Microplastics, a new type of ecological pollutant, have now become a major environmental concern worldwide. Polystyrene microplastics (PS), one of the most abundant form of microplastics, cause deleterious effects across species. Melatonin (MT), which is secreted by pineal gland, exhibits protective role against pollutant-induced damage. However, whether MT could ameliorate PS-induced neurodevelopmental toxicity remain unclear. In our study, zebrafish embryos were treated with PS (0.5, 25 mg/L) in the presence or absence of MT (1 μM) from 4 h post-fertilization (hpf) to 144 hpf. Locomotion behavior, oxidative stress, apoptosis, proliferation and development of caudal primary (Cap) motoneuron axon were analyzed. Gene expression was determined by qRT-PCR or whole-mount in situ hybridization. Results showed that PS exposure significantly reduced swimming speed of zebrafish larvae and induced excessive reactive oxygen species (ROS), apoptosis and aberrant proliferation. In addition, PS treatment markedly shortened the length of Cap motoneuron axons and decreased expression of neurodevelopment related genes. While, MT administration considerably rescued the neurodevelopmental toxicity of PS. Mechanistically, MT activated nrf2 (nuclear factor-E2-related factor 2) - isl2a (ISL LIM homeobox 2a) axis to antagonize the side effects of PS. In all, our findings suggest that PS exposure during early life lead to aberrant neurodevelopment of zebrafish, and MT might be a therapeutic option for protecting such disorder.

Introduction Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various diseases, including cancer. However, little is known about lncRNAs in human brain gliomas. Material and methods We examined lncRNA profiles from three glioma specimens using lncRNA expression...

Background: Craniosynostosis, defined as premature fusion of one or more cranial sutures, affects approximately 1 in every 2000–2500 live births. Sagittal craniosynostosis (CS), the most prevalent form of isolated craniosynostosis, is caused by interplay between genetic and perinatal environmental insults. However, the underlying details remain largely unknown. Methods: The proband (a female monochorionic twin diagnosed with CS), her healthy co-twin sister and parents were enrolled. Obstetric history was extracted from medical records. Genetic screening was performed by whole exome sequencing (WES) and confirmed by Sanger sequencing. Functional annotation, conservation and structural analysis were predicted in public database. Phenotype data of Axin2 knockout mice was downloaded from The International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org). Results: Obstetric medical records showed that, except for the shared perinatal risk factors by the twins, the proband suffered additional persistent breech presentation and intrauterine growth restriction. We identified a heterozygous mutation of Axin2 (c.1181G > A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. This mutation is not reported in Asian population and results in replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of Axin2 protein, which is highly conserved across species. The mutation was predicted to be potentially deleterious by in silico analysis. Incomplete penetrance of Axin2 haploinsufficiency was found in female mice. Conclusions: Axin2 (c.1181G > A, p.R394H, rs200899695) mutation confers susceptibility and perinatal risk factors trigger the occurrence of sagittal craniosynostosis. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis in Chinese population.

Objective: To study the effect of total cranial reconstruction for sagittal synostosis (scaphocephaly) deformity in Chinese children. Methods: A retrospective analysis was performed involving 23 children with isolated non-syndromic sagittal synostosis who were treated by total calvarial vault remodeling after 1 year of age from May 2015 to June 2019 in the Department of Neurosurgery, Children's Hospital of Nanjing Medical University. The authors reconstruct patients’ pre- and post-operative cranial thin-section CT scan images and those of the control group. The cephalic index (traditional, normative), intracranial volume, horizontal point of maximum width (H-PMW), vertical point of maximum width (V-PMW), frontal to head height ratio and occipital to head height ratio data were analyzed using a paired t test or Wilcoxon signed-rank test. Results: Twenty-three patients met the inclusion criteria, including 19 males and 4 females. The ratio of males to females was 4.7:1. All patients underwent total cranial reconstruction. The average age was 26.52 months (13–48 months), the average operation time was 214.13 minutes (150–265 minutes), and the average amount of suspended erythrocytes was 200 ml (100–400 ml). The cranial morphology of all patients improved significantly after the operation. The traditional cephalic index (pre-operative: 0.70 (0.04); post-operative: 0.78 (0.02)) and normative cephalic index (pre-operative: 0.68 (0.03); post-operative: 0.77 (0.02)) were significantly increased (P < 0.0001). The mean horizontal point of maximum width improved from 0.54 to 0.56 (P = 0.0043), the mean vertical point of maximum width decreased from 0.59 to 0.54 (P = 0.0006), the frontal height decreased from 0.89 to 0.77 (P < 0.0001), and the occipital height improved from 0.78 to 0.88 (P < 0.0001). The intracranial volume increased from 1287.35 to 1426.90 cm³ (P < 0.0001). All of the children had a good skull shape and no recurrence of deformity. Conclusions: Total calvarial reconstruction can effectively correct scaphocephaly in Chinese children, expand cranial volume, reduce cranial height, shorten fronto-occipital diameters and enlarge biparietal diameters.

Background: Gut microbiota has been reported to be associated with a series of metabolic diseases including metabolic bone disease. However, study about gut microbiota and craniosynostosis (CS) is very rare. We aim to investigate the gut microbiota composition in CS patients and assess the possible relationship. Methods: A total of 30 infants with CS and 30 infants with non-CS treated in Children’s Hospital of Nanjing Medical University of Jiangsu Province from June 2021 to March 2022 were finally included in this study. All processing and analysis are carried out using 16S ribosomal RNA (rRNA) high-throughput gene sequencing. Results: The CS group have significantly lower levels of family, genus, and species than non-CS group (all P<0.05). Furthermore, Staphylococcales and Lactobacillales at the order level, Enterococcaceae and Staphylococcaceae at the family level, and Enterococcus and Staphylococcus at the genus level were significantly enriched in the CS group (all P<0.05). Additionally, functional prediction showed that six metabolic pathways significantly differed between the two groups (all P<0.05). Of those, pathways involving polycyclic aromatic hydrocarbon degradation (P=0.030) and penicillin and cephalosporin biosynthesis (P=0.027) were more abundant in CS group than in non-CS group. Conclusions: Gut microbiota was statistically associated with the development of CS, and several taxa and specific functional pathways with significantly altered abundance have been identified in CS patients. These findings can provide clues for the study on the mechanism and early diagnosis of CS.

Background: Craniosynostosis (CS), a heterogeneous craniofacial disorder caused by premature fusion of cranial sutures, is sub‐classified anatomically by suture involvement (sagittal, metopic, coronal, lambdoid) and phenotypically into isolated/non‐syndromic forms or syndromic (CS with extracranial anomalies). Pathogenic variants in multiple genetic loci have been implicated in CS, with particular significance attributed to allelic variants in IL11RA (interleukin‐11 receptor alpha subunit; OMIM#600939). Clinical observations of individuals with IL11RA mutations indicate syndromic CS, characterized by dental anomalies and Crouzon‐like facial features.Methods: Genetic analyses were carried out utilizing whole‐exome sequencing, with subsequent validation through direct Sanger sequencing. IL11RA biallelic pathogenic variants were detected and further analyzed by multiple in silico prediction tools, including 3D protein modeling.Results: Our cohort comprises six pediatric patients presenting with CS linked to biallelic pathogenic mutations in IL11RA, including two previously unreported variants (p.Pro218Argfs*140, p.Trp132Ter). Three‐dimensional protein structure modeling and molecular docking simulations demonstrated that four missense variants (p.Pro116Leu, p.Glu126Gly, p.Gly231Val, p.Leu236Pro) disrupt hydrogen bond networks critical for maintaining the IL‐11 receptor alpha subunit's tertiary structure, significantly reducing ligand‐binding affinity to both interleukin‐11 (IL‐11) and gp130.Conclusion: This study describes the clinical phenotype of six children with craniosynostosis and reveals novel variants in the IL11RA gene, thereby broadening the genotypic spectrum associated with this gene. Given the scarcity of patients reported in the literature, a detailed examination of the specific clinical and molecular characteristics will benefit our understanding of craniosynostosis caused by IL11RA variants.