Synaptic abnormality is an important pathologic feature of autism spectrum disorders (ASDs) and responsible for various behavioral defects in these neurodevelopmental disorders. Microglia are the major immune cells in the brain and also play an important role in synapse refinement. Although dysregulated synaptic pruning by microglia during the brain development has been associated with ASDs, the underlying mechanism has yet to be fully elucidated. Herein, we observed that expression of Transmembrane protein 59 (TMEM59), a protein recently shown to regulate microglial function, was decreased in autistic patients. Furthermore, we found that both male and female mice with either complete or microglia-specific loss of Tmem59 developed ASD-like behaviors. Microglial TMEM59-deficient mice also exhibited enhanced excitatory synaptic transmission, increased dendritic spine density, and elevated levels of excitatory synaptic proteins in synaptosomes. TMEM59-deficient microglia had impaired capacity for synapse engulfment both in vivo and in vitro. Moreover, we demonstrated that TMEM59 interacted with the C1q receptor CD93 and TMEM59 deficiency promoted CD93 protein degradation in microglia. Downregulation of CD93 in microglia also impaired synapse engulfment. These findings identify a crucial role of TMEM59 in modulating microglial function on synapse refinement during brain development and suggest that TMEM59 deficiency may contribute to ASDs through disrupting phagocytosis of excitatory synapse and thus distorting the excitatory-inhibitory (E/I) neuronal activity balance.

ObjectivesTo examine the psychometric properties of the Chinese version of the C-Compassion Fatigue (CF)-Short Scale among 4 independent samples of Chinese emergency workers (medical workers and firefighters).DesignCross-sectional.Setting6 hospitals in Zhejiang Province and 12 fire stations in Shanghai.ParticipantsEmergency workers (medical and firefighters) were consecutively recruited and divided into 4 groups: the MW1 group (medical workers, n=167), the FF1 group (firefighters, n=157), the MW2 group (medical workers, n=265) and the FF2 group (firefighters, n=231).InterventionsAll patients completed the C-CF-Short Scale to identify factors associated with compassion fatigue. The MW1 and FF1 groups were used for the exploratory analyses. The MW2 and FF2 groups were used for the confirmatory factor analyses.Primary and secondary outcome measuresFactor loading, correlations with previously validated questionnaires (the Ego-Resiliency Scale, the Social Support Questionnaire and the Job Pressure Scale) and Cronbach's α coefficient were tested for each factor.ResultsThe C-CF-Short Scale demonstrated excellent construct validity and good internal consistency. Specifically, the results of exploratory factor analyses in the MW1 and FF1 groups showed that secondary trauma and job burnout were associated with compassion fatigue in these emergency workers. The confirmatory factor analyses in the MW2 and FF2 groups indicated that all the fit indices of the 2-factor model were satisfactory. Finally, the Cronbach's α coefficient of each factor was excellent.ConclusionsThe findings suggest that the C-CF-Short Scale has good psychometric properties and can be applied to study Chinese emergency workers.

Many neurological disorders exhibit sex differences and sex-specific therapeutic responses. Unfortunately, significant amounts of studies investigating molecular and cellular mechanisms underlying these neurological disorders use primary cell cultures with undetermined sexes; and this may be a source for contradictory results among different studies and impair the validity of study conclusion. Herein, we comprehensively compared sexual dimorphism of gene expression in primary neurons, astrocytes, and microglia derived from neonatal mouse brains. We found that overall sexually dimorphic gene numbers were relatively low in these primary cells, with microglia possessing the most (264 genes), neurons possessing the medium (69 genes), and astrocytes possessing the least (30 genes). KEGG analysis indicated that sexually dimorphic genes in these three cell types were strongly enriched for the immune system and immune-related diseases. Furthermore, we identified that sexually dimorphic genes shared by these primary cells dominantly located on the Y chromosome, including Ddx3y, Eif2s3y, Kdm5d, and Uty. Finally, we demonstrated that overexpression of Eif2s3y increased synaptic transmission specifically in male neurons and caused autism-like behaviors specifically in male mice. Together, our results demonstrate that the sex of primary cells should be considered when these cells are used for studying the molecular mechanism underlying neurological disorders with sex-biased susceptibility, especially those related to immune dysfunction. Moreover, our findings indicate that dysregulation of sexually dimorphic genes on the Y chromosome may also result in autism and possibly other neurological disorders, providing new insights into the genetic driver of sex differences in neurological disorders.

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Microorganisms play an important role in natural material and elemental cycles. Many common and general biology research techniques rely on microorganisms. Machine learning has been gradually integrated with multiple fields of study. Machine learning, including deep learning, aims to use mathematical insights to optimize variational functions to aid microbiology using various types of available data to help humans organize and apply collective knowledge of various research objects in a systematic and scaled manner. Classification and prediction have become the main achievements in the development of microbial community research in the direction of computational biology. This review summarizes the application and development of machine learning and deep learning in the field of microbiology and shows and compares the advantages and disadvantages of different algorithm tools in four fields: microbiome and taxonomy, microbial ecology, pathogen and epidemiology, and drug discovery.