The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case–control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD): −7.46 ng/mL, 95% confidence interval (CI): −10.26; −4.66 ng/mL, p < 0.0001, I2 = 98%). Quantitative integration of 10 case–control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR: 5.23, 95% CI: 3.13; 8.73, p < 0.0001, I2 = 78.2%). Analysis of 15 case–control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case–control studies (MD: −6.2, 95% CI: −9.62; −2.78, p = 0.0004, I2 = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD: −3.15, 95% CI: −6.57; 0.26, p = 0.07, I2 = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR: 1.54, 95% CI: 1.12; 2.10, p = 0.0071, I2 = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance.

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy—quasi-paired cohort—and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

30Growing evidence suggests that autism spectrum disorder (ASD) is highly associated with 31 dysbiosis in the gut microbiome. However, results of metagenome-based microbiome 32 studies are not always consistent due to great individual diversity that overwhelms 33 disease-associated alterations. Here, we proposed a novel analysis strategy-quasi-paired 34 cohort and applied it to a metagenomic study of ASD microbiomes. By comparing the 35 paired samples of ASD and neurotypical subjects, we identified significant deficiencies in 36 ASD children in detoxifying enzymes and pathways, which showed strong correlations to 37 mitochondrial damage. Diagnostic models with these detoxifying enzymes accurately 38 discriminated ASD individuals from controls, and the dysfunction score inferred from the 39 model increased with the clinical rating scores of ASD. Conclusively, our findings suggest 40 a previously undiscovered mechanism in which impaired microbial detoxification leads to 41 toxicant accumulation and mitochondrion damage contributes to the pathogenesis of ASD. 42 This novel mechanism points to future therapeutic strategies of rebuilding microbial 43 detoxification for ASD. 44 45 MAIN TEXT 46 47 131 Hs37 human genomes by BWA (mem module with default parameters) (http://bio-132

Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficit in childhood without satisfactory medical intervention. Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive technique derived from acupuncture and has been shown to have similar therapeutic effects in many diseases. Valproic acid- (VPA-) induced ASD is a known model of ASD in rats. The therapeutic efficacy of TEAS was evaluated in the VPA model of ASD in the present study. The offspring of a VPA-treated rat received TEAS in the early life stage followed by a series of examinations conducted in their adolescence. The results show that following TEAS treatment in early life, the social and cognitive ability in adolescence of the offspring of a VPA rat were significantly improved. In addition, the abnormal pain threshold was significantly corrected. Additional studies demonstrated that the dendritic spine density of the primary sensory cortex was decreased with Golgi staining. Results of the transcriptomic study showed that expression of some transcription factors such as the neurotrophic factor were downregulated in the hypothalamus of the VPA model of ASD. The reduced gene expression was reversed following TEAS. These results suggest that TEAS in the early life stage may mitigate disorders of social and recognition ability and normalize the pain threshold of the ASD rat model. The mechanism involved may be related to improvement of synaptic plasticity.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox‐responsive and emissive TPE‐ss covalent organic framework (COF) nanocarrier by integrating aggregation‐induced emission luminogens and redox‐responsive disulfide motifs into the COF skeleton is developed. TPE‐ss COF allows for efficient loading and delivery of matrine, a renowned anti‐cryptosporidial drug, which significantly reduces MI/R‐induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5 min after 30 min of ischemia. Moreover, TPE‐ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE‐ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE‐ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri‐reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.