Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs is very similar to that of organophosphorus pesticides, leading to concerns about their neurotoxicity. A few epidemiological studies have been published with inconsistent results on this topic, and a systematic scoping review is needed to provide an overview or map of the current evidence on the relationship of OPFRs with neurodevelopmental toxicity. Therefore, MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) were systematically searched for articles published in the last two decades. Nine eligible articles were included in the present systematic scoping review for adherence to the predefined PECOS (population, exposure, comparison, outcome, study design) statement. Six studies were conducted in the USA, and the remaining three studies were conducted in Austria, Norway and China. A total of 2 581 children (1 203 females and 1 378 males) were included. Half of the included studies focused on the adverse effects of OPFR exposure on cognition in children, while others primarily focused on the behaviors of children. In summary, the current evidence suggests inverse associations between early-life exposure to OPFRs and the childhood intelligence quotient and internalizing behavior and positive relationships of OPFR exposure with externalizing behavior. However, some differences in the timing of sample collection for exposure measurements, in the individual OPFR metabolites available, in the neurodevelopmental scales for outcome measurement, and in the statistical methods used to analyze the data are noted. In addition, further studies are warranted to evaluate some important issues, such as sex differences in the association, exposure-sensitive periods, and cumulative exposure risk assessment.

The N-terminal domain of Three Prime Repair Exonuclease 1 (TREX1) is catalytically active and can degrade dsDNA or ssDNA in the cytosol, whereas the C-terminal domain is primarily involved in protein localization. TREX1 deficiency induces cytosolic DNA accumulation as well as activation of the cGAS-STING-IFN signaling pathway, which results in tissue inflammation and autoimmune diseases. Furthermore, TREX1 expression in cancer immunity can be adaptively regulated to promote tumor proliferation, making it a promising therapeutic target.

The association between prenatal phthalate mixture exposure and the risk of autism spectrum disorder (ASD) in children, as well as the potential mechanism and impact of maternal vitamin D, remains unclear. We analyzed data from 3209 mother-child pairs. The associations between prenatal phthalate exposure and autistic traits in children aged 1.5, 3, 5, and 6 years were explored. Furthermore, the modifying effects of maternal vitamin D and the adverse outcome pathway, which elucidates the contribution of phthalates to ASD, were estimated. Exposure to a phthalate mixture was associated with an increased risk of ASD in children aged 1.5-6 years. For mothers with 25(OH)D deficiency, an exposure‒response relationship was observed between phthalate mixtures in early to mid-pregnancy and autistic traits in children aged 3 years. However, this association was not observed for mothers with sufficient prenatal 25(OH)D levels. The potential mechanism of action of di(2-ethylhexyl) phthalate (DEHP) exposure may involve affecting GRIN2B, inhibiting NMDAR in the postsynaptic membrane, disrupting synaptic function, and impairing learning and memory, ultimately leading to ASD development. Importantly, maternal vitamin D supplementation was demonstrated to mitigate the risk of ASD associated with phthalate exposure. Reducing phthalate exposure during pregnancy may be associated with a decreased risk of autistic traits in children. Furthermore, adequate vitamin D supplementation could potentially mitigate the impact of phthalates on these traits. Additionally, the proposed biological mechanism provides insight into how phthalate exposure may contribute to the development of ASD.

To investigate the intra- and inter-limb muscle coordination mechanism of human hands-and-knees crawling by means of muscle synergy analysis, surface electromyographic (sEMG) signals of 20 human adults were collected bilaterally from 32 limb related muscles during crawling with hands and knees at different speeds. The nonnegative matrix factorization (NMF) algorithm was exerted on each limb to extract muscle synergies. The results showed that intra-limb coordination was relatively stable during human hands-and-knees crawling. Two synergies, one relating to the stance phase and the other relating to the swing phase, could be extracted from each limb during a crawling cycle. Synergy structures during different speeds kept good consistency, but the recruitment levels, durations, and phases of muscle synergies were adjusted to adapt the change of crawling speed. Furthermore, the ipsilateral phase lag (IPL) value which was used to depict the inter-limb coordination changed with crawling speed for most subjects, and subjects using the no-limb-pairing mode at low speed tended to adopt the trot-like mode or pace-like mode at high speed. The research results could be well explained by the two-level central pattern generator (CPG) model consisting of a half-center rhythm generator (RG) and a pattern formation (PF) circuit. This study sheds light on the underlying control mechanism of human crawling.

Cerebral palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function. Since the major brain injury associated with CP is white matter injury (WMI), especially, in preterm infants, we established a “multi-hit” rat model to mimic human WMI in symptomatology and at a histological level. In our WMI model, pups suffering from limb paresis, incoordination, and direction difficulties fit the performance of CP. Histologically, they present with fewer neural cells, inordinate fibers, and more inflammatory cell infiltration, compared to the control group. From the electron microscopy results, we spotted neuronal apoptosis, glial activation, and myelination delay. Besides, the abundant appearance of IBA1-labeled microglia also implied that microglia play a role during neuronal cell injury. After activation, microglia shift between the pro-inflammatory M1 type and the anti-inflammatory M2 type. The results showed that LPS/infection stimulated IBA1 + (marked activated microglia) expression, downregulated CD11c + (marked M1 phenotype), and upregulated Arg 1 + (marked M2 phenotype) protein expression. It indicated an M1 to M2 transition after multiple infections. In summary, we established a “multi-hit” WMI-induced CP rat model and demonstrated that the microglial activation correlates tightly with CP formation, which may become a potential target for future studies.