Organophosphate Esters in Building Materials from China: Levels, Sources, Emissions, and Preliminary Assessment of Human Exposure.

Source characteristics and health risks of indoor organophosphate esters (OPEs) are limited by the lack of knowledge on emission processes. This study attempted to integrate the contents and emissions of OPEs from indoor building materials to assess human health effects. Thirteen OPEs were investigated in 80 pieces of six categories of building materials. OPEs are ubiquitous in the building materials and ∑13OPE contents varied significantly (p < 0.05) from 72.8 ng/g (seam agent) to 109,900 ng/g (wallpaper). Emission characteristics of OPEs from the building materials were examined based on a microchamber method. Depending on the sample category, the observed initial area-specific emission rates of ∑13OPEs varied from 154 ng/m2/h (carpet) to 2760 ng/m2/h (wooden floorboard). Moreover, the emission rate model was developed to predict the release levels of individual OPEs, quantify source contributions, and assess associated exposure risks. Source apportionments of indoor OPEs exhibited heterogeneities in multiple environmental media. The joint OPE contribution of wallpaper and wooden floorboard to indoor dust was up to 94.8%, while latex paint and wooden floorboard were the main OPE contributors to indoor air (54.2%) and surface (76.1%), respectively. Risk assessment showed that the carcinogenic risks of tris(2-chloroethyl) phosphate (3.35 × 10-7) were close to the acceptable level (1 × 10-6) and deserved special attention.

Psychometric soundness and predictive factors of the NCAST Parent-Child Interaction Teaching Scale in urban Chinese population.

BACKGROUND: Quality of parent-child interaction in early childhood functions as a critical indicator of nurturing care and is strongly associated with short-term and long-term development (health, cognition, language, social emotion, well-being, etc.). NCAST PCI Teaching Scale (PCI-TS), a video-based assessment regarded as a gold standard to measure PCI, has been widely used worldwide. However, its psychometric soundness among the urban Chinese population is unclear. This study assesses the PCI-TS's reliability and validity and explores predictive factors among urban Chinese parent-child dyads. METHODS: PCI-TS was adopted to code mother-child interaction among urban Chinese dyads recruited during the children's regular health checks in local maternal and child health centres. Reliability was evaluated by internal consistency (Cronbach'α coefficient) and test-retest reliability (Pearson correlation) with an average interval of 18 days. Score distribution of each subscale and total scale were compared with NCAST Database and Canadian community sample by single sample t-test. Criteria-related validity was conducted by Infant-Toddler Home Observation Measurement of the Environment (Pearson correlation). Predictive factors was performed by multiple linear regression. RESULTS: Four hundred and twenty-nine eligible mother-child dyads were included for data analysis among the 466 recruited samples. Four qualified local paediatricians accomplished video coding with an average agreement of 86%. The PCI-TS has strong reliability among the Chinese population with the Cronbach'α coefficients of the Caregiver-Infant total score, Caregiver total and Infant total scores of 0.81, 0.81 and 0.74, respectively; an acceptable test-retest reliability (r = 0.73, p < 0.01); and moderate correlation with IT-HOME, ranging from 0.53 to 0.62. Child age, birth weight, maternal education, full-time housewife, living with grandparent(s) and living space were predictive factors on PCI-TS in the Chinese population. CONCLUSION: PCI-TS showed good psychometric properties for measuring mother-child interactions among urban Chinese dyads, offering clinicians and researchers a practical tool to evaluate PCI objectively. Child age, maternal education and living space were beneficial factors, while full-time mothers and living with grandparent(s) were risk factors.

Reallocation of time between preschoolers' 24-h movement behaviours and executive functions: A compositional data analysis.

The objectives of the survey were to explored the associations of the 24-h movement behaviours (MB) with executive functions (EFs) and quantified the predicted changes in EFs following allocation of time among behaviours. In the cross-sectional survey, 135 preschoolers (3 ~ 5 years) were enrolled. Physical activity (PA) and sedentary (SED) time were objectively measured employing an ActiGraph GT9X. Sleep time was reported by parents. EFs were assessed using the iPad-based Early Years Toolbox which is a collection of computerized tasks consisting of brief tasks assessed from games administered and scored according to protocol. To explore the associations of the 24-h MB with EFs, compositional multiple linear regression was employed. To quantify the predicted changes in EFs following allocation of time among behaviours, compositional isotemporal substitution was used. Moderate-to-vigorous physical activity (MVPA) was positively related to cognitive flexibility. Replacing sleep or SED with MVPA was associated with positive changes in cognitive flexibility. When MVPA was replaced with sleep or SED, the predicted detriments to cognitive flexibility were larger than predicted benefits of replacing sleep or SED with MVPA. The findings highlight the key role of intensity of PA for preschoolers' EFs and the importance of meeting recommended levels of MVPA.

A Facile machine learning multi-classification model for Streptococcus agalactiae clonal complexes.

BACKGROUND: The clinical significance of group B streptococcus (GBS) was different among different clonal complexes (CCs), accurate strain typing of GBS would facilitate clinical prognostic evaluation, epidemiological investigation and infection control. The aim of this study was to construct a practical and facile CCs prediction model for S. agalactiae. METHODS: A total of 325 non-duplicated GBS strains were collected from clinical samples in Xinhua Hospital, Shanghai, China. Multilocus sequence typing (MLST) method was used for molecular classification, the results were analyzed to derive CCs by Bionumeric 8.0 software. Antibiotic susceptibility test was performed using Vitek-2 Compact system combined with K-B method. Multiplex PCR method was used for serotype identification. A total of 45 virulence genes associated with adhesion, invasion, immune evasion were detected by PCR method and electrophoresis. Three types of features, including antibiotic susceptibility (A), serotypes (S) and virulence genes (V) tests, and XGBoost algorithm was established to develop multi-class CCs identification models. The performance of proposed models was evaluated by the receiver operating characteristic curve (ROC). RESULTS: The 325 GBS were divided into 47 STs, and then calculated into 7 major CCs, including CC1, CC10, CC12, CC17, CC19, CC23, CC24. A total of 18 features in three kinds of tests (A, S, V) were significantly different from each CC. The model based on all the features (S&A&V) performed best with AUC 0.9536. The model based on serotype and antibiotic resistance (S&A) only enrolled 5 weighed features, performed well in predicting CCs with mean AUC 0.9212, and had no statistical difference in predicting CC10, CC12, CC17, CC19, CC23 and CC24 when compared with S&A&V model (all p > 0.05). CONCLUSIONS: The S&A model requires least parameters while maintaining a high accuracy and predictive power of CCs prediction. The established model could be used as a promising tool to classify the GBS molecular types, and suggests a substantive improvement in clinical application and epidemiology surveillance in GBS phenotyping.

Global effect of COVID-19 pandemic on physical activity, sedentary behaviour and sleep among 3- to 5-year-old children: a longitudinal study of 14 countries.

BACKGROUND: The restrictions associated with the 2020 COVID-19 pandemic has resulted in changes to young children's daily routines and habits. The impact on their participation in movement behaviours (physical activity, sedentary screen time and sleep) is unknown. This international longitudinal study compared young children's movement behaviours before and during the COVID-19 pandemic. METHODS: Parents of children aged 3-5 years, from 14 countries (8 low- and middle-income countries, LMICs) completed surveys to assess changes in movement behaviours and how these changes were associated with the COVID-19 pandemic. Surveys were completed in the 12 months up to March 2020 and again between May and June 2020 (at the height of restrictions). Physical activity (PA), sedentary screen time (SST) and sleep were assessed via parent survey. At Time 2, COVID-19 factors including level of restriction, environmental conditions, and parental stress were measured. Compliance with the World Health Organizations (WHO) Global guidelines for PA (180 min/day [≥60 min moderate- vigorous PA]), SST (≤1 h/day) and sleep (10-13 h/day) for children under 5 years of age, was determined. RESULTS: Nine hundred- forty-eight parents completed the survey at both time points. Children from LMICs were more likely to meet the PA (Adjusted Odds Ratio [AdjOR] = 2.0, 95%Confidence Interval [CI] 1.0,3.8) and SST (AdjOR = 2.2, 95%CI 1.2,3.9) guidelines than their high-income country (HIC) counterparts. Children who could go outside during COVID-19 were more likely to meet all WHO Global guidelines (AdjOR = 3.3, 95%CI 1.1,9.8) than those who were not. Children of parents with higher compared to lower stress were less likely to meet all three guidelines (AdjOR = 0.5, 95%CI 0.3,0.9). CONCLUSION: PA and SST levels of children from LMICs have been less impacted by COVID-19 than in HICs. Ensuring children can access an outdoor space, and supporting parents' mental health are important prerequisites for enabling pre-schoolers to practice healthy movement behaviours and meet the Global guidelines.

Relationships between dietary diversity and early childhood developmental outcomes in rural China.

The period from birth to 2years of age is highly sensitive with respect to the relationship between nutrition and neurodevelopment, but data regarding the association between dietary diversity and early childhood neurodevelopment are limited. We sought to examine the association of two feeding indicators-minimum dietary diversity (MDD) and minimum meal frequency (MMF)-with the neurodevelopment of children aged 6-23 months, using data from a cross-sectional survey conducted in six rural counties in China. Data on 1,534 children were analysed using logistic regression to explore the associations between dietary diversity and early neurodevelopment, with adjustments for the age, sex and prematurity of the child; the age, sex and educational level of the caregiver; and family size, income and simulative care practices and resources. We found that 32.4% of children had suspected developmental delays based on the Chinese version of the Ages and Stages Questionnaires Version 3, whereas 77.0% and 39.2% failed to meet the MDD and MMF, respectively. Meeting the MDD was associated with a 39% lower risk of developmental delays (AOR = 0.61, 95% CI [0.43, 0.86]). There was a significant association between MDD and reduced likelihood of developmental delays in gross motor, fine motor, problem-solving and personal social subscales, whereas MMF was only associated with a lower risk of developmental delays in the gross motor subscale (AOR = 0.63, 95% CI [0.42, 0.94]). We observed an inverse dose-response relationship between the number of food groups consumed and the risk of developmental delays (P < .001).

Proportion of kindergarten children meeting the WHO guidelines on physical activity, sedentary behaviour and sleep and associations with adiposity in urban Beijing.

BACKGROUND: World Health Organisation (WHO) Guidelines on Physical Activity, Sedentary Behaviour and Sleep for Children under 5 Years of Age were released in 2019. The aim of this study was to examine the proportion of Chinese kindergarten children who met each individual guideline and each combination of the guidelines and the associations with adiposity. METHODS: Participants were 254 kindergarten children aged 4.1-6.3 years recruited from three kindergartens in urban area of Beijing. Physical activity, sedentary behaviour and sleep duration were assessed using 24-h accelerometry over three consecutive days. Screen time was reported by parents. Weight and height were measured; and children were categorised into normal weight and overweight/obese groups according to the WHO age- and sex- specific criteria. Frequency analyses were performed to examine the proportion of children meeting individual and combination of these guidelines. Logistics regression analyses were conducted to examine the associations between guideline compliance and adiposity. RESULTS: The proportion of children who met the physical activity (≥ 3 h daily physical activity, including ≥1 h daily moderate- to vigorous-intensity physical activity (MVPA)), sedentary screen time (< 1 h/day), and sleep guidelines (10-13 h/day) were 65.4, 88.2 and 29.5%, respectively; only 15.0% met all three guidelines and 2.7% did not meet any of the guidelines. Not meeting the physical activity guideline, sleep guideline, or combination of any two guidelines, or all three guidelines was not associated with overweight or obesity; however, children who did not meet the sedentary screen time guidelines were at higher risk for overweight and obesity (odds ratio = 3.76, 95% CI: 1.50-9.45). CONCLUSIONS: In our study, only a small proportion of children met all three guidelines. Most Chinese kindergarten children met physical activity guidelines or screen time guidelines, whereas fewer children met sleep guideline. Not meeting sedentary screen time guidelines was associated with adiposity, which warrant further interventions for limiting screen time in young children.

[Influence of genetic and environment factors on aggressive behavior in twin children].

OBJECTIVE: To investigate the influence of genetic and environmental factors on aggressive behavior in twin children, and to provide clues for further exploring the causal relationship between such factors and aggressive behavior. METHODS: A questionnaire was used to investigate aggressive behavior, temperament type and parenting style among 261 twin children aged 4-12.8 years. The Holzinger method and the maximum likelihood method were used to construct a structural equation model for the estimation of heritability. Binary logistic regression analysis, multivariate linear regression analysis and general linear model analysis were used to analyze the association between aggressive behavior and environmental factors in twin children. RESULTS: The heritability of aggressive behavior was 44.4% in twin children and the score of aggressive behavior showed moderate heritability (60.9% in boys and 65.6% in girls). The multivariate analysis showed that the score of aggressive behavior in twin children was affected by the mother's emotional warmth/understanding, the mother's punishment/severity and the father's overprotection (P<0.05). There was an interaction between the mother's emotional warmth/understanding and the father's overprotection (P<0.05). CONCLUSIONS: Both genetic and environmental factors have influence on children's aggressive behavior, and parenting style is the main environmental factor affecting the aggressive behavior of twin children.

Rare Deleterious PARD3 Variants in the aPKC-Binding Region are Implicated in the Pathogenesis of Human Cranial Neural Tube Defects Via Disrupting Apical Tight Junction Formation.

Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial neural tube defect (NTD) susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, P < 0.05, OR = 3.3). These NTD-specific variants were significantly enriched in the aPKC-binding region (6/138 vs. 0/274, P < 0.01). The East Asian cohort in the ExAC database and another Chinese normal cohort further supported this association. Over-expression analysis in HEK293T and MDCK cells confirmed abnormal aPKC binding or interaction for two PARD3 variants (p.P913Q and p.D783G), resulting in defective tight junction formation via disrupted aPKC binding. Functional analysis in human neural progenitor cells and chick embryos revealed that PARD3 knockdown gave rise to abnormal cell polarity and compromised the polarization process of neuroepithelial tissue. Our studies suggest that rare deleterious variants of PARD3 in the aPKC-binding region contribute to human cranial NTDs, possibly by disrupting apical tight junction formation and subsequent polarization process of the neuroepithelium.

[Effects of rs4274224 polymorphisms in the DRD2 gene and family factors on the regularity based on the temperament in school-age children].

OBJECTIVE: To study the effects of rs4274224 polymorphisms in the DRD2 gene, family factors and their interaction on the regularity in school-age children. METHODS: The rs4274224 polymorphisms were genotyped using Sequenom Mass Array. The regularity was assessed based on the Middle Childhood Temperament Questionnaire (MCTQ). The parental rearing pattern was assessed with Egna Minnen av Bardnodnauppforstran (EMBU). The family function was assessed using Family Cohesion and Adaptability Scale (FACES II-CV). RESULTS: The regularity score in children with AA genotype of rs4274224 in the DRD2 gene was significantly lower than in those with GA/GG genotype (2.9±0.6 vs 3.1±0.7; P<0.05). The results of multiple regression analysis showed that the regularity was related to child gender, father's education level and family adaptability. The results of logistic regression analysis showed that the main factors influencing the regularity were family adaptability and its interaction with rs4274224 polymorphisms. The regularity was better in children with high family adaptability than in those with low family adaptability (OR=0.112, P<0.01). The children with AA genotype and low family adaptability were tend to be associated with low regularity (OR=21.554, P<0.01). CONCLUSIONS: The regularity based the temperament for school-age children might be influenced by family adaptability and its interaction with rs4274224 polymorphisms.

[Association between rs1079595 polymorphisms in the DRD2 gene and the distractibility based the temperament in school-age children].

OBJECTIVE: To study the association between rs1079595 polymorphisms in the DRD2 gene and the distractibility in school-age children. METHODS: The genotyping at rs1079595 was performed and the distractibility was measured based on the temperament questionnaire in 120 8-12 years old school-age children in order to analyze the effects of the rs1079595 polymorphism and its interaction with the gender, age and delivery mode on the distractibility. RESULTS: There was an association between the distractibility and rs1079595 polymorphisms. The distractibility score in children with GG/GT genotypes was significantly higher than in children with the TT genotype (4.3 ± 0.6 vs 4.0 ± 0.7; P<0.05). The interaction between rs1079595 polymorphisms and the delivery mode produced an effect on the distractibility. The normal delivery children with T alleles were associated with a low distractibility (OR=0.037, P<0.01). CONCLUSIONS: The distractibility based the temperament might be influenced by the rs1079595 polymorphism and its interaction with the delivery mode in school-age children.

Prevalence and Correlates of Adherence to the Global Total Physical Activity Guideline Based on Step Counting Among 3- to 4-Year-Olds: Evidence From SUNRISE Pilot Studies From 17 Countries.

BACKGROUND: There is limited evidence from globally diverse samples on the prevalence and correlates of meeting the global guideline of 180 minutes per day of total physical activity (TPA) among 3- to 4-year-olds. METHODS: Cross-sectional study involving 797 (49.2% girls) 3- to 4-year-olds from 17 middle- and high-income countries who participated in the pilot phases 1 and 2 of the SUNRISE International Study of Movement Behaviours in the Early Years. Daily step count was measured using thigh-worn activPAL accelerometers. Children wore the accelerometers for at least one 24-hour period. Children were categorized as meeting the TPA guideline based on achieving ≥11,500 steps per day. Descriptive analyses were conducted to describe the proportion of meeting the TPA guideline for the overall sample and each of the sociodemographic variables, and 95% CIs were calculated. Multivariable logistic regression was used to determine the sociodemographic correlates of meeting the TPA guideline. RESULTS: Mean daily step count was 10,295 steps per day (SD = 4084). Approximately one-third of the sample (30.9%, 95% CI, 27.6-34.2) met the TPA guideline. The proportion meeting the guideline was significantly lower among girls (adjusted OR [aOR] = 0.70, 95% CI, 0.51-0.96) and 4-year-olds (aOR = 0.50, 95% CI, 0.34-0.75) and higher among rural residents (aOR = 1.78, 95% CI, 1.27-2.49) and those from lower middle-income countries (aOR = 1.35, 95% CI, 0.89-2.04). CONCLUSIONS: The findings suggest that a minority of children might meet the TPA guideline globally, and the risk of not meeting the guideline differed by sociodemographic indicators. These findings suggest the need for more surveillance of TPA in young children globally and, possibly, interventions to improve childhood health and development.

[The method and efficacy for screening neonatal tetanus in high risk areas in China].

OBJECTIVES: To establish a method for screening neonatal tetanus (NT) in high risk areas in China using multi-sources data. METHODS: We adopted six NT-related indicators from National Notifiable Disease Report System (NNDRS) and National Maternal and Child Health Annual Report System, to calculate weighted high-risk score at prefecture level in 2010 and 2011. And we selected the top 30 high risk cities, and compared the scores with the actual NT incidence ranking and WHO scoring. RESULTS: The highest areas distributed in the Southwest of China with poor and minority population, and the Southeast part with high density of migrants. In the leading 30 prefectures with high score between the methods of weighted high-risk scoring and reported NT incidence ranking, there were 8 different. In comparison of the results of the methods of weighed high-risk scoring and WHO scoring, 276 prefectures in 340 distributed were divided into the same ranking groups, with Kappa coefficient 0.56 (P < 0.01). The Chi-Square association coefficient was 0.74 (P < 0.01), which showed a high correlation. But there were 10 different prefectures in the leading 36 prefectures between the two methods. CONCLUSION: The weighted scoring method included several possible factors influencing NT incidence and took their weights into consideration. Thereby, compared with WHO scoring method, this method could be more appropriate for the reality in China.

A multisource mass transfer model for simulating VOC emissions from paints.

Indoor decoration generates a large number of volatile organic compounds (VOCs), which are simultaneously released from different paints. Nevertheless, the interaction mechanism of pollutant diffusion from multisource building materials (such as primer and finish) needs to be examined. In this paper, a multisource mass transfer model for VOC emissions from different combinations of paints is established, and the analytical solution is derived. The finite difference method is used to simulate the experimental results of VOC release in the environmental chambers, and its convergence and stability are verified. Using the optimization parameters of the single-source model and the law of conservation of mass, the key parameters of the multisource mass transfer model are obtained. The results show that the established model is in excellent agreement with both experimental data and literature data. In addition, the Little number Lt is used to analyse the change trend from the initial released concentration in the single-source and multisource models.

Professional Feeding Guidance Improved Infants' Self-Feeding Proportion during Complementary Foods Introduction in Beijing, China: An Exploratory Study.

An exploratory study was undertaken to examine the prevalence of infants' feeding patterns in Beijing, China, as well as the factors linked to infants' self-feeding proportion during the introduction of complementary foods, and the impact of professional feeding guidance on this proportion. A total of 122 families with infants aged 6-11 months from Beijing were included in the study. A descriptive analysis was employed to assess the prevalence of infants' feeding patterns, while generalized linear model analysis was utilized to investigate the factors associated with these patterns. All families were provided with comprehensive and personalized professional guidance regarding the introduction of complementary foods for infants. However, 64 families were lost to follow-up, leaving 58 families who were re-evaluated and queried after one month. To exclude the influence of infants aging, both the 64 families prior to receiving feeding guidance, and the 58 families after receiving feeding guidance, were included in the analysis. The families with infants aged 6-8 months and 9-11 months were compared separately based on the presence or absence of feeding guidance. Statistical tests, including the Wilcoxon rank-sum test and χ2 test, were conducted to assess any significant differences. The study revealed that the proportion of infants engaging in self-feeding was found to be remarkably low (10% [0%, 40%]). Furthermore, a significant positive association was observed between the proportion of infants engaging in self-feeding and their age (p < 0.001). Notably, after receiving professional feeding guidance, the proportion of infants engaging in self-feeding significantly increased (from 1% [0%, 20%] to 30% [10%, 50%], p < 0.001 for infants aged 6-8 months; from 20% [10%, 50%] to 40% [30%, 50%], p < 0.001 for infants aged 9-11 months). These findings contribute valuable insights for improving postnatal care practices during the introduction of complementary foods for infants.

Effectiveness and cost-effectiveness of a group-based intervention to improve social-emotional development of young children in poverty-stricken areas: A cluster randomized controlled trial.

Background: Social-emotional ability is key to the well-being and future success of children; however, disparities in social-emotional development during an individual's early age can last a lifetime, which is particularly evident among children living in poverty-stricken areas. We aimed to determine the effectiveness, cost-effectiveness, and feasibility of a group-based intervention called the Care Group on social-emotional development for families living in poverty-stricken counties. Methods: We conducted a cluster (township) randomized controlled trial (C-RCT) every two weeks from July 2019 to June 2020 in a poverty-stricken area located in Shanxi, China. The outbreak of the COVID-19 pandemic suspended the implementation of the intervention in January 2020. The caregiver-child pairs in the intervention group participated in 12 group-based sessions with a structured curriculum and learning materials emphasizing nurturing ability and early childhood development. We applied a difference-in-differences (DID) model to estimate the intervention's impact. The analysis follows the intention-to-treat (ITT) principle. We used standard economic costing methods to estimate the cost of implementing the Care Group over the intervention period and adopted a societal perspective in the analysis. Results: We included 322 eligible caregiver-child pairs in the baseline (intervention n = 136, control n = 186) and surveyed 258 pairs in the endline (intervention n = 117, control n = 141). Compared with the control group, children in the intervention group had significantly fewer social-emotional problems (adjusted mean difference of Z score = -0.374, 95% CI = -0.718, -0.030, P = 0.033) six months after intervention. In the first year, the annual cost of implementing Care Group was US$146.10 per child, reduced to US$47.20 per child in the second year due to the exclusion of non-recurrent costs. The incremental cost-effectiveness ratio (ICER) was US$390.60. Conclusions: Care Group is an effective approach for promoting children's social-emotional development in poverty-stricken areas at an affordable cost and with high feasibility for scale-up. Considering the planned per capita health expenditure of the Chinese government for 2022, we believe that the presented evidence makes a solid scientific and financial case for integrating the Care Group intervention into the basic public health services (BPHS) package. Registration: Chinese Clinical Trials Registry (ChiCTR): ChiCTR1900022894.

Moderate-intensity continuous training has time-specific effects on the lipid metabolism of adolescents.

Background and Objectives: Moderate-intensity continuous training (MICT) is used to observe lipidomic effects in adults. However, the efects of MICT on lipid metabolism in adolescents remain unclear. Therefore, we aimed to longitudinally characterize the lipid profile in adolescents during different periods of 6-week MICT. Methods: Fifteen adolescents undertook bicycle training at 65% of maximal oxygen consumption. Plasma samples were collected at four time points (T0, T1, T2, and T3). Targeted lipidomics was assessed by ultra-performance liquid chromatography-tandem mass spectrometry to characterize the plasma lipid profiles of the participants to identify the lipids present at differing concentrations and changes in lipid species with time. Results: MICT afected the plasma lipid profiles of the adolescents. The concentrations of diglycerides, phosphatidylinositol, lysophosphatidic acid, lysophosphatidylcholine, and lysophosphatidylethanolamine were increased at T1, decreased at T2, and increased again at T3. Fatty acids (FAs) showed an opposite trend. Ether-linked alkylphosphatidylcholine and triglycerides were significantly increased and remained high. Sphingolipid concentrations initially decreased and then remained low. Therefore, a single bout of exercise had substantial efects on lipid metabolism, but by T3, fewer lipid species were present at significantly diferent concentrations and the magnitudes of the remaining diferences were smaller than those at earlier times. Among all the changed lipids, only DG(14:1/18:1), HexCer(d18:1/22:1) and FA(22:0) showed no significant correlations with any other 51 lipids (P < 0.05). Glycerides and phospholipids showed positive correlations with each other (P < 0.05), but FAs were significantly negatively correlated with glycerides and phospholipids while positively with other FAs (P < 0.05). Pathway enrichment analysis showed that 50% of the metabolic pathways represented were related to lipid metabolism and lipid biosynthesis. Conclusion: MICT increases ether-linked alkylphosphatidylcholine and triglyceride concentrations. Diglyceride, phosphatidylinositol, and lysophosphatidylcholine concentrations initially rise and then decrease 6 weeks after MICT, but FA concentrations show an opposite trend. These changes might correlate with lipid metabolism or biosynthesis pathways.

Exercise training ameliorates myocardial phenotypes in heart failure with preserved ejection fraction by changing N6-methyladenosine modification in mice model.

Heart failure with preserved ejection fraction (HFpEF) shows complicated and not clearly defined etiology and pathogenesis. Although no pharmacotherapeutics have improved the survival rate in HFpEF, exercise training has become an efficient intervention to improve functional outcomes. Here, we investigated N6-methyladenosine (m6A) RNA methylation modification in a "two-hit" mouse model with HFpEF and HFpEF with exercise (HFpEF + EXT). The manner of m6A in HFpEF and HFpEF + EXT hearts was explored via m6A-specific methylated RNA immunoprecipitation followed by high-throughput and RNA sequencing methods. A total amount of 3992 novel m6A peaks were spotted in HFpEF + EXT, and 426 differently methylated sites, including 371 hypermethylated and 55 hypomethylated m6A sites, were singled out for further analysis (fold change >2, p < 0.05). According to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, unique m6A-modified transcripts in HFpEF + EXT were associated with apoptosis-related pathway and myocardial energy metabolism. HFpEF + EXT had higher total m6A levels and downregulated fat mass and obesity-related (FTO) protein levels. Overexpression of FTO cancels out the benefits of exercise in HFpEF + EXT mice by promoting myocyte apoptosis, myocardial fibrosis and myocyte hypertrophy. Totally, m6A is a significant alternation of epitranscriptomic processes, which is also a potentially meaningful therapeutic target.

Association of Gestational Age at Birth With Subsequent Neurodevelopment in Early Childhood: A National Retrospective Cohort Study in China.

Background: The association between preterm birth and neurodevelopmental delays have been well examined, however, reliable estimates for the full range of gestational age (GA) are limited, and few studies explored the impact of post-term birth on child development. Objective: This study aimed to examine the long-term neuropsychological outcomes of children born in a full range of GA with a national representative sample in China. Methods: In this retrospective population-based cohort study, a total of 137,530 preschoolers aged 3-5 years old (65,295/47.5% females and 72,235/52.5% males) were included in the final analysis. The Ages and Stages Questionnaires-Third Edition (ASQ-3) was completed by parents to evaluate children's neurodevelopment. The associations between GA and neurodevelopment were analyzed by a generalized additive mixed model with thin plate regression splines. Logistic regression was also conducted to examine the differences in children's development with different GAs. Results: There was a non-linear relationship between GA and children's neurodevelopmental outcomes with the highest scores at 40 weeks gestational age. The adjusted risks of GAs (very and moderately preterm, late-preterm, early-term, and post-term groups) on suspected developmental delays were observed in communication (OR were 1.83, 1.28, 1.13, and 1.21 respectively, each p < 0.05), gross motor skill (OR were 1.67, 1.38, 1.10, and 1.05 respectively, each p < 0.05), and personal social behavior (OR were 1.01, 1.36, 1.12, and 1.18 respectively, each p < 0.05). The adjusted OR of very and moderately preterm, late-preterm, and early-term were observed in fine motor skills (OR were 1.53, 1.22, and 1.09 respectively, each p < 0.05) and problem-solving (OR were 1.33, 1.12, and 1.06 respectively, each p < 0.05). Conclusion: GAs is a risk factor for neurodevelopmental delays in preschoolers after controlling for a wide range of covariates, and 40-41 weeks may be the ideal delivery GA for optimal neurodevelopmental outcomes. Close observation and monitoring should be considered for early- and post-term born children as well as pre-term children.

Cooccurrence of Antibiotic Resistance and Hypervirulence in High-Risk Carbapenem-Resistant K14.K64 and Wzi209 Klebsiella pneumoniae Strains Driven by Plasmids and Their Derivatives.

Emerging hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a severe public health problem worldwide. To assess the cooccurrence of CRKP and hv-CRKP, a total of 1,181 CRKP isolates were collected from 2009 to 2018, covering their initial occurrence to outbreaks. Overall, two major capsular serotypes, namely, wzi209-CRKP and K14.K64-CRKP, were identified as being prevalent in pediatric and adult patients, respectively. Most isolates carried blaKPC, and the blaKPC-carrying hybrid plasmid IncFII-IncR, which was stable and transferable, was identified. The conjugation region (traN/traC) of IncFII-IncR was found to be variable, and the genes were used as markers to identify the transmission of strains among patient groups in this study. Notably, hv-CRKP was characterized by screening for four virulence genes (rmpA, iroN, terW, and rmpA2) in all 977 blaKPC-carrying K14.K64-CRKP and wzi209-CRKP strains. Two virulence types, namely, rmpA/iroN/terW/rmpA2 positive and terW/rmpA2 positive, were found. The corresponding virulence plasmids Vir1, i.e., nonconjugative IncFIB(k)-IncHI1B, and Vir2, i.e., conjugative antibiotic-resistant IncFIB-IncHI1B, were further characterized. Both Vir1 and Vir2 were stable, and the transferability of Vir2 was significantly higher than that of IncFII-IncR. However, none of the Vir1- or Vir2-carrying strains exhibited the hypervirulent phenotype. Meanwhile, hv-CRKP (terW/rmpA2 positive) was found in late 2018 among wzi209-CRKP strains. The corresponding Vir2-related fragment was characterized as chromosomally integrated, which dramatically enhanced the virulence of wzi209-CRKP. Transmission of hv-CRKP among patient groups was also confirmed according to virulence elements. Taken together, CRKP and hv-CRKP occurred on a large scale. Plasmids and their derivatives played an important role on this process. Surveillance and intervention of hv-CRKP are urgently needed. IMPORTANCE Currently, an increasing number of hv-CRKP strains have been reported and pose a substantial threat to public health worldwide, because these strains are considered to be simultaneously hypervirulent, carbapenem resistant, and transmissible. In this study, we provided a complete transition process of CRKP and hv-CRKP from their early emergence to outbreak in 10 years. We identified two epidemic groups, K14.K64 (wzi64)-CRKP and wzi209-CRKP, in adult and pediatric patients, respectively. K14.K64 (wzi64)-CRKP was widely present, while wzi209-CRKP was rarely reported as an epidemic type. We discovered a large scale of hv-CRKP transmission from CRKP and determined the importance of antibiotic resistance and virulence plasmids and their derivatives for the transition of CRKP and hv-CRKP. Two virulence plasmids coexist in out hospital, but neither of them enhanced virulence. Notably, we found a newly emerged type of CRKP, hypervirulent wzi209-CRKP, which had dramatically enhanced virulence, making it a great threat to human health.