Lead exposure induced transgenerational developmental neurotoxicity by altering genome methylation in Drosophila melanogaster.

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due to its adverse effects on cognitive development, especially in children exposed to low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying the transgenerational effects of Pb exposure-induced neurotoxicity remain poorly understood. In this study, we utilized Drosophila, a powerful developmental animal model, to investigate this phenomenon. Our findings demonstrated that Pb exposure during the developmental stage had a profound effect on the neurodevelopment of F0 fruit flies. Specifically, we observed a loss of correlation between the terminal motor area and muscle fiber area, along with an increased frequency of the ß-lobe midline crossing phenotype in mushroom bodies. Western blot analysis indicated altered expression levels of synaptic vesicle proteins, with a decrease in Synapsin (SYN) and an increase in Bruchpilot (BRP) expression, suggesting changes in synaptic vesicle release sites. These findings were corroborated by electrophysiological data, showing an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP) following Pb exposure. Importantly, our results further confirmed that the developmental neurotoxicity resulting from grandparental Pb exposure exhibited a transgenerational effect. The F3 offspring displayed neurodevelopmental defects, synaptic function abnormalities, and repetitive behavior despite lacking direct Pb exposure. Our MeDIP-seq analysis further revealed significant alterations in DNA methylation levels in several neurodevelopmental associated genes (eagle, happyhour, neuroglian, bazooka, and spinophilin) in the F3 offspring exposed to Pb. These findings suggest that DNA methylation modifications may underlie the inheritance of acquired phenotypic traits resulting from environmental Pb exposure.

Developmental neurotoxic effects of bisphenol A and its derivatives in Drosophila melanogaster.

As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the ß lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.

Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.

Barriers and facilitators to physical activity participation in patients with head and neck cancer: a scoping review.

BACKGROUND: Patients with head and neck cancer (HNC) usually experienced disfigurement, dysfunction, and psychosocial distress, leading to a decline in their quality of life. Physical activity (PA) is recommended for such patients. Despite the proven benefits of participating in PA, the compliance of patients with HNC is still poor. Hence, the factors influencing PA participation and adherence in patients with HNC need to be explored. OBJECTIVES: This study aimed to (1) identify barriers and enablers of PA in adult patients living with HNC and (2) map barriers and facilitators to the Capability-Opportunity-Motivation-Behavior (COM-B) model. ELIGIBILITY CRITERIA: Types of studies: Studies with qualitative, quantitative, and mixed designs were included in this review. TYPES OF PARTICIPANTS: The current review takes into account patients with HNC aged 18 years or above. Types of interventions: This review considered all studies focusing on full-body PA. TYPES OF OUTCOMES: This scoping review focused on studies examining health behavior, patients' compliance, and facilitators and/or barriers to PA engagement. Five databases (Ovid Medline, Ovid Embase, CINAHL, Cochrane Library, and PsycINFO) were searched following the methodology for scoping reviews from inception to July 2021. DATA EXTRACTION: The extracted data included author(s)/year of publication, country, main purpose of the study, sample size/disease site and stage, methodology and methods, type of treatment, and main findings/barriers, or facilitators. RESULTS: A total of 22 studies were finally selected. The top three barriers were physical-related issues, time pressures, and low motivation or interest. Most facilitators included perceived psychological, health, and social benefits and preference for the model of PA. The most frequent COM-B model components were physical capability, automatic motivation, and physical opportunity. CONCLUSIONS: Patients with HNC have unique facilitators and barriers to participating in PA. Interventions must leverage facilitators and limit barriers to exercise so as to increase compliance with exercise. Future studies should test the effectiveness of behavioral change measures based on the factors influencing the COM-B model.

Epidemiological Analysis of 1234 Cases of Laryngeal Cancer in Shanxi Province, China.

BACKGROUND: Laryngeal cancer is a common malignancy of the head and neck, especially in northern China, including Shanxi province. This study intends to describe the epidemiological characteristics of laryngeal cancer in Shanxi Province, China, in order to support prevention and treatment efforts. METHODS: Retrospective analysis of the medical records of patients diagnosed with laryngeal cancer in hospitals in Shanxi Province from 2008 to 2012. RESULTS: The average annual incidence rate of laryngeal cancer in Shanxi province from 2008 to 2012 was 0.70/105, the Chinese population standardized incidence rate was 0.57/105 and the world population standardized incidence rate was 0.60/105. The city with the highest incidence of laryngeal cancer in Shanxi Province is Taiyuan, followed by Yangquan, and the lowest incidence are Yuncheng and Jincheng. The cases included 723 farmers (58.6%), 338 workers (27.4%), 95 government cadres (7.7%), 35 unemployed individuals (2.8%), 30 teachers (2.4%) and 13 individuals with other occupations (1.1%). The incidence of laryngeal cancer in rural areas was 0.78/105, while urban areas was 0.60/105. Of 1006 patients with smoking and drinking status reported, there were 238 both smoking and drinking (23.7%), 491 only smoking but not drinking (48.8%), 4 only drinking but not smoking (0.4%), 273 both not smoking and not drinking (27.1%) (P<0.001), and there were 695 males smoking (95.3%), 34 females smoking (4.7%) (P<0.001). Of 879 patients for whom the primary cancer location was known, 406 cases (46.2%) were supraglottic and 428 cases (48.7%) were glottic. Among 1009 patients with known pathological classification, the vast majority had squamous cell carcinoma (992 cases, 98.3%). CONCLUSIONS: To sum up, the incidence of laryngeal cancer in Shanxi Province exhibited a relatively stable trend from 2008 to 2012, and the incidence is higher in men than in women in all years. The high percentage of smokers in this study underscores the importance of smoking as a risk factor for laryngeal cancer, whereas rates of drinking did not appear to be linked. Incidence of laryngeal cancer was higher in rural areas than in urban areas, a pattern that differs from other regions of China and internationally.

AlloDriver: a method for the identification and analysis of cancer driver targets.

Identifying the variants that alter protein function is a promising strategy for deciphering the biological consequences of somatic mutations during tumorigenesis, which could provide novel targets for the development of cancer therapies. Here, based on our previously developed method, we present a strategy called AlloDriver that identifies cancer driver genes/proteins as possible targets from mutations. AlloDriver utilizes structural and dynamic features to prioritize potentially functional genes/proteins in individual cancers via mapping mutations generated from clinical cancer samples to allosteric/orthosteric sites derived from three-dimensional protein structures. This strategy exhibits desirable performance in the reemergence of known cancer driver mutations and genes/proteins from clinical samples. Significantly, the practicability of AlloDriver to discover novel cancer driver proteins in head and neck squamous cell carcinoma (HNSC) was tested in a real case of human protein tyrosine phosphatase, receptor type K (PTPRK) through a L1143F driver mutation located at the allosteric site of PTPRK, which was experimentally validated by cell proliferation assay. AlloDriver is expected to help to uncover innovative molecular mechanisms of tumorigenesis by perturbing proteins and to discover novel targets based on cancer driver mutations. The AlloDriver is freely available to all users at http://mdl.shsmu.edu.cn/ALD.

Evaluation and revision of core postoperative nursing outcomes for laryngeal carcinoma in China.

BACKGROUND: The core nursing outcomes for laryngeal carcinoma in China needed further screening and revision. This study aimed to evaluate and revise a questionnaire according to the "Core Nursing Outcomes for Otorhinolaryngology Head-Neck" of the Nursing Outcomes Classification (NOC, 5th Edition), and determine suitable postoperative nursing outcomes for patients with laryngeal carcinoma in China. METHODS: The commonly used postoperative nursing outcomes for laryngeal carcinoma were screened using a questionnaire given to 93 nurses. An initial expert consultation questionnaire was constructed to discuss the indicators for each nursing outcome. A total of 20 experts were identified using the Delphi method, and their recommendations and revisions on the selected nursing outcomes were collected. RESULTS: A total of 14 postoperative core nursing outcomes and 69 indicators were identified for postoperative patients with laryngeal carcinoma, which are subordinate to 4 domains of the NOC: "Physiologic Health", "Psychosocial Health", "Health Knowledge & Behavior", and "Perceived Health". CONCLUSIONS: The screening and revision of the NOC outcomes and indicators of the Delphi method could be applied to assess the effect of nursing intervention and the quality of the nursing service in China.

Default mode network changes in fibromyalgia patients are largely dependent on current clinical pain.

Differences in fMRI resting-state connectivity of the default mode network (DMN) seen in chronic pain patients are often interpreted as brain reorganization due to the chronic pain condition. Nevertheless, patients' pain at the time of fMRI might influence the DMN because pain, like cognitive stimuli, engages attentional mechanisms and cognitive engagement is known to alter DMN activity. Here, we aimed to dissociate the influence of chronic pain condition (trait) from the influence of current pain experience (state) on DMN connectivity in patients with fibromyalgia (FM). We performed resting-state fMRI scans to test DMN connectivity in FM patients and matched healthy controls in two separate cohorts: (1) in a cohort not experiencing pain during scanning (27 FM patients and 27 controls), (2) in a cohort with current clinical pain during scanning (16 FM patients and 16 controls). In FM patients without pain during scanning, the connectivity of the DMN did not differ significantly from controls. By contrast, FM patients with current clinical pain during the scan had significantly increased DMN connectivity to bilateral anterior insula (INS) similar to previous studies. Regression analysis showed a positive relationship between DMN-midINS connectivity and current pain. We therefore suggest that transient DMN disruptions due to current clinical pain during scanning (current pain state) may be a substantial contributor to DMN connectivity disruptions observed in chronic pain patients.

Development of two psychological experience questionnaires for screening violence-related mental health disorders of non-psychiatric inpatients.

BACKGROUND: Increased violent events happen in the general hospitals in China and yet non-psychiatric departments do not have tools for violence-tendency screening. METHODS: The current study developed and evaluated two Inpatient Psychological Experience Questionnaires (IPEQs) for the screening of violence-related six mental health disorders: (Inpatient Psychological Experience Questionnaire-1 (IPEQ-1): anxiety, depression and suicidality; Inpatient Psychological Experience Questionnaire-2 (IPEQ-2): paranoid personality disorder, emotionally unstable personality disorder and histrionic personality disorder). Two initial IPEQs (IPEQ-1: 37 items and IPEQ-2: 30 items) were developed and assessed by domain experts. Then 1210 inpatients were recruited and divided into three groups (160, 450 and 600 samples, respectively) for IPEQs item selection and evaluation. During the two-stage item selection, three statistical methods including Pearson's correlation coefficient, exploratory factor analysis and item response theory were applied. For the item evaluation, Cronbach's alpha coefficient, test-retest reliability, criterion-related validity and construct validity of the final questionnaires were measured. RESULTS: Twelve items were selected for each IPEQs. Cronbach's alpha coefficients were 0.91 and 0.78 for IPEQ-1 and IPEQ-2, respectively. Test-retest replication ratios were 0.95 and 0.87 for IPEQ-1 and IPEQ-2, respectively. Correlation coefficients between different disorders and their related-tools scores were [0.51, 0.44] and [0.40, 0.44] for IPEQ-1 and IPEQ-2, respectively and were significant (P < 0.01). Confirmatory factor analysis supported the validity of the final IPEQs (P < 0.05), and the model fit index met the criterion generally. CONCLUSION: The IPEQs developed in this study could be effective and easy-to-use tools for screening inpatients with violence-intendancy in non-psychosomatic departments.

Promoter Methylation-Regulated miR-145-5p Inhibits Laryngeal Squamous Cell Carcinoma Progression by Targeting FSCN1.

Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 (FSCN1) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1. Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1. Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC.

A validation study of the Job Crafting Scale among nurses in public hospitals in China.

PURPOSE: To verify the reliability and validity of the Job Crafting Scale among nurses in Chinese public hospitals. BACKGROUND: Job crafting is an important organisational variable for medical institutions. Although the Japanese and Spanish versions of the Job Crafting Scale are available, this scale has not been validated in Chinese nurses. METHODS: A convenience sample of 2,095 registered hospital nurses was recruited from 25 provinces in mainland China from June 2019 to July 2019. Descriptive analyses were performed. Reliability and correlation analyses, exploratory factor analyses and confirmatory factor analyses of data collected using the Chinese version of the Job Crafting Scale were also conducted. FINDINGS: The Chinese version of the Job Crafting Scale has good validity and reliability. The goodness-of-fit indices for confirmatory factor analysis were acceptable (CFI = 0.933, NFI = 0.927, TLI = 0.920, IFI = 0.933). The Cronbach α coefficient for the total scale was .920, and the coefficients for each dimension of this scale were between .804 and .894. CONCLUSION: The Chinese version of the Job Crafting Scale has good reliability and validity, which supports its use as an effective tool to measure the working level of job crafting among nurses in public hospitals in China. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers may use reliable and effective tools, including the Chinese version of the Job Crafting Scale, to determine the level of job crafting at their institutions and to develop effective interventions to improve it.

Nurses' mental health and patient safety: An extension of the Job Demands-Resources model.

AIM: We employed the job demands-resources model to examine the impacts of job demands and resources on Chinese nurses' mental health and patient safety. BACKGROUND: Employee mental health and patient safety represent important organisational goals in most hospitals. However, their relationships to insomnia, professional resources and job crafting, as related to the job demands-resources model among nurses, remain unclear. METHODS: A convenience sample of 2095 registered hospital nurses was recruited from 25 provinces of mainland China from June 2019 to July 2019. Data were collected using self-reported questionnaires that included the following instruments: the Chinese version of the Athens Insomnia Scale, the Practice Environment Scale of the Nursing Work Index, the Job Crafting Scale, the Emotional Exhaustion Scale, the Utrecht Work Engagement Scale, the General Health Questionnaire and the Safety Attitudes Questionnaire. RESULTS: The final model confirmed our hypotheses: burnout mediated the relationship between actual job demands and mental health; work engagement mediated the relationship between perceived job resources and attitudes with regard to patient safety; and job crafting enhanced work engagement and practice environment. CONCLUSION: The job demands-resources model was extended based on the nurses' job characteristics and mental health, as well as patient safety. IMPLICATIONS FOR NURSING MANAGEMENT: These findings may contribute to nursing management strategies that encourage employees to prevent burnout, promote work engagement and job crafting, and in turn promote nurses' mental health and patient safety.

Identification of miR-145-5p-Centered Competing Endogenous RNA Network in Laryngeal Squamous Cell Carcinoma.

This study intends to investigate the transcriptional regulatory role of miR-145-5p in laryngeal squamous cell carcinoma (LSCC). LSCC cell line TU-177 is transfected with miR-145-5p mimics, generating miR-145-5p-overexpression LSCC cells. Whole transcriptome microarrays are used to investigate the differentially expressed lncRNAs, circRNAs, mRNAs, and miRNAs. The target genes of miRNAs are predicted and performed functional annotation. Additionally, the circRNAs, lncRNAs, and mRNAs that interact with miRNAs are predicted, and then the competing endogenous RNAs (ceRNAs) are predicted. Microarray analysis identifies 26 miRNAs, 248 mRNAs, 1118 lncRNAs, and 382 circRNAs differentially expressed in miR-145-5p overexpressed LSCC cells. Overall, 675 target genes are identified for the differentially expressed miRNAs, which involved in cell adhesion associated gene ontology (GO) terms, and MAPK and FoxO signaling pathways. The up-regulated mRNAs involved in the pathway of ABC transporters, while the down-regulated mRNAs involved in pathway of olfactory transduction. Moreover, 149 ceRNAs are predicted, which are associated with apoptosis, Wnt pathway, and metabolic pathway. Furthermore, qPCR results confirm that miR-145-5p affects expression of lncRNAs, miRNAs, mRNAs, and circRNAs in LSCC cells. Collectively, miR-145-5p may be inhibits LSCC progression via ceRNA-mediated pathways, such as WNT2B-miR-145-5p-NONHSAT127539.2, CASP10-miR-145-5p-NONHSAT127539.2, CASP10-miR-145-5p-circ_0003519, and TPO-miR-145-5p-circ_0003519.

Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma.

Dysregulation of fascin actin-bundling protein 1 (FSCN1) enhances cell proliferation, invasion, and motility in laryngeal squamous cell carcinoma (LSCC), while the mechanism remains unclear. Here, co-immunoprecipitation and mass spectrometry is utilized to identify potential FSCN1-binding proteins. Functional annotation of FSCN1-binding proteins are performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Furthermore, the protein-protein interaction network of FSNC1-binding proteins is constructed and the interactions between FSCN1 and novel identified interacting proteins AIMP1 and LTA4H are validated. Moreover, the expression and functional role of AIMP1 and LTA4H in LSCC are investigated. A total of 123 proteins are identified as potential FSCN1-binding proteins, and functional annotation shows that FSCN1-binding proteins are significantly enriched in carcinogenic processes, such as filopodium assembly-regulation and GTPase activity. Co-IP/western blotting and immunofluorescence confirm that AIMP1 and LTA4H bind and colocalize with FSCN1. Furthermore, both AIMP1 and LTA4H are upregulated in LSCC tissues, and knockdown of AIMP1 or LTA4H inhibits LSCC cell proliferation, migration, and invasion. Collectively, the identification of FSCN1-binding partners enhances understanding of the mechanism of FSCN1-mediated malignant phenotypes, and these findings indicate that FSCN1 binds to AIMP1 and LTA4H might promote the progression of LSCC.

Efficacy of laser surgery versus radiotherapy for treatment of glottic carcinoma: a systematic review and meta-analysis.

Laser surgery and radiotherapy are the two most common ways to treat glottic carcinomas, which is more efficacious and remains controversial. PubMed, Embase, and Cochrane Library were searched to identify relevant studies of laser surgery versus radiotherapy in patients with glottic carcinomas through April 2017. Sensitivity analysis and subgroup analysis were performed to evaluate heterogeneity. Eighteen studies were selected, which included 2480 patients. Patients who had laser surgery had higher rates of laryngeal preservation (OR 3.852; 95% CI 1.922-7.721) and overall survival (OR 1.388; 95% CI 1.063-1.811) versus who had radiotherapy. No significant differences were observed between laser surgery and radiotherapy on local control (OR 1.186; 95% CI 0.759-1.854), recurrence (OR 0.758; 95% CI 0.445-1.289), or disease-specific survival (OR 1.597; 95% CI 0.887-2.876). There were clinical benefits for patients with glottic carcinoma after laser surgery compared with radiotherapy with respect to survival and laryngeal preservation.

Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex.

UNLABELLED: Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. SIGNIFICANCE STATEMENT: Growing interest in affective touch has identified a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, cast doubt on the separation of touch discrimination and affect. We used functional magnetic resonance imaging and repetitive transcranial magnetic stimulation to demonstrate the representation of touch discrimination and intensity in S1, but the representation of pleasantness in the anterior cingulate cortex, not S1. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. Our study contributes to growing delineation of the affective touch system, a crucial step in understanding its dysregulation in numerous clinical conditions such as autism, eating disorders, depression, and chronic pain.

Compromised Neurocircuitry in Chronic Blast-Related Mild Traumatic Brain Injury.

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel-wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front-limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto-parieto-temporal association fibers (superior longitudinal fasciculus), and the fronto-striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast-exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post-concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352-369, 2017. © 2016 Wiley Periodicals, Inc.

FSCN1 is upregulated by SNAI2 and promotes epithelial to mesenchymal transition in head and neck squamous cell carcinoma.

In this study, we investigated whether there is any association between the expression of FSCN1 and SNAI2 and the possible underlying mechanisms in head and neck squamous cell carcinoma (HNSC). In addition, we also investigated whether FSCN1 modulates epithelial-to-mesenchymal transition (EMT) in HNSC cells. Microarray data of dysregulated genes in HNSC were searched in GEO datasets. The association between FSCN1 expression and the 5-year/10-year overall survival (OS), as well as the correlation between the expression of FSCN1 and SOX2, MYBL2, SNAI2, STAT1, and SOX4, was analyzed based on data in TCGA HNSC cohort (TCGA-HNSC). The binding site of SNAI2 in FSCN1 promoter was verified using luciferase reporter assay. SCC9 and SCC15 cells were transfected with pCMV-SNAI2 or pCMV-FSCN1 expression vector or the empty control. Alteration of E-cadherin, Claudin 1, Vimentin, and N-cadherin was then quantified. Our results showed that FSCN1 is significantly upregulated in HNSC tissues compared with the normal control tissues. High FSCN1 expression is associated with worse 5-year and 10-year OS among the HNSC patients. Bioinformatic prediction showed a highly possible SNAI2 binding site in FSCN1 promoter and following luciferase reporter assay verified this site. SNAI2 overexpression significantly increased FSCN1 expression at both mRNA and protein level. FSCN1 overexpression reduced the expression of E-cadherin and Claudin 1, but increased the expression of Vimentin and N-cadherin in SCC9 and SCC-15 cells. Therefore, we infer that FSCN1 is a downstream effector of SNAI2 in promoting EMT in HNSC cells.

Aurora-A modulates MMP-2 expression via AKT/NF-κB pathway in esophageal squamous cell carcinoma cells.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. It is necessary to identify new markers for predicting tumor progression and therapeutic molecular targets. It has been reported that overexpressions of Aurora-A and matrix metalloproteinases 2 (MMP-2) may promote the malignant development of tumor. However, the relationship between Aurora-A and MMP-2 expression in tumor patients has not been investigated. In addition, the underlying mechanisms that Aurora-A regulates MMP-2 expression are still not fully elucidated. In this study, we demonstrated that Aurora-A and MMP-2 were overexpressed in ESCC tissues compared with paired normal adjacent tissues (P < 0.0001). Overexpression of Aurora-A was associated with the lymph node metastasis of ESCC (P = 0.01). Significantly, Aurora-A protein expression was positively correlated with MMP-2 protein expression in ESCC tissues (r = 0.66, P < 0.0001) as well as in ESCC cell lines. The level of Aurora-A expression was also positively correlated with the invasion capability of ESCC cells. Furthermore, Aurora-A overexpression significantly increased ESCC cell invasion by the upregulation of MMP-2 expression. In addition, Aurora-A overexpression promoted nuclear factor-kappaB (NF-κB) activation, and Aurora-A-mediated MMP-2 upregulation was abrogated by NF-κB inhibitor. Further analysis showed that activation of NF-κB was severely attenuated by AKT inhibitor in cells overexpressing Aurora-A. Taken together, these data indicate that Aurora-A overexpression upregulates MMP-2 expression through activating AKT/NF-κB signaling pathway in ESCC cells. These findings reveal that Aurora-A may be used as an important indicator for the judgment of malignant behavior of ESCC, and may be an attractive target for cancer therapy.