Association of obesity and menarche SNPs and interaction with environmental factors on precocious puberty.

BACKGROUND: Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population. METHODS: This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty. RESULTS: The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty. CONCLUSIONS: The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention. IMPACT: This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.

Daytime sleep duration during infancy as an indicator for cognitive development at school age: a prospective cohort study.

STUDY OBJECTIVES: The reduction in daytime sleep during early life is considered one of the indicators of the maturation of sleep patterns, which is closely associated with cognitive development. The current study aims to analyze the relationships between daytime sleep duration (DSD) during infancy and cognitive development at 6 and 10 years. METHODS: The study included 262 mothers with their newborns from the Shanghai Sleep Birth Cohort Study, spanning eleven follow-ups from 42 days to 10 years. Sleep parameters were assessed using parent-report questionnaires at each follow-up, and cognitive development was evaluated with the Wechsler Intelligence Scale for Children, 4th edition at 6 and 10 years. RESULTS: Two distinct DSD trajectories in early childhood were identified: "typical DSD" (66.7%) and "infancy excessive DSD" (33.3%). Children in the "infancy excessive DSD" trajectory exhibited lower working memory scores than those in the "typical DSD" trajectory at 6 years (Mean difference=5.90, 95% CI [1.83, 9.96], p=0.005) and 10 years (Mean difference=4.37, 95% CI [0.26, 8.48], p=0.037). Additional analysis in a relatively homogeneous sample consistently showed correlations between DSD trajectories and working memory performance. No consistent significant differences were found in other domains of cognitive development. CONCLUSIONS: Excessive daytime sleep during infancy may serve as an early indicator for poor working memory at school age. These findings raise concerns about the long-term cognitive development of infants with excessive DSD.

Event-Triggered Finite-Time Formation Control of Underactuated Multiple ASVs with Prescribed Performance and Collision Avoidance.

In this paper, an event-triggered finite-time controller is proposed for solving the formation control problems of underactuated multiple autonomous surface vessels (ASVs), including asymmetric mass matrix, collision avoidance, maintaining communication distances and prescribed performance. First, to not only avoid collisions between the follower and leader but also maintain an effective communication distance, a desired tracking distance is designed to be maintained. Second, an improved barrier Lyapunov function (BLF) is proposed to implement the tracking error constraint. In addition, the relative threshold event-triggering strategy effectively solves the communication pressure problem and greatly saves communication resources. Finally, based on coordinate transformation, line of sight (LOS) and dynamic surface control (DSC), a comprehensive finite-time formation control method is proposed to avoid collisions and maintain communication distance. All the signals of the proposed control system can be stabilized in finite time (PFS). The numerical simulation results verify the effectiveness of the proposed control system.

The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study.

BACKGROUND: Childhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring's adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring's adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association. METHODS: Included participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring's body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators. RESULTS: The mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37-0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring's SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint-BMI association, respectively. CONCLUSIONS: Maternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.

Robust Adaptive Self-Structuring Neural Network Bounded Target Tracking Control of Underactuated Surface Vessels.

This paper studies the target-tracking problem of underactuated surface vessels with model uncertainties and external unknown disturbances. A composite robust adaptive self-structuring neural-network-bounded controller is proposed to improve system performance and avoid input saturation. An extended state observer is proposed to estimate the uncertain nonlinear term, including the unknown velocity of the tracking target, when only the measurement values of the line-of-sight range and angle can be obtained. An adaptive self-structuring neural network is developed to approximate model uncertainties and external unknown disturbances, which can effectively optimize the structure of the neural network to reduce the computational burden by adjusting the number of neurons online. The input-to-state stability of the total closed-loop system is analyzed by the cascade stability theorem. The simulation results verify the effectiveness of the proposed method.

Association of Obesity and Body Fat Percentage with Pubertal State in Six- to Nine-Year-Old Chinese Females.

Background: An early trend in the mean age of pubertal onset appears in adolescents, but the association between body fat percentage (BF%) of children and precocious puberty is unclear. The aim of the study was to analyze the association of sexual development with BF% in girls. Methods: A total of 407 females were included in this cross-sectional study. BF% was measured by Inbody S10, International Obesity Task Force was used to judge overweight or obesity, and early puberty was defined as a younger age than the median age in each of the pubertal Tanner stages. Logistic regression analysis was used to test relationships between pubertal states and independent variables, including age, weight, waist circumference (WC), type of school, and residency. Results: Females with early puberty exhibited higher anthropometry data (such as weight, BMI, BF%) than females with normal maturation (p < 0.001). Weight, BMI, WC, BF% residency, and school type were related to pubertal state (p < 0.001). Females with higher BF% were more likely to exhibit early puberty (odds ratio = 1.138, 95% confidence interval = 1.046-1.237). The students who lived in urban areas and studied in public schools had a lower risk of early puberty. Moreover, BF% continuously increased with age in 6- to 9-year-old girls. Conclusions: Females with higher BF% may be more likely to exhibit early puberty. In future studies, more research is needed to analyze this mechanism of how BF% influences puberty development.

Association between vaccinations and clinical manifestations in children with COVID-19.

BACKGROUND: The infection rate of Coronavirus Disease 2019 (COVID-19) in children was less than that in adults. However, the underlining reason is not well known. METHODS: Children with COVID-19 were recruited from two Children's Hospitals in Wuhan and Shanghai in this case-control study. The associations of initial symptoms with age, vaccinations of Bacillus Calmette Guerin (BCG), and influenza and pathogens were determined by Chi-square t-test. RESULTS: We evaluated 248 confirmed cases, and 56 suspected cases with COVID-19. The median age was 6.82 years old, and 118 cases (38.82%) were girls. Furthermore, 30.26% of all patients were asymptomatic cases. The percentage of asymptomatic cases vaccinated with BCG was not significantly higher than that without BCG vaccination [86/280 (30.71%) vs. 6/13 (46.15%), P=0.203], and initial symptoms were not related with immunized influenza vaccine (P=0.267). Compared to parameters in pediatric patients with normal body temperatures, patients with fever had higher C reactive protein (CRP) (P<0.001). CONCLUSIONS: Pediatric COVID-19 patients with BCG vaccinations exhibit similar clinical manifestations compared to those without BCG vaccinations, and the severity of symptoms in pediatric patients may be related to the maturity of immune function.

Cohort Profile: The Shanghai Sleep Birth Cohort Study.

BACKGROUND: Sleep disturbances in women occur frequently throughout pregnancy. Previous studies have demonstrated that the increasing incidence of physiological and psychological illness is concurrent with increasing sleep deprivation and poor sleep quality in adults and children. OBJECTIVES: The Shanghai Sleep Birth Cohort Study (SSBCS) was established to examine the effect of sleep disturbances during the third trimester on emotional regulation of mothers; to assess the effect of maternal sleep during pregnancy on the growth and development of children; and to explore the influence of children's sleep characteristics on physical and social-emotional development. POPULATION: The study was conducted in the Renji Hospital in Pudong New District, Shanghai from May 2012 to July 2013. Women and their newborns who met the inclusion criteria and agreed to participate in this study were recruited to the SSBCS. METHODS: The follow-up visits for children were conducted at the age of 42 days, 3, 6, 9, 12, 18, and 24 months, and 3, 4, and 6 years. Data on demographic factors, physical examination, sleep assessment, developmental and psychiatric assessment, diet records, and biological samples were collected throughout the study. PRELIMINARY RESULTS: A total of 277 pregnant women were recruited to the study; the response rate was 64.3%. 37.9% of the pregnant women had poor sleep quality and 12.0% suffered from depression. Infant sleep patterns changed during the first year of life, but most sleep characteristics showed little variation from 6 to 12 months. CONCLUSIONS: The SSBCS is an on-going prospective cohort study with follow-up to 6 years. The detailed data on demographic factors, sleep assessment, physical examinations, neurodevelopmental and psychiatric assessment, diet records, and biological samples make this research platform an important resource for examining the potential effects of sleep characteristics on both maternal and child health.

Associations of short sleep duration with appetite-regulating hormones and adipokines: A systematic review and meta-analysis.

In the current study, a systematic review and meta-analysis were conducted to summarize and assess whether short sleep duration is associated with appetite-regulating hormones and adipokine levels. Reference databases were searched for studies related to sleep and appetite-regulating hormones and adipokines. Qualitative and quantitative syntheses were conducted to evaluate the relationship between sleep duration and the level of appetite-regulating hormones and adipokines, including leptin, ghrelin, adiponectin, resistin, and orexin. Twenty-one of 3536 studies, covering a total of 2250 participants, met the inclusion criteria. Leptin, ghrelin, and adiponectin were included in the meta-analysis. Ghrelin levels were higher in the short sleep group (standard mean difference [SMD] = 0.14, 95% CI [0.03, 0.25], p = 0.01). Significant differences between the short sleep group and recommended sleep group were also noted in leptin level experimental subgroup studies (SMD = 0.19, 95% CI [0.03, 0.35], p = 0.02) and ghrelin level cross-sectional subgroup studies (SMD = 0.14, 95% CI [0.02, 0.27], p = 0.03). A rise in leptin and ghrelin levels were also observed in sleep deprivation groups (SMD = 0.24, 95% CI [0.10, 0.39], p = 0.001 and SMD = 0.18, 95% CI [0.04, 0.33], p = 0.01, respectively). In conclusion, short sleep duration is associated with an increased ghrelin level, while sleep deprivation had a significant effect on the levels of both leptin and ghrelin.

SnS2 Nanosheets/H-TiO2 Nanotube Arrays as a Type†II Heterojunctioned Photoanode for Photoelectrochemical Water Splitting.

Improving the separation efficiency of photogenerated electron-hole pairs and the conductivity of electrons to photoanode substrates are critical to achieve high-performance photoelectrochemical (PEC) water splitting. Here, a SnS2 /H-TiO2 /Ti heterojunction photoanode was fabricated with SnS2 nanosheets vertically grown on hydrogen-treated TiO2 (H-TiO2 ) nanotube arrays on a Ti substrate. It showed a significantly enhanced photocurrent of 4.0 mA cm-2 at 1.4 V (vs. reversible hydrogen electrode) under AM 1.5 G illumination, 70 times higher than that of SnS2 /TiO2 /Ti. Kelvin probe force microscopy measurements indicated that photogenerated electrons could be easily transported through the SnS2 /H-TiO2 interface but not through the SnS2 /TiO2 interface. Through hydrogen treatment, defects were created in H-TiO2 nanotubes to convert type I junctions to type II with SnS2 nanosheets. As a result, a high efficiency of electron-hole separation at the SnS2 /H-TiO2 interface and a high electron conductivity in H-TiO2 nanotubes were achieved and improved PEC performance. These findings show an effective route towards high-performance photoelectrodes for water splitting.

HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells.

High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma.

Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.

To correct a DNA mutation in the human genome for gene therapy, homology-directed repair (HDR) needs to be specific and have the lowest off-target effects to protect the human genome from deleterious mutations. Zinc finger nucleases, transcription activator-like effector nuclease (TALEN) and CRISPR-CAS9 systems have been engineered and used extensively to recognize and modify specific DNA sequences. Although TALEN and CRISPR/CAS9 could induce high levels of HDR in human cells, their genotoxicity was significantly higher. Here, we report the creation of a monomeric endonuclease that can recognize at least 33 bp by fusing the DNA-recognizing domain of TALEN (TALE) to a re-engineered homing endonuclease I-SceI. After sequentially re-engineering I-SceI to recognize 18 bp of the human ß-globin sequence, the re-engineered I-SceI induced HDR in human cells. When the re-engineered I-SceI was fused to TALE (TALE-ISVB2), the chimeric endonuclease induced the same HDR rate at the human ß-globin gene locus as that induced by TALEN, but significantly reduced genotoxicity. We further demonstrated that TALE-ISVB2 specifically targeted at the ß-globin sequence in human hematopoietic stem cells. Therefore, this monomeric endonuclease has the potential to be used in therapeutic gene targeting in human cells.