Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Early gesture development as a predictor of autism spectrum disorder in elevated-likelihood infants of ASD.

BACKGROUND: Gesture difficulties have been reported in later-born siblings of children with autism spectrum disorder (ASD). Careful observation of gesture development during the first two years of children at elevated likelihood (EL) of developing ASD may identify behavioral indicators that facilitate early diagnosis. METHODS: This study enrolled 47 EL infants and 27 low-likelihood (LL) infants to explore gesture developmental trajectories and the predictive value of gesture to expedite the early detection of core characteristics of ASD. Gesture frequency, communication function, and integration ability were observed and coded from a semi-structured assessment administered longitudinally across 9-19 months of age. We conducted the Autism Diagnostic Observation Schedule assessment at 18-19 months for ASD's core characteristics. RESULTS: The development of joint attention (JA) gestures was slower in the EL than in the LL group. The trajectories of the two groups began to diverge at 14-18 months. Children who reached the diagnostic cutoff point for ASD showed reductions in social interaction gestures at 12-13 months, in gestures integrated with any two communication skills (G-M) at 15-16 months; and in gestures integrated with eye contact (G-E) at 18-19 months. Overall gesture and G-M integration were associated with an overall ADOS communication and social interaction score. CONCLUSIONS: The developmental trajectories of JA gestures of EL and LL children differed. G-M gestures represent early indicators that may be a predictor of ASD.

VMT/ACP/Dextran composite nanosheets against dental caries through promoting mineralization of dentin tubules, pH buffering, and antibacterial.

Dental caries is a worldwide public healthcare concern, and is closely related to the acidic environment that caused by bacterial decomposition of food. In this study, a two-step ion exchange liquid-phase stripping method was applied to strip out vermiculite (VMT) nanosheets, then amorphous calcium phosphate (ACP) and dextran were inserted between the VMT nanosheets interlayer to obtain a composite two-dimension nanosheets (VMT/ACP/Dextran). VMT/ACP/Dextran composite nanosheets exhibited excellent biocompatibility and could provide exogenous Ca2+and PO43- from ACP, provide SiO44-, Mg2+, Fe2+ and obtain buffering pH and antibacterial properties from VMT, as well as improve suspension stability and targeting Streptococcus mutans through glucan. The in vitro study showed that the composite materials could promote the mineralization and sealing of dentin tubules by releasing active ions, buffer pH 4.5 (a value close to the pH in the dental plaque environment) to pH 6.6-7.1 (values close to the pH in human saliva) through ion exchange, and exert antibacterial effects by targeting Streptococcus mutans and exerting oxidase like and peroxidase like activities to produce reactive oxygen species (ROS). The in vivo animal study showed that daily cleaning teeth using VMT/ACP/Dextran composite nanosheets could effectively reduce the incidence rate and severity of dental caries in rats. Taking together, the developed VMT/ACP/Dextran composite nanosheets, which integrated the excellent properties of VMT, ACP and dextran, can effectively prevent dental caries through a combination of factors such as buffering acids, antibacterial properties, and promoting calcification, and may be used as an active ingredient for daily oral hygiene or filling materials to prevent and treat dental caries.

Depressive Disorder Recognition Based on Frontal EEG Signals and Deep Learning.

Depressive disorder (DD) has become one of the most common mental diseases, seriously endangering both the affected person's psychological and physical health. Nowadays, a DD diagnosis mainly relies on the experience of clinical psychiatrists and subjective scales, lacking objective, accurate, practical, and automatic diagnosis technologies. Recently, electroencephalogram (EEG) signals have been widely applied for DD diagnosis, but mainly with high-density EEG, which can severely limit the efficiency of the EEG data acquisition and reduce the practicability of diagnostic techniques. The current study attempts to achieve accurate and practical DD diagnoses based on combining frontal six-channel electroencephalogram (EEG) signals and deep learning models. To this end, 10 min clinical resting-state EEG signals were collected from 41 DD patients and 34 healthy controls (HCs). Two deep learning models, multi-resolution convolutional neural network (MRCNN) combined with long short-term memory (LSTM) (named MRCNN-LSTM) and MRCNN combined with residual squeeze and excitation (RSE) (named MRCNN-RSE), were proposed for DD recognition. The results of this study showed that the higher EEG frequency band obtained the better classification performance for DD diagnosis. The MRCNN-RSE model achieved the highest classification accuracy of 98.48 ± 0.22% with 8-30 Hz EEG signals. These findings indicated that the proposed analytical framework can provide an accurate and practical strategy for DD diagnosis, as well as essential theoretical and technical support for the treatment and efficacy evaluation of DD.

[Characterization of genetic variants in children with refractory epilepsy].

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION: 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

Adipose-specific BMP and activin membrane-bound inhibitor (BAMBI) deletion promotes adipogenesis by accelerating ROS production.

With the improvement of people's living standards, the number of obese patients has also grown rapidly. It is reported that the level of oxidative stress in obese patients has significantly increased, mainly caused by the increase in reactive oxygen species (ROS) levels in adipose tissue. Studies have shown that the use of siRNA to interfere with bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression could promote adipocyte differentiation, and under hypoxic conditions, BAMBI could act as a regulator of HIF1α to regulate the polarity damage of epithelial cells. In view of these results, we speculated that BAMBI may regulate adipogenesis by regulating the level of ROS. In this study, we generated adipose-specific BAMBI knockout mice (BAMBI AKO) and found that compared with control mice, BAMBI AKO mice showed obesity when fed with high-fat diet, accompanied by insulin resistance, glucose intolerance, hypercholesterolemia, and increased inflammation in adipose tissue. Interestingly, adipose-specific deficiency of BAMBI could cause an increase in the expression level of Nox4, thereby promoting ROS production in cytoplasm and mitochondria and the DNA-binding activity of C/EBPß and ultimately promoting adipogenesis. Consistently, our findings indicated that BAMBI may be a reactive oxygen regulator to affect adipogenesis, thereby controlling obesity and metabolic syndrome.

Effect of Swell1 on regulating chondrocyte hypertrophy during the condylar osteochondral development process in mice.

Chondrocyte hypertrophy is a significant factor in cartilage development, yet the molecular mechanism for cell volume expand during the process is remains unclear. In the present study, the relationship between Swell1, a cell volume regulated anion channel, and chondrocyte hypertrophy was explored. The results reveal that the spatiotemporal expression of Swell1 was similar with the development process of hypertrophic chondrocytes in condyles. Through Col10a1 mediated knock out of Swell1 in hypertrophy chondrocytes, we found that there are less obvious boundary between different condylar cartilage layers in which increased hypertrophic chondrocytes were scattered in all three cartilage layers. The cortical bone mass and bone mineral density in the subchondral bone significantly increased. Additionally, knock out of Swell1 could increase the expression of OCN in the femur condyle. Based on the aforementioned findings, a conclusion could be drawn that Swell1 is a significant factor in chondrocyte hypertrophy during the condylar osteochondral development process, and there was some difference between the mandibular and femur condyles, which will provide some new clues for understanding the development of cartilage and related diseases.

Reorganization of Brain Functional Network during Task Switching before and after Mental Fatigue.

Mental fatigue is a widely studied topic on account of its serious negative effects. But how the neural mechanism of task switching before and after mental fatigue remains a question. To this end, this study aims to use brain functional network features to explore the answer to this question. Specifically, task-state EEG signals were recorded from 20 participants. The tasks include a 400-s 2-back-task (2-BT), followed by a 6480-s of mental arithmetic task (MAT), and then a 400-s 2-BT. Network features and functional connections were extracted and analyzed based on the selected task switching states, referred to from Pre_2-BT to Pre_MAT before mental fatigue and from Post_MAT to Post_2-BT after mental fatigue. The results showed that mental fatigue has been successfully induced by long-term MAT based on the significant changes in network characteristics and the high classification accuracy of 98% obtained with Support Vector Machines (SVM) between Pre_2-BT and Post_2-BT. when the task switched from Pre_2-BT to Pre_MAT, delta and beta rhythms exhibited significant changes among all network features and the selected functional connections showed an enhanced trend. As for the task switched from Post_MAT to Post_2-BT, the network features and selected functional connectivity of beta rhythm were opposite to the trend of task switching before mental fatigue. Our findings provide new insights to understand the neural mechanism of the brain in the process of task switching and indicate that the network features and functional connections of beta rhythm can be used as neural markers for task switching before and after mental fatigue.

Effects of Sarcoptes scabiei Translationally Controlled Tumor Protein (TCTP) on Histamine Release and Degranulation of KU812 Cells.

Scabies is a common parasitic dermatological infection worldwide that is often neglected. Scabies mites stimulate host inflammatory symptoms via secreted and excreted proteins, which induce basophil and mast cell degranulation and host histamine release. However, the mechanism of degranulation and histamine release is unclear. Moreover, the Sarcoptes scabiei translationally controlled tumor protein (TCTP) is predicted as an excreted protein, which may be involved in host inflammatory response regulation. First, we evaluated S. scabiei TCTP gene (SsTCTP) transcription in larvae, nymphs, and adults by qRT-PCR, and SsTCTP transcription was highest in larvae, followed by nymphs. Second, we found that the S. scabiei TCTP recombinant protein (rSsTCTP) promoted mice histamine release in vivo by Evans blue Miles assay. Therefore, to further explore the possible role of S. scabiei TCTP in host inflammatory response regulation, we established a degranulation model of KU812 cells. The results of the degranulation model suggested that rSsTCTP could induce enhanced degranulation of KU812 cells and increase the secretion of histamine and the expression of IL-4, IL-6, and IL-13 in vitro. In conclusion, we speculate that scabies mites could stimulate host histamine release and Th2 response by excreting S. scabiei TCTP.

Driving Fatigue Detection with Three Non-Hair-Bearing EEG Channels and Modified Transformer Model.

Driving fatigue is the main cause of traffic accidents, which seriously affects people's life and property safety. Many researchers have applied electroencephalogram (EEG) signals for driving fatigue detection to reduce negative effects. The main challenges are the practicality and accuracy of the EEG-based driving fatigue detection method when it is applied on the real road. In our previous study, we attempted to improve the practicality of fatigue detection based on the proposed non-hair-bearing (NHB) montage with fewer EEG channels, but the recognition accuracy was only 76.47% with the random forest (RF) model. In order to improve the accuracy with NHB montage, this study proposed an improved transformer architecture for one-dimensional feature vector classification based on introducing the Gated Linear Unit (GLU) in the Attention sub-block and Feed-Forward Networks (FFN) sub-block of a transformer, called GLU-Oneformer. Moreover, we constructed an NHB-EEG-based feature set, including the same EEG features (power ratio, approximate entropy, and mutual information (MI)) in our previous study, and the lateralization features of the power ratio and approximate entropy based on the strategy of brain lateralization. The results indicated that our GLU-Oneformer method significantly improved the recognition performance and achieved an accuracy of 86.97%. Our framework demonstrated that the combination of the NHB montage and the proposed GLU-Oneformer model could well support driving fatigue detection.

Vacuum-Assisted Thermal Annealing of CsPbI3 for Highly Stable and Efficient Inorganic Perovskite Solar Cells.

Inorganic cesium lead iodide perovskite CsPbI3 is attracting great attention as a light absorber for single or multi-junction photovoltaics due to its outstanding thermal stability and proper band gap. However, the device performance of CsPbI3 -based perovskite solar cells (PSCs) is limited by the unsatisfactory crystal quality and thus severe non-radiative recombination. Here, vacuum-assisted thermal annealing (VATA) is demonstrated as an effective approach for controlling the morphology and crystallinity of the CsPbI3 perovskite films formed from the precursors of PbI2 , CsI, and dimethylammonium iodide (DMAI). By this method, a large-area and high-quality CsPbI3 film is obtained, exhibiting a much reduced trap-state density with prolonged charge lifetime. Consequently, the solar cell efficiency is raised from 17.26 to 20.06 %, along with enhanced stability. The VATA would be an effective approach for fabricating high-performance thin-film CsPbI3 perovskite optoelectronics.

Targeted inhibition of ATP5B gene prevents bone erosion in collagen-induced arthritis by inhibiting osteoclastogenesis.

Bone resorption by osteoclasts is an energy consuming activity, which depends on mitochondrial ATP. ATP5B, a mitochondrial ATP synthase beta subunit, is a catalytic core involved in producing ATP. Here, we investigated the contribution of ATP5B in osteoclast differentiation and joint destruction. ATP5B (LV-ATP5B) targeting or non-targeting (LV-NC) siRNA containing lentivirus particles were transduced into bone marrow macrophage derived osteoclasts or locally administered to arthritic mouse joints. Inhibition of ATP5B reduced the expression of osteoclast related genes and proteins, suppressed bone resorption by significantly impairing F-actin formation and decreased the levels of adhesion-associated proteins. In addition, ATP5B deficiency caused osteoclast mitochondrial dysfunction and, impaired the secretion of vacuole protons and MMP9. Importantly, inhibition of ATP5B expression, protected arthritis mice from joint destructions although serum levels of inflammatory mediators (TNF-α, IL-1ß) and IgG2α antibodies were unaffected. These results demonstrate an essential function of ATP5B in osteoclast differentiation and bone resorption, and suggest it as a potential therapeutic target for protecting bones in RA.

miR-324-5p promotes adipocyte differentiation and lipid droplet accumulation by targeting Krueppel-like factor 3 (KLF3).

miRNAs, a kind of noncoding small RNA, play a significant role in adipose differentiation. In this study, we explored the effect of miR-324-5p in adipose differentiation, and found that miR-324-5p could promote adipocytes differentiation and increase body weight in mice. We overexpressed miR-324-5p during adipocytes differentiation, by oil red O and bodipy staining found that lipid accumulation was increased, and the expression level of adipogenic related genes were significantly increased. And the opposite experimental results were obtained after inhibiting miR-324-5p. In vivo, we injected miR-324-5p agomiR in obese mice and found that body weight, adipocyte area, and adipogenic-related gene expression level were significantly increased but lipolytic genes were decreased. To further explore the mechanism of miR-324-5p regulation in lipid accumulation, we constructed Krueppel-like factor 3 (KLF3) 3'-untranslated region luciferase reporter vector and KLF3 pcDNA 3.1 overexpression vector, and found that miR-324-5p was able to directly target KLF3. Overall, in this study we found that miR-324-5p could promote mice preadipoytes differentiation and increase mice fat accumulation by targeting KLF3.

Multisite-Occupancy-Driven Efficient Multiple Energy Transfer: A Straightforward Strategy to Achieve Single-Composition White-Light Emission in Ce3+-, Tb3+-, and Mn2+-Doped Silicate Phosphors.

It is unquestionably true that site occupation and energy transfer play important roles in the luminescent properties of optical materials from both practical applications and theoretical research. In this paper, multisite-occupancy-driven multiple energy transfers were used as a straightforward strategy to achieve single-composition white-light emission in Ce3+-, Tb3+-, and Mn2+-doped Ba1.2Ca0.8SiO4 (BCS) phosphors. The Ce3+-, Tb3+-, and Mn2+-doped T-phase orthosilicate BCS samples were synthesized by traditional solid-state reactions. The phase composition was checked via X-ray diffraction (XRD), and the luminescent properties were systematically studied by photoluminescence spectroscopy and fluorescence decay curves. A detailed study on the efficient and multiple energy transfers of Ce I → Mn2+, Ce II → Tb3+, and Ce II → Tb3+ → Mn2+ was carried out. Satisfactorily, the selected phosphor exhibits a high internal quantum efficiency (QE) of 81% and good thermal stability. In addition, an evident negative thermal quenching phenomenon, i.e., the emission intensity increases with increasing temperature, is provided. Moreover, the mechanism of negative thermal quenching was proposed. On the basis of these excellent luminescence properties, a white LED with color-rendering index (Ra = 89) was fabricated by integrating the phosphor on an n-UV 365 nm chip. These results show that the materials present potential application in the field of phosphor-converted white LEDs.

Mental Fatigue Has Great Impact on the Fractal Dimension of Brain Functional Network.

Mental fatigue has serious negative impacts on the brain cognitive functions and has been widely explored by the means of brain functional networks with the neuroimaging technique of electroencephalogram (EEG). Recently, several researchers reported that brain functional network constructed from EEG signals has fractal feature, raising an important question: what are the effects of mental fatigue on the fractal dimension of brain functional network? In the present study, the EEG data of alpha1 rhythm (8-10 Hz) at task state obtained by a mental fatigue model were chosen to construct brain functional networks. A modified greedy colouring algorithm was proposed for fractal dimension calculation in both binary and weighted brain functional networks. The results indicate that brain functional networks still maintain fractal structures even when the brain is at fatigue state; fractal dimension presented an increasing trend along with the deepening of mental fatigue fractal dimension of the weighted network was more sensitive to mental fatigue than that of binary network. Our current results suggested that mental fatigue has great regular impacts on the fractal dimension in both binary and weighted brain functional networks.

Triptolide enhances lipolysis of adipocytes by enhancing ATGL transcription via upregulation of p53.

Lipolysis is an essential physiological activity of adipocytes. The Patatin Like Phospholipase Domain Containing 2 (PNPLA2) gene encodes the enzyme adipose triglyceride lipase (ATGL) responsible for triglyceride hydrolysis, the first step in lipolysis. In this study, we investigated the potential of triptolide (TP), a natural plant extract, to induce weight loss by examining its effect on ATGL expression. We found that long- and short-term TP administration reduced body weight and fat weight and increased heat production in brown adipose tissue in wild-type C57BL/6 mice. In 3T3-L1 fibroblasts and porcine adipocytes, TP treatment reduced the number of lipid droplets as determined by Oil Red O and BODIPY staining, with concomitant increases in free fatty acid and triglyceride levels in the culture medium. Combined treatment with TP and p53 inhibitor reversed these lipolytic effects. We next amplified the ATGL promoter region and identified conserved p53 binding sites in the sequence by in silico analysis. The results of the dual-luciferase reporter assay using a construct containing the ATGL promoter harboring the p53 binding site showed that p53 induces ATGL promoter activity and consequently, ATGL transcription. These results demonstrate that TP has therapeutic value as an anti-obesity agent and acts by promoting lipolysis via upregulation of p53 and ATGL transcription.

Regulatory role of Golgi brefeldin A resistance factor-1 in amyloid precursor protein trafficking, cleavage and Aß formation.

ß-amyloid peptide (Aß) deposition derived from sequential cleavage of the amyloid precursor protein (APP) through the amyloidogenic pathway is an important characteristic feature of Alzheimer's disease (AD). During this process, cellular trafficking plays a crucial role. A large Sec7-domain containing ADP-ribosylation factor guanine nucleotide exchange factor (ARF-GEF), Golgi brefeldin A resistance factor 1 (GBF1) has been reported to initiate the ADP-ribosylation factor (Arf) activation cascade at trans-Golgi network, which plays a crucial function at the endoplasmic reticulum-Golgi interface. In this study, we investigated the role of GBF1 in APP transmembrane transport and Aß formation. Using APP/PS1 (presenilin 1) overexpressing transgenic mice, we demonstrate that GBF1 has upregulated the expression of APP, indicating a role for GBF1 in APP physiological process. Knocking down of GBF1 using small interfering has significantly increased the intracellular but not the surface expression of APP. In contrast, overexpression of wild-type (WT) and guanine nucleotide exchange factor (GEF) in the activated form but not the GEF deficient mutation induced continuous activation of GBF1, which subsequently increased the surface level of APP. Interestingly, inhibition of GBF1 by c(BFA) also impaired APP trafficking and induced endoplasmic reticulum (ER) stress in SH-SY5Y cells. Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD.

BAMBI shuttling between cytosol and membrane is required for skeletal muscle development and regeneration.

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) gene encodes a transmembrane protein and is involved in multiple physiological and pathological processes, such as inflammatory response, tumor development and progression, cell proliferation and differentiation. A previous study suggested that BAMBI may interact with the Wnt/ß-catenin signaling pathway via promoting ß-catenin nuclear translocation associated with C2C12 myogenic myoblast differentiation. However, its biological function in skeletal muscle still remains unknown and requires further characterization. The present work sought to investigate its biological function in skeletal muscle, especially the physiological roles of BAMBI during skeletal muscle growth and regeneration. Our current work suggests that BAMBI protein is highly expressed in skeletal muscle and is only detected in cytosolic fraction in the resting muscle. Moreover, BAMBI protein is co-localized in fast-twitch (glycolytic) fibers, but not in slow-twitch (oxidative) fibers. Comparing with the cytosolic trapping in resting muscle, BAMBI protein is enriched on cellular membrane during the muscle growth and regeneration, suggesting that BAMBI-mediated a significant signaling pathway may be an essential part of muscle growth and regeneration.

Effects of Mental Fatigue on Small-World Brain Functional Network Organization.

Brain functional network has been widely applied to investigate brain function changes among different conditions and proved to be a small-world-like network. But seldom researches explore the effects of mental fatigue on the small-world brain functional network organization. In the present study, 20 healthy individuals were included to do a consecutive mental arithmetic task to induce mental fatigue, and scalp electroencephalogram (EEG) signals were recorded before and after the task. Correlations between all pairs of EEG channels were determined by mutual information (MI). The resulting adjacency matrices were converted into brain functional networks by applying a threshold, and then, the clustering coefficient (C), characteristic path length (L), and corresponding small-world feature were calculated. Through performing analysis of variance (ANOVA) on the mean MI for every EEG rhythm, only the data of α1 rhythm during the task state were emerged for the further explorations of mental fatigue. For a wide range of thresholds, C increased and L and small-world feature decreased with the deepening mental fatigue. The pattern of the small-world characteristic still existed when computed with a constant degree. Our present findings indicated that more functional connectivities were activated at the mental fatigue stage for efficient information transmission and processing, and mental fatigue can be characterized by a reduced small-world network characteristic. Our results provide a new perspective to understand the neural mechanisms of mental fatigue based on complex network theories.

MicroRNA-214-3p Targeting Ctnnb1 Promotes 3T3-L1 Preadipocyte Differentiation by Interfering with the Wnt/ß-Catenin Signaling Pathway.

Differentiation from preadipocytes into mature adipocytes is a complex biological process in which miRNAs play an important role. Previous studies showed that miR-214-3p facilitates adipocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. The detailed function and molecular mechanism of miR-214-3p in adipocyte development is unclear. In this study, the 3T3-L1 cell line was used to analyze the function of miR-214-3p in vitro. Using 5-Ethynyl-2'-deoxyuridine (EdU) staining and the CCK-8 assay, we observed that transfection with the miR-214-3p agomir visibly promoted proliferation of 3T3-L1 preadipocytes by up-regulating the expression of cell cycle-related genes. Interestingly, overexpression of miR-214-3p promoted 3T3-L1 preadipocyte differentiation and up-regulated the expression of key genes for lipogenesis: PPARγ, FABP4, and Adiponectin. Conversely, inhibition of miR-214-3p repressed 3T3-L1 preadipocyte proliferation and differentiation, and down-regulated the expression of cell cycle-related genes and adipogenic markers. Furthermore, we proved that miR-214-3p regulates 3T3-L1 preadipocyte differentiation by directly targeting the 3'-untranslated regions (3'UTR) of Ctnnb1, which is an important transcriptional regulatory factor of the Wnt/ß-Catenin pathway. Taken together, the data indicate that miR-214-3p may positively regulate preadipocyte proliferation and enhance differentiation through the Wnt/ß-Catenin signaling pathway.