activity relationship (SAR) analysis revealed that hydroxylation, particularly at the C-3 position, enhanced activity, while glycosylation and methoxylation reduced it. Mechanistic studies demonstrated that these compounds bind to distinct amino acid residues within the active site of α-glucosidase, inducing conformational changes and exerting different types of inhibition, leading to varying inhibitory mechanisms. Additionally, 15 compounds reduced postprandial blood glucose levels, with C3, C16, C17, C19, and C28 confirmed as novel in vivo inhibitors. Notably, two compositions of flavonoids combined at their individually ineffective concentrations exhibited significant inhibitory effects. Conclusions: This study provides a comprehensive evaluation of AR-related flavonoids as α-glucosidase inhibitors and offers valuable insights for the development of highly effective, low-toxicity, flavonoid-based, antidiabetic therapeutics and functional foods.

1 Introduction In the 20th century, toxicology made slow progress due to overreliance on animal-based assays, incompatible with 3R ethical guidelines while dealing with species-specific inaccuracies, excessive resource use, and sluggish workflows that delayed progress. [...]traditional in vivo animal tests often contained uncertainties, making it challenging to reliably project chemical toxicities in humans. Zhang et al. established a “toxic component-traditional Chinese medicine-adverse reaction” database targeting traditional Chinese medicines containing toxic components (such as Aconitum alkaloids, mineral medicines, and Arisaema family herbs), identifying four major clinical risk factors: drug-related factors (containing cold and cool medicinal properties/allergenic components), medication-related factors (overdose/treatment duration), individual factors (allergic constitution/special populations), and regulatory factors (incomplete instructions). Innovative in vitro and cross-species platforms have enhanced toxicity prediction.Ma et al.conducted a 90-day rat study of Lithocarpus litseifolius extract, establishing a no-observed-adverse-effect level (NOAEL) of 2,000 mg/kg/day and validating its safety for traditional medicine applications.Sung et al.introduced MDTR (Multi-Dimensional Transcriptomic Ruler), a knowledge-guided tool for quantifying liver toxicity via KEGG pathways in transcriptomic data. [...]it is essential that we stress raising awareness of predictive toxicology and strictly evaluating associated risks, as these aspects are the foundation for turning scientific advances into practical safety frameworks.

Comprehensive analysis of water use and pollution management plays an important role in regional water security and sustainable socio-economic development. This study applies the environmental Kuznets curve (EKC), Gini index and elasticity coefficient methods to conduct an investigation of industrial and domestic water use and pollution management in Shandong. The results show that industrial water pollution generally displayed a coordinated relationship with socio-economic development, while an uncoordinated relationship occurred between domestic water pollution and socio-economic development. Meanwhile, the Gini index between domestic water use and population in 2017 (0.101) was superior to that of 2003 (0.165), and the Gini index of industrial water use and second industry output in 2017 (0.273) was better than that of 2003 (0.292), indicating that the allocation and equity of domestic and industrial water use in Shandong kept to a good development trend. Additionally, the industrial effect is better than the domestic effect in terms of the control of wastewater emissions and the governance of typical pollutants in wastewater. Accordingly, domestic water pollution has gradually become one of the major sources of water pollution, and the allocation of industrial and domestic water use has room to improve further in Shandong. Conjunctive use of the aforementioned three methods provides an approach to investigate the integrated management of water use and water pollution control from multiple angles.

Cervical high-grade squamous intraepithelial lesion (HSIL) is a well-recognized precursor to cervical squamous cell carcinoma (CSCC). This study aims to explore molecular mechanisms underlying this transition. The datasets of HSIL and CSCC were downloaded from gene expression omnibus database (GEO). HSIL and CSCC coexpression modules were analyzed by Weighted gene coexpression network analysis (WGCNA). Enrichment analysis were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). The immune microenvironment (TIME) was analyzed by CIBERSORT. Receiver operating characteristic (ROC) curve, and survival analysis were performed. The binding of FEN1 and its upstream regulator PCNA was determined by protein interaction, correlation analysis and rigid docking. Immune infiltration, immune checkpoint and docking with small molecule inhibitors was also analyzed. In vitro experiments were conducted to investigate the function and underlying mechanisms of FEN1 in HSIL and CSCC. A total of 30 sequentially expressed shared genes were identified as potential drug targets. Immune infiltration revealed an imbalance of M1/M2 macrophages, T γδ cells and T cells CD4 memory resting were negatively associated with tumor progression, forming a pro-cancer effect at the HSIL stage and progressing toward CSCC. The key gene FEN1 was over-expressed in HSIL and CSCC, and correlated with the prognosis of CSCC ( P  < 0.05). FEN1 interacts with PCNA to regulate macrophage-mediated immune infiltration, increase the risk of immune escape, and decrease the sensitivity to immune checkpoints. Small molecule inhibitor binds to FEN1 docking and inhibits its regulation. FEN1 expression is upregulated in both HSIL and CSCC, with a more pronounced increase in CSCC. Knockdown of FEN1 significantly inhibits the proliferation of cervical cancer cells. This study identifies FEN1 as a biomarker and therapeutic target to truncate or reverse CSCC progression at the HSIL stage.

This study aimed to develop and validate a predictive risk model for postoperative nausea and vomiting (PONV) in patients undergoing day-case hysteroscopic surgery. The candidate predictors were identified by systematic literature review. Patients who met the study criteria were divided into training group and validation group. The time-period validation was used for the external validation of the model. The candidate predictors with statistical significance through lasso regression analyses were included in multifactor logistic regression analyses. The calibration and receiver operating characteristic (ROC) curves were utilized to assess the accuracy of model. Decision curve analysis (DCA) was used to assess the clinical benefit of Nomogram. All statistical analyses were constructed by RStudio software (version 4.2.1). A total of five predictors were included in the PONV risk prediction model: (1) motion sickness (OR, 8.53; 95% CI, 6.21-11.81), (2) anesthesia time (OR, 4.20; 95% CI, 2.09-8.65), (3) fasting time (OR, 1.17; 95% CI, 1.13-1.22), (4) anxiety score (OR, 1.10; 95% CI, 1.08-1.12), and (5) artificial airway (OR, 0.54; 95% CI, 0.39-0.74). The area under the ROC curve for the training cohort and validation cohort was 85.0% (95% CI: 82.6-87.5%) and 80.3% (76.2-84.3%), respectively. The predictive model demonstrated potential in predicting the risk of PONV in patients undergoing day-case hysteroscopic surgery.

This study aims to examine the current professional benefit perception among nursing interns and explore their interactions with perspective taking, compassion satisfaction, and secondary traumatic stress. The professional benefit perception is a crucial determinant in the career decisions of nursing interns. Understanding the pathways through which various factors influence this perception can inform the development of targeted intervention strategies. Such strategies are essential for preventing the attrition of nursing professionals and addressing the shortage of nursing human resources. A cross-sectional design. Cross-sectional data were obtained from Inner Mongolia, China. To examine the influencing factors and pathways, multiple linear regression and the Hayes PROCESS macro were employed. The study encompassed 427 nursing interns, whose perception of professional benefits was assessed at a moderate to high level, with a mean score of 4.29 ± 0.61. This perception was significantly affected by perspective taking (  = 3.990,  < 0.001), compassion satisfaction (  = 9.073,  < 0.001), secondary traumatic stress (  = -3.918,  < 0.001), overall satisfaction, and academic performance. Compassion satisfaction served as a mediator in the relationship between perspective taking and professional benefit perception, with a mediation effect value of 0.167, constituting 62.78% of the total effect. Furthermore, secondary traumatic stress moderated the relationship between compassion satisfaction and professional benefit perception, with an interaction effect value of  = 0.067 (  < 0.05). The professional benefit perception among nursing interns is shaped by a multitude of factors. Consequently, clinical educators should consider integrating these multidimensional factors to develop precise intervention programs aimed at enhancing professional identity and supporting the development of nursing talent.

This article explores the problems that EFL learners may encounter when they perceive content-based learning materials. The main questions include: (A) Will inferior reading skills or improper use of learning strategies affect these problems? (B) What are the characteristics of the specific linguistic of reading comprehension that initiate academic problems? (C) How does the learner's learning strategy cause or initiate problems? The data used in this research are learners' midterm exam scores and the frequency of learning strategies employed by students. Including qualitative data in the form of student statements obtained from unstructured participatory interviews, in a descriptive and qualitative way based on content-based reading skills theory and learning strategies, this article will conduct a comprehensive analysis of these materials. As a result of data analysis, there is a situation in which the problems encountered by English readers in understanding content-based learning materials are initiated by inferior reading ability and improper application of learning strategies. The linguistic features of reading comprehension that initiate this problem are the lack of understanding of grammatical features, the low level of vocabulary acquisition, the lack of awareness of sensory construction, and the problems of discourse comprehension. The problems encountered when dealing with learning strategies are improper use of learning strategies, unclear learning goals and poor learning habits.