A novel defined programmed cell death related gene signature for predicting the prognosis of serous ovarian cancer.

PURPOSE: This study aims to explore the contribution of differentially expressed programmed cell death genes (DEPCDGs) to the heterogeneity of serous ovarian cancer (SOC) through single-cell RNA sequencing (scRNA-seq) and assess their potential as predictors for clinical prognosis. METHODS: SOC scRNA-seq data were extracted from the Gene Expression Omnibus database, and the principal component analysis was used for cell clustering. Bulk RNA-seq data were employed to analyze SOC-associated immune cell subsets key genes. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were utilized to calculate immune cell scores. Prognostic models and nomograms were developed through univariate and multivariate Cox analyses. RESULTS: Our analysis revealed that 48 DEPCDGs are significantly correlated with apoptotic signaling and oxidative stress pathways and identified seven key DEPCDGs (CASP3, GADD45B, GNA15, GZMB, IL1B, ISG20, and RHOB) through survival analysis. Furthermore, eight distinct cell subtypes were characterized using scRNA-seq. It was found that G protein subunit alpha 15 (GNA15) exhibited low expression across these subtypes and a strong association with immune cells. Based on the DEGs identified by the GNA15 high- and low-expression groups, a prognostic model comprising eight genes with significant prognostic value was constructed, effectively predicting patient overall survival. Additionally, a nomogram incorporating the RS signature, age, grade, and stage was developed and validated using two large SOC datasets. CONCLUSION: GNA15 emerged as an independent and excellent prognostic marker for SOC patients. This study provides valuable insights into the prognostic potential of DEPCDGs in SOC, presenting new avenues for personalized treatment strategies.

Performance improvement of atherosclerosis risk assessment based on feature interaction.

BACKGROUND AND OBJECTIVE: Cardiovascular disease is a leading cause of mortality and premature death. Early intervention in asymptomatic individuals through risk assessment can reduce the incidence of disease. Atherosclerosis is a major cause of cardiovascular disease and early detection can effectively prevent and treat it. In this study, we used real patient data to evaluate the risk of atherosclerosis, assisting doctors in diagnosis and reducing the incidence of cardiovascular disease. METHODS: We proposed a multi-stage atherosclerosis risk assessment model that includes three main stages: (i) SMOTE and decorrelation weighting algorithm technology were added to the causal stability middle layer to address class imbalance in the dataset and reduce the impact of feature-induced dataset distribution shifts on model differences. (ii) The feature interaction layer considered possible feature interactions and classified features by different categories. By adding more effective feature information, the accuracy and generalizability of the model were improved. (iii) In the integrated model layer, we chose LightGBM as the decision tree integration model for risk assessment because it has higher accuracy and robustness compared to other machine learning algorithms. RESULTS: The final model used a dataset containing 21 original features and 17 interaction features, achieving excellent performance under a 10-fold cross-validation strategy. The macro accuracy reached 93.86%, macro precision was 94.82%, macro recall was 93.52%, and macro F1 score was as high as 93.37%. These indicators demonstrate the accuracy and robustness of the model in atherosclerosis risk assessment. CONCLUSION: The model provides strong support for the prevention and diagnosis of cardiovascular disease. Through atherosclerosis risk assessment, the model can help doctors develop personalized prevention and treatment plans, which is of great significance for the prevention and treatment of cardiovascular disease.

Near-infrared-guided NO generator for combined NO/photothermal/chemodynamic therapy of bacterial infections.

Nitric oxide (NO)-based gas therapy approaches are promising in the treatment of infections; however, these strategies are hindered by poor delivery to the target site, which leads to unsatisfactory effects. In this study, we developed a NO-controlled platform (SCM@HA) via NO-generating mesoporous silica nanoparticles co-doped with sodium nitroprusside and copper sulphide to control NO production under near-infrared (NIR)-laser irradiation. Irradiation with an 808 nm NIR laser rapidly triggered the release of NO from the particles to actualise gas therapy. Photothermal therapy (PTT) also increased the local microenvironment temperature, and the close relationship between chemodynamic therapy (CDT) and temperature suggests that the increasing temperature facilitates in its working. The hydroxyl radicals generated by CDT can destroy the structure of bacteria in acidic environments. The germicidal activity of the nanoparticles was determined by the combined action of PTT, CDT, and NO-based gas therapy. The nanoparticles showed bactericidal activity in vitro against bacterial strains Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Finally, the anti-infective efficacy in vivo in S. aureus-infected mouse model was demonstrated. Thus, the synergistic antimicrobial effects of NO-generating silica nanoparticles have good potential for the non-antibiotic treatment of bacterial infections in wounds. STATEMENT OF SIGNIFICANCE: Bacterial infections and resistance are challenging health threats. Therefore, the development of an antibiotic-independent method is essential for the treatment of wound bacterial infections. In this study, NO-generating nanoparticles loaded with sodium nitroprusside in copper sulphide-doped mesoporous silica were prepared to control the long-term release of NO using near-infrared laser, which has good efficacy of PTT and CDT. The bactericidal effects of as-prepared nanoparticles against S. aureus and S. typhimurium have been well elucidated. This study proposes a feasible method in the field of NO-based therapy, thus paving the way that will benefit for the treatment of bacterial infections in wounds.

Bioinformatic Analysis Identifies Potential Extracellular Matrix Related Genes in the Pathogenesis of Early Onset Preeclampsia.

Early-onset preeclampsia (EOPE) is a complex pregnancy complication that poses significant risks to the health of both mothers and fetuses, and research on its pathogenesis and pathophysiology remains insuffcient. This study aims to explore the role of candidate genes and their potential interaction mechanisms in EOPE through bioinformatics analysis techniques. Two gene expression datasets, GSE44711 and GSE74341, were obtained from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) between EOPE and gestational age-matched preterm control samples. Functional enrichment analysis was performed utilizing the kyoto encyclopedia of genes and genomes (KEGG), gene ontology (GO), and gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed using the STRING database, and hub DEGs were identified through Cytoscape software and comparative toxicogenomics database (CTD) analysis. Furthermore, a diagnostic logistic model was established using these hub genes, which were confirmed through reverse transcription polymerase chain reaction (RT-PCR). Finally, immune cell infiltration was analyzed using CIBERSORT. In total, 807 DEGs were identified in the GSE44711 dataset (451 upregulated genes and 356 downregulated genes), and 787 DEGs were identified in the GSE74341 dataset (446 upregulated genes and 341 downregulated genes). These DEGs were significantly enriched in various molecular functions such as extracellular matrix structural constituent, receptor-ligand activity binding, cytokine activity, and platelet-derived growth factor. KEGG and GSEA annotation revealed significant enrichment in pathways related to ECM-receptor interaction, PI3K-AKT signaling, and focal adhesion. Ten hub genes were identified through the CytoHubba plugin in Cytoscape. Among these hub genes, three key DEGs (COL1A1, SPP1, and THY1) were selected using CTD analysis and various topological methods in Cytoscape. The diagnostic logistic model based on these three genes exhibited high efficiency in predicting EOPE (AUC = 0.922). RT-PCR analysis confirmed the downregulation of these genes in EOPE, and immune cell infiltration analysis suggested the significant role of M1 and M2 macrophages in EOPE. In conclusion, this study highlights the association of three key genes (COL1A1, SPP1, and THY1) with EOPE and their contribution to high diagnostic efficiency in the logistic model. Additionally, it provides new insights for future research on EOPE and emphasizes the diagnostic value of these identified genes. More research is needed to explore their functional and diagnostic significance in EOPE.

Autoimmune diseases and risk of gestational diabetes mellitus: a Mendelian randomization study.

AIMS: Observational studies have reported that autoimmune diseases are associated with gestational diabetes mellitus (GDM), but the causality is unknown. The study aimed to evaluate the potential causal effect of autoimmune diseases on GDM. METHODS: A two-sample Mendelian randomization (MR) study was designed using the summary statistics of GDM (123,579 individuals) and three common autoimmune diseases, including inflammatory bowel disease (IBD, 59,957 individuals), rheumatoid arthritis (RA, 80,799 individuals) and systemic lupus erythematosus (SLE, 14,267 individuals), from the genome-wide association study (GWAS). The fixed-effects inverse variance weighted (IVW) was used to deduce the causal association between autoimmune diseases and GDM, and sensitivity analyses were further performed. RESULTS: The inverse variance weighting (IVW) method showed that RA and SLE increased the risk of GDM (RA: OR = 1.076, 95%CI = 1.033-1.122, P = 4.649E-04; SLE: OR = 1.025, 95%CI = 1.001-1.049, P = 0.044). But there were no any associations of IBD with GDM (P > 0.05). No significant horizontal pleiotropy was found by MR Egger regression (IBD: P for intercept = 0.905; RA: P for intercept = 0.103; SLE = P for intercept = 0.608). CONCLUSION: This two-sample MR study found that both SLE and RA are positively associated with the risk of GDM. Our findings provide help for the future prevention and treatment of GDM to reduce associated maternal and fetal complications. However, more research is needed to obviate the role of the GC and the HCQ to ensure this relationship is causal.

Three-Direction Fusion for Accurate Volumetric Liver and Tumor Segmentation.

Biomedical image segmentation of organs, tissues and lesions has gained increasing attention in clinical treatment planning and navigation, which involves the exploration of two-dimensional (2D) and three-dimensional (3D) contexts in the biomedical image. Compared to 2D methods, 3D methods pay more attention to inter-slice correlations, which offer additional spatial information for image segmentation. An organ or tumor has a 3D structure that can be observed from three directions. Previous studies focus only on the vertical axis, limiting the understanding of the relationship between a tumor and its surrounding tissues. Important information can also be obtained from sagittal and coronal axes. Therefore, spatial information of organs and tumors can be obtained from three directions, i.e. the sagittal, coronal and vertical axes, to understand better the invasion depth of tumor and its relationship with the surrounding tissues. Moreover, the edges of organs and tumors in biomedical image may be blurred. To address these problems, we propose a three-direction fusion volumetric segmentation (TFVS) model for segmenting 3D biomedical images from three perspectives in sagittal, coronal and transverse planes, respectively. We use the dataset of the liver task provided by the Medical Segmentation Decathlon challenge to train our model. The TFVS method demonstrates a competitive performance on the 3D-IRCADB dataset. In addition, the t-test and Wilcoxon signed-rank test are also performed to show the statistical significance of the improvement by the proposed method as compared with the baseline methods. The proposed method is expected to be beneficial in guiding and facilitating clinical diagnosis and treatment.

Protective role of metformin in preeclampsia via the regulation of NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways by activating AMPK.

INTRODUCTION: Preeclampsia (PE) is a pregnancy complication that leads to hypertension and proteinuria and causes maternal mortality. Metformin (MET) is an oral hypoglycemic agent that activates AMPK-regulated signaling pathways and inhibits inflammation and oxidative stress responses. This study explored MET's roles and molecular mechanisms in PE. METHODS: The protein or mRNA expression of signaling pathways and inflammation-related genes were detected by Western blotting and RT-qPCR and cell viability was analyzed with MTT. In addition, flow cytometry was used to assess apoptosis, and mitochondrial membrane potential was detected using JC-1 staining with flow cytometry. Moreover, LDH Cytotoxicity Assay Kit detected the release of LDH, and ROS, MDA, or SOD kits detected oxidative stress-related factors. RESULTS: MET significantly inhibited inflammatory damage and oxidative stress responses in LPS-induced HTR-8/SVneo cells. Besides, MET could activate AMPK and then affect NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways in LPS-induced HTR-8/SVneo cells. Compound C (an AMPK inhibitor) significantly reversed MET's effects on LPS-stimulated HTR-8/SVneo cells. DISCUSSION: MET attenuated inflammatory and oxidative stress of HTR-8/SVneo cells in PE by activating AMPK to regulate NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways, suggesting that MET was a potential therapeutic drug for PE.

A multimodal radiomic machine learning approach to predict the LCK expression and clinical prognosis in high-grade serous ovarian cancer.

We developed and validated a multimodal radiomic machine learning approach to noninvasively predict the expression of lymphocyte cell-specific protein-tyrosine kinase (LCK) expression and clinical prognosis of patients with high-grade serous ovarian cancer (HGSOC). We analyzed gene enrichment using 343 HGSOC cases extracted from The Cancer Genome Atlas. The corresponding biomedical computed tomography images accessed from The Cancer Imaging Archive were used to construct the radiomic signature (Radscore). A radiomic nomogram was built by combining the Radscore and clinical and genetic information based on multimodal analysis. We compared the model performances and clinical practicability via area under the curve (AUC), Kaplan-Meier survival, and decision curve analyses. LCK mRNA expression was associated with the prognosis of HGSOC patients, serving as a significant prognostic marker of the immune response and immune cells infiltration. Six radiomic characteristics were chosen to predict the expression of LCK and overall survival (OS) in HGSOC patients. The logistic regression (LR) radiomic model exhibited slightly better predictive abilities than the support vector machine model, as assessed by comparing combined results. The performance of the LR radiomic model for predicting the level of LCK expression with five-fold cross-validation achieved AUCs of 0.879 and 0.834, respectively, in the training and validation sets. Decision curve analysis at 60 months demonstrated the high clinical utility of our model within thresholds of 0.25 and 0.7. The radiomic nomograms were robust and displayed effective calibration. Abnormally high expression of LCK in HGSOC patients is significantly correlated with the tumor immune microenvironment and can be used as an essential indicator for predicting the prognosis of HGSOC. The multimodal radiomic machine learning approach can capture the heterogeneity of HGSOC, noninvasively predict the expression of LCK, and replace LCK for predictive analysis, providing a new idea for predicting the clinical prognosis of HGSOC and formulating a personalized treatment plan.

Role of necroptosis and immune infiltration in preeclampsia: novel insights from bioinformatics analyses.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication that can adversely affect the mother and fetus. Necroptosis is a recently discovered new form of programmed cell death involved in the pathological process of various pregnancy complications. Our study aimed to identify the necroptosis-related differentially expressed genes (NRDEGs), create a diagnosis model and related disease subtypes model based on these genes, and further investigate their relationship with immune infiltration. METHODS: In this study, we identified NRDEGs by analyzing data from various databases, including Molecular Signatures, GeneCards, and Gene Expression Omnibus (GEO). Using minor absolute shrinkage and selection operator (LASSO) and logistic Cox regression analysis, we developed a novel PE diagnosis model based on NRDEGs. Furthermore, we developed PE subtype models using consensus clustering analysis based on key gene modules screened out by weighted correlation network analysis (WGCNA). Finally, we identified the difference in immune infiltration between the PE and control groups as well as between both PE subtypes by analyzing the immune cell infiltration across combined datasets and PE datasets. RESULTS: Our study discovered that the necroptosis pathway was significantly enriched and active in PE samples. We identified nine NRDEGs that involved in this pathway, including BRAF, PAWR, USP22, SYNCRIP, KRT86, MERTK, BAP1, CXCL5, and STK38. Additionally, we developed a diagnostic model based on a regression model including six NRDEGs and identified two PE subtypes: Cluster1 and Cluster2, based on key module genes. Furthermore, correlation analysis showed that the abundance of immune cell infiltration was related to necroptosis genes and PE disease subtypes. CONCLUSION: According to the present study, necroptosis is a phenomenon that occurs in PE and is connected to immune cell infiltration. This result suggests that necroptosis and immune-related factors may be the underlying mechanisms of PE pathophysiology. This study opens new avenues for future research into PE's pathogenesis and treatment options.

Prevalence, clinical characteristics, and 3-dimensional radiographic analysis of supernumerary teeth in Guangzhou, China: a retrospective study.

OBJECTIVE: The aim was to investigate the prevalence and clinical and 3-dimensional (3D) radiographic characteristics of supernumerary teeth (ST) in a paediatric dental population. The factors associated with ST eruption potential were analysed, and the optimal extraction time for nonerupted ST was discussed. METHODS: A retrospective study was performed in a 13,336-participant baseline population aged 3-12 years for whom panoramic radiographs had been obtained in the hospital from 2019 to 2021. The medical records and radiographic data were reviewed to identify patients with ST. Both the demographic variables and ST characteristics were recorded and analysed . RESULTS: In total, 890 patients with 1,180 ST were screened from the 13,336 baseline population. The ratio of males (679) to females (211) was approximately 3.2:1. Generally, ST occurred singularly and were frequently found in the maxilla (98.1%). A total of 40.8% of ST were erupted, and the 6-year-old age group presented the highest eruption rate (57.8%). The eruption rate of ST was highly negatively correlated with age. A total of 598 patients additionally underwent cone- beam computed tomography (CBCT). According to the CBCT images, the majority of ST were conical, normally oriented, palatally situated, nonerupted and symptomatic. The most common ST-associated complication was failed eruption of adjacent teeth. In addition, symptomatic ST were more common in the 7- to 8- and 9- to 10-year-old age groups. The eruption rate of ST was 25.3% among the patients who had undergone CBCT. A normal orientation and the labial position were significant protective factors for ST eruption, with odds ratios (ORs) of 0.004 (0.000-0.046) and 0.086 (0.007-1.002), respectively. Age and the palatal position were significant risk factors, with ORs of 1.193 (1.065-1.337) and 2.352 (1.377-4.02), respectively. CONCLUSIONS: This study provides a detailed analysis of ST characteristics in 3-12 year old children. Age as well as the position and orientation of ST were reliable predictors of the ST eruption. An age of 6 years old may be the optimal time for extraction of nonerupted ST to maximize the utilization of eruption potential and reduce the incidence of ST-associated complications.

Expression of HMGB1-TLR4 in Placentas from Preeclamptic Pregnancies and Its Effect on Proliferation and Invasion of HTR-8/SVneo Cells.

OBJECTIVES: Placental inflammation possibly underlies preeclampsia (PE) pathogenesis. This study aimed to investigate the expression of the high mobility box group 1 (HMGB1)-toll-like receptor 4 (TLR4) signalling pathway in preeclamptic placentas and determine whether HMGB1 regulates the biological behaviour of trophoblasts in vitro. DESIGN: Placental biopsies were taken from 30 preeclamptic patients and 30 normotensive controls. In vitro experiments were carried out in HTR-8/SVneo human trophoblast cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: HMGB1, TLR4, and nuclear factor kappa B (NF-κB) mRNA and protein were quantified to compare their expression in human placentas from preeclamptic and normotensive pregnancies. HTR-8/SVneo cells were stimulated with HMGB1 (50-400 µg/L) for 6-48 h, and proliferation and invasion of HTR-8/SVneo cells were measured via Cell Counting Kit-8 and transwell assays. HTR-8/SVneo cells were also transfected with HMGB1 and TLR4 small interfering RNA (siRNA) to investigate the effect of knocking down these proteins. The mRNA and protein expression of TLR4, NF-κB, and matrix metalloproteinase 9 (MMP-9) were determined using quantitative real-time PCR and Western blotting, respectively. Data were analysed with either a t-test or one-way analysis of variance. RESULTS: The mRNA and protein levels of HMGB1, TLR4, and NF-κB were significantly higher in the placentas from preeclamptic pregnancies than from normal pregnancies (p < 0.05). HMGB1 stimulation (at concentrations up to 200 µg/L) of HTR-8/SVneo cells significantly increased invasion and proliferation over time. However, at an HMGB1 stimulation concentration of 400 µg/L, the invasion and proliferation ability of HTR-8/SVneo cells decreased. Compared to controls, mRNA and protein expression levels of TLR4, NF-κB, and MMP-9 increased (mRNA level fold change: 1.460, 1.921, 1.667; protein level fold change: 1.600, 1.750, 2.047) when stimulated with HMGB1 (p < 0.05) but decreased when HMGB1 was knocked down (p < 0.05). TLR4 siRNA transfection combined with HMGB1 stimulation reduced the mRNA (fold change: 0.451) and protein (fold change: 0.289) expression of TLR4 (p < 0.05), while NF-κB and MMP-9 were unaffected (p > 0.05). LIMITATIONS: Only one trophoblast cell line was used in this study, and the findings were not confirmed in animal studies. CONCLUSIONS: This study explored the pathogenesis of PE from two aspects: inflammation and trophoblast invasion. The overexpression of HMGB1 in placentas from preeclamptic pregnancies suggests this protein may be involved in PE pathogenesis. In vitro, HMGB1 was found to regulate the proliferation and invasion of HTR-8/SVneo cells by activating the TLR4-NF-κB-MMP-9 pathway. These findings have implications for targeting HMGB1 could be a therapeutic strategy for treating PE. In the future, we will further verify this in vivo and in other trophoblast cell lines, further exploring the molecular interactions of the pathway.

Association between very advanced maternal age women with gestational diabetes mellitus and the risks of adverse infant outcomes: a cohort study from the NVSS 2014-2019.

BACKGROUND: To evaluate the association between gestational diabetes mellitus (GDM) and infant outcomes in women of very advanced maternal age (vAMA) (≥45 years). METHODS: This cohort study utilized data from the National Vital Statistics System (NVSS) database (2014-2019) in the United States. Preterm birth was the primary outcome, which was subdivided into extremely preterm, very preterm, and moderate or late preterm. The secondary outcomes were neonatal intensive care unit (NICU) admission, low birthweight and small for gestational age. Univariate and multivariate logistic regression analyses were used to explore the association between GDM and infant outcomes among vAMA women. Subgroup analyses were performed based on race and use of infertility treatment. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total of 52,544 vAMA pregnant women were included. All analysis made comparisons between women with vAMA and GDM and women with vAMA and no GDM. Women with GDM had a significantly higher risk of preterm birth than those without GDM (OR = 1.26, 95%CI = 1.18-1.36, P < 0.001). Compared with women without GDM, those with GDM had a significantly increased risk of moderate or late preterm birth (OR = 1.27, 95%CI = 1.18-1.37, P < 0.001); no significant association of GDM with extremely preterm birth and very preterm birth was observed. Women with GDM had a significantly greater risk of NICU admission than those without (OR = 1.33, 95%CI = 1.23-1.43, P < 0.001). GDM was associated with a significantly lower risk of low birthweight (OR = 0.91, 95%CI = 0.84-0.98, P = 0.010), and no significant association was found between GDM and small for gestational age (OR = 0.95, 95%CI = 0.87-1.03, P = 0.200) in vAMA women. CONCLUSION: vAMA women with GDM had an increased risk of preterm birth, especially moderate or late preterm birth. NICU admission and low birthweight were also associated with GDM among vAMA women.

Effectiveness of online caries management platform in children's caries prevention: A randomized controlled trial.

Purpose: To construct an online caries management platform and evaluate its efficacy in children's caries prevention based on caries risk. Methods: The study participants were second-grade pupils. The caries risk assessment tool (CAT) was used to grade caries risk for all participants, who were randomly divided into the experimental (114 pupils) and control (111 pupils) groups. The experimental group used the Internet for caries management, while the control group was managed by traditional lecturing in classroom. The caries status of each surface of the first permanent molars was recorded. The basic information and oral health knowledge, attitude, and behaviors of participants were collected by questionnaire. One year later, outcome data were collected. Pearson's chi-squared test was used to analyze the caries risk assessment items and oral health behaviors. The Mann-Whitney U-test was used to analyze the decayed-missing-filled surfaces (DMFS) index, plaque index, and scores of oral health knowledge and attitude. P < 0.05 was considered statistically significant. This study was available on the website of Chinese Clinical Trials Register (No: MR-44-22-012947). Results: After 1 year, the oral health knowledge score was improved by 20.58% (P < 0.001) in the experimental group and 6.02% in the control group. The plaque index was improved by 49.60% (P < 0.001) in the experimental group and 21.01% in the control group. The DMFS index increased in both groups but there were no significant differences (P = 0.608). The experimental group had a better improvement effect in caries risk assessment items than the control group, including "whether the frequency of eating sugary snacks or drinks between meals is more than 3 times/day" (P = 0.033) and the use of fluoridated toothpaste (P = 0.020). The experimental group was better than the control group in reported oral health behaviors, including frequency of eating sweets before sleep (P = 0.032), brushing time (P = 0.001), and the filled rate (proportion of FS in DMFS) of first permanent molars (P = 0.003). Conclusions: The online caries management platform showed more advantages than traditional lecturing in improving oral health knowledge and behaviors (oral hygiene practice, sugar consumption behavior, and medical treatment behavior). This platform provides a reliable implementation path for the occurrence and continuous improvement of oral health-related behaviors.

Ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis: a clinical analysis of 5 cases.

OBJECTIVES: To analyse the clinical features, diagnosis, treatment, and prognosis of anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis associated with ovarian mature teratomas. MATERIAL AND METHODS: Retrospectively analysed the clinical-laboratory data of five patients with anti-NMDAR encephalitis combined with ovarian teratoma at a single centre between March 2016 and June 2019. RESULTS: The mean age of the patients was 22.40 ± 2.89 years (range, 19-26 years). Five patients had premonitory fever symptoms, clinical manifestations of mental disorder or convulsions for starting, with varying degrees of involuntary movement. Brain MRI and electroencephalography lacked specificity, and cerebrospinal fluid resistance NMDAR antibody detection was the key to diagnosis. All patients experienced good outcomes in response to immunotherapy combined with ovarian tumour resection, with a median follow-up time of 36 months (range, 16-55 months). The MRS value of five patients decreased significantly half a year after surgery, and no encephalitis or ovarian tumour relapses were reported. CONCLUSIONS: Anti-NMDA encephalitis caused by ovarian teratoma is mostly a non-specific clinical manifestation of neurological and mental abnormalities, which can be easily misdiagnosed and delayed, and doctors should fully recognise the disease, early diagnosis, and timely surgical intervention to improve the prognosis of patients.

GSH-depleting and H2O2-self-supplying hybrid nanozymes for intensive catalytic antibacterial therapy by photothermal-augmented co-catalysis.

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS2/CuO2) is rationally constructed by simply decorating ultrasmall CuO2 nanodots onto lamellar MoS2 platelets of hydrangea-like MoS2 nanocarrier via a covalent Cu-S bond. The MoS2/CuO2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H2O2 produced by acid-triggered decomposition of the decorated CuO2 into hydroxyl radical (•OH). Meanwhile, the MoS2/CuO2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced CDT. More importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS2/CuO2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H2O2 and consuming GSH. Importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.

Puerarin protects against H2O2-induced apoptosis of HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis.

INTRODUCTION: Preeclampsia seriously affects the health of pregnant women and fetuses. It has been reported that puerarin has a positive therapeutic effect on the treatment of preeclampsia. In this study, oxidative stress-induced trophoblast cell injury was established to explore the potential interaction between puerarin and preeclampsia. METHODS: A CCK-8 assay was performed to investigate the effect of puerarin on the viability of HTR-8/SVneo cells. To mimic oxidative stress-induced trophoblast cell injury, human villous trophoblasts (HTR-8/SVneo) were treated with H2O2. Then, the relationships among MMP2, VEGFA and miR-20a-5p in HTR-8/SVneo cells were confirmed using a dual-luciferase reporter assay. Finally, Western blot assays were performed to measure the expression levels of MMP2, VEGFA, p-Akt, Akt, Bcl-2 and cleaved caspase 3. RESULTS: In this study, puerarin eliminated H2O2-induced cytotoxicity of HTR-8/SVneo cells. In addition, puerarin was able to reverse H2O2-induced apoptosis and metastasis inhibition in cells. Meanwhile, puerarin significantly abrogated H2O2-induced mitochondrial membrane potential (MMP) decline in HTR-8/SVneo cells. And, MMP2 and VEGFA were identified as direct targets of miR-20a-5p. Furthermore, puerarin reversed H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis. DISCUSSION: All these data indicated that puerarin could abolish H2O2-induced growth inhibition in HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/AKT axis.

Gold-Platinum Nanodots with High-Peroxidase-like Activity and Photothermal Conversion Efficiency for Antibacterial Therapy.

Combined therapeutic strategies for bacterial infection have attracted worldwide attention owing to their faster and more effective therapy with fewer side effects compared with monotherapy. In this work, gold-platinum nanodots (AuPtNDs) are simply and quickly synthesized by a one-step method. They not only exhibit powerful peroxidase-like activity but also confer a higher affinity for hydrogen peroxide (H2O2), which is 3.4 times that of horseradish peroxidase. Under 808 nm laser irradiation, AuPtNDs also have excellent photothermal conversion efficiency (50.53%) and strong photothermal stability. Excitingly, they can combat bacterial infection through the combination of chemodynamic and photothermal therapy. In vitro antibacterial results show that the combined antibacterial strategy has a broad-spectrum antibacterial property against both Escherichia coli (Gram negative, 97.1%) and Staphylococcus aureus (Gram positive, 99.3%). Animal experiments further show that nanodots can effectively promote the healing of bacterial infection wounds. In addition, owing to good biocompatibility and low toxicity, they are hardly traceable in the main organs of mice, which indicates that they can be well excreted through metabolism. These results reveal the application potential of AuPtNDs as a simple and magic multifunctional nanoparticle in antibacterial therapy and open up new applications for clinical anti-infective therapy in the near future.

The impact of caries status on supragingival plaque and salivary microbiome in children with mixed dentition: a cross-sectional survey.

BACKGROUND: Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for caries development in first permanent molar (FPM); nevertheless, to the best of our knowledge, there are no reports on the effects of deciduous teeth caries on the microbiome of healthy FPM. Additionally, it remains unclear whether saliva can be used instead of supragingival plaque for caries microbial studies. Therefore, we aimed to elucidate this issue, and to characterize and compare the oral microbiome of healthy FPMs in children with different caries statuses and that from children with and without caries in a similar microhabitat, by PacBio sequencing. Currently, few studies have investigated the oral microbiome of children using this technique. METHODS: Thirty children (aged 7-9 years) with mixed dentition were enrolled; 15 had dental caries, and 15 did not. Supragingival plaques of deciduous molars and maxillary FPMs, and non-stimulating saliva samples were collected. DNA was extracted and the v1-v9 regions of 16S rRNA were amplified. Subsequently, PacBio sequencing and bioinformatic analyses were performed for microbiome identification. RESULTS: The microbial alpha diversity of the saliva samples was lower than that of the supragingival plaque (p < 0.05); however, no differences were detected between deciduous teeth and FPMs (p > 0.05). In addition, the alpha and beta diversity of children with and without caries was also similar (p > 0.05). Nonmetric multidimensional scaling and Adonis analyses indicated that the microbial structure of salivary and supragingival plaque samples differ (p < 0.05). Further analysis of deciduous teeth plaque showed that Streptococcus mutans, Propionibacterium acidifaciens, and Veillonella dispar were more abundant in children with caries than in those without (p < 0.05); while in FPMs plaque, Selenomonas noxia was more abundant in healthy children (p < 0.05). No differences in microorganisms abundance were found in the saliva subgroups (p > 0.05). CONCLUSION: We have determined that supragingival plaque was the best candidate for studying carious microbiome. Furthermore, S. mutans, V. dispar, and P. acidifaciens were highly associated with deciduous teeth caries. S. noxia may be associated with the abiding health of FPM; however, this requires additional studies.

Factors Affecting Future Caries Occurrence Among Preschoolers in Northern Guangdong: A Longitudinal Study.

PURPOSE: This study aimed to investigate the new development of caries among preschoolers in northern Guangdong and to assess caries-related factors to distinguish groups with different caries risk levels. METHODS: Baseline data were recorded for participants from September to November 2019, and participants were reexamined from September to November 2020. A longitudinal observation of 11,973 preschoolers was conducted. The simplified debris index (DI-S) and decayed-missing-filled tooth (dmft) index values were obtained for each participant. RESULTS: Factors associated with whether caries would occur in the future and one-year increase in dmft (Δdmft) included baseline dmft, baseline DI-S, and baseline age. The risk ratio (RR) of caries occurrence and the number of teeth with new-onset caries were 4.482 (95% confidence interval, 4.056-4.957) and 2.945 (2.742-3.165) in the participants with baseline dmft ≥3, which were higher than those with baseline dmft =1 or 2. In the baseline caries-free group, whether caries would occur in the future was related to the baseline DI-S (95% confidence interval, 0.022-0.062). The caries incidence of maxillary central incisors (27.9%) was the highest among teeth of preschoolers without caries at baseline, whereas the caries incidence of mandibular first deciduous molars (42.7%) was the highest among teeth of preschoolers with caries at baseline. CONCLUSION: Baseline dmft is a good predictor of future caries. Children with baseline caries-free status, baseline dmft >0, and baseline dmft ≥3 should be treated with preventive interventions of different intensities and frequencies. The occurrence of future caries in baseline caries-free participants is related to oral hygiene status. Measures to prevent caries on smooth surfaces, such as topical fluoridation, should be applied to all preschoolers. Preschoolers with caries at baseline may be given priority for pit and fissure sealing.