Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study.

BACKGROUND: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. METHODS: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer's disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. RESULTS: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00-2.02), ADHD (1.51, 1.15-1.98), schizophrenia (1.47, 1.15-1.87), and AD (1.57, 1.16-2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. CONCLUSIONS: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Fe-Catalyzed Domino Intramolecular Nucleophilic Substitution of 4-Hydroxychromen-2-one and Pyran-2-one/Ring Opening of Activated Arene: An Easy Access to 2,3-Disubstituted Furo[3,2,-c]coumarins and Furo[3,2,-c]pyran-4-ones via Nonsymmetric Triarylmethanes.

A one-pot synthesis of functionalized 2,3-disubstituted furo[3,2,-c]coumarins and furo[3,2,-c]pyran-4-ones under hydrated ferric sulfate catalysis was performed. It was revealed that the reaction proceeds with intramolecular cyclofunctionalization of nonsymmetric triarylmethanes via ring opening of 2-methylfuran followed by recyclization, resulting in the selective formation of desired products. The versatility of this method was demonstrated via the succinct synthesis of an anticoagulant agent analogue and 2,3-disubstituted benzofurans.

[Treatment of behavioral disorders by risperidone in children with autism].

OBJECTIVE: To study the effect of risperidone treatment on behavioral disorders in children with autism. METHODS: Forty children with behavioral disorders (aged from 5 to 12 years) were treated with risperidone for 8 weeks. The behavioral symptoms were evaluated by the Clinical Global Impression (CGI) and the Autism Treatment Evaluation Checklist (ATEC) before and after the treatment. The adverse events related to risperidone treatment were observed. RESULTS: The score of severity of illness and the ATEC total scores were significantly reduced 8 weeks after risperidone treatment. Besides the social intercourse ability, great improvements have been shown on the verbal communication, apperception and behavioural symptoms by the ATEC. No severe adverse events related to risperidone treatment were observed. CONCLUSIONS: Risperidone can significantly improve the behavioral disorders in children with autism and is well-tolerated.

[Influential factors for the sensory integration training effects in children with autism].

OBJECTIVE: There are many factors affecting the sensory integration training (SIT) effects in children with autism. This study explored the influential factors for SIT effects in the aspect of the model of sensory processing. METHODS: Ninety-three autistic children aged 1.8-8.3 years were evaluated by the autism behavior checklist (ABC) and the Dunn's model of sensory processing. The SIT effects were evaluated by the sensory integrative schedule. The effects of sex, age, ABC scores and the Dunn's model of sensory processing were investigated by logistic regression analysis. RESULTS: Logistic regression analysis showed that ABC scores (Wald=6.768, <0.01) and the Dunn's model of sensory processing (Wald=13.549, <0.01) were influential factors for the SIT effects. The Dunn's model of sensory processing was shown as a more important influential factor. Sex (Wald=1.549, >0.05) and age (Wald=0.010, >0.05) were not related to the STT effects. CONCLUSIONS: The Dunn's model of sensory processing is a major influential factor for the SIT effects in children with autism.