The negative regulation on neurogenesis has been implicated in fluoride neurotoxicity, while the evidence is limited. To explore whether fluoride interferes with neurogenesis via the Notch1 signaling and the potential alleviation effects of carvacrol (CAR), we conducted in vivo and in vitro experiments, as well as epidemiological analyses in this study. The results showed that urinary fluoride levels and circulating Notch1 levels were associated with IQ levels in boys. NaF-treated rats had fewer neurons, lower densities of dendritic spines, depressed neurogenesis, and impaired learning and memory abilities. In vitro experiments using undifferentiated PC12 cells mimicking neurogenesis revealed that NaF suppressed differentiation and neurite outgrowth. Besides, Notch1 signaling activation was detected in vivo and in vitro. The latter was confirmed using an in vitro model supplemented with DAPT, a potent Notch1 inhibitor. Furthermore, CAR supplementation negatively regulated NICD1 and Hes1 expressions and promoted hippocampal neurogenesis, thereby improving neurological functions in NaF-treated rats. These findings indicated that the inhibition of neurogenesis in hippocampi induced by fluoride via Notch1 signaling activation may be one of the underlying mechanisms of its neurotoxicity, and that CAR significantly alleviated the neurotoxicity of NaF via the Notch1 signaling.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive.
OBJECTIVE: This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function.
METHODS: The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function.
RESULTS: The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ.
CONCLUSIONS: Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

UNASSIGNED: Malingering of neuropsychological damage is common among traumatic brain injury patients pursuing disability compensation in forensic contexts. There is an urgent need to explore differences in neuropsychological assessment outcomes with different levels of cooperation.
UNASSIGNED: A total of 420 participants with severe traumatic brain injury were classified into malingering group, partial cooperation group, and complete cooperation group according to the Binomial forced-choice digit memory test. The Wechsler Adult Intelligence Scale, event-related potential component, and Symptom Checklist 90 were applied subsequently to assess the psychological status of participants.
UNASSIGNED: Participants in the malingering group presented lower scores in the binomial forced-choice digit memory test and the Wechsler Adult Intelligence Scale, lower P3 amplitude, and simultaneously higher scores in the Symptom Checklist 90 than the other two groups. The actual intelligence quotient of participants with malingering tendencies ranged mostly between normal and marginal damage, and they often reported elevated whole scale scores in the Symptom Checklist 90. The Cooperation Index (defined as the ratio of positive symptom distress index to global severity index, CI) was proposed and validated to function as an embedded validity indicator of the Symptom Checklist 90, and the area under the receiver operating characteristic (ROC) curve was 0.938. When valued at 1.28, CI has the highest classification ability in differentiating malingering from non-malingering. Combined with the CI and P3 amplitude, the area under the ROC curve for malingering diagnosis further reached 0.952.
UNASSIGNED: Any non-optimal effort in a forensic context will lead to unexpected deviation in psychology evaluation results. CI is a potential candidate to act as an embedded validity indicator of the Symptom Checklist 90. The combination of CI and P3 amplitude can help to identify malingering in participants after severe traumatic brain injury.

BACKGROUND: While prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children.
METHODS: A total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR).
RESULTS: In GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (β = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (β = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (β = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR.
CONCLUSIONS: Prenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs.

It is now well understood that HIV-positive individuals, even those under effective ART, tend to develop a spectrum of cognitive, motor, and/or mood conditions which are contemporarily referred to as HIV-associated neurocognitive disorder (HAND), and which is directly related to HIV-1 infection and HIV-1 replication in the central nervous system (CNS). As HAND is known to induce difficulties associated with attention, concentration, and memory, it is thus legitimate and pertinent to speculate upon the possibility that HIV infection may well influence human cognition and intelligence. We therefore propose herein to review the concept of intelligence, the concept of cells of intelligence, the influence of HIV on these particular cells, and the evidence pointing to differences in observed intelligence quotient (IQ) scores between HIV-positive and HIV-negative individuals. Additionally, cumulative research evidence continues to draw attention to the influence of the gut on human intelligence. Up to now, although it is known that HIV infection profoundly alters both the composition and diversity of the gut microbiota and the structural integrity of the gut, the influence of the gut on intelligence in the context of HIV infection remains poorly described. As such, we also provide herein a review of the different ways in which HIV may influence human intelligence via the gut-brain axis. Finally, we provide a discourse on perspectives related to HIV and human intelligence which may assist in generating more robust evidence with respect to this issue in future studies. Our aim is to provide insightful knowledge for the identification of novel areas of investigation, in order to reveal and explain some of the enigmas related to HIV infection.

This study analyzed the effect of China\'s fluorosis prevention and control program, which has been in effect for more than 40 years, and the impact of fluorosis on children\'s health. Relevant research studies were retrieved from the following online databases from the time of their inception to May 2022: PubMed, ScienceDirect, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang. The Review Manager 5.3 software was used in statistical analyses. This article included seventy studies: Thirty-eight studies reported the effect of improving water quality and reducing fluoride content, the incidence rate of dental fluorosis in children, and the level of urinary fluoride, and thirty-two studies reported the intelligence quotient (IQ) and health status of children. Following water improvement strategies, the fluoride levels in drinking water decreased significantly; urinary fluoride levels and dental fluorosis decreased significantly in children. With regard to the effect of fluorosis on the IQ of children, the results showed that the IQ of children in areas with a high fluoride of fluorosis was lesser than that in areas with a low fluoride, and this difference was significant. Based on the prevalence of dental fluorosis and its effect on the intelligence of children, it appears that reducing fluoride levels in drinking water and monitoring water quality are important strategies for the prevention and treatment of fluorosis.

At present, the application of DNA methylation (DNAm) biomarkers in environmental health risk assessment (EHRA) is more challenging due to the unclearly quantitative relationship between them. We aimed to explore the role of FAM50B and PTCHD3 at the level of signaling pathways, and establish the quantitative relationship between them and children\'s intelligence quotients (IQs). DNAm of target regions was measured in multiple cell models and was compared with the human population data. Then the dose-response relationships of lead exposure with neurotoxicity and DNAm were established by benchmark dose (BMD) model, followed by potential signaling pathway screening. Results showed that there was a quantitative linear relationship between children\'s IQs and FAM50B/PTCHD3 DNAm (DNAm between 51.40 % - 78.78 % and 31.41 % - 74.19 % for FAM50B and PTCHD3, respectively), and this relationship was more significant when children\'s IQs > 90. The receiver operating characteristic (ROC) and calibration curves showed that FAM50B/PTCHD3 DNAm had a satisfying accuracy and consistency in predicting children\'s IQs, which was confirmed by sensitivity analysis of gender and CpG site grouping data. In cell experiments, there was also a quantitative linear relationship between FAM50B DNAm and reactive oxygen species (ROS) production, which was mediated by PI3K-AKT signaling pathway. In addition, the lead BMD of ROS was close to that of FAM50B DNAm, suggesting that FAM50B DNAm was a suitable biomarker for the risk assessments of adverse outcomes induced by lead. Taken collectively, these results suggest that FAM50B/PTCHD3 can be applied to EHRA and the prevention/intervention of adverse effects of lead on children\'s IQs.

There are noteworthy sex disparities in the prevalence of autism spectrum disorders (ASD), while findings regarding the sex differences in core symptoms are inconsistent. There are few relevant studies on sex differences in mainland China. This study was dedicated to a deeper understanding of the impact of sex differences on the clinical presentation of ASD with fluent language. We retrospectively studied 301 children with ASD (58 females) and utilized raw scores from the ADI-R and ADOS and the intelligence quotient (IQ) to measure symptomatology. Based on the Full-Scale IQ (FS-IQ), a binary split of average, above-average IQ (high-IQ), and below-average IQ (low IQ) occurs at 85. Across the entire sample, males and females are comparable in the FS-IQ, while males scored higher in the Perceptual Reasoning Index (PRI) (F = 7.812, p = 0.006). ADI-R did not find any statistically significant sex differences in the diagnostic cutoff score satisfaction or the raw domain scores. While a significant effect of sex on ADOS social affect domain scores was found in the total sample [λ = 0.970, partial η2  = 0.030, F (3,295) = 3.019, p = 0.030]. Tests of between-subjects effects revealed that males scored higher than females mainly in the ADOS reciprocal social interaction subcategory (partial η2  = 0.022, F = 6.563, p = 0.011). Stratified analysis revealed that the effect of sex on ADOS reciprocal social interaction subcategory scores only significant in the low-IQ children with ASD (partial η2  = 0.092, F = 10.088, p = 0.002). In general, overall cognitive functioning is similar across males and females with ASD, while males have a higher perceptual reasoning ability. Females with ASD are more likely to have comorbid intellectual impairment than males, and they could require additional intervention support. Autistic children with low IQs are more likely to exhibit sex differences in their core symptoms than children with high IQs. Intelligence plays a key role in sex-based differences in the core symptoms of ASD.

Epidemiological evidence on the association between prenatal exposure to Perfluoroalkyl substances (PFAS) and child cognition remains unclear. Thus, we aimed to investigate whether prenatal exposure to PFAS is associated with intelligence quotient (IQ) in offspring.
This study population included 2031 mother-child pairs in the Shanghai Birth Cohort (SBC) enrolled during 2013-2016. Ten PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in maternal plasma samples collected in early gestation between 9 and 16 weeks of gestation. Child IQ was assessed using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV) at 4 years of age. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into tertiles) and child IQ. A quantile g-computation approach was used to evaluate the joint and independent effects of PFAS on IQ. We also examined whether the associations varied by child sex.
We found no significant associations between ln-transformed nine individual PFAS and child full scale IQ (FSIQ) or subscale IQ after adjusting for potential confounders. The observed associations were not modified by child sex. PFAS in tertiles showed the same pattern. Results from quantile g-computation showed that PFAS mixture was not associated with child IQ; perfluorobutane sulfonate was negatively associated with FSIQ (β, -0.81; 95 % CI: -1.55, -0.07), and perfluorooctane sulfonate was also associated with lower fluid reasoning index scores (β, -1.61; 95 % CI: -3.07, -0.16) while adjusting for the other PFAS.
PFAS mixture during early pregnancy was not associated with child IQ. For certain individual PFAS, there were inverse associations with FSIQ or subscale IQ. Considering the evidence is still inconsistent, further research is needed to confirm or refute these results in other populations and to elucidate the potential neurotoxicology of PFAS.

There are limited studies on the associations between prenatal exposure to constituents of fine particulate matter (PM2.5) and children\'s intelligence quotient (IQ). Our study aimed to explore the associations between prenatal PM2.5 and its six constituents and the IQ levels of 6-year-old children. We included 512 mother-child pairs. We used a satellite-based modelling framework to estimate prenatal PM2.5 and its six constituents (ammonium, sulfate, nitrate, organic carbon, soil dust, and black carbon). We assessed the children\'s IQ using the short form of the Wechsler Intelligence Scale. Perceptual Reasoning Index (PRI), Verbal Comprehension Index (VCI), and Full Scale IQ (FSIQ) scores were computed. The multiple informant model (MIM) was applied to explore the trimester specific effects of PM2.5 and its six constituents\' exposure on children\'s PRI, VCI, and FSIQ. To examine whether the duration of breastfeeding and physical activity (PA) could modify the effects of PM2.5 on children\'s IQ, we stratified the analyses according to the duration of breastfeeding (≤6 and >6 months) and time of outdoor activities after school (≤2 and >2 h/week). The first trimester PM2.5 and its five constituents\' exposures were inversely associated with FSIQ [β = -1.34, 95 % confidence interval [CI] (-2.71, 0.04) for PM2.5] and PRI [β = -2.18, 95 %CI (-3.80, -0.57) for PM2.5] in children. The associations were magnified among boys and those with less outdoor activities or shorter breastfeeding duration. Our results indicate that prenatal PM2.5 and several of its main constituents\' exposure may disrupt cognitive development in children aged 6 years. More PA and longer breastfeeding duration may alleviate the detrimental effects of prenatal PM2.5 exposure on children\'s cognitive function.