Gearbox fault diagnosis method based on lightweight channel attention mechanism and transfer learning.

In practical engineering, the working conditions of gearbox are complex and variable. In varying working conditions, the performance of intelligent fault diagnosis model is degraded because of limited valid samples and large data distribution differences of gearbox signals. Based on these issues, this research proposes a gearbox fault diagnosis method integrated with lightweight channel attention mechanism, and further realizes the cross-component transfer learning. First, time-frequency distribution of original signals is obtained by wavelet transform. It could intuitively reflect local characteristics of signals. Secondly, based on a local cross-channel interaction strategy, a lightweight efficient channel attention mechanism (LECA) is designed. The kernel size of 1D convolution is affected by channel number and coefficients. Multi-scale feature input is used to retain more detailed features of different dimensions. A lightweight convolutional neural network is constructed. Finally, a transfer learning method is applied to freeze lower structures of the network and fine-tune higher structures of the model using small samples. Through experimental verification, the proposed model could effectively utilize samples. The application of transfer learning could realize accurate and fast fault classification of small samples, and achieve good gearbox fault diagnosis effect under varying working conditions and cross-component conditions.

Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach.

The proteolysis targeting chimera (PROTAC) strategy results in the down-regulation of unwanted protein(s) for disease treatment. In the PROTAC process, a heterobifunctional degrader forms a ternary complex with a target protein of interest (POI) and an E3 ligase, which results in ubiquitination and proteasomal degradation of the POI. While ternary complex formation is a key attribute of PROTAC degraders, modification of the PROTAC molecule to optimize ternary complex formation and protein degradation can be a labor-intensive and tedious process. In this study, we take advantage of DNA-encoded library (DEL) technology to efficiently synthesize a vast number of possible PROTAC molecules and describe a parallel screening approach that utilizes DNA barcodes as reporters of ternary complex formation and cooperative binding. We use a designed PROTAC DEL against BRD4 and CRBN to describe a dual protein affinity selection method and the direct discovery of novel, potent BRD4 PROTACs that importantly demonstrate clear SAR. Such an approach evaluates all the potential PROTACs simultaneously, avoids the interference of PROTAC solubility and permeability, and uses POI and E3 ligase proteins in an efficient manner.

Integrated 16S rDNA sequencing and metabolomics to explore the intestinal changes in children and rats with dental fluorosis.

Dental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.

Extendible ghost imaging with high reconstruction quality in strong scattering medium.

Ghost imaging (GI) possesses significant application prospects in scattering imaging, which is a classic example of underdetermined conversion problem in optical field. However, even under the framework of single-pixel imaging (SPI), a challenge remains unresolved, i.e., structured patterns may be damaged by scattering media in both the emissive and receiving optical paths. In this study, an extendible ghost imaging, a numerical reproduction of the qualitative process using deep learning (DL)-based GI is presented. First, we propose and experimentally verify a brief degradation-guided reconstruction (DR) approach with a neural network to demonstrate the degradation principle of scattering, including realistic dataset simulations and a new training structure in the form of a convolutional neural network (CNN). Then, a novel photon contribution model (PCM) with redundant parameters is proposed to generate intensity sequences from the forward direction through volumetric scattering media; the redundant parameters are constructed and relate to the special output configuration in a lightweight CNN with two branches, based on a reformulated atmospheric scattering model. The proposed scheme recovers the semantics of targets and suppresses the imaging noise in the strong scattering medium, and the obtained results are very satisfactory for applications to scattering media of more practical scenarios and are available for various scattering coefficients and work distances of an imaging prototype. After using DL methods in computational imaging, we conclude that strategies embedded in optics or broader physical factors can result in solutions with better effects for unanalyzable processes.

PAC-FragmentDEL - photoactivated covalent capture of DNA-encoded fragments for hit discovery.

We describe a novel approach for screening fragments against a protein that combines the sensitivity of DNA-encoded library technology with the ability of fragments to explore what will bind. Each of the members of the library consists of a fragment which is linked to a photoactivatable diazirine moiety. Split and pool synthesis combines each fragment with a set of linkers with the version of the library reported here containing some 70k different compounds, each with an individual DNA code. Incubation of the library with a protein sample is followed by photoactivation, washing and subsequent PCR and sequencing which allows the individual fragment hits to be identified. We illustrate how the approach allows successful hit fragment identification using only microgram quantities of material for two targets. PAK4 is a kinase for which conventional fragment screening has generated many advance leads. The as yet undrugged target, 2-epimerase, presents a more challenging active site for identification of hit compounds. In both cases, PAC-FragmentDEL identified fragments validated as hits by ligand-observed NMR measurements and crystal structure determination of off-DNA sample binding to the proteins.

Expanding the DNA-encoded library toolbox: identifying small molecules targeting RNA.

DNA-encoded library (DEL) technology is a powerful tool for small molecule identification in drug discovery, yet the reported DEL selection strategies were applied primarily on protein targets in either purified form or in cellular context. To expand the application of this technology, we employed DEL selection on an RNA target HIV-1 TAR (trans-acting responsive region), but found that the majority of signals were resulted from false positive DNA-RNA binding. We thus developed an optimized selection strategy utilizing RNA patches and competitive elution to minimize unwanted DNA binding, followed by k-mer analysis and motif search to differentiate false positive signal. This optimized strategy resulted in a very clean background in a DEL selection against Escherichia coli FMN Riboswitch, and the enriched compounds were determined with double digit nanomolar binding affinity, as well as similar potency in functional FMN competition assay. These results demonstrated the feasibility of small molecule identification against RNA targets using DEL selection. The developed experimental and computational strategy provided a promising opportunity for RNA ligand screening and expanded the application of DEL selection to a much wider context in drug discovery.

The Index of Esophageal Cancer Related Ischemic Stroke: A Retrospective Patient Control Study.

Purpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke. Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden's J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors. Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051-1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002-1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628-3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index. Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.

Association between fluoride exposure and behavioural outcomes of school-age children: a pilot study in China.

To assess the association between fluoride exposure and children's behavioural outcomes, we recruited 325 resident school-age children (7-13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children's behavioural outcomes were assessed by Conners' Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% CI: 2.74, 5.28) and a 97% (OR = 1.97, 95% CI: 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.

Effect of cattle farm exposure on oropharyngeal and gut microbial communities and antibiotic resistance genes in workers.

Livestock farms are recognized as the main sources of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) with potential implications for human health. In this study, we systematically analyzed microbiome composition, distribution of ARGs and mobile genetic elements (MGEs) in the oropharynx and gut of workers in cattle farms and surrounding villagers, cattle feces and farm air, and the relationship of microbial communities among farm air, cattle feces and farmworkers (oropharynx and gut). Exposure to the farm environment may have remodeled farmworkers' oropharynx and gut microbiota, with reduced microbial diversity (P < 0.05) and enrichment of some opportunistic pathogenic bacteria like Shigella, Streptococcus, and Neisseria in the oropharynx. Meanwhile, compared with villagers, ARG abundance in oropharynx of farmworkers increased significantly (P < 0.05), but, no significant difference in gut (P > 0.05). Microbial composition and ARG profile in farmworkers might be influenced by working time and work type, ARG abundance in farmworkers' gut was positively correlated with working time (P < 0.01), and higher ARG abundance was found in the oropharynx of drovers. The network analysis revealed that 4 MGEs (tnpA-01, tnpA-04, Tp614, and IS613), 5 phyla (e.g. Bacteroidetes, Fusobacteria, and TM7), and 6 genera were significantly associated with 37 ARGs (ρ > 0.6, P < 0.01). Overall, our results indicated that farm exposure may have affected the microbial composition and increased ARG abundance of farmworkers. Transmission of some ARGs may have occurred among the environment, animals and humans via host bacteria, which might pose a potential threat to human health.

A Novel Scalarized Scaffold Hopping Algorithm with Graph-Based Variational Autoencoder for Discovery of JAK1 Inhibitors.

We have developed a graph-based Variational Autoencoder with Gaussian Mixture hidden space (GraphGMVAE), a deep learning approach for controllable magnitude of scaffold hopping in generative chemistry. It can effectively and accurately generate molecules from a given reference compound, with excellent scaffold novelty against known molecules in the literature or patents (97.9% are novel scaffolds). Moreover, a pipeline for prioritizing the generated compounds was also proposed to narrow down our validation focus. In this work, GraphGMVAE was validated by rapidly hopping the scaffold from FDA-approved upadacitinib, which is an inhibitor of human Janus kinase 1 (JAK1), to generate more potent molecules with novel chemical scaffolds. Seven compounds were synthesized and tested to be active in biochemical assays. The most potent molecule has 5.0 nM activity against JAK1 kinase, which shows that the GraphGMVAE model can design molecules like how a human expert does but with high efficiency and accuracy.

Time-course miRNA alterations and SIRT1 inhibition triggered by adolescent lead exposure in mice.

Sirtuin 1 (SIRT1), the NAD-dependent histone deacetylase, has been extensively investigated due to its cognitive protective effect. Studies suggest microRNAs (miRNAs) and histone modifications are key epigenetic regulators of gene expression and play important role in brain development. We previously showed that cognitive impairment by lead (Pb) was associated with downregulation of SIRT1, but the epigenetic role of this is unclear. Thus, we exposed 4-week-old male mice to 0.2% lead acetate solution for three months, and subsequently extracted brain homogenate from mice cortex and hippocampus at the age of 1, 4, and 16 months, respectively. In this study, we found that the protein level of SIRT1 was inhibited in the hippocampus and cortex of 16-month-old aged mice exposed to Pb. Moreover, changes in the levels of miR-138-5p and miR-141-3p, which were considered to the mechanistic target of SIRT1 by bioinformatic analysis, were negative correlations SIRT1 protein expression. We also found miR-34c-3p expression was increased in the cortex of mice at the age of 16 months. Collectively, our results showed the expression of neural SIRT1 and three selected microRNAs at different age nodes of mice for the first time of following Pb exposure. Our results suggest that additional efforts should focus on the consequences of early Pb exposure from an epigenetic perspective.

Revealing the distribution characteristics of antibiotic resistance genes and bacterial communities in animal-aerosol-human in a chicken farm: From One-Health perspective.

Antibiotics in breeding industry can enter the environment through multiple pathways, thus accelerating the emergence and spread of antibiotic resistance genes (ARGs), among which aerosol transmission is easily achieved and often overlooked. To elucidate the role of aerosols in this situation, the present study investigated the distribution characteristics of 107 ARG subtypes (targeting to eight different ARG types) and nine mobile genetic elements (MGEs) and bacterial community in animal (chicken cloaca), environment (aerosols) and human (nasopharynx) of a chicken farm (n = 42) in Henan Province. In total, 116 ARG subtypes and MGEs were identified in the poultry farm. The total bacterial concentration of aerosols inside the chicken house (3.117 × 104 CFU/m3) exceeded the corresponding limit. The microbial communities in the samples of cloaca swab (C) and the workers' nasopharyngeal swab (N) were closer, while the abundance distribution of ARGs/ MGEs in cloacal swab (C) and aerosol (AI) in chicken house were much similar. There were certain consistency of the microbial community structure and the distribution of ARGs among the three groups of chicken cloaca, air aerosol, and workers' nasopharynx. Our results highlighted that animal breeding does have a certain impact on the surrounding environment and human, and aerosols play an important role in this process.

Attenuation of Pb-induced Aß generation and autophagic dysfunction via activation of SIRT1: Neuroprotective properties of resveratrol.

This study examined the neuroprotective properties of resveratrol (Res) and its target sirtuin1 (SIRT1) against lead (Pb)-mediated toxicity and discovered that both resveratrol treatment and SIRT1 overexpression restored blocked autophagic flux as well as reduced ß-amyloid (Aß) contents. Four-week-old male C57BL/6 mice were employed to consumed 0.2% Pb(Ac)2 solution or deionized water for 3 months followed by 12 months of Res (50 mg/kg BW) or vehicle gavage. In in vitro study, SH-SY5Y cells were pretreated with the SIRT1 activator SRT1720 (2 µM) or the inhibitor EX527 (2 µM) for 2 h, then 25 µM of Pb(Ac)2 was added and incubated for 48 h. Western blotting, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and Lyso-Tracker Red Staining were next used to estimate the potential alterations of the autophagic pathway as well as BACE1-mediated amyloid processing in response to Pb exposure, respectively. Our data revealed that Res treatment or SIRT1 activation resisted the induction of autophagy by Pb exposure through inhibition of LC3 and Beclin-1 expression and promoted the degradation of Aß and Tau phosphorylation. Besides, the SIRT1 activator (SRT1720) downregulated the expression of BACE1, the rate-limiting enzyme for Aß production, by inhibiting the activation of nuclear factor-κB (NF-κB) in Pb-treated SH-SY5Y cells, which resulted in reduced Aß production. Collectively, we verified the role of Res-SIRT1-autophagy as well as the SIRT1-NF-κB-BACE1 pathway in Pb-induced neuronal cell injury by in vivo or in vitro models. Our findings further elucidate the important role of SIRT1 and Res in counteracting Pb neurotoxicity, which may provide new interventions and targets for the subsequent treatment of neurodegenerative diseases.

Description method with automatically configurable Gaussian radial basis function for complex freeform surface.

The description of deformable mirror (DM) surface, which is usually a complex freeform surface, affects the measurement speed and accuracy in a real-time interferometric measurement system with a DM as the dynamic compensator. We propose an accurate and fast description method with automatically configurable Gaussian radial basis function. The distribution and shape factors of GRBFs are related to the complexity of the surface with sufficient flexibility to improve the accuracy, and the fitting results are automatically obtained using a traversal optimization algorithm, which can improve the fitting speed by reducing the number of time-consuming calculations. The feasibility is verified by numerical and practical experiment.

Resveratrol reverses hippocampal synaptic markers injury and SIRT1 inhibition against developmental Pb exposure.

Lead (Pb) exposure damages synaptic structural plasticity that results in cognitive impairment. Resveratrol, a natural polyphenolic compound, is one of the most potent agonists of silencing information regulator 1 (SIRT1) discovered to date. However, the effects of SIRT1 on synaptic functional plasticity in early life Pb exposure are not well studied. Herein, the purpose of this study is to investigate the expression of synaptic markers and SIRT1 in rats exposed to Pb and to evaluate the regulatory effect of resveratrol during this process. The Pb exposed male SD pups were treated with resveratrol (50 mg/kg/d) or EDTA (150 mg/kg/d) followed by hippocampal and blood sampling for analysis at postnatal day 21 (PND21). In the Morrris water maze test, resveratrol treatement protected the rats against Pb-induced impairment of learning and memory (P < 0.05). Resveratrol also enhanced the expression of brain-derived neurotrophic factor (BDNF, P < 0.001 vs 0.2% Pb group), and reversed the effects of Pb exposure on SIRT1(P < 0.001 vs 0.2% Pb group). The DG, CA1 and CA3 regions of the hippocampus showed a considerable increase in the expression of pre- and postsynaptic proteins (P < 0.001 vs 0.2% Pb group). In conclusion, our study demonstrated that resveratrol, through the activation of SIRT1, played a protective role against Pb-induced defects in synaptic plasticity, and suggested a new potential adjuvant treatment for Pb poisoning.

Resveratrol improved hippocampal neurogenesis following lead exposure in rats through activation of SIRT1 signaling.

Lead (Pb) poses a potential environmental risk factor for cognitive dysfunction during early life and childhood. Resveratrol is considered a promising antioxidant with respect to the prevention of cognitive deficits and act as a potent SIRT1 agonist. Herein, this study aims to investigate the profile of neurogenesis markers following Pb exposure and to determine the regulatory role of resveratrol in this process. We confirmed firstly the protective effects of resveratrol against Pb-induced impairments of hippocampal neurogenesis in Male SD rats. Pb exposure early in life caused the altered expression of Ki-67, NeuN, caspase-3 and SIRT1 signaling, thereby resulting in spatial cognitive impairment of adolescent rats. As expected, resveratrol reduced cognitive damage and promoted neurogenesis in Pb-induced injury by regulation of SIRT1 pathway. Collectively, our study establishes the efficacy of resveratrol as a neuroprotective agent and provides a strong rationale for further studies on SIRT1-mediated mechanisms of neuroprotective functions.

Synthetic system design method for off-axis stabilized zoom systems with a high zoom ratio.

Stabilized zoom systems possess the advantages such as the simplified system layout, improved system stability, enhanced imaging performance, and a high zoom speed. The complex system design to achieve high performances requires calculations or investigations of the initial system for optimization and improvements, and thus, specific design techniques are pursued. In this study, we propose an automatic optical design scheme of synthetic characteristics for the off-axis stabilized zoom systems, which using focal length variable (FLV) opto-electronic elements and with a high zoom ratio. The study aims at evaluating and synthetically achieving the zooming properties and the image quality balance of entire focus imaging. The multi-element stabilized zoom systems are characterized using the Gaussian brackets expressions and their optimal solution ranges for high zoom ratios are deduced to achieve non-defocusing imaging in specific stroke ranges of FLV elements. Then considering the analytical characterization of the off-axis-induced primary aberrations at multi-conjugate positions, we use a conic surface to deduce the basic expression of the nodal aberration. Thereby the nonlinear global merit function is established with a semi-empirical mathematical model based on nodal aberration theory and nonlinear zoom equation for maintaining the stability of focal length and image plane drift. And the theory of Pareto Optimality is employed in the process of verifying the superiority of the solutions. Finally, a series of solutions for a high zoom ratio and aberration compensation are implemented and the optimal configurations with conical surfaces for an off-axis stabilized zoom system are obtained.

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p ＜ 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.

Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility.

BACKGROUND: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ). METHODS: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven's Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ. RESULTS: The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (ß = - 4.965, 95% CI: - 9.198, - 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children's IQ scores (95% CI: - 19.2, - 3.5, P = 0.005). CONCLUSIONS: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.