GC Snakes: An Efficient and Robust Segmentation Model for Hot Forging Images.

Machine vision is a desirable non-contact measurement method for hot forgings, as image segmentation has been a challenging issue in performance and robustness resulting from the diversity of working conditions for hot forgings. Thus, this paper proposes an efficient and robust active contour model and corresponding image segmentation approach for forging images, by which verification experiments are conducted to prove the performance of the segmentation method by measuring geometric parameters for forging parts. Specifically, three types of continuity parameters are defined based on the geometric continuity of equivalent grayscale surfaces for forging images; hence, a new image force and external energy functional are proposed to form a new active contour model, Geometric Continuity Snakes (GC Snakes), which is more percipient to the grayscale distribution characteristics of forging images to improve the convergence for active contour robustly; additionally, a generating strategy for initial control points for GC Snakes is proposed to compose an efficient and robust image segmentation approach. The experimental results show that the proposed GC Snakes has better segmentation performance compared with existing active contour models for forging images of different temperatures and sizes, which provides better performance and efficiency in geometric parameter measurement for hot forgings. The maximum positioning and dimension errors by GC Snakes are 0.5525 mm and 0.3868 mm, respectively, compared with errors of 0.7873 mm and 0.6868 mm by the Snakes model.

Pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 reinfections compared to those with a single infection: a retrospective cohort study.

BACKGROUND: To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. METHODS: This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission. RESULTS: We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms. CONCLUSION: Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes.

NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression.

Gastric cancer (GC) is an aggressive malignancy with poor patient outcomes. NAT10 is an acetyltransferase that has been reported to contribute to GC progression. In-depth investigation into the underlying molecular mechanisms driven by NAT10 could help identify therapeutic targets to improve GC treatment. Here, we found that NAT10 forms condensates to regulate RNA dynamics and promote GC progression. In GC patient samples, elevated NAT10 expression correlated with an unfavorable prognosis, advanced disease stage, and metastasis. NAT10 enhanced proliferation, migration, and invasion of GC cells, supported growth of patient-derived organoids, and accelerated tumor development. A C-terminal intrinsically disordered region mediated liquid-liquid phase separation (LLPS) of NAT10 and was essential for its tumor-promoting function in GC. Moreover, NAT10 interacted with the splicing factor SRSF2, leading to its acetylation and increased stability. Acetylated SRSF2 directly bound to the pre-mRNA of the m6A reader YTHDF1, resulting in enhanced YTHDF1 exon 4 skipping and upregulation of a short YTHDF1 transcript that could stimulate GC cell proliferation and migration. Furthermore, YTHDF1 exon 4 skipping correlated with NAT10 and SRSF2 expression and was associated with a more aggressive phenotype in GC patient samples. Together, this study uncovers the role of NAT10 LLPS in modulating YTHDF1 splicing through SRSF2 acetylation to drive GC progression, providing insights into the oncogenic mechanism of NAT10.

Selective STAT3 inhibitor STX-0119 alleviates osteoarthritis progression by modulating the STAT3/PPARγ signaling pathway.

Osteoarthritis (OA), characterized by chronic pain, significantly affects the quality of life of affected individuals. Key factors in OA pathogenesis include cartilage degradation and inflammation. Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, plays a pivotal role in mediating inflammation. STX-0119 has been verified as a small molecular compound that can specifically inhibit STAT3. However, the efficacy of STX-0119 in the treatment of OA remains to be evaluated. Therefore, the aim of this study was to explore the therapeutic effects and molecular mechanisms of STX-0119 in the treatment of OA. We found that the expression of phosphorylated STAT3 is upregulated in human OA cartilage as well as in the cartilage of a mouse model of OA. In vivo, joint injection of STX-0119 into OA mice alleviated cartilage degeneration without affecting the subchondral bone. Additionally, STX-0119 could inhibit the phosphorylation of STAT3 in the cartilage. In vitro, STX-0119 suppressed inflammatory responses in chondrocytes and promoted anabolic metabolism in an interleukin-1ß-induced chondrocyte inflammation model. Additionally, the results of transcriptome sequencing and lentiviral infection assays demonstrated that in chondrocytes, STX-0119 induces the upregulation of peroxisome proliferators-activated receptor gamma (PPARγ) expression by inhibiting STAT3 phosphorylation. Finally, in ex vivo cultures of human cartilage samples, STX-0119 was reaffirmed to inhibit cartilage degeneration via the STAT3/PPARγ signaling pathway. Together, our findings support the potential of STX-0119 for development as a therapeutic agent targeting STAT3 for the treatment of OA.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.

Diagnostic Study of Nodular Pulmonary Cryptococcosis Based on Radiomic Features Captured from CT Images.

BACKGROUND: Radiomics can quantify pulmonary nodule characteristics non-invasively by applying advanced imaging feature algorithms. Radiomic textural features derived from Computed Tomography (CT) imaging are broadly used to predict benign and malignant pulmonary nodules. However, few studies have reported on the radiomics-based identification of nodular Pulmonary Cryptococcosis (PC). OBJECTIVE: This study aimed to evaluate the diagnostic and differential diagnostic value of radiomic features extracted from CT images for nodular PC. METHODS: This retrospective analysis included 44 patients with PC (29 males, 15 females), 58 with Tuberculosis (TB) (39 males, 19 females), and 60 with Lung Cancer (LC) (20 males, 40 females) confirmed pathologically. Models 1 (PC vs. non-PC), 2 (PC vs. TB), and 3 (PC vs. LC) were established using radiomic features. Models 4 (PC vs. TB) and 5 (PC vs. LC) were established based on radiomic and CT features. RESULTS: Five radiomic features were predictive of PC vs. non-PC model, but accuracy and Area Under the Curve (AUC) were 0.49 and 0.472, respectively. In model 2 (PC vs. TB) involving six radiomic features, the accuracy and AUC were 0.80 and 0.815, respectively. Model 3 (PC vs. LC) with six radiomic features performed well, with AUC=0.806 and an accuracy of 0.76. Between the PC and TB groups, model 4 combining radiomics, distribution, and PI, showed AUC=0.870. In differentiating PC from LC, the combination of radiomics, distribution, PI, and RBNAV achieved AUC=0.926 and an accuracy of 0.90. CONCLUSION: The prediction models based on radiomic features from CT images performed well in discriminating PC from TB and LC. The individualized prediction models combining radiomic and CT features achieved the best diagnostic performance.

Epidemiological Characterisation of Chronic Diseases Among Civil Servants in Hebei Province, China: A Cross-Sectional Real-World Study of Approximately 50,000 Adults.

Background: The objective of this investigation was to explore the health status and epidemiological features of civil servants working in Hebei Province, China. Methods: Data was collected through a cross-sectional survey that involved 50,039 adult civil servants in Hebei Province. The research was conducted at the Hebei Provincial Medical Examination Centre and included inquiries about demographics, health behaviours, chronic illnesses, and abnormal check-up indicators. Statistical data were used to determine the prevalence of chronic diseases and abnormal health examination indicators. Subgroup analyses by sex were then conducted to calculate the similarities and differences in health status between men and women. Results: The findings of the survey indicate that 14.2% of individuals who work in civil service suffer from obesity. Additionally, a considerable proportion of this group display poor health behaviours, including smoking and alcohol consumption. Hypertension (21.03%), dyslipidaemia (10.88%), and diabetes mellitus (8.56%) were identified as the top three chronic diseases, while cardiovascular diseases were prevalent at 6.27% among civil servants. Ultrasound showed a high prevalence of fatty liver, non-smooth gallbladder and liver cysts (44.61%, 33.24% and 23.26% respectively). The occurrence of pulmonary nodules was alarmingly high at 88.48%, while thyroid nodules were found in as much as 62.65% of patients. Abnormal E/A values≤1, prostate hyperplasia, breast nodules, and carotid plaques were also prevalent, with percentages ranging from 46.76% to 63.04%. In subgroup analyses by gender, the prevalence of chronic diseases and abnormal screening indicators was consistently higher in men than in women, with the exception of thyroid nodules and thyroid surgery. Conclusion: The survey revealed a large proportion of civil servants in Hebei Province, China, suffering from chronic diseases, underscoring the necessity for enhanced attention to chronic disease prevention and management in this group and emphasising the requirement for focused interventions aimed at improving health outcomes.

Effect of Semaglutide and Empagliflozin on Pulmonary Structure and Proteomics in Obese Mice.

Objective: This study utilized proteomics to investigate changes in protein expression associated with lung health in obese mice exposed to semaglutide and empagliflozin through a high-fat diet. Methods: Twenty-eight male C57BL/6JC mice were randomly assigned to two groups: a control diet group (n = 7) and a high-fat diet group (n = 21). The HFD group was further divided into three groups: HFD group (n = 7), Sema group (n = 7), and Empa group (n = 7). Post-treatment, mice underwent assessments including glucose tolerance, lipids, oxidative stress markers, body weight, lung weight, and structure. Proteomics identified differentially expressed proteins (DEPs) in lung tissue, and bioinformatics analyzed the biological processes and functions of these proteins. Results: Semaglutide and empagliflozin significantly attenuated obesity-induced hyperglycemia, abnormal lipid metabolism, oxidative stress response, and can decrease alveolar wall thickness, enlarge alveolar lumen, and reduce collagen content in lung tissue. Both medications also attenuated lung elastic fibre cracking and disintegration. In the HFD/NCD group, there were 66 DEPs, comprising 30 proteins that were increased and 36 that were decreased. Twenty-three DEPs overlapped between Sema/HFD and Empa/HFD, with 11 up-regulated and 12 down-regulated simultaneously. After analysing DEPs in different groups, four proteins - LYVE1, BRAF, RGCC, and CHMP5 - were all downregulated in the HFD group and upregulated by semaglutide and empagliflozin treatment. Conclusion: This study demonstrates that obesity induced by a high-fat diet causes a reduction in the expression of LYVE1, BRAF, RGCC, and CHMP5 proteins, potentially affecting lung function and structure in mice. Significantly, the administration of semaglutide and empagliflozin elevates the levels of these proteins, potentially offering therapeutic benefits against lung injury caused by obesity. Merging semaglutide with empagliflozin may exert a more pronounced impact.

Exploring the sexual experiences and challenges of individuals with cerebral palsy.

PURPOSE: Cerebral palsy (CP) is a prevalent motor disorder affecting children, with evolving demographics indicating an increasing survival into adulthood. This shift necessitates a broader perspective on CP care, particularly in addressing the often overlooked aspect of sexuality. The purpose of this study was to investigate experiences of, challenges with, and related factors of sexuality and intimacy that people with CP are facing. METHODS: This was a descriptive and cross-sectional single institution survey among individuals with CP, ages 18 to 65, who had the ability to independently complete an online survey. RESULTS: A total of 40 respondents participated in the survey (Gross Motor Function Classification System [GMFCS] level I/II, 32.5%; III, 35%; IV, 32.5%). Of those, 45% were partnered, 60% had past sexual experience, 47.5% were currently sexually active at the time of submitting the survey, 80% had masturbation experience, and 45.8% believed it had positive effect on their self-esteem. Only 10% received sex education tailored for people with disability, whereas school (72.5%) and internet (35%) were the most common sources of sex education. Muscle spasms, positioning difficulty, and pain/discomfort were the most common physical challenges experienced during intimate activity amongst all function stratifications. Stratification analysis showed that, compared to higher functioning respondents, a smaller proportion of lower functioning respondents were partnered (GMFCS IV, 23.1%; quadriplegic, 31.6%), had past or current sexual experience (GMFCS IV, 44.4%, 36.4%; quadriplegic, 42.1%, 26.3%, respectively), and had masturbation experience (GMFCS IV, 61.5%); Also, they had worse Quality of Life Scale scores on average (GMFCS IV, 88.4; quadriplegic, 88.3) and a higher rate of reported positive effects of sexual experiences on self-esteem than negative (GMFCS IV, 38.5%; quadriplegic, 35%).

Association of Concomitant MRI-Determined Anterolateral Complex Injury With Quantitative Measurements of Altered Rotational Tibiofemoral Position on MRI in Patients With ACL Injury.

Background: Reduced graft failure rates have been reported after anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex (ALC) augmentation. However, the preoperative diagnosis of concomitant ALC injury remains a clinical challenge. Purpose: To identify the altered rotational tibiofemoral position on magnetic resonance imaging (MRI) in ACL-injured patients with concomitant ALC injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Based on the evaluation of ALC abnormalities on MRI scans by experienced surgeons, 123 patients with nonchronic (<3 months) ACL injury confirmed by arthroscopy were included. The patients were divided into 2 groups-an ALC-injured group (n = 57) and an ALC-intact group (n = 66). The altered rotational tibiofemoral position was evaluated and compared by quantitatively measuring internal rotational tibial subluxation (IRTS) and axial internal tibial rotation (ITRa) on MRI. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to identify the factors associated with concomitant MRI-determined ALC injury. Results: The ALC-injured group showed significantly increased IRTS (P < .001), ITRa (P < .001), lateral anterior tibial subluxation (ATS) (P < .001), and global ATS (GATS) (P = .002) compared with the ALC-intact group, while no significant difference in medial ATS (P = .810) was observed. A strong positive correlation was identified between IRTS and ITRa (rP = 0.809; P < .001). Multivariate analyses revealed that IRTS (P < .001) and GATS (P = .016) were associated factors for the presence of concomitant MRI-determined ALC injury. IRTS (area under the curve [AUC] = 0.734) was more strongly associated with the outcome than GATS (AUC = 0.658) in ROC analyses, suggesting a more significant internal rotational subluxation than anterior subluxation of the tibia. An IRTS threshold of 3.1 mm demonstrated a specificity of 84.2% for indicating the presence of concomitant MRI-determined ALC injury. Conclusion: The presence of concomitant MRI-determined ALC injury in ACL-injured patients was associated with a significant increase in IRTS and ITRa compared with those with intact ALC, indicating that these MRI measurements of the altered rotational tibiofemoral position could serve as potential quantifiable indicators for identifying concomitant ALC injury in clinical practice.

Nonsteroidal Anti-Inflammatory Drug Injections versus Steroid Injections in the Management of Upper and Lower Extremity Orthopedic Conditions: A Systematic Review with Meta-Analysis.

BACKGROUND: Although corticosteroid injections are an effective treatment for musculoskeletal pathologies, they may not be suitable for all patients. The purpose of this systematic review was to compare clinical outcomes between patients who received NSAID and corticosteroid injections for various orthopedic conditions. METHODS: Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched, and meta-analyses were performed using a random-effects model for outcomes presented in three or more studies. Other studies were qualitatively analyzed. RESULTS: A total of 28 articles with 2113 patients were included. A meta-analysis of five studies in patients with shoulder impingement syndrome demonstrated that there was no significant difference in the pain visual analogue scale (VAS) between subacromial NSAID injections and corticosteroid injections at 1 month [weighted mean difference (WMD) -0.244; 95% CI, -1.232 to 0.745; I2, 94.5%]. For patients with knee osteoarthritis, a meta-analysis of three studies demonstrated that there was no significant difference between intraarticular NSAID injections and corticosteroid injections in pain VAS at 1 month (WMD 0.754; 95% CI, -0.413 to 1.921; I2, 90.2%) and 3 months (WMD-0.089; 95% CI, -0.345 to 0.166; I2, 0%). A review of the studies assessing pain outcomes for hip osteoarthritis, adhesive capsulitis, and plantar fasciitis showed no significant differences between the NSAID and corticosteroid groups. CONCLUSION: NSAID injections may be safe and effective alternatives to steroid injections, especially in shoulder impingement syndrome and knee osteoarthritis.

Correlation Between Glycolipid Metabolism Levels and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus.

Purpose: We investigate the correlation between glucose and lipid metabolism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and its diagnostic and predictive value. Patients and Methods: A retrospective analysis involved 620 patients diagnosed with T2DM, categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=340) and the diabetic retinopathy group (DR, n=280). We collected baseline patient data, calculated the ratio of glycated hemoglobin (HbA1c) to high-density lipoprotein cholesterol (HDL-C), and analyzed its association with Type 2 Diabetic Retinopathy. Results: HbA1c/HDL-C in DR group exhibited significantly higher than the NDR group (P<0.001). Mantel-Haenszel's chi-square trend analysis indicated a notable linear trend (P<0.001) between HbA1c/HDL-C and DR. HbA1c/HDL-C revealed moderate positive correlations with DR, r=0.342, P<0.001. Binary logistic regression analysis showed systolic blood pressure (SBP), diabetes course, fasting blood glucose (FBG) and HbA1c/HDL-C as independent risk factors for DR in T2DM patients. Restrictive cubic spline analysis demonstrated a significant nonlinear relationship between HbA1c/HDL-C and DR (P total trend <0.001, P nonlinear = 0.0196). ROC curve analysis identified that HbA1c/HDL-C had the highest diagnostic accuracy for DR, with an area under the ROC curve (AUC) of 0.711, 53.2% sensitivity, and 78.2% specificity. Conclusion: Our study shows that HbA1c/HDL-C is an independent risk factor for DR in patients with type 2 diabetes. HbA1c/HDL-C has good diagnostic value for DR and can be used as a biological index for early screening of DR.

Separation of anti-TMV active components and modes of action of Omphalia lapidescens.

BACKGROUND: Omphalia lapidescens is a saprophytic and parasitic fungus belonging to the Polypora genus of Tricholomataceae. It has repellent, insecticidal, anti-inflammatory and immunomodulatory effects. RESULT: This study found that the extract of O. lapidescens had significant anti-TMV activity, and the main active component was homopolysaccharide LW-1 by Bioassay-guided fractionation. LW-1 is a glucan with ß-(1,3) glucoside bond as the main chain and ß-(1,6) glucoside bond as the branch chain, with molecular weight in the range of 172,916-338,827 Da. The protective and inactive efficacies of LW-1(100 mg/L) against TMV were 78.10% and 48.20%, but had no direct effect on the morphology of TMV particles. The results of mechanism of action showed that LW-1 induced the increase of the activity of defense enzymes such as POD, SOD and PAL in Nicotiana glutinosa. The overexpression of resistance genes such as NPR1, PR1 and PR5, and the increase of SA content. Further transcriptome sequencing showed that LW-1 activated MAPK signaling pathway, plant-pathogen interaction pathway and glucosinolide metabolic pathway in Arabidopsis thaliana. Besides, LW-1 induced crops resistance against plant pathogenic fungi. CONCLUSION: Taken together, the anti-TMV mechanism of LW-1 was to activate MAPK signaling pathway, inducing overexpression of resistance genes, activating plant immune system, and improving the synthesis and accumulation of plant defencins such as glucosinolide. LW-1-induced plant disease resistance has the advantages of broad spectrum and long duration, which has the potential to be developed as a new antiviral agent or plant immune resistance inducer.

SETD2 loss in renal epithelial cells drives epithelial-to-mesenchymal transition in a TGF-ß-independent manner.

Histone-lysine N-methyltransferase SETD2 (SETD2), the sole histone methyltransferase that catalyzes trimethylation of lysine 36 on histone H3 (H3K36me3), is often mutated in clear cell renal cell carcinoma (ccRCC). SETD2 mutation and/or loss of H3K36me3 is linked to metastasis and poor outcome in ccRCC patients. Epithelial-to-mesenchymal transition (EMT) is a major pathway that drives invasion and metastasis in various cancer types. Here, using novel kidney epithelial cell lines isogenic for SETD2, we discovered that SETD2 inactivation drives EMT and promotes migration, invasion, and stemness in a transforming growth factor-beta-independent manner. This newly identified EMT program is triggered in part through secreted factors, including cytokines and growth factors, and through transcriptional reprogramming. RNA-seq and assay for transposase-accessible chromatin sequencing uncovered key transcription factors upregulated upon SETD2 loss, including SOX2, POU2F2 (OCT2), and PRRX1, that could individually drive EMT and stemness phenotypes in SETD2 wild-type (WT) cells. Public expression data from SETD2 WT/mutant ccRCC support the EMT transcriptional signatures derived from cell line models. In summary, our studies reveal that SETD2 is a key regulator of EMT phenotypes through cell-intrinsic and cell-extrinsic mechanisms that help explain the association between SETD2 loss and ccRCC metastasis.

Exploring Route-Specific Pharmacokinetics of PFAS in Mice by Coupling in Vivo Tests and Physiologically Based Toxicokinetic Models.

BACKGROUND: Oral ingestion, inhalation, and skin contact are important exposure routes for humans to uptake per- and polyfluoroalkyl substances (PFAS). However, nasal and dermal exposure to PFAS remains unclear, and accurately predicting internal body burden of PFAS in humans via multiple exposure pathways is urgently required. OBJECTIVES: We aimed to develop multiple physiologically based toxicokinetic (PBTK) models to unveil the route-specific pharmacokinetics and bioavailability of PFAS via respective oral, nasal, and dermal exposure pathways using a mouse model and sought to predict the internal concentrations in various tissues through multiple exposure routes and extrapolate it to humans. METHODS: Mice were administered the mixed solution of perfluorohexane sulfonate, perfluorooctane sulfonate, and perfluorooctanoic acid through oral, nasal, and dermal exposure separately or jointly. The time-dependent concentrations of PFAS in plasma and tissues were determined to calibrate and validate the individual and combined PBTK models, which were applied in single- and repeated-dose scenarios. RESULTS: The developed route-specific PBTK models successfully simulated the tissue concentrations of PFAS in mice following single or joint exposure routes as well as long-term repeated dose scenarios. The time to peak concentration of PFAS in plasma via dermal exposure was much longer (34.1-83.0 h) than that via nasal exposure (0.960 h). The bioavailability of PFAS via oral exposure was the highest (73.2%-98.0%), followed by nasal (33.9%-66.8%) and dermal exposure (4.59%-7.80%). This model was extrapolated to predict internal levels in human under real environment. DISCUSSION: Based on these data, we predict the following: PFAS were absorbed quickly via nasal exposure, whereas a distinct hysteresis effect was observed for dermal exposure. Almost all the PFAS to which mice were exposed via gastrointestinal route were absorbed into plasma, which exhibited the highest bioavailability. Exhalation clearance greatly depressed the bioavailability of PFAS via nasal exposure, whereas the lowest bioavailability in dermal exposure was because of the interception of PFAS within the skin layers. https://doi.org/10.1289/EHP11969.

Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle.

The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA-mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-ß signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM-receptor interaction, focal adhesion and TGF-ß signaling, might be involved in the occurrence of CHDs.

The Combination of Remnant Cholesterol and Waist Circumference Offers Predictive Value for Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study from a Medical Examination Center.

Objective: To explore the association between levels of remnant cholesterol (RC) and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population, ultimately leading to the assessment of a novel proposed model combining RC and waist circumference (R-W) as a predictor of NAFLD incidence. Methods: A cross-sectional analysis was conducted of 4913 subjects undergoing physical examinations at Hebei General Hospital, with ultrasound findings being used to classify patients into individuals with and without NAFLD. Median RC values were used to separate subjects into those with low and high levels of RC, after which the predictive performance of RC and the novel R-W model when used to assess NAFLD risk was assessed through multifactorial logistic regression analyses and receiver operating characteristic curves. Results: Subjects exhibiting higher RC levels were found to exhibit an elevated risk of NAFLD incidence with or without adjusting for confounding factors. The binary logistic regression analysis-based R-W model may thus offer utility as a tool to gauge the risk of NAFLD in the general population, as it outperformed RC or WC alone, particularly when assessing women or individuals < 45 years of age. The area under the ROC curve for this combined R-W model was 0.813 (0.802, 0.824), with respective sensitivity and specificity values of 83.86% and 63.91%, all of which were significantly higher than corresponding values for RC and WC (P < 0.001). Conclusion: The present supports a strong association between RC levels and NAFLD in the general populace, and the combined R-W model exhibits greater utility as a tool to predict NAFLD incidence relative to RC or WC in isolation, particularly for individuals who are female or <45 years old.

Exploring the Correlation Between the Systemic Immune Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Type 2 Diabetic Retinopathy.

Purpose: Systemic immune inflammation index (SII), systemic inflammatory response index (SIRI) are new inflammation indicators calculated after integrating multiple indicators in blood routine. This study aims to investigate the correlation between the SII, SIRI and type 2 diabetic retinopathy (T2DR) and the diagnostic significance of these indices in T2DR. Patients and Methods: A retrospective analysis involved 500 patients diagnosed with type 2 diabetes (T2DM), categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=256) and the diabetic retinopathy group (DR, n=244). We calculated SII and SIRI, and analyzed their associations with T2DR. Results: The DR group exhibited significantly higher SII and SIRI values compared to the NDR group (P<0.001). Mantel-Haenszel's chi-square trend analysis revealed a notable linear trend (P<0.001) between SII, SIRI, and DR. SII and SIRI exhibited moderate positive correlations with DR, (r=0.354, P<0.001; r=0.469, P<0.001), respectively. Binary logistic regression analysis identified SII and SIRI as independent risk factors for DR. Restrictive cubic spline analysis demonstrated a significant linear relationship between SII and DR (P total trend <0.001, P nonlinear = 0.0657). Stratification by gender indicated that SII is more sensitive to the onset of DR in men. A significant nonlinear relationship was observed between SIRI and DR (P total trend <0.001, P nonlinear = 0.0025), with no gender-related differences in SIRI's association with DR. ROC curve analysis demonstrated that the combined use of SII and SIRI achieved the highest diagnostic accuracy for DR, with an AUC of 0.782, 74.6% sensitivity, and 69.9% specificity. Conclusion: Our findings suggested that SII and SIRI as independent risk factors for DR. The high accuracy of SII combined with SIRI in diagnosing DR underscores their potential as early biological indicators for DR diagnosis.

Ultra-High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates.

SCOPE: Ready-to-feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra-high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development. METHODS AND RESULTS: UHT-treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants. After 5 days, blood leukocytes, markers of systemic immunity and inflammation, kidney structure and function are evaluated. No consistent differences between UHT and PAST pigs are observed. However, SUHT increases plasma TNFα and IL-6 and reduces neutrophils and in vitro response to LPS. In SUHT pigs, the immature kidneys show minor upregulation of gene expressions related to inflammation (RAGE, MPO, MMP9) and oxidative stress (CAT, GLO1), together with glomerular mesangial expansion and cell injury. The increased inflammatory status in SUHT pigs appears unrelated to systemic levels of MRPs. CONCLUSION: SUHT feeding may impair systemic immunity and affect kidney development in preterm newborns. The systemic effects may be induced by local gut inflammatory effects of MRPs. Optimal processing and length of storage are critical for UHT-treated liquid IFs for preterm infants.