A novel endolysin from an Enterococcus faecalis phage and application.

Enterococcus faecalis is the primary species detected in cases of secondary persistent infection resulting from root canal therapy failure. Due to the overuse of antibacterial agents, E. faecalis has developed resistance to these drugs, making it challenging to treat clinical diseases caused by E. faecalis infection. Therefore, there is an urgent need to explore new alternative drugs for treating E. faecalis infections. We aimed to clone and express the genes of phage endolysins, purify the recombinant proteins, and analyze their antibacterial activity, lysis profile, and ability to remove biofilm. The crude enzyme of phage endolysin pEF51 (0.715 mg/mL), derived from phage PEf771 infecting E. faecalis, exhibited superior bacterial inhibitory activity and a broader bactericidal spectrum than its parental phage PEf771. Furthermore, pEF51 demonstrated high efficacy in eliminating E. faecalis biofilm. Therapeutic results of the infected Sprague-Dawley (SD) rat model indicated that among 10 SD rats, only one developed a thoracic peritoneal abscess and splenic peritoneal abscess after 72 h of treatment with pEF51. This suggests that pEF51 could provide protection against E. faecalis infection in SD rats. Based on the 16S rDNA metagenomic data of the intestinal microbial community of SD rats, endolysin pEF51 exerted a certain influence on the diversity of intestinal microorganisms at the genus level. Thus, pEF51 may serve as a promising alternative to antibiotics in the management of E. faecalis infection.

Factor structure and longitudinal invariance for the Chinese Mainland version of the Edinburgh postnatal depression scale during pregnancy.

BACKGROUND: There are inconsistent results on the Edinburgh Postnatal Depression Scale's (EPDS) factor structure and longitudinal invariance among different cultures. Furthermore, limited relevant studies in Chinese pregnant women exist. PURPOSE: To test the factor structure of the Chinese Mainland EPDS during pregnancy and conduct longitudinal invariance analyses. METHODS: A national multi-centre cohort study was conducted among 1207 pregnant women selected consecutively by convenience sampling from five hospitals in Zhuhai, Taiyuan, Haidian, Changchun, and Shenzhen in China between August 2015 and October 2016. Depression was measured by the EPDS during gestational weeks 10-13, 15-18, 23-25, 30-32 and 36-37, respectively.s RESULTS: Three factors with eigenvalues nearly larger than 1.0 were optimal for the Chinese Mainland EPDS, labelled "anxiety," "anhedonia," and "depression," and contained items 3-5, 1-2, and 6-10, respectively. The confirmatory factor analysis results of standardized root mean square residual (SRMR) = 0.034, root mean square error of approximation (RMSEA) = 0.049, comparative fit index (CFI) = 0.968, Tucker-Lewis index (TLI) = 0.954, and χ2, p < 0.05 indicated good fit. For the longitudinal invariance tests, the configural invariance was met, with the CFI and TLI both higher than 0.90 and the RMSEA lower than 0.08 (CFI = 0.919, TLI = 0.908, and RMSEA = 0.034). The metric-, scalar-, and strict invariances were met. CONCLUSIONS: The three-factor model of the Chinese Mainland EPDS is invariant in pregnancy, suggesting stability and comparability in identifying the women screened positive at different points during pregnancy and making the scale feasible to screen prenatal depression and anxiety simultaneously.

Silica nanoparticles containing nano-silver and chlorhexidine respond to pH to suppress biofilm acids and modulate biofilms toward a non-cariogenic composition.

OBJECTIVES: Dental caries is caused by acids from biofilms. pH-sensitive nanoparticle carriers could achieve improved targeted effectiveness. The objectives of this study were to develop novel mesoporous silica nanoparticles carrying nanosilver and chlorhexidine (nMS-nAg-Chx), and investigate the inhibition of biofilms as well as the modulation of biofilm to suppress acidogenic and promote benign species for the first time. METHODS: nMS-nAg was synthesized via a modified sol-gel method. Carboxylate group functionalized nMS-nAg (COOH-nMS-nAg) was prepared and Chx was added via electrostatic interaction. Minimal inhibitory concentration (MIC), inhibition zone, and growth curves were evaluated. Streptococcus mutans (S. mutans), Streptococcus gordonii (S. gordonii), and Streptococcus sanguinis (S. sanguinis) formed multispecies biofilms. Metabolic activity, biofilm lactic acid, exopolysaccharides (EPS), and TaqMan real-time polymerase chain reaction (RT-PCR) were tested. Biofilm structures and biomass were observed by scanning electron microscopy (SEM) and live/dead bacteria staining. RESULTS: nMS-nAg-Chx possessed pH-responsive properties, where Chx release increased at lower pH. nMS-nAg-Chx showed good biocompatibility. nMS-nAg-Chx exhibited a strong antibacterial function, reducing biofilm metabolic activity and lactic acid as compared to control (p < 0.05, n = 6). Moreso, biofilm biomass was dramatically suppressed in nMS-nAg-Chx groups. In control group, there was an increasing trend of S. mutans proportion in the multispecies biofilm, with S. mutans reaching 89.1% at 72 h. In sharp contrast, in nMS-nAg-Chx group of 25 µg/mL, the ratio of S. mutans dropped to 43.7% and the proportion of S. gordonii and S. sanguinis increased from 19.8% and 10.9 to 69.8% and 56.3%, correspondingly. CONCLUSION: pH-sensitive nMS-nAg-Chx had potent antibacterial effects and modulated biofilm toward a non-cariogenic tendency, decreasing the cariogenic species nearly halved and increasing the benign species approximately twofold. nMS-nAg-Chx is promising for applications in mouth rinse and endodontic irrigants, and as fillers in resins to prevent caries.

A novel holin from an Enterococcus faecalis phage and application in vitro and in vivo.

Enterococcus faecalis, a conditional pathogenic bacterium, is prevalent in the intestinal, oral, and reproductive tracts of humans and animals, causing a variety of infectious diseases. E. faecalis is the main species detected in secondary persistent infection from root canal therapy failure. Due to the abuse of antibacterial agents, E. faecalis has evolved its resistant ability. Therefore, it is difficult to treat clinical diseases infected by E. faecalis. Exploring new alternative drugs for treating E. faecalis infection is urgent. We cloned and expressed the gene of phage holin, purified the recombinant protein, and analyzed the antibacterial activity, lysis profile, and ability to remove bacterial biofilm. It showed that the crude enzyme of phage holin pEF191 exhibited superior bacterial inhibiting activity and a broader lysis host range compared to the parent phage PEf771. In addition, pEF191 demonstrated high efficacy in eliminating E. faecalis biofilm. The therapeutic results of the Sprague-Dawley (SD) rats model infected showed that pEf191 did not affect SD rats, indicating that pEF191 provided greater protection against E. faecalis infection in SD rats. Based on the 16 S rDNA data of SD rats intestinal microorganism population, holin pEF191 exhibited no impact on the diversity of intestinal microorganisms at the phylum and genus levels and improved the relative abundance of favorable bacteria. Thus, pEF191 may serve as a promising alternative to antibiotics in the management of E. faecalis infection.

Marnyiella aurantia, gen. nov., sp. nov., a novel bacterial species of the family Weeksellaceae that could produce flexirubin type pigments.

Two Gram-stain-negative, non-spore-forming, rod-shaped, and obligately aerobic bacteria, designated strains CX-624T and cx-311, were isolated from soil samples in Qinghai Province, China. The two strains grew best at 28 °C on the plate with Tryptone soya agar (TSA). Cells formed circular, convex, translucent, smooth, and orange colonies with approximately 1.0 mm diameter after 2 days of incubation on TSA at 28 °C. The strains were oxidase-negative and catalase-positive. The predominant cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0, and major polar lipids included phosphatidylethanolamine, an unidentified aminophospholipid, four unidentified lipids and an aminolipid. MK-6 was the sole menaquinone in strain CX-624T. Comparative analysis of the nearly full-length 16S rRNA gene sequences showed strains CX-624T and cx-311 were member of the family Weeksellaceae, with the highest similarity to Kaistella haifensis H38T (96.66 %), Epilithonimonas pallida DSM 18015T (96.59 %), and Chryseobacterium gambrini DSM 18014T (96.53 %). Both phylogenetic analysis of the 16S rRNA gene and 177 core genes revealed that strains CX-624T and cx-311 formed an independent clade. Average nucleotide identity values (< 72.64 %), average amino-acid identity values (<72.61 %) and digital DNA-DNA hybridization (< 21.10 %) indicated that the strains CX-624T and cx-311 should constitute a novel genus. The DNA G+C contents of strains CX-624T and cx-311 were 43.0 mol% and 42.7 mol%. According to the data obtained in this study, strain CX-624T represents a novel species belonging to a novel genus of the Weeksellaceae, for which the name Marnyiella aurantia gen. nov., sp. nov. is proposed. The type strain is CX-624T (=GDMCC 1.1714T = JCM 33925T).

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission.

PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Predictors of immune persistence induced by two-dose BBIBP-CorV vaccine in high-risk occupational population.

BACKGROUND: The immune protection from infection may wane over time as neutralizing antibody levels decline. We aimed to develop a nomogram to predict long-term immune persistence induced by two-dose BBIBP-CorV vaccine and calculate the neutralizing antibody decline probability of individuals. METHODS: In the initial study, a total of 809 participants were recruited and randomly allocated (1:1:1) to vaccination group with three two-dose schedules on days 0 and 14, 0 and 21, or 0 and 28. The participants with neutralizing antibody titers of 16 or above on day 28 after the second dose were followed up at month 3, 6 and 10. Multivariable Cox proportional hazards regression model and nomogram model were used to identify predictors associated with maintaining of neutralizing antibody levels during 10 months after the second dose. RESULTS: A total of 744 participants followed up at day 28 after the second dose. The participants with age ≥ 50 (aHR = 3.556, 95 %CI: 1.141-4.884, P = 0.028) were associated with a high risk of response loss (titers < 16). The participants who were in 0-28 d group (aHR = 0.403, 95 %CI: 0.177-0.919, P = 0.031), had an influenza vaccination history (aHR = 0.468, 95 %CI: 0.267-0.921, P = 0.033) or were female (aHR = 0.542, 95 %CI: 0.269-0.935, P = 0.035) tended to maintain immune persistence during 10 months after the second dose. The nomogram was constructed and showed moderate discrimination[C-index:0.711 (95 %CI: 0.652-0.770); AUC: 0.731 (95 %CI: 0.663-0.792)] and good calibration. CONCLUSIONS: From 28 days to 10 months after receipt of the second dose of the BBIBP-CorV vaccine, neutralizing antibody levels were substantially decreased, especially among men, among persons 50 years of age or older, among persons with the 0-14 d group, and among persons without history of influenza vaccination. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706.

DNA methylation analysis reveals the effect of arsenic on gestational diabetes mellitus.

BACKGROUND: Arsenic (As) exposure is one of the risk factors for gestational diabetes mellitus (GDM). This study aimed to explore the effect of As-exposure on DNA methylation in GDM and to establish a risk assessment model of GDM in As exposed pregnant women. METHOD: We collected elbow vein blood of pregnant women before delivery to measure As concentration and DNA methylation data. Then compared the DNA methylation data and established a nomogram. RESULT: We identified a total of 10 key differentially methylated CpGs (DMCs) and found 6 corresponding genes. Functions were enriched in Hippo signaling pathway, cell tight junction, prophetic acid metabolism, ketone body metabolic process, and antigen processing and presentation. A nomogram was established that can predict GDM risks (c-index = 0.595, s:p = 0.973). CONCLUSION: We found 6 genes associated with GDM with high As exposure. The prediction of the nomograms has been proven to be effective.

Prenatal polymetallic exposure and small for gestational age: A case-control study in Taiyuan, China.

BACKGROUND: Studies focused on independent effects of metals on small for gestational age, failing to account for potential interdependence among metals. METHODS: In this case-control study, we selected 187 pregnant women and 187 matched controls from the First Hospital of Shanxi Medical University. Determination of 12 elements in the venous blood of pregnant women before delivery by ICP-MS. Logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with SGA. RESULTS: An increased risk of SGA was associated with As (OR= 1.06,95%CI: 1.01,1.12), Cd (OR= 1.24,95%CI: 1.04,1.47) and Pb (OR= 1.05,95%CI: 1.02,1.08), while Zn (OR= 0.58,95%CI: 0.45,0.76) and Mn (OR= 0.97,95%CI: 0.94,0.99) were protective factors for SGA. In the WQSR positive model, the mixture of heavy metals has a positive combined effect on SGA (OR= 1.74,95%CI: 1.15, 2.62), with Sb and Cd having the highest weights. The BKMR models confirmed that the metal mixture was associated with decreased risk of SGA when the concentration of 12 metals was between the 30th percentile and the 65th percentile, and Zn and Cd had the greatest independent effect. Zn and SGA may not be linearly correlated, higher Zn level may reduce the effect of Cd on the risk of SGA. CONCLUSIONS: Our study suggested that exposure to multiple metals was associated with risk of SGA, and the observed association with multiple metals was dominated by Zn, Cd. Sb exposure during pregnancy may also increase the risk of SGA.

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

Sleep disturbance and anxiety symptoms among asymptomatic COVID-19 carriers in Shanghai, China: the mediating role of entrapment and defeat.

BACKGROUND: The COVID-19 pandemic increases the risk of psychological problems, especially for the infected population. Sleep disturbance and feelings of defeat and entrapment are well-documented risk factors of anxiety symptoms. Exploring the psychological mechanism of the development of anxiety symptoms is essential for effective prevention. This study aimed to examine the mediating effects of entrapment and defeat in the association between sleep disturbance and anxiety symptoms among asymptomatic COVID-19 carriers in Shanghai, China. METHODS: A cross-sectional study was conducted from March to April, 2022. Participants were 1,283 asymptomatic COVID-19 carriers enrolled from the Ruijin Jiahe Fangcang Shelter Hospital, Shanghai (59.6% male; mean age = 39.6 years). Questionnaire measures of sleep disturbance, entrapment, defeat, anxiety symptoms, and background characteristics were obtained. A mediation model was constructed to test the mediating effects of entrapment and defeat in the association between sleep disturbance and anxiety symptoms. RESULTS: The prevalence rates of sleep disturbance and anxiety symptoms were 34.3% and 18.8%. Sleep disturbance was positively associated with anxiety symptoms (OR [95%CI] = 5.013 [3.721-6.753]). The relationship between sleep disturbance and anxiety symptoms (total effect: Std. Estimate = 0.509) was partially mediated by entrapment (indirect effect: Std. Estimate = 0.129) and defeat (indirect effect: Std. Estimate = 0.126). The mediating effect of entrapment and defeat accounted for 50.3% of the association between sleep disturbance and anxiety symptoms. CONCLUSION: Sleep disturbance and anxiety symptoms were prevalent among asymptomatic COVID-19 carriers. Entrapment and defeat mediate the association between sleep disturbance and anxiety symptoms. More attention is needed to monitoring sleep conditions and feelings of defeat and entrapment to reduce the risk of anxiety.

Gender-Specific and U-Shaped Relationship Between Serum Uric Acid and All-Cause Mortality Among Chinese Older Adults: A National Population-Based Longitudinal Study.

Objectives: This study aimed to prospectively investigate gender-specific relationship between hyperuricemia and all-cause mortality among Chinese older adults. Methods: The study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2008-2018, a prospective nationwide cohort of older adults in China. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for all-cause mortality. Restricted cubic splines (RCS) were conducted to explore the dose-response relationship between SUA levels and all-cause mortality. Results: For older women, compared to the participants in the third quartile of SUA level, those in the highest quartile of SUA was associated with significantly higher risk of all-cause mortality in the fully adjusted model (HR: 1.41, 95% CI: 1.03-1.92). No significant associations between SUA levels and all-cause mortality were observed in older men. The present study further found a U-shaped non-linear relationship between SUA levels and all-cause mortality in both sexes of older population (P for non-linear <0.05). Conclusions: This study provided prospective epidemiological evidence for the predictive role of SUA on all-cause mortality among the Chinese aging population over 10 years of follow-up, while revealing considerable gender-related differences.

Novel bioactive dental restorations to inhibit secondary caries in enamel and dentin under oral biofilms.

OBJECTIVE: To provide the first review on cutting-edge research on the development of new bioactive restorations to inhibit secondary caries in enamel and dentin under biofilms. State-of-the-art bioactive and therapeutic materials design, structure-property relationships, performance and efficacies in oral biofilm models. DATA, SOURCES AND STUDY SELECTION: Researches on development and assessment new secondary caries inhibition restorations via in vitro and in vivo biofilm-based secondary caries models were included. The search of articles was carried out in Web of Science, PubMed, Medline and Scopus. CONCLUSIONS: Based on the found articles, novel bioactive materials are divided into different categories according to their remineralization and antibacterial biofunctions. In vitro and in vivo biofilm-based secondary caries models are effective way of evaluating the materials efficacies. However, new intelligent and pH-responsive materials were still urgent need. And the materials evaluation should be performed via more clinical relevant biofilm-based secondary caries models. CLINICAL SIGNIFICANCE: Secondary caries is a primary reason for dental restoration failures. Biofilms produce acids, causing demineralization and secondary caries. To inhibit dental caries and improve the health and quality of life for millions of people, it is necessary to summarize the present state of technologies and new advances in dental biomaterials for preventing secondary caries and protecting tooth structures against oral biofilm attacks. In addition, suggestions for future studies are provided.

The application of mesoporous silica nanoparticles as a drug delivery vehicle in oral disease treatment.

Mesoporous silica nanoparticles (MSNs) hold promise as safer and more effective medication delivery vehicles for treating oral disorders. As the drug's delivery system, MSNs adapt to effectively combine with a variety of medications to get over systemic toxicity and low solubility issues. MSNs, which operate as a common nanoplatform for the co-delivery of several compounds, increase therapy effectiveness and show promise in the fight against antibiotic resistance. MSNs offer a noninvasive and biocompatible platform for delivery that produces long-acting release by responding to minute stimuli in the cellular environmen. MSN-based drug delivery systems for the treatment of periodontitis, cancer, dentin hypersensitivity, and dental cavities have recently been developed as a result of recent unparalleled advancements. The applications of MSNs to be embellished by oral therapeutic agents in stomatology are discussed in this paper.

The top 100 most cited articles on COVID-19 vaccine: a bibliometric analysis.

This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.

The trajectories and associations of insomnia symptoms with addictive behaviours in adolescents: A two-year longitudinal study.

Insomnia displays heterogeneous trajectories across adolescence, which may induce addictive behaviours, including internet gaming disorder and substance use. This study aimed to investigate the latent trajectory classes of insomnia symptoms over 2 years and to examine the associations between insomnia trajectories and these addictive behaviours. Participants were 910 adolescents from six middle schools in Shanghai, China (52.7% males; mean age = 13.17 years). The three-wave survey measured insomnia symptoms, internet gaming disorder, substance use, depressive symptoms, and sociodemographic characteristics from 7th to 9th grade. Latent class growth modelling was performed to identify the latent trajectory classes of insomnia symptoms. Then multivariable logistic regressions were conducted within the best-fitting latent class growth model to examine the associations of insomnia trajectories with internet gaming disorder and substance use. Two latent trajectory classes of insomnia symptoms were recognised: the non-insomnia group (71.8%) and the insomnia group (28.2%). In the multivariable analysis controlling for baseline demographic variables and depressive symptoms, the insomnia group had a higher risk of developing internet gaming disorder (OR = 2.203 [95% CI: 1.258-3.858]) and substance use (OR = 2.215 [95% CI: 1.324-3.705]) compared with the non-insomnia group. These findings add to a growing body of research on heterogeneous trajectories of insomnia symptoms during adolescence, suggesting that intervention strategies are needed to target the characteristics or developmental patterns of different insomnia subgroups. The ultimate goal is to mitigate the impact of insomnia symptoms on adolescent addictive behaviours.

Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission

ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Effect of the Modified Methacrylate-Based Root Canal Sealer in Single-Cone Technique.

This study aimed to modify EndoREZ with 2.5% dimethylaminododecyl methacrylate (DMADDM) and 1% magnetic nanoparticles (MNP) to study its sealing property, penetration and long-term antibacterial and therapeutic effect in the single-cone technique (SCT) compared with EndoREZ and iRoot SP. Thirty single-root human maxillary premolars were assigned into three groups and obturated with three different root canal sealers by SCT. Every specimen was then scanned using micro-CT to analyze void fraction, and void volumes and confocal laser scanning microscope (CLSM) was used to study the dentin penetration. The long-term antimicrobial effects were tested in vitro before and after aging 1 and 4 weeks by the single-strain Enterococcus faecalis biofilm model. In addition, the beagle canine model of apical periodontitis (AP) was utilized to judge and compare the therapeutic effect of three sealers in SCT. The void fraction and void volumes of the modified root canal sealer were not significantly different from iRoot SP (p > 0.05) but were lower than EndoREZ (p < 0.05). The modified root canal sealant displayed a greater penetration, long-term antibacterial property, and treatment effect than the other groups (p < 0.05). This indicated that after being modified with DMADDM and MNP, it showed better performance in SCT.