Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Research Progress on Microbial Community Succession in the Postmortem Interval Estimation.

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Highly Integrated µGC Based on a Multisensing Progressive Cellular Architecture with a Valveless Sample Inlet.

Microscale gas chromatographs (µGCs) promise in-field analysis of volatile organic compounds (VOCs) in environmental and industrial monitoring, healthcare, and homeland security applications. As a step toward addressing challenges with performance and manufacturability, this study reports a highly integrated monolithic chip implementing a multisensing progressive cellular architecture. This architecture incorporates three µGC cells that are customized for different ranges of analyte volatility; each cell includes a preconcentrator and separation column, two complementary capacitive detectors, and a photoionization detector (PID). An on-chip carrier gas filter scrubs ambient air for the analysis. The monolithic chip, with all 16 components, is 40.3 × 55.7 mm2 in footprint. To accommodate surface adsorptive and low-volatility analytes, the architecture eliminates the commonly used inlet valve, eliminating the need for chemically inactive surfaces in the valves and pumps, allowing the use of standard parts. Representative analysis is demonstrated from a nonpolar 14-analyte mixture, a polar 12-analyte mixture, and a 3-phosphonate ester mixture, covering a wide vapor pressure range (0.005-68.5 kPa) and dielectric constant range (1.8-23.2). The three types of detectors show highly complementary responses. Quantitative analysis is shown in the tens to hundreds ppb range. With 200 mL samples, the projected detection limits reach 0.12-4.7 ppb. Limited tests performed at 80% humidity showed that the analytes with vapor pressures <12 kPa were unaffected. A typical full run takes 28 min and consumes 2.3 kJ energy for the fluidic elements (excluding electronics). By eliminating chip-to-chip fluidic interconnections and requiring just one custom-fabricated element, this work presents a path toward high-performance and highly manufacturable µGCs.

A Review of the Main Classifications of Lumbar Spondylolisthesis.

OBJECTIVE: This study was conducted to review the main classifications and to present author's recommendations. METHODS: Review of English language medical literature. RESULTS: In recent decades, classification systems of lumbar spondylolisthesis have been proposed based on many factors, from essential causes to combinations of imaging features and clinical manifestations; the latter type of system is more clinically practical. We have systematically listed the main types of classification systems in chronological order to make it easier for clinicians to find the type of diagnosis and treatment suitable for their patients and develop an appropriate treatment plan. CONCLUSIONS: Classification systems for lumbar spondylolisthesis have been proposed that have been based on the study of the essential causes or the combination of imaging features and clinical manifestations; the latter type of system is more clinically practical. We still have much work to do in exploring a more applicable classification of lumbar spondylolisthesis.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs / 中华肿瘤杂志

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

Control Software Design for a Multisensing Multicellular Microscale Gas Chromatography System.

Microscale gas chromatography (µGC) systems are miniaturized instruments that typically incorporate one or several microfabricated fluidic elements; such systems are generally well suited for the automated sampling and analysis of gas-phase chemicals. Advanced µGC systems may incorporate more than 15 elements and operate these elements in different coordinated sequences to execute complex operations. In particular, the control software must manage the sampling and analysis operations of the µGC system in a time-sensitive manner; while operating multiple control loops, it must also manage error conditions, data acquisition, and user interactions when necessary. To address these challenges, this work describes the investigation of multithreaded control software and its evaluation with a representative µGC system. The µGC system is based on a progressive cellular architecture that uses multiple µGC cells to efficiently broaden the range of chemical analytes, with each cell incorporating multiple detectors. Implemented in Python language version 3.7.3 and executed by an embedded single-board computer, the control software enables the concurrent control of heaters, pumps, and valves while also gathering data from thermistors, pressure sensors, capacitive detectors, and photoionization detectors. A graphical user interface (UI) that operates on a laptop provides visualization of control parameters in real time. In experimental evaluations, the control software provided successful operation and readout for all the components, including eight sets of thermistors and heaters that form temperature feedback loops, two sets of pressure sensors and tunable gas pumps that form pressure head feedback loops, six capacitive detectors, three photoionization detectors, six valves, and an additional fixed-flow gas pump. A typical run analyzing 18 chemicals is presented. Although the operating system does not guarantee real-time operation, the relative standard deviations of the control loop timings were <0.5%. The control software successfully supported >1000 µGC runs that analyzed various chemical mixtures.

Development and Evaluation of Orthographic Knowledge Awareness Scale for Children Aged 6-12 Years.

Objective: This study primarily aimed to develop an orthographic knowledge awareness scale in Mandarin for children aged 6-12 years. Related factors affecting orthographic knowledge awareness in children were analyzed, and a basis for individualized intervention was provided to improve reading and writing. Methods: A conceptual framework for orthographic knowledge awareness in children aged 6-12 years was determined through a detailed reading of the literature on Chinese character orthography, combined with qualitative interviews of the target population and consultation with experts. The orthographic knowledge awareness scale initially consisted of three versions: for grades 1-2 (210 items), grades 3-4 (207 items), and grades 5-6 (220 items), accumulating a total of 637 items. The initial scale was then used for the study involving children aged 6-12 years in Maanshan City, Jiangsu Province. Various approaches to screening items were comprehensively used to determine the formal version of the orthographic knowledge awareness scale. The official scale was ultimately used to conduct the third round of surveys among 1,354 children aged 6-12 years in ordinary primary schools located in 5 cities in Jiangsu Province, namely, Changzhou, Lianyungang, Nantong, Xuzhou, and Yangzhou. The reliability, validity, and discriminating power of the formal scale were evaluated. Results: A total of 360 items were included in the formal version of the orthographic knowledge awareness scale. The formal scale was divided into three versions for grades 1-2, 3-4, and 5-6. Each grade version consisted of 120 items. The scale was composed of the stroke awareness test, radical awareness test, and left-right reversal test. The cumulative variance contribution rates of grades 1-2, 3-4, and 5-6 were 82.47, 61.71, and 64.19%, respectively. The Cronbach's α coefficients of the three-grade version of the scale were 0.989, 0.946, and 0.938; the split-half reliability coefficients were 0.925, 0.766, and 0.847; and the test-retest reliability coefficients were 0.847, 0.895, and 0.8928, respectively. Conclusion: The proposed orthographic knowledge awareness scale for children aged 6-12 years exhibits good reliability and validity. The formal scale consisted of two dimensions: identification of left-right reversal at the stroke and radical levels and the left-right reversal at the whole character level. The two dimensions can more comprehensively reflect the ability of children to discriminate orthographic structures.

Pathway of Diatoms Enter Experimental Rabbits through the Lymphatic System of the Digestive Tract.

OBJECTIVES: To study whether diatoms can enter the body through the lymphatic system of the digestive tract. METHODS: Twenty experimental rabbits were divided into the test group and the control group randomly, and intragastric administration was performed with 20 mL water sample from the Pearl River and 20 mL ultrapure water, respectively. After 30 min, lymph, lungs, livers and kidneys were extracted for the diatom test. The concentration, size and type of diatoms were recorded. RESULTS: The concentration of diatoms of the test group was higher than that of the control group (P<0.05). In the test group, Stephanodiscus, Coscinodiscus, Cyclotella, Melosira, Nitzschia, Synedra, Cymbella, and Navicula were detected; in the control group, Stephanodiscus, Coscinodiscus and Cyclotella were detected. The long diameter and the short diameter of diatoms of the test group were higher than those of the control group (P<0.05). In the test group, 1-2 diatoms were detected in 3 lung samples and 2 liver samples, which were Stephanodiscus or Cyclotella, and no diatoms were detected in the kidney samples; in the control group, 1-2 diatoms were detected in 2 lung samples and 3 liver samples, which were Stephanodiscus or Coscinodiscus, and no diatoms were detected in the kidney samples. CONCLUSIONS: Diatoms can enter the body through the lymphatic fluid, which is one of the reasons for the presence of diatoms in tissues and organs of non-drowning cadavers.

Effects of Digestive Temperature and Time on Diatom Test.

OBJECTIVES: To study the effects of temperature and time for diatoms digestion and find out suitable digestive temperature and time. METHODS: Eighty pieces of liver tissues were collected, each piece of tissue was 2 g, and 2 mL Pearl River water was added to each piece of tissue. The digestion temperature was set at 100 ℃, 120 ℃, 140 ℃, 160 ℃, 180 ℃ and the digestion time was set at 40, 50, 60, 70, 80 min. The liver tissue and water mixture were divided into 8 portions in each group. All the samples were tested by microwave digestive - vacuum filtration - automated scanning electron microscopy method. The quantity of diatom recovered and the quality of residue on the membrane were recorded. RESULTS: When the digestion time was set to 60 min, there were statistically significant differences in the number of diatoms recovered at different temperatures (P<0.05). The maximum number of diatoms recovered was (28 797.50±6 009.67) at 140 ℃, and the minimum residue was (0.60±0.28) mg at 180 ℃. When the digestion temperature was set at 140 ℃, there were statistically significant differences in the number of diatoms recovered at different digestion times (P<0.05). The number of diatoms recovered was the highest at 40 min, it was up to (20 650.88±1 950.29), and the residue quality of each group had no statistical significance among different digestion time groups(P>0.05). CONCLUSIONS: The effect of diatom digestion is related to temperature and time. When the digestion temperature was 140 ℃ and the digestion time was 40, 50 and 60 min, it is favorable for diatom test.

Comparison of Application of MD-VF-Auto SEM Method and Plankton Gene Multiplex PCR System in the Diagnosis of Drowning.

OBJECTIVES: To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning. METHODS: Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated. RESULTS: The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system (P<0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues (P>0.05). CONCLUSIONS: MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.

Application of Diatoms Quantitative Analysis in the Diagnosis of Drowning.

OBJECTIVES: To retrospectively analyze diatom test cases of corpses in water and discuss the value of quantitative analysis of diatoms in the diagnosis of drowning. METHODS: A total of 490 cases of water-related death were collected. They were divided into drowning group and postmortem immersion group according to the cause of death. Diatoms in lung, liver, kidney tissue and water sample were analyzed quantitatively by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM) method. The ratios of content of diatoms in lung tissue and water sample (CL/CD) were calculated. RESULTS: The results of diatom test for three organs (lung, liver and kidney) were all positive in 400 cases (85.5%); the content of diatom in lung, liver, kidney tissues, and water samples of drowning group were (113 235.9±317 868.1), (26.7±75.6), (23.3±52.2) and (12 113.3±21 760.0) cells/10 g, respectively; the species of diatom were (7.5±2.8), (2.6±1.9), (2.9±2.1) and (8.9±3.0) types, respectively; the CL/CD of drowning group and postmortem immersion group were (100.6±830.7) and (0.3±0.4), respectively. CONCLUSIONS: Quantitative analysis of diatoms can provide supportive evidence for the diagnosis of drowning, and the parameter CL/CD can be introduced into the analysis to make a more accurate diagnosis of drowning.

Vitamin A supplementation ameliorates prenatal valproic acid-induced autism-like behaviors in rats.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive stereotyped behaviors. Prenatal exposure to the anticonvulsant drug valproic acid (VPA) is reported to induce ASD in human and ASD-like phenotypes in rodents. Unfortunately, the etiology and pathogenesis of ASD remains unclear. METHODS: Pregnant rats received an intraperitoneal injection of 600 mg/kg VPA on E12.5 to construct the ASD rat model in offspring. The different expression of long non-coding RNA (lncRNA) and mRNA profiles in the hippocampus were determined by RNA sequencing to investigate potential mechanisms of VPA-induced ASD. Gene Ontology (GO) and pathway enrichment analysis were performed to predict the function of dysregulated lncRNAs. Co-expression network and real-time polymerase chain reaction (RT-PCR) analysis were conducted to validate the potential regulatory lncRNA-mRNA network. RESULTS: VPA increased the total distance, time spent in the central zone and self-grooming (open field test) in rats. Meanwhile, VPA induced social impairment (three-chamber sociability test) and repetitive behaviors (marble burying test). A total of 238 lncRNAs and 354 mRNAs were differentially expressed in the VPA group. In addition, the dysregulated lncRNAs were involved in neural function and developmental processes of ASD. 5 lncRNAs and 7 mRNAs were differently expressed and included in the lncRNA-mRNA co-expression network. RT-PCR confirmed the upregulation of 4 lncRNAs and 6 mRNAs, and identified a potential regulatory network of NONRATT021475.2 (lncRNA) and Desert hedgehog (Dhh). Moreover, VPA decreased the serum vitamin A (VA) levels in offspring rats on postnatal day (PND) 21 and 49. Importantly, VA supplementation significantly restored VPA-induced autism-related behaviors and upregulation of NONRATT021475.2 and Dhh in the hippocampus of ASD rats. CONCLUSION: This study not only contributed to understand the importance of lncRNAs and mRNAs in the progression of ASD, but also identified VA as a potential therapy for the condition. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author with reasonable request.

Identification of key genes and pathways between mild-moderate and severe asthmatics via bioinformatics analysis.

Severe asthma is the main reason for death and disability caused by asthma. However, effective biomarkers for severe asthma have not been identified. Here, we aimed to identify potential biomarkers in severe asthma. We identified 202 differentially expressed genes (DEGs) between severe asthma and mild-moderate asthma after integrating the results from GSE69683 and GSE27011 datasets. The enrichment analysis indicated that 202 DEGs were associated with metabolism- and immune-related processes. 10 hub genes were identified by Cytoscape and five of these genes' AUC (area under the curve) values were greater than 0.6 in GSE69683. The AUC value reached to 0.701 when combined SEC61A1 and ALDH18A1 expression. The expression of the five hub genes was verified in an external dataset. The network analysis revealed that transcription factor (TF) WT1, ZEB1, RERE, FOSL1, and miR-20a may be involved in the development of asthma. In addition, we found cyclosporine and acetaminophen could interact with these hub genes and may be negatively associated with most of the five hub genes according to previous reports. Overall, key genes were identified between mild-moderate and severe asthmatics, which contributed to the understanding of the development of asthma.

Research Progress in Vitamin A and Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Over the past few decades, many studies have investigated the effects of VA supplementation in ASD patients and the relationship between vitamin A (VA) levels and ASD. VA is an essential micronutrient that plays an important role in various systems and biological processes in the form of retinoic acid (RA). Recent studies have shown that serum VA concentration is negatively correlated with the severity of ASD. The lack of VA during pregnancy or early fetal development can affect brain development and lead to long-term or even permanent impairment in the learning process, memory formation, and cognitive function. In addition, VA deficiency has been reported to have a major impact on the gastrointestinal function of children with ASD, while VA supplementation has been shown to improve the symptoms of ASD to a certain extent. This paper provides a comprehensive review of the relationship between VA and ASD.

The protective effect and potential mechanism of NRXN1 on learning and memory in ADHD rat models.

The learning and memory network is highly complex and remains unclear. The hippocampus is the location of learning and memory function. Impairment of synaptic morphology and synaptic plasticity (i.e., long-term potentiation) appears to cause learning and memory deficits. Several studies have indicated the role of NRXN1 in regulating the synaptic function, but little is known on its role in learning and memory dysfunction associated with attention deficit and hyperactivity disorder (ADHD). Our results showed that overexpression and interference of NRXN1 in vivo, respectively, affected learning and memory, as was assessed by Morris water maze tests, in spontaneously hypertensive rats (SHRs) and Sprague Dawley (SD) rats. We found that SD rats performed better after methylphenidate (MPH) treatment in salvage trials. Accordingly, the change of NRXN1 led to altered synapse-related gene (PSD95, SYN1, GAP43, NLGN1) expression, further providing evidence of its role in the maintenance of synaptic plasticity. We also verified that the expression of synapse-related genes synchronously changed with NRXN1expression in the behavioral assessment. The expression of NRXN1 was confirmed to affect the expression of synapse-related genes after its interference and overexpression in the primary hippocampal neurons in vitro. These results confirmed our hypothesis that NRXN1 might nucleate an overall trans-synaptic signaling network that controls synaptic plasticity and is responsible for impairments in learning and memory in ADHD. These findings suggest a possible protective role of NRXN1 in learning and memory in ADHD. Further RNA-seq sequencing revealed significant differences in the expression of 5-hydroxytryptamine receptor (5-HT6R), which was further verified at the cellular level, and the mechanism of NRXN1 affecting synaptic plasticity was preliminarily discussed.

Hand anthropometry and its relation to grip/pinch strength in children aged 5 to 13 years.

OBJECTIVE: To evaluate the development level of children's physiological hand shape indicators and their relationship with grip/pinch strength. METHODS: Hand shape and grip/pinch strength in 1255 Chinese children aged 5 to 13 years were prospectively measured. Development curves of physiological hand shape indicators and grip/pinch strength were constructed. RESULTS: The physiological hand shape indicators (full length, middle finger length, width, and wrist thickness) and grip/pinch strength of boys and girls increased with age and showed statistically significant differences at different ages. In most age groups, hand shape indicators and grip/pinch strength were larger in boys than in girls of the same age. After puberty, the physiological hand shape indicators and grip/pinch strength increased more rapidly in girls than in boys of the same age, and the differences gradually decreased thereafter. Moreover, a significant difference in pinch strength between the right and left hands was observed in most age groups. Pearson correlation analysis showed that the physiological hand shape indicators were significantly positively correlated with grip/pinch strength, height, weight, and body mass index. CONCLUSIONS: This study revealed the relationship between physiological hand shape indicators and grip/pinch strength and provided reference ranges of physiological hand shape indicators and grip/pinch strength for children.

Distinct long non-coding RNA and mRNA expression profiles in the hippocampus of an attention deficit hyperactivity disorder model in spontaneously hypertensive rats and control wistar Kyoto rats.

The incidence of attention deficit hyperactivity disorder (ADHD) in children is increasing. Long non-coding RNAs (lncRNAs) participate in many biological processes involved in the regulation of gene expression. Although numerous lncRNAs have been proven to be crucial in brain development and associated with its degeneration, changes in lncRNA expression profiles during ADHD progression and their possible roles remain unclear. The purpose of this study is to investigate the expression profiles of lncRNAs in hippocampus from an ADHD model in spontaneously hypertensive rats (SHRs) and in normal control Wistar Kyoto (WKY) rats. We determined the expression profiles of lncRNAs and mRNAs in SHRs and WKY rats using microarray analysis technology. Then, differentially expressed lncRNAs were confirmed by real-time polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analysis of differentially expressed mRNAs or nearby genes was used to predict the possible functions of the lncRNAs. A gene co-expression network was established to study the relationship between expression of lncRNAs and related mRNAs. A total of 267 differentially expressed lncRNAs (including 144 upregulated and 123 downregulated) and 311 differentially expressed mRNAs were identified in SHRs, compared to those in WKY rats. Subsequently, 15 lncRNAs were selected and confirmed by RT-PCR analysis. GO and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis showed that the dysregulated lncRNAs are involved in brain developmental processes and neuronal function and maintenance. Co-expression network analysis revealed the close relationship between the differentially expressed lncRNAs and mRNAs. Additionally, co-expression analysis of dysregulated lncRNAs with their downstream genes, which are reported in nervous system and regulation of learning and memory, indicated that lncRNA NONRATT0006598.2 was related to Baiap2 gene, which may participate in ADHD progress. Our findings contribute to understand the importance of lncRNAs and mRNAs in the progression of ADHD, and identify potential therapeutic targets for ADHD treatment.

Reliability and validity of Handwriting Test for Preschool Children (HT-PRE): A new tool to assess the handwriting ability of preschool children aged 5-6 years old in Mainland China.

BACKGROUND: Handwriting ability is related to many neuronal functions, such as visual-perceptual skills, orthographic coding, motor planning and execution, kinesthetic feedback and visual-motor coordination. To date, there is no specific assessment tool for to assess preschool children's handwriting ability in Mainland China. Our study aimed to develop a tool to assess the handwriting ability of children aged 5-6 years old in Mainland China and to analyze its reliability and validity. METHODS: The investigation comprised three phases: 1) original tool generation, 2) tool revision, 3) reliability analysis (i.e., interrater, test-retest) and validity analysis (i.e., content, criterion). RESULTS: The sample included a total of 482 children. The internal consistency (Cronbach alpha) was 0.74. The test-retest correlation coefficients ranged from 0.38 to 0.80. As expected, our data showed an improving trend in handwriting, and differences in respect to age and gender. When compared with the 'handwriting difficulty' group, each subtest score of children in the 'normal' group showed significant differences (p < 0.05). The correlation validity, compared with the visual-motor integration development test (VMI), was 0.17-0.52. CONCLUSION: The Handwriting Test for Preschool Children (HT-PRE), which is a newly developed handwriting screening tool for preschool children aged 5-6 years old in Mainland China, has displayed a very good internal consistency, acceptable test-retest reproducibility, and good criterion-based validity, and has also shown good application prospects for handwriting difficulty screening in a clinical setting.