Identification and Mendelian randomization validation of pathogenic gene biomarkers in obstructive sleep apnea.

Background: By 2020, obstructive sleep apnea (OSA), a prevalent respiratory disorder, had affected 26.6-43.2% of males and 8.7-27.8% of females worldwide. OSA is associated with conditions such as hypertension, diabetes, and tumor progression; however, the precise underlying pathways remain elusive. This study aims to identify genetic markers and molecular mechanisms of OSA to improve understanding and treatment strategies. Methods: The GSE135917 dataset related to OSA was obtained from the GEO database. Differentially expressed genes (DEGs) were subsequently identified. Weighted gene co-expression network analysis (WGCNA) was conducted to pinpoint disease-associated genes. The intersection of these data enabled the identification of potential diagnostic DEGs. Further analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies, exploration of protein-protein interactions based on these genes, and an examination of immune infiltration. Mendelian randomization was employed to validate core genes against the Genome-Wide Association Study database. Results: A total of 194 DEGs were identified in this study. WGCNA network analysis highlighted 2,502 DEGs associated with OSA. By intersecting these datasets, 53 diagnostic DEGs primarily involved in metabolic pathways were identified. Significant alterations were observed in immune cell populations, including memory B cells, plasma cells, naive CD4 T cells, M0 macrophages, and activated dendritic cells. CETN3, EEF1E1, PMM2, GTF2A2, and RRM2 emerged as hub genes implicated in the pathogenesis. A line graph model provides diagnostic insights. Mendelian randomization analysis confirmed a causal link between CETN3 and GTF2A2 with OSA. Conclusion: Through WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA.

Association of obstructive sleep apnea syndrome with polycystic ovary syndrome through bidirectional Mendelian randomization.

Background: Observational studies have established a link between polycystic ovary syndrome (PCOS) and obstructive sleep apnea syndrome (OSAS), with obesity being a significant confounding factor that complicates the understanding of causality. This study seeks to clarify the causal relationship by utilizing bidirectional two-sample Mendelian randomization (MR) analysis. Methods: A bidirectional MR strategy was implemented to investigate the potential causal relationship between PCOS and OSAS. Instrumental variables (IVs) for PCOS were sourced from a dataset comprising 3,609 cases and 229,788 controls. For OSAS, statistical data were obtained from a genome-wide association study (GWAS) involving 38,998 subjects, alongside a control group of 336,659 individuals. Our MR analysis utilized several methods, including inverse variance weighted (IVW), weighted mode, weighted median, simple mode, and MR-Egger, primarily focusing on the IVW technique. Sensitivity tests were conducted to ensure the robustness of our findings. Results: Utilizing the IVW method, we identified a notable causal association from OSAS to PCOS, with an odds ratio (OR) of 1.463 and a 95% confidence interval (CI) of 1.086-1.971 (p = 0.012). In the opposite direction, PCOS also appeared to significantly affect OSAS development, indicated by an OR of 1.041 and a 95% CI of 1.012-1.072 (p = 0.006). The MR-Egger intercept test showed no evidence of directional pleiotropy, affirming the credibility of our causal findings (p > 0.05). Conclusion: This study suggests a bidirectional causal relationship between PCOS and an increased risk of OSAS. These insights could guide future screening and prevention strategies for both conditions.

S100A10 promotes cancer metastasis via recruitment of MDSCs within the lungs.

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.

Intestinal microbiota and tuberculosis: Insights from Mendelian randomization.

Respiratory tuberculosis (RTB), a global health concern affecting millions of people, has been observationally linked to the gut microbiota, but the depth and nature of this association remain elusive. Despite these findings, the underlying causal relationship is still uncertain. Consequently, we used the Mendelian randomization (MR) method to further investigate this potential causal connection. We sourced data on the gut microbiota from a comprehensive genome-wide association study (GWAS) conducted by the MiBioGen Consortium (7686 cases, and 115,893 controls). For RTB, we procured 2 distinct datasets, labeled the Fingen R9 TBC RESP and Fingen R9 AB1 RESP, from the Finnish Genetic Consortium. To decipher the potential relationship between the gut microbiota and RTB, we employed MR on both datasets. Our primary mode of analysis was the inverse variance weighting (IVW) method. To ensure robustness and mitigate potential confounders, we meticulously evaluated the heterogeneity and potential pleiotropy of the outcomes. In the TBC RESP (RTB1) dataset related to the gut microbiota, the IVW methodology revealed 7 microbial taxa that were significantly associated with RTB. In a parallel vein, the AB1 RESP (RTB2) dataset highlighted 4 microbial taxa with notable links. Notably, Lachnospiraceae UCG010 was consistently identified across both datasets. This correlation was especially evident in the data segments designated Fingen R9 TBC RESP (OR = 1.799, 95% CI = 1.243-2.604) and Finngen R9 AB1 RESP (OR = 2.131, 95% CI = 1.088-4.172). Our study identified a causal relationship between particular gut microbiota and RTB at the level of prediction based on genetics. This discovery sheds new light on the mechanisms of RTB development, which are mediated by the gut microbiota.

Metagenomic analysis revealed the association between gut microbiota and different ovary responses to controlled ovarian stimulation.

The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI) < 0.5 and 25 IVF cycles with FOI ≥ 0.5 were included in this study. Baseline demographic characteristics were compared between the two groups. Metagenomic sequencing was performed to analyze fecal microbial community profiles. Mice were used to evaluate the effect of Bifidobacterium_longum on ovarian response to stimulation. Compared with FOI < 0.5 group, women in group with FOI ≥ 0.5 had significant more oocytes retrieved (p < 0.01). Prevotella_copri, Bateroides_vulgatus, Escherichia_coli and Bateroides_stercoris were more abundant in FOI < 0.5 group while Bifidobacterium_longum, Faecalibacterium_prausnitzii, Ruminococcus_gnavus and Bifidobacterium_pseudocatenula were more abundant in FOI ≥ 0.5 group. After adjusting for women's age and BMI, Pearson correlation analysis indicated alteration of gut microbiome was related with serum E2, FSH, number of oocytes retrieved and clinical pregnancy rate. Animal study showed ovarian response will be improved after Bifidobacterium_longum applied. An increased abundance of Bacteroidetes and Prevotella copri, as well as a decreased abundance of Bifidobacterium longum, have been found to be associated with poor ovarian responsiveness. Changes in gut microbiomes have been observed to be correlated with certain clinical characteristics. The potential enhancement of ovarian response may be facilitated by the integration of Bifidobacterium longum.

Sequential Ring Opening/In Situ SO2-Capture/Alkynylation of Cyclopropanols with Alkynyl Triflones Initiated by Energy Transfer.

A visible-light-triggered ring opening/in situ SO2-capture/alkynylation sequence of cyclopropyl alcohols with alkynyl triflones using 4CzIPN as a triplet energy transfer photocatalyst is herein described. This metal-free protocol provides a straightforward and atom-economical approach to alkynyl-substituted γ-keto sulfones with a broad scope of substituents. In this transformation, alkynyl triflones could be used as both radical acceptors and SO2 donors. Preliminary experimental mechanistic studies and synthetic utility are also demonstrated.

Catalyst-Free α-trans-Selective Hydroboration and (E)-Selective Deuterated Semihydrogenation of Alkynyl Sulfones.

Here, we present a straightforward α-trans-selective hydroboration of alkynyl sulfones with NHC-boranes without the need for a catalyst. This reaction is compatible with a wide range of substrates for efficiently producing structurally diverse α-borylated vinyl sulfones in satisfactory yields. The hydride transfer from NHC-borane 2a to alkynyl triflone 1b is studied by density functional theory (DFT) calculations for trans-hydroboration. Moreover, a regiodivergent deuterated semihydrogenation of alkynyl triflones has also been developed using D2O as the deuterium source. A variety of diversity-oriented D-containing vinyl triflones were prepared in good to excellent yields with excellent deuterium incorporation ratios. Synthetic manipulations of the deuterated products are achieved for the conversion into valuable deuterated molecules, indicating the utility of this protocol.

Se-methylselenocysteine inhibits the progression of non-small cell lung cancer via ROS-mediated NF-κB signaling pathway.

Se-methylselenocysteine (MSC) is recognized for its potential in cancer prevention, yet the specific effects and underlying processes it initiates within non-small cell lung cancer (NSCLC) remain to be fully delineated. Employing a comprehensive array of assays, including CCK-8, colony formation, flow cytometry, MitoSOX Red staining, wound healing, transwell, and TUNEL staining, we evaluated MSC's effects on A549 and 95D cell lines. Our investigation extended to the ROS-mediated NF-κB signaling pathway, utilizing Western blot analysis, P65 overexpression, and the application of IκB-α inhibitor (BAY11-7082) or N-acetyl-cysteine (NAC) to elucidate MSC's mechanism of action. In vivo studies involving subcutaneous xenografts in mice further confirmed MSC's inhibitory effect on tumor growth. Our findings indicated that MSC inhibited the proliferation of A549 and 95D cells, arresting cell cycle G0/G1 phase and reducing migration and invasion, while also inducing apoptosis and increasing intracellular ROS levels. This was accompanied by modulation of key proteins, including the upregulation of p21, p53, E-cadherin, Bax, cleaved caspase-3, cleaved-PARP, and downregulation of CDK4, SOD2, GPX-1. MSC was found to inhibit the NF-κB pathway, as evidenced by decreased levels of P-P65 and P-IκBα. Notably, overexpression of P65 and modulation of ROS levels with NAC could attenuate MSC's effects on cellular proliferation and metastasis. Moreover, MSC significantly curtailed tumor growth in vivo and disrupted the NF-κB signaling pathway. In conclusion, our research demonstrates that MSC exhibits anticancer effects against NSCLC by modulating the ROS/NF-κB signaling pathway, suggesting its potential as a therapeutic agent in NSCLC treatment.

Pharmacological interventions for the treatment of obstructive sleep apnea syndrome.

Obstructive Sleep Apnea Syndrome (OSAS) affects 13-33% of males and 6-9% of females globally and poses significant treatment challenges, including poor adherence to Continuous Positive Airway Pressure (CPAP) and residual excessive sleepiness (RES). This review aims to elucidate the emerging interest in pharmacological treatments for OSAS, focusing on recent advancements in this area. A thorough analysis of extensive clinical trials involving various drugs, including selective dopamine reuptake inhibitors, selective norepinephrine inhibitors, combined antimuscarinic agents, and orexin agonists, was conducted. These trials focused on ameliorating respiratory metrics and enhancing sleep quality in individuals affected by OSAS. The studied pharmacological agents showed potential in improving primary outcomes, notably the apnea-hypopnea index (AHI) and the Epworth sleepiness scale (ESS). These improvements suggest enhanced sleep quality and symptom management in OSAS patients. With a deeper understanding of OSAS, pharmacological interventions are emerging as a promising direction for its effective management. This review provides a comprehensive overview of the current state of drug research in OSAS, highlighting the potential of these treatments in addressing the disorder's complex challenges.

Comparison of ANN and LR models for predicting Carbapenem-resistant Klebsiella pneumoniae isolates from a southern province of China's RNSS data.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious threat to public health due to its limited treatment options and high mortality rate. This study aims to identify the risk factors of carbapenem resistance in patients with K. pneumoniae isolates and develop CRKP prediction models using logistic regression (LR) and artificial neural network (ANN) methods. METHODS: We retrospectively analysed the data of 49,774 patients with Klebsiella pneumoniae isolates from a regional nosocomial infection surveillance system (RNSS) between 2018 and 2021. We performed logistic regression analyses to determine the independent predictors for CRKP. We then built and evaluated LR and ANN models based on these predictors using calibration curves, ROC curves, and decision curve analysis (DCA). We also applied the Synthetic Minority Over-Sampling Technique (SMOTE) to balance the data of CRKP and non-CRKP groups. RESULTS: The LR model showed good discrimination and calibration in both training and validation sets, with areas under the ROC curve (AUROC) of 0.824 and 0.825, respectively. The DCA indicated that the LR model had clinical usefulness for decision making. The ANN model outperformed the LR model both in the training set and validation set. The SMOTE technique improved the performance of both models for CRKP detection in training set, but not in the validation set. CONCLUSION: We developed and validated LR and ANN models for predicting CRKP based on RNSS data. Both models were feasible and reliable for CRKP inference and could potentially assist clinicians in selecting appropriate empirical antibiotics and reducing unnecessary medical resource utilization.

Risk exploration and prediction model construction for linezolid-resistant Enterococcus faecalis based on big data in a province in southern China.

BACKGROUND: Enterococcus faecalis is a common cause of healthcare-associated infections. Its resistance to linezolid, the antibiotic of last resort for vancomycin-resistant enterococci, has become a growing threat in healthcare settings. METHODS: We analyzed the data of E. faecalis isolates from 26 medical institutions between 2018 and 2020 and performed univariate and multivariate logistic regression analyses to determine the independent predictors for linezolid-resistant E. faecalis (LREFs). Then, we used the artificial neural network (ANN) and logistic regression (LR) to build a prediction model for linezolid resistance and performed a performance evaluation and comparison. RESULTS: Of 12,089 E. faecalis strains, 755 (6.25%) were resistant to linezolid. Among vancomycin-resistant E. faecalis, the linezolid-resistant rate was 24.44%, higher than that of vancomycin-susceptible E. faecalis (p < 0.0001). Univariate and multivariate regression analyses showed that gender, age, specimen type, length of stay before culture, season, region, GDP (gross domestic product), number of beds, and hospital level were predictors of linezolid resistance. Both the ANN and LR models constructed in the study performed well in predicting linezolid resistance in E. faecalis, with AUCs of 0.754 and 0.741 in the validation set, respectively. However, synthetic minority oversampling technique (SMOTE) did not improve the prediction ability of the models. CONCLUSION: E. faecalis linezolid-resistant rates varied by specimen site, geographic region, GDP level, facility level, and the number of beds. At the same time, community-acquired E. faecalis with linezolid resistance should be monitored closely. We can use the prediction model to guide clinical medication and take timely prevention and control measures.

Historical transformation of healthy promotion patterns among children and adolescents in China / 中国学校卫生

Abstract@#In order to identify new pattern and experience of school health, and to elaborate on the progress and trends in children and adolescents health promotion, the present article presents historical changes in health promotion approaches for children and adolescents in China, making strategic shift from "prevention and treatment of student common disease centered" to "student healthy development centered", fostering policy changes from "special school health services" to " comprehensive school health services", enacting the paradigm shift from "biomedical disease prevention and health care" model to "promoting social and behavioral success for learning" model, using various methods including needs analysis, trend research and judgment, system evaluation, and empirical evidence. The fast, substantial and extensive transformation delivers sustainable long term value and will continue to respond to the needs of the times and make steady and long term progress.

Causal relationship between levels of myeloperoxidase and obstructive sleep apnea: a bidirectional two-sample Mendelian randomization study.

Background: Several observational studies have investigated the association between myeloperoxidase (MPO) and obstructive sleep apnea (OSA). However, the nature of this relationship remains uncertain due to potential selection and confounding biases. To resolve this, we conducted a bidirectional two-sample Mendelian randomization (MR) study to scrutinize the causal relationship between MPO and OSA. Methods: Instrumental variables (IVs) for OSA were sourced from the publicly available FinnGen dataset, encompassing 38,998 OSA cases and 336,659 controls. Data on MPO were sourced from a study of 21,758 individuals conducted by the European Bioinformatics Institute (EBI). The primary MR analysis utilized the inverse-variance weighted (IVW) method, with MR-Egger intercept and leave-one-out methods assessing pleiotropy and Cochran's Q test determining heterogeneity. Results: The IVW analysis indicated a causal relationship between heightened MPO levels and an increased incidence of OSA. Individuals with elevated MPO levels manifested a higher propensity to develop OSA, exhibiting an odds ratio (OR) of 1.075 and a 95% confidence interval (CI) of 1.011-1.143 (p = 0.021). Conversely, the reciprocal analysis unveiled no significant association between OSA and heightened MPO levels (p = 0.643). No directional pleiotropy was identified through the MR-Egger intercept test (p > 0.05). Conclusion: Our study provides evidence of an association between elevated MPO levels and an increased incidence of OSA. However, OSA does not necessarily lead to elevated MPO levels. When patients present with high MPO levels, screening for OSA may be advisable, considering their clinical characteristics.

The Presence, Location, and Degree of Late Gadolinium Enhancement in Relation to Myocardial Dysfunction and Poor Prognosis in Patients with Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) typically develop myocardial fibrosis. No studies have investigated the clinical significance of the presence, location, and degree of fibrosis in SLE patients. Seventy-four SLE patients were included. Thirty-seven non-autoimmune disease patients and thirty-seven healthy individuals were included as controls. Myocardial fibrosis was evaluated at cardiac magnetic resonance via a qualitative and quantitative assessment of late gadolinium enhancement (LGE). Myocardial function was measured via speckle-tracking echocardiography. All patients were followed up for the occurrence of major adverse cardiac events (MACE). The presence, locations, and degrees of LGE disturbed regional and global myocardial function. The presence of LGE, left ventricular free-wall LGE (LVFW LGE), and severe LGE were all independent predictors of MACE in SLE patients [LGE presence HR: 3.746 (1.434-9.79), p = 0.007; LVFW LGE HR: 2.395 (1.023-5.606), p = 0.044; severe LGE HR: 3.739 (1.241-11.266), p = 0.019]. LGE combined with SLE-related organ damage identified patients at high risk of MACE (p < 0.001). In conclusion, the presence, degree, and location of LGE were associated with myocardial dysfunction. The presence, location, and degree of LGE had the potential to independently predict poor prognosis and improve risk stratification in SLE patients.

Relationship between three dietary indices and health-related quality of life among rural elderly in China: a cross-sectional study.

Purpose: This study aimed to explore the association between health-related quality of life (HRQOL) and diet quality using three evidence-based dietary indices among older people in rural China. Methods: This cross-sectional study included 1,258 rural older people (mean age 72.32 years; 55.6% female). HRQOL was assessed using the European Five Dimension Health Scale (EQ-5D), and dietary intake was assessed using a Food Frequency Questionnaire. Three dietary scoring indices, including the Alternate Healthy Eating Index, Dietary Approaches to Stop Hypertension, and Dietary Diversity Score (DDS), were calculated to assess and analyze the relationship between these dietary indices and quality of life. Results: The EQ-5D score was 0.95 ± 0.10, and the EQ-Visual Analog Scale (VAS) score was 76.76 ± 14.44. All three groups with higher dietary indices had higher quality of life scores. After controlling for covariates in multivariate adjusted binary logistic regression analyzes, participants in the top tertile of DDS had higher quality of life scores than those in the bottom tertile. DDS was consistently associated with EQ-5D (Model 2: OR = 1.567, p = 0.001; Model3: OR = 1.351, p = 0.044) and EQ-VAS (Model 2: OR = 1.830, p < 0.001; Model 3: OR = 1.383, p = 0.047), significantly different from the other groups. Conclusion: Older people in rural China who adhere to various foods experience a better quality of healthy life.

Identification of Myocardial Scarring Using Contrast-Free Cardiac MRI in Patients With Autoimmune Rheumatic Diseases.

BACKGROUND: Late gadolinium enhancement (LGE) cardiac MRI is the method of choice in revealing the presence of myocardial scarring, but its availability remains limited in clinical practice. PURPOSE: To assess myocardial scarring in patients with autoimmune rheumatic diseases (ARDs) using contrast-free cardiac MRI with a radiomics model. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-two patients (mean age, 41 years ± 15, 62 men) with or without ARDs, grouped into a training set of 153 patients and a testing set of 39 patients. FIELD STRENGTH/SEQUENCE: 3.0 T/ cine imaging with a balanced steady-state free precession sequence, T1 mapping with a modified Look-Locker inversion recovery sequence, and LGE imaging with a phase-sensitive inversion recovery gradient echo sequence. ASSESSMENT: LGE assessment was the reference standard for identifying myocardial scarring. Based on motion features extracted from cine images and tissue characterization features extracted from native T1 maps, a fully automated radiomics model with T1, cine MRI, or combined inputs was developed. STATISTICAL TESTS: Logistic regression model was used to detect myocardial scarring using contrast-free cardiac MRI parameters. Receiver operating characteristic curves were analyzed to assess the accuracy, sensitivity, and specificity in detecting myocardial scarring. Sensitivities of the models were further assessed in patients with various myocardial scarring proportions. Z-statistic and dice coefficient were assessed to compare the performance. P-values <0.05 were considered significant. RESULTS: The multivariable regression model exhibited an accuracy of 85.3%, a sensitivity of 93.5%, and a specificity of 50.0%. The radiomics model with T1 and cine MRI input exhibited an accuracy of 75.7%, a sensitivity of 60.9%, and a specificity of 85.5%. Moreover, the radiomics model showed a sensitivity of 90.9% among patients with >25% myocardial scarring. DATA CONCLUSIONS: The proposed radiomics model allowed for the identification of myocardial scarring similar to LGE, but on contrast-free cardiac MRI in patients with ARDs. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

New dammarane-type triterpenoids from hydrolyzate of total Gynostemma pentaphyllum saponins with protein tyrosine phosphatase 1B inhibitory activity.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Multiparametric MRI combined with clinical factors to predict glypican-3 expression of hepatocellular carcinoma.

Objectives: The present study aims at establishing a noninvasive and reliable model for the preoperative prediction of glypican 3 (GPC3)-positive hepatocellular carcinoma (HCC) based on multiparametric magnetic resonance imaging (MRI) and clinical indicators. Methods: As a retrospective study, the subjects included 158 patients from two institutions with surgically-confirmed single HCC who underwent preoperative MRI between 2020 and 2022. The patients, 102 from institution I and 56 from institution II, were assigned to the training and the validation sets, respectively. The association of the clinic-radiological variables with the GPC3 expression was investigated through performing univariable and multivariable logistic regression (LR) analyses. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (GPC3-negative HCCs) in the training set, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. Next, a prediction nomogram was developed and validated for patients with GPC3-positive HCC. The performance of the nomogram was evaluated through examining its calibration and clinical utility. Results: Based on the results obtained from multivariable analyses, alpha-fetoprotein levels > 20 ng/mL, 75th percentile ADC value < 1.48 ×103 mm2/s and R2* value ≥ 38.6 sec-1 were found to be the significant independent predictors of GPC3-positive HCC. The SMOTE-LR model based on three features achieved the best predictive performance in the training (AUC, 0.909; accuracy, 83.7%) and validation sets (AUC, 0.829; accuracy, 82.1%) with a good calibration performance and clinical usefulness. Conclusions: The nomogram combining multiparametric MRI and clinical indicators is found to have satisfactory predictive efficacy for preoperative prediction of GPC3-positive HCC. Accordingly, the proposed method can promote individualized risk stratification and further treatment decisions of HCC patients.

Et2Zn-Mediated Radical (3 + 2) Cycloaddition of Vinyl Azides with Ethyl Iododifluoroacetate to Access 3,3-Difluoro-γ-lactams.

A diethylzinc-mediated radical (3 + 2) cycloaddition of vinyl azides with ethyl iododifluoroacetate is presented. The developed reaction features good functional group tolerance, broad substrate scope, and operational simplicity, enabling efficient assembly of a wide range of 3,3-difluoro-γ-lactam derivatives bearing an O-substituted quaternary carbon center in moderate to good yields. The utility of the method is showcased by a scaled-up reaction, conversion of the product, and late-stage structural modifications of a variety of pharmaceutical compounds.