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1.
Microbiome ; 12(1): 120, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956705

ABSTRACT

BACKGROUND: Functional redundancy (FR) is widely present, but there is no consensus on its formation process and influencing factors. Taxonomically distinct microorganisms possessing genes for the same function in a community lead to within-community FR, and distinct assemblies of microorganisms in different communities playing the same functional roles are termed between-community FR. We proposed two formulas to respectively quantify the degree of functional redundancy within and between communities and analyzed the FR degrees of carbohydrate degradation functions in global environment samples using the genetic information of glycoside hydrolases (GHs) encoded by prokaryotes. RESULTS: Our results revealed that GHs are each encoded by multiple taxonomically distinct prokaryotes within a community, and the enzyme-encoding prokaryotes are further distinct between almost any community pairs. The within- and between-FR degrees are primarily affected by the alpha and beta community diversities, respectively, and are also affected by environmental factors (e.g., pH, temperature, and salinity). The FR degree of the prokaryotic community is determined by deterministic factors. CONCLUSIONS: We conclude that the functional redundancy of GHs is a stabilized community characteristic. This study helps to determine the FR formation process and influencing factors and provides new insights into the relationships between prokaryotic community biodiversity and ecosystem functions. Video Abstract.


Subject(s)
Bacteria , Biodiversity , Glycoside Hydrolases , Polysaccharides , Glycoside Hydrolases/metabolism , Glycoside Hydrolases/genetics , Polysaccharides/metabolism , Bacteria/genetics , Bacteria/classification , Bacteria/metabolism , Ecosystem , Microbiota , Prokaryotic Cells/metabolism , Prokaryotic Cells/classification , Phylogeny , Hydrogen-Ion Concentration
2.
Heliyon ; 10(9): e30346, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707427

ABSTRACT

Short-form video apps, such as TikTok, have become popular worldwide. Compared to traditional social media, they have powerful push algorithms and are more entertaining, which might lead to some negative effects. Research has attempted to identify the relationship between short-form video use and depression, but the processes mechanism underly the relationship was few in number. The present study explored the association between short-form video use and depression among Chinese adolescents and analyzed the mediating roles of need gratification and short-form video addiction. The participants included 1302 senior high school students (Mage = 16.03, SD = 0.76, 42.6 % boys). And a structure equation model with chain mediating was established using Mplus. The results showed (1) a direct association between short-form video use and adolescent depression, (2) that entertainment need gratification, social-related need gratification, and short-form video addiction acted as chain mediating factors, and (3) no gender difference in the model. The present study's findings revealed the important mediating role of addictive behavior between normal use behavior and depression and suggested that preventative and interventional plans based on need gratification should be developed to reduce short-form video addiction and improve mental health.

3.
Psychol Res Behav Manag ; 17: 2067-2081, 2024.
Article in English | MEDLINE | ID: mdl-38800525

ABSTRACT

Purpose: With the increasing ubiquity of smartphones in our daily lives, technoference has emerged as a novel threat to family relationships and child development. This study explored the impact of parent-child technoference on child problematic smartphone use and its underlying mechanism and potential gender difference among children. Participants and Methods: The participants were 3032 fourth-grade students (42.6% female; 80.6% one-child families; 32.9% lower income level families, 33.3% middle income level families; Mage = 10.59 years, SD=0.32) from 535 primary schools. Students in the target classes were invited to participate anonymously in the questionnaire survey in classrooms. Then, SPSS, AMOS and other software were used to analyze the data. Results: 1) Parent-child technoference, negative parenting styles and child problematic smartphone use were positively correlated with each other, while they were negatively correlated with parent-child relationship; 2) Parent-child technoference can not only directly and positively predict child problematic smartphone use, but also indirectly and positively predict child problematic smartphone use through parent-child relationship and negative parenting styles respectively; 3) Parent-child relationship and negative parenting styles play a chain mediating role between parent-child technoference and child problematic smartphone use; 4) There are significant gender differences in the chain mediation model. Conclusion: The results showed that parent-child technoference significantly affected child problematic smartphone use through a chain mediation of parent-child relationship and negative parenting styles. Gender differences were observed, with girls experiencing a more pronounced disruption in the parent-child relationship, while boys were more likely to develop problematic smartphone use. In cases of strained parent-child relationships due to technoference, girls also tended to perceive more negative parenting styles. These findings promote parents' understanding of the influencing factors and mechanisms of child problematic smartphone use, especially helpful for follow-up measures to prevent and intervene child problematic smartphone use from the perspective of families and parents.

4.
J Fungi (Basel) ; 10(4)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38667970

ABSTRACT

Trunk canker poses a major threat to the production of Chinese hickory tree (Carya cathayensis Sarg.), which is primarily determined by Botryosphaeriaceae. In our previous work, we identified Botryosphaeria dothidea as the predominant pathogen of this disease. However, it is still unclear about corresponding gene families and mechanisms associated with B. dothidea's pathogenicity on Chinese hickory tree. Here, we present a comparative analysis of high-quality genome assemblies of Botryosphaeria dothidea and other isolated pathogens, showing highly syntenic relationships between B. dothidea and its closely related species and the conservative evolution of the Botryosphaeriaceae family. Higher GC contents were found in the genomes of B. dothidea and three other isolated pathogens (Botryshaeria cortices, Botryshaeria fabicerciana, and Botryshaeria qingyuanensis) compared to Macrophomina phaseolina, Neofusicoccum parvum, Diplodia corticola, and Lasiodiplodia theobromae. An investigation of genes specific to or expanded in B. dothidea revealed that one secreted glucanase, one orsellinic acid biosynthesis enzyme, and two MFS transporters positively regulated B. dothidea's pathogenicity. We also observed an overrepresentation of viral integrase like gene and heterokaryon incompatibility proteins in the B. dothidea's genome. In addition, we observed one LRR-domain-containing protein and two Sec-domain-containing proteins (Sec_1 and Sec_7) that underwent positive selection. This study will help to understand B. dothidea's pathogenicity and potential influence on the infection of Chinese hickory, which will help in the development of disease control and ensure the security of Chinese hickory production.

5.
Mol Neurobiol ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38564138

ABSTRACT

Neurological diseases are a major cause of the global burden of disease. Although the mechanisms of the occurrence and development of neurological diseases are not fully clear, most of them are associated with cells mediating neuroinflammation. Yet medications and other therapeutic options to improve treatment are still very limited. Single-cell RNA sequencing (scRNA-seq), as a delightfully potent breakthrough technology, not only identifies various cell types and response states but also uncovers cell-specific gene expression changes, gene regulatory networks, intercellular communication, and cellular movement trajectories, among others, in different cell types. In this review, we describe the technology of scRNA-seq in detail and discuss and summarize the application of scRNA-seq in exploring neurological diseases, elaborating the corresponding specific mechanisms of the diseases as well as providing a reliable basis for new therapeutic approaches. Finally, we affirm that scRNA-seq promotes the development of the neuroscience field and enables us to have a deeper cellular understanding of neurological diseases in the future, which provides strong support for the treatment of neurological diseases and the improvement of patients' prognosis.

6.
Nucleic Acids Res ; 52(D1): D724-D731, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37823598

ABSTRACT

Microorganisms encode most of the functions of life on Earth. However, conventional research has primarily focused on specific environments such as humans, soil and oceans, leaving the distribution of functional families throughout the global biosphere poorly comprehended. Here, we present the database of the global distribution of prokaryotic protein families (GDPF, http://bioinfo.qd.sdu.edu.cn/GDPF/), a data resource on the distribution of functional families across the global biosphere. GDPF provides global distribution information for 36 334 protein families, 19 734 superfamilies and 12 089 KEGG (Kyoto Encyclopedia of Genes and Genomes) orthologs from multiple source databases, covering typical environments such as soil, oceans, animals, plants and sediments. Users can browse, search and download the distribution data of each entry in 10 000 global microbial communities, as well as conduct comparative analysis of distribution disparities among multiple entries across various environments. The GDPF data resource contributes to uncovering the geographical distribution patterns, key influencing factors and macroecological principles of microbial functions at a global level, thereby promoting research in Earth ecology and human health.


Subject(s)
Ecology , Prokaryotic Cells , Proteins , Animals , Humans , Soil , Multigene Family , Proteins/genetics
7.
Mol Autism ; 14(1): 42, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37936174

ABSTRACT

BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1± female mice with Mapt± male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Fragile X Syndrome , Animals , Mice , Male , Female , Mice, Knockout , Autistic Disorder/genetics , tau Proteins/genetics , tau Proteins/metabolism , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/genetics , Fragile X Syndrome/metabolism , Disease Models, Animal
8.
Arch Public Health ; 81(1): 149, 2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37592329

ABSTRACT

BACKGROUND: By analyzing 23 evaluation indicators included in 14 national basic public health service programs in a region of Hohhot City, Inner Mongolia Autonomous Region, China, the performance of basic public health services in the region in 2021 were analyzed to clarify the implementation and conduct of relevant programs. We also use this study as a basis to radiate the work of municipal basic public health services centered on the region and the outstanding problems reflected and to provide theoretical contents and suggestions that can be referred to for the same regions in central and western China as well as worldwide. METHODS: Using the TOPSIS method as the basis for the data analysis method, the evaluation indexes are ranked in terms of their proximity to the idealized target, and combined with the entropy value method, Technique for order preference by similarity to an ideal solution (TOPSIS) and rank-sum ratio (RSR) were used to rank 14 basic health care providers by grade. A comprehensive evaluation of the performance of basic public health services in a region of Hohhot City, Inner Mongolia Autonomous Region in 2021 was conducted through a joint model of entropy -weighted TOPSIS and RSR, making full use of the characteristics and advantages of the fuzzy joint, and conducting a comprehensive analysis from the perspective of the ratio weight and the method of graded calculation, making the study more distinguishable and measureable. RESULTS: In this study, for the regional basic public health services, a total of 23 evaluation indicators of basic public health service projects were included, among which the top three indicators with the weight of the entropy value method indicators were found to include the rate of Chinese medicine health management for the elderly, the rate of health management for the elderly, and the BCG vaccination rate after the analysis of the weight of the indicators; After the entropy-weighted TOPSIS evaluation showed that the Ci values of the regions were found to be between 0.378 and 0.715 through the calculation of the positive and negative ideal values of each indicator; RSR staging method evaluation showed that three community health centers (X2, X10, X12) had excellent evaluations of basic public health services; The number of evaluations as poor and moderate are 2 (X3, X9) and 9 (X1, X4, X5, X6, X7, X8, X11, X13, X14), respectively; Finally, the results of the entropy-weighted TOPSIS method and the fuzzy joint model of RSR staging method are basically consistent with the overall trend of the above two methods, and the reliability and credibility of the research results are high. CONCLUSION: The entropy-weighted TOPSIS and RSR joint model can evaluate the effectiveness of basic public health services in a more comprehensive and holistic way. The results of the RSR staging results and the related weight ratio analysis show that the basic public health service programs in Hohhot, Inner Mongolia Autonomous Region are relatively balanced, but there are some differences; The same genus of elderly Chinese medicine health management rate, health management rate of the elderly, BCG vaccination rate several indicators accounted for a higher weight, its correlation with the key population-related items is high, suggesting that the future key population health service items should be focused on, and future research should be suggested from two key research.

9.
Sensors (Basel) ; 23(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36904612

ABSTRACT

In this paper, a cutting-edge video target tracking system is proposed, combining feature location and blockchain technology. The location method makes full use of feature registration and received trajectory correction signals to achieve high accuracy in tracking targets. The system leverages the power of blockchain technology to address the challenge of insufficient accuracy in tracking occluded targets, by organizing the video target tracking tasks in a secure and decentralized manner. To further enhance the accuracy of small target tracking, the system uses adaptive clustering to guide the target location process across different nodes. In addition, the paper also presents an unmentioned trajectory optimization post-processing approach, which is based on result stabilization, effectively reducing inter-frame jitter. This post-processing step plays a crucial role in maintaining a smooth and stable track of the target, even in challenging scenarios such as fast movements or significant occlusions. Experimental results on CarChase2 (TLP) and basketball stand advertisements (BSA) datasets show that the proposed feature location method is better than the existing methods, achieving a recall of 51% (27.96+) and a precision of 66.5% (40.04+) in the CarChase2 dataset and recall of 85.52 (11.75+)% and precision of 47.48 (39.2+)% in the BSA dataset. Moreover, the proposed video target tracking and correction model performs better than the existing tracking model, showing a recall of 97.1% and a precision of 92.6% in the CarChase2 dataset and an average recall of 75.9% and mAP of 82.87% in the BSA dataset, respectively. The proposed system presents a comprehensive solution for video target tracking, offering high accuracy, robustness, and stability. The combination of robust feature location, blockchain technology, and trajectory optimization post-processing makes it a promising approach for a wide range of video analytics applications, such as surveillance, autonomous driving, and sports analysis.

10.
J Cell Mol Med ; 27(9): 1214-1226, 2023 05.
Article in English | MEDLINE | ID: mdl-36977207

ABSTRACT

Duplications of the Xq28 region are a common cause of X-linked intellectual disability (XLID). The RAB39B gene locates in Xq28 and has been implicated in disease pathogenesis. However, whether increased dosage of RAB39B leads to cognitive impairment and synaptic dysfunction remains elusive. Herein, we overexpressed RAB39B in mouse brain by injecting AAVs into bilateral ventricles of neonatal animals. We found that at 2 months of age, neuronal overexpression of RAB39B impaired the recognition memory and the short-term working memory in mice and resulted in certain autism-like behaviours, including social novelty defect and repetitive grooming behaviour in female mice. Moreover, overexpression of RAB39B decreased dendritic arborization of primary neurons in vitro and reduced synaptic transmission in female mice. Neuronal overexpression of RAB39B also altered autophagy without affecting levels and PSD distribution of synaptic proteins. Our results demonstrate that overexpression of RAB39B compromises normal neuronal development, thereby resulting in dysfunctional synaptic transmission and certain intellectual disability and behavioural abnormalities in mice. These findings identify a molecular mechanism underlying XLID with increased copy numbers of Xq28 and provide potential strategies for disease intervention.


Subject(s)
Autistic Disorder , Intellectual Disability , Animals , Mice , Female , Intellectual Disability/genetics , Intellectual Disability/metabolism , Neurons/metabolism , Autistic Disorder/genetics , Synaptic Transmission , Animals, Newborn , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
11.
Front Aging Neurosci ; 15: 1087823, 2023.
Article in English | MEDLINE | ID: mdl-36761179

ABSTRACT

Parkinson's disease (PD) is a common neurodegenerative movement disorder with undetermined etiology. A major pathological hallmark of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra. Loss-of-function mutations in the RAB39B gene, which encodes a neuronal-specific small GTPase RAB39B, have been associated with X-linked intellectual disability and pathologically confirmed early-onset PD in multiple families. However, the role of RAB39B in PD pathogenesis remains elusive. In this study, we treated Rab39b knock-out (KO) mice with MPTP to explore whether RAB39B deficiency could alter MPTP-induced behavioral impairments and dopaminergic neuron degeneration. Surprisingly, we found that MPTP treatment impaired motor activity and led to loss of tyrosine hydroxylase-positive dopaminergic neurons and gliosis in both WT and Rab39b KO mice. However, RAB39B deficiency did not alter MPTP-induced impairments. These results suggest that RAB39B deficiency does not contribute to PD-like phenotypes through compromising dopaminergic neurons in mice; and its role in PD requires further scrutiny.

12.
Nucleic Acids Res ; 51(D1): D452-D459, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36243963

ABSTRACT

Antimicrobial toxins help prokaryotes win competitive advantages in intraspecific or interspecific conflicts and are also a critical factor affecting the pathogenicity of many pathogens that threaten human health. Although many studies have revealed that antagonism based on antimicrobial toxins plays a central role in prokaryotic life, a database on antimicrobial toxins remains lacking. Here, we present the prokaryotic antimicrobial toxin database (PAT, http://bioinfo.qd.sdu.edu.cn/PAT/), a comprehensive data resource collection on experimentally validated antimicrobial toxins. PAT has organized information, derived from the reported literature, on antimicrobial toxins, as well as the corresponding immunity proteins, delivery mechanisms, toxin activities, structural characteristics, sequences, etc. Moreover, we also predict potential antimicrobial toxins in prokaryotic reference genomes and show the taxonomic information and environmental distribution of typical antimicrobial toxins. These details have been fully incorporated into the PAT database, where users can browse, search, download, analyse and view informative statistics and detailed information. PAT resources have already been used in our prediction and identification of prokaryotic antimicrobial toxins and may contribute to promoting the efficient investigation of antimicrobial toxin functions, the discovery of novel antimicrobial toxins, and an improved understanding of the biological roles and significance of these toxins.


Subject(s)
Toxins, Biological , Humans , Databases, Factual , Genome , Prokaryotic Cells/metabolism , Toxins, Biological/chemistry , Toxins, Biological/metabolism
13.
Mol Ther Methods Clin Dev ; 27: 246-258, 2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36320413

ABSTRACT

Fragile X syndrome (FXS) is caused by the loss of the fragile X messenger ribonucleoprotein 1 (FMRP) encoded by the FMR1 gene. Gene therapy using adeno-associated virus (AAV) to restore FMRP expression is a promising therapeutic strategy. However, so far AAV gene therapy tests for FXS only utilized rodent FMRPs driven by promoters other than the human FMR1 promoter. Restoration of human FMRP in appropriate cell types and at physiological levels, preferably driven by the human FMR1 promoter, would be more suitable for its clinical use. Herein, we generated two human FMR1 promoter subdomains that effectively drive gene expression. When AAVs expressing two different human FMRP isoforms under the control of a human FMR1 promoter subdomain were administered into bilateral ventricles of neonatal Fmr1 -/y and wild-type (WT) mice, both human FMRP isoforms were expressed throughout the brain in a pattern reminiscent to that of mouse FMRP. Importantly, human FMRP expression attenuated social behavior deficits and stereotyped and repetitive behavior, and reversed dysmorphological dendritic spines in Fmr1 -/y mice, without affecting WT mouse behaviors. Our results demonstrate that human FMR1 promoter can effectively drive human FMRP expression in the brain to attenuate Fmr1 -/y mouse deficits, strengthening the notion of using AAV gene therapy for FXS treatment.

14.
Curr Psychol ; : 1-15, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35967488

ABSTRACT

To explore the influence and mechanism of parent-child relationship on adolescents' problematic smartphone use, a sample of 3355 Chinese adolescents (M age=16.93, SD = 0.49, range: 14-19 years old; 48% boys) is recruited to measure parent-child relationship, problematic smartphone use, personal growth initiative, and school belonging. The results are as follows. (1) After controlling for gender, age and time spent online per day, parent-child relationship is negatively correlated with problematic smartphone use, and the negative association between parent-child relationship and problematic smartphone use is mediated by the personal growth initiative. (2) The association between parent-child relationship and problematic smartphone use, the association between parent-child relationship and personal growth initiative, and the association between personal growth initiative and problematic smartphone use are all moderated by school belonging and are stronger in adolescents with a high level of school belonging. The present study highlights the mediating role of personal growth initiative and the moderating role of school belonging in the association between parent-child relationship and problematic smartphone use. This study also contributes to a better understanding of the effects, paths, and conditions of parent-child relationship on the problematic smartphone use of adolescents and provides constructive suggestions for preventing adolescents' problematic smartphone use in the mobile Internet era.

15.
Am J Orthod Dentofacial Orthop ; 162(2): e63-e70, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35660339

ABSTRACT

INTRODUCTION: This study aimed to compare the designed and achieved mesiodistal angulation of maxillary canines and posterior teeth (MCPT) for first premolar extraction with clear aligner treatment and identify the main influencing factors for preventing MCPT tipping toward the extraction space. METHODS: A total of 21 adults with first premolar extraction were recruited. The designed and achieved tooth movement of MCPT was measured by superimposing their respective pretreatment and posttreatment cone-beam computed tomography images and compared with the designed tooth movement in ClinCheck using the paired t test and scatter plot analysis. Influencing factors, including dental arch length change, canine distalization, and initial mesiodistal angulation, were analyzed using the linear mixed-effect model. RESULTS: Designed distal crown tipping (second premolar, 10.73 ± 3.22°; first molar, 9.83 ± 3.60°; second molar, 7.18 ± 2.36°) significantly increased the distal inclination of the second premolar (2.50° ± 5.15°; P ï¼œ0.001), first molar (1.07° ± 4.14°; P ï¼œ0.001), and second (0.70° ± 3.78°; P ï¼œ0.001). Furthermore, mesial tipping (8.59° ± 6.03°; P ï¼œ0.001) achieved appropriate distal crown tipping of canines (-6.43° ± 5.04°; P ï¼œ0.001). The implemented preliminary formulas showed that shortening of the dental arch length, the distance of canine distalization, and initial mesiodistal angulation were closely related to the antitipping design. CONCLUSIONS: Designed distal crown tipping of posterior teeth and mesial crown tipping of canines might prevent unwanted crown tipping toward the extraction space during space closure. The proposed preliminary formula could guide antitipping designs in clear aligner treatment.


Subject(s)
Maxilla , Orthodontic Appliances, Removable , Bicuspid/diagnostic imaging , Bicuspid/surgery , Maxilla/diagnostic imaging , Molar , Tooth Movement Techniques
16.
Front Microbiol ; 13: 925454, 2022.
Article in English | MEDLINE | ID: mdl-35711777

ABSTRACT

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.

17.
J Neurosci ; 42(25): 4958-4979, 2022 06 22.
Article in English | MEDLINE | ID: mdl-35606143

ABSTRACT

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.SIGNIFICANCE STATEMENT Microglia play an important role in synapse refinement. Dysregulated synaptic pruning by microglia during brain development has been associated with autism spectrum disorders (ASDs). However, the underlying mechanism has yet to be fully elucidated. Herein, we observe that the expression of Transmembrane protein 59 (TMEM59), an autophagy-related protein, is decreased in autistic patients. Moreover, we find ASD-like behaviors in mice with complete loss and with microglia-specific loss of Tmem59 Mechanistic studies reveal that TMEM59 deficiency in microglia impairs their synapse engulfment ability likely through destabilizing the C1q receptor CD93, thereby leading to enhanced excitatory neurotransmission and increased dendritic spine density. Our findings demonstrate a crucial role of microglial TMEM59 in early neuronal development and provide new insight into the etiology of ASDs.


Subject(s)
Autistic Disorder , Microglia , Animals , Autistic Disorder/genetics , Autistic Disorder/metabolism , Female , Humans , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Microglia/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuronal Plasticity/physiology , Phagocytosis , Synapses/physiology
18.
Clin Immunol ; 237: 108987, 2022 04.
Article in English | MEDLINE | ID: mdl-35346864

ABSTRACT

Metabolic reprogramming of immune cells has been proven to be important for systemic lupus erythematosus (SLE). This study aims to understand the role of SLC7A5, an amino acid transporter, in SLE. We analyzed SLC7A5 mRNA expression of SLE patients compared to healthy controls using GEO database, and found that it was increased in CD4+ T cells and CD19+ B cells. We then confirmed the expression up-regulation using flow cytometry and found that the proportion of SLC7A5+ cells and its expression were increased in peripheral blood T and B cells from SLE patients. Importantly, SLC7A5 expression in T and B cells was positively correlated with blood urea nitrogen and serum creatinine. Therefore, we conclude that SLC7A5, up-regulating in circulating T and B cells, correlates with kidney function, suggesting its potential role in mediating renal damage in SLE, which provides novel insight into SLE pathogenesis and provides a potential biomarker for disease.


Subject(s)
Kidney , Large Neutral Amino Acid-Transporter 1 , Lupus Erythematosus, Systemic , Antigens, CD19 , B-Lymphocytes , Flow Cytometry , Humans , Kidney/pathology , Large Neutral Amino Acid-Transporter 1/genetics , Lupus Erythematosus, Systemic/complications , T-Lymphocytes
19.
Front Cell Dev Biol ; 9: 669798, 2021.
Article in English | MEDLINE | ID: mdl-34307355

ABSTRACT

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.

20.
BMJ Open ; 6(6): e011279, 2016 06 30.
Article in English | MEDLINE | ID: mdl-27363817

ABSTRACT

OBJECTIVES: To 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). DESIGN: Cross-sectional. SETTING: 6 hospitals in Zhejiang Province and 12 fire stations in Shanghai. PARTICIPANTS: Emergency 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). INTERVENTIONS: All 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 MEASURES: Factor 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. RESULTS: The 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. CONCLUSIONS: The findings suggest that the C-CF-Short Scale has good psychometric properties and can be applied to study Chinese emergency workers.


Subject(s)
Compassion Fatigue/diagnosis , Emergency Responders/psychology , Firefighters/psychology , Surveys and Questionnaires , Adult , Burnout, Professional , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Humans , Male , Psychometrics
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