Effects of exercise interventions on brain-derived neurotrophic factor levels in overweight and obesity: A systematic review and meta-analysis.

Background: /Objective. An explosion in global obesity epidemic poses threats to the healthcare system by provoking risks of many debilitating diseases, including cognitive dysfunction. Physical activity has been shown to alleviate the deleterious effects of obesity-associated cognitive deficits across the lifespan. Given the strong neuroprotective role of brain-derived neurotrophic factor (BDNF) and exercise training as a known modulator for its elevation, this systematic review sought to examine the strength of the association between exercise and BDNF levels in healthy people with overweight and obesity. Methods: Six electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database, and SPORTDiscus) were searched from their inceptions through December 2022. The primary outcome of interest was BDNF levels. Interventional studies (randomized and quasi-experimental) with English full text available were included. Risk of bias of the included studies was assessed using the Physiotherapy Evidence Database Scale. Data were extracted for meta-analyses by random-effects models. Results: Thirteen studies (n = 750), of which 69.2% (9/13) had low risk of bias, were included. In the meta-analysis, exercise interventions had no significant effect on resting BDNF levels (standardized mean difference: -0.30, 95% CI -0.80 to 0.21, P = 0.25). Subgroup analyses also indicated no effects of age and types of control groups being compared on moderating the association. Conclusion: To further inform the role of BDNF in obesity-related cognitive functioning, rigorous studies with larger samples of participants and raw data available were imperatively deserved.

Patterns of sedentary behavior among older women with urinary incontinence and urinary symptoms: a scoping review.

BACKGROUND: Independent of physical activity, sedentary behavior has emerged as a significant risk factor for health. Particularly, older adults spent as high as 13 h daily on sedentary activities, which account for 98% of their awake times. Although there is growing evidence revealing the potential association between sedentary behavior and urinary incontinence (UI) across populations of different ages, the relationship between sedentary behavior and urinary symptoms in older women, who are twice as likely to have UI than older men, has not been reviewed. This scoping review aimed to synthesize available evidence of the relationship between sedentary behavior and urinary symptoms in noninstitutionalized older women. METHODS: Six electronic databases (PubMed, Web of Science, SPORTDiscus, Ovid Nursing Database, EMBASE, and MEDLINE) were searched from their inception to April 2023. Observational and experimental studies that measured sedentary behavior using objective and/or self-reported methods in older women aged 60 + years having any type of UI, with English full texts available, were included. Relevant data, including sedentary patterns (types, definitions, measurements, and daily patterns) and UI types were tabulated. A narrative synthesis of the findings was also conducted. RESULTS: A total of seven studies (n = 1,822) were included for review and reporting. Objective measurement showed that older women with UI were engaged in > 8 h sedentary activities daily (493.3-509.4 min/day), which accounted for 73% of their awake times. The duration of self-reported sedentary behavior was lower than the time measured objectively, and the average weekday sitting time was 300-380 min/day. With or without adjustment for confounding factors (e.g., age and number of vaginal deliveries), the daily proportion of sedentary time and average duration of sedentary bouts were positively associated with the prevalence of urgency UI. Notably, sedentary patients with UI were more likely to have lower urinary tract symptoms, including bothersome incontinence, to use incontinence products, and to have nocturia episodes, than their age-matched counterparts who were less sedentary. CONCLUSION: Our findings suggest a potential relationship between sedentary behavior and UI in older women, but the causality of the relationship remains unclear. To further inform the clinical role of sedentary behavior in the context of UI, a greater number of rigorous studies with a prospective study design is urgently needed.

Effect of exercise interventions on brain-derived neurotrophic factor expression in people with overweight and obesity: protocol for a systematic review and meta-analysis.

INTRODUCTION: Epidemic obesity ('globobesity') has led to a considerable rise in the prevalence and incidence of many disabling conditions, including cognitive dysfunction. Recent evidence has suggested that habitual exercise can alleviate the deleterious effects of obesity on cognitive functioning across the lifespan. Given that there is a potential link among obesity, exercise, cognitive health and brain-derived neurotrophic factor (BDNF), this systematic review aims to critically appraise interventional trials on exercise and BDNF and to estimate the pooled effect of exercise training on BDNF levels among healthy individuals with overweight and obesity. METHODS AND ANALYSIS: Six electronic databases-PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database and SPORTDiscus-will be searched from their inception through December 2022. Only interventional studies, including randomised controlled trials and quasi-experimental studies, with full text available and reported in English will be included. The primary outcomes will be changes in BDNF levels among healthy subjects with overweight and obesity following either acute or chronic bouts of exercise interventions. Two reviewers will independently conduct data extraction and risk of bias assessment for included trials using the Physiotherapy Evidence Database Scale. We will produce a narrative synthesis, with findings categorised by sex, age groups and types of exercise training. Data will be extracted and pooled for meta-analyses using random-effects models. ETHICS AND DISSEMINATION: No formal ethical approval is required for this systematic review. The findings of this review will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023414868.

Development and validation of the Chinese oral anticoagulants knowledge tool (C-OAKT): A pilot study.

Objective: To develop and validate an oral anticoagulant knowledge tool for Chinese-speaking patients treated with warfarin or direct oral anticoagulants (DOACs) in Hong Kong. Method: This pilot validation study consisted of the following three phases: (1) the development of a knowledge tool and content validity assessment; (2) a pilot study of 200 participants, consisting of 100 patients taking warfarin or DOACs, 50 pharmacists, and 50 members of the general public; and (3) known-group validity and reliability assessments. Results: A 19-item "Chinese Oral Anticoagulants Knowledge Tool (C-OAKT)" was developed with a scale content validity index of 0.95. The mean score for known-group validity was significantly higher in the pharmacist group than the patient groups, and the patient groups scored significantly higher than the general public (mean ± standard deviation [SD] = 90.00 ± 7.11 vs. 51.55 ± 17.49 vs. 19.0 ± 15.42, respectively; p < 0.001). The mean score was higher for patients who attended a pharmacist-managed anticoagulant therapy management clinic (PAC) than for non-PAC patients (mean ± SD = 56.80 ± 13.60 vs. 46.30 ± 9.43; p = 0.004). An analysis of internal consistency showed a Cronbach's alpha value of 0.86. Conclusion: The results of the pilot validation study suggested that the C-OAKT is a valid and reliable instrument for assessing patients' knowledge of oral anticoagulants in ambulatory care settings. Innovations: This is the first validated Chinese version of an anticoagulant knowledge assessment tool. This tool will be utilized in public hospitals in Hong Kong, and will facilitate future research exploring the relationship between anticoagulant knowledge and patient-related outcomes.

Long-read genome assemblies for the study of chromosome expansion: Drosophila kikkawai, Drosophila takahashii, Drosophila bipectinata, and Drosophila ananassae.

Flow cytometry estimates of genome sizes among species of Drosophila show a 3-fold variation, ranging from ∼127 Mb in Drosophila mercatorum to ∼400 Mb in Drosophila cyrtoloma. However, the assembled portion of the Muller F element (orthologous to the fourth chromosome in Drosophila melanogaster) shows a nearly 14-fold variation in size, ranging from ∼1.3 Mb to >18 Mb. Here, we present chromosome-level long-read genome assemblies for 4 Drosophila species with expanded F elements ranging in size from 2.3 to 20.5 Mb. Each Muller element is present as a single scaffold in each assembly. These assemblies will enable new insights into the evolutionary causes and consequences of chromosome size expansion.

Long-read genome assemblies for the study of chromosome expansion: Drosophila kikkawai , Drosophila takahashii , Drosophila bipectinata , and Drosophila ananassae.

Flow cytometry estimates of genome sizes among species of Drosophila show a 3-fold variation, ranging from ∼127 Mb in Drosophila mercatorum to ∼400 Mb in Drosophila cyrtoloma . However, the assembled portion of the Muller F Element (orthologous to the fourth chromosome in Drosophila melanogaster ) shows a nearly 14-fold variation in size, ranging from ∼1.3 Mb to > 18 Mb. Here, we present chromosome-level long read genome assemblies for four Drosophila species with expanded F Elements ranging in size from 2.3 Mb to 20.5 Mb. Each Muller Element is present as a single scaffold in each assembly. These assemblies will enable new insights into the evolutionary causes and consequences of chromosome size expansion.

Supporting the democratization of science during a pandemic: genomics Course-based Undergraduate Research Experiences (CUREs) as an effective remote learning strategy.

The initial phase of the COVID-19 pandemic changed the nature of course delivery from largely in-person to exclusively remote, thus disrupting the well-established pedagogy of the Genomics Education Partnership (GEP; https://www.thegep.org). However, our web-based research adapted well to the remote learning environment. As usual, students who engaged in the GEP's Course-based Undergraduate Research Experience (CURE) received digital projects based on genetic information within assembled Drosophila genomes. Adaptations for remote implementation included moving new member faculty training and peer Teaching Assistant office hours from in-person to online. Surprisingly, our faculty membership significantly increased and, hence, the number of supported students. Furthermore, despite the mostly virtual instruction of the 2020-2021 academic year, there was no significant decline in student learning nor attitudes. Based on successfully expanding the GEP CURE within a virtual learning environment, we provide four strategic lessons we infer toward democratizing science education. First, it appears that increasing access to scientific research and professional development opportunities by supporting virtual, cost-free attendance at national conferences attracts more faculty members to educational initiatives. Second, we observed that transitioning new member training to an online platform removed geographical barriers, reducing time and travel demands, and increased access for diverse faculty to join. Third, developing a Virtual Teaching Assistant program increased the availability of peer support, thereby improving the opportunities for student success. Finally, increasing access to web-based technology is critical for providing equitable opportunities for marginalized students to fully participate in research courses. Online CUREs have great potential for democratizing science education.

Manual annotation of Drosophila genes: a Genomics Education Partnership protocol.

Annotating the genomes of multiple species allows us to analyze the evolution of their genes. While many eukaryotic genome assemblies already include computational gene predictions, these predictions can benefit from review and refinement through manual gene annotation. The Genomics Education Partnership (GEP; https://thegep.org/) developed a structural annotation protocol for protein-coding genes that enables undergraduate student and faculty researchers to create high-quality gene annotations that can be utilized in subsequent scientific investigations. For example, this protocol has been utilized by the GEP faculty to engage undergraduate students in the comparative annotation of genes involved in the insulin signaling pathway in 27 Drosophila species, using D. melanogaster as the reference genome. Students construct gene models using multiple lines of computational and empirical evidence including expression data (e.g., RNA-Seq), sequence similarity (e.g., BLAST and multiple sequence alignment), and computational gene predictions. Quality control measures require each gene be annotated by at least two students working independently, followed by reconciliation of the submitted gene models by a more experienced student. This article provides an overview of the annotation protocol and describes how discrepancies in student submitted gene models are resolved to produce a final, high-quality gene set suitable for subsequent analyses. The protocol can be adapted to other scientific questions (e.g., expansion of the Drosophila Muller F element) and species (e.g., parasitoid wasps) to provide additional opportunities for undergraduate students to participate in genomics research. These student annotation efforts can substantially improve the quality of gene annotations in publicly available genomic databases.

G-OnRamp: Generating genome browsers to facilitate undergraduate-driven collaborative genome annotation.

Scientists are sequencing new genomes at an increasing rate with the goal of associating genome contents with phenotypic traits. After a new genome is sequenced and assembled, structural gene annotation is often the first step in analysis. Despite advances in computational gene prediction algorithms, most eukaryotic genomes still benefit from manual gene annotation. This requires access to good genome browsers to enable annotators to visualize and evaluate multiple lines of evidence (e.g., sequence similarity, RNA sequencing [RNA-Seq] results, gene predictions, repeats) and necessitates many volunteers to participate in the work. To address the technical barriers to creating genome browsers, the Genomics Education Partnership (GEP; https://gep.wustl.edu/) has partnered with the Galaxy Project (https://galaxyproject.org) to develop G-OnRamp (http://g-onramp.org), a web-based platform for creating UCSC Genome Browser Assembly Hubs and JBrowse genome browsers. G-OnRamp also converts a JBrowse instance into an Apollo instance for collaborative genome annotations in research and educational settings. The genome browsers produced can be transferred to the CyVerse Data Store for long-term access. G-OnRamp enables researchers to easily visualize their experimental results, educators to create Course-based Undergraduate Research Experiences (CUREs) centered on genome annotation, and students to participate in genomics research. In the process, students learn about genes/genomes and about how to utilize large datasets. Development of G-OnRamp was guided by extensive user feedback. Sixty-five researchers/educators from >40 institutions participated through in-person workshops, which produced >20 genome browsers now available for research and education. Genome browsers generated for four parasitoid wasp species have been used in a CURE engaging students at 15 colleges and universities. Our assessment results in the classroom demonstrate that the genome browsers produced by G-OnRamp are effective tools for engaging undergraduates in research and in enabling their contributions to the scientific literature in genomics. Expansion of such genomics research/education partnerships will be beneficial to researchers, faculty, and students alike.

G-OnRamp: a Galaxy-based platform for collaborative annotation of eukaryotic genomes.

SUMMARY: G-OnRamp provides a user-friendly, web-based platform for collaborative, end-to-end annotation of eukaryotic genomes using UCSC Assembly Hubs and JBrowse/Apollo genome browsers with evidence tracks derived from sequence alignments, ab initio gene predictors, RNA-Seq data and repeat finders. G-OnRamp can be used to visualize large genomics datasets and to perform collaborative genome annotation projects in both research and educational settings. AVAILABILITY AND IMPLEMENTATION: The virtual machine images and tutorials are available on the G-OnRamp web site (http://g-onramp.org/deployments). The source code is available under an Academic Free License version 3.0 through the goeckslab GitHub repository (https://github.com/goeckslab). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association of Markers of Proinflammatory Phenotype and Beige Adipogenesis with Metabolic Syndrome in Chinese Centrally Obese Adults.

BACKGROUND: Visceral adiposity is associated with higher productions of C-reactive protein (CRP) and interleukin-6 (IL-6). Inflammation of obese adipose tissues could contribute to systemic metabolic dysregulation, especially thermogenic activity of white adipose tissues, namely, beige adipogenesis, characterized by altered irisin expression. Thus, we investigated the roles of inflammation and adipocyte beiging in Chinese centrally obese (CO) adults with metabolic syndrome (MetS). METHODS: This cross-sectional study was conducted on 54 CO and 58 non-CO subjects drawn from 1492 Chinese people with age and sex matched during November 2010 and August 2013. Twenty (37.0%) of the CO subjects fulfilled the IDF worldwide definition of MetS. Serum CRP, IL-6, and irisin levels were examined. RESULTS: Higher CRP and IL-6, but lower irisin, levels were manifested in MetS versus non-MetS subjects with or without CO. Multiple linear regression identified high-density lipoprotein cholesterol level as the only independent risk factor for irisin level. Categorized by median of CRP and IL-6 levels, a lower irisin level was only observed in high CRP group. CONCLUSION: Under the condition of central obesity, chronic inflammation and impaired beige adipogenesis are associated with MetS in Chinese adults.

Association between sonographically measured mesenteric fat thickness and brachial artery flow-mediated dilation in Chinese young male adults.

Objective To investigate the potential correlation between sonographically measured mesenteric fat thickness (MFT) and brachial artery flow-mediated dilation (FMD) in a sample of healthy Chinese male young adults. Methods Healthy male participants were recruited from Hong Kong Polytechnic University for this prospective observational study. The physical activity readiness questionnaire and ultrasound measurements of carotid intima media thickness were used to screen for clinically healthy subjects. MFT and brachial artery FMD were measured by ultrasound, and body mass index (BMI) was recorded. Results A total of 34 healthy male subjects, aged 19-26 years (mean ± SD BMI, 21.7 ± 3.2 kg/m2) were included. Pearson's correlation coefficient test showed that brachial artery FMD had a statistically significant inverse relationship with BMI and with Log (MFT). Further stepwise multiple linear regression analysis showed that Log (MFT), and not BMI, was an independent predictor of impaired brachial artery FMD. Conclusions Sonographic measurements of MFT were an independent predictor of brachial artery FMD in Chinese male young adults.

Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element.

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

Sonographic evaluation of the immediate effects of eccentric heel drop exercise on Achilles tendon and gastrocnemius muscle stiffness using shear wave elastography.

BACKGROUND: Mechanical loading is crucial for muscle and tendon tissue remodeling. Eccentric heel drop exercise has been proven to be effective in the management of Achilles tendinopathy, yet its induced change in the mechanical property (i.e., stiffness) of the Achilles tendon (AT), medial and lateral gastrocnemius muscles (MG and LG) was unknown. Given that shear wave elastography has emerged as a powerful tool in assessing soft tissue stiffness with promising intra- and inter-operator reliability, the objective of this study was hence to characterize the stiffness of the AT, MG and LG in response to an acute bout of eccentric heel drop exercise. METHODS: Forty-five healthy young adults (36 males and nine females) performed 10 sets of 15-repetition heel drop exercise on their dominant leg with fully-extended knee, during which the AT and gastrocnemius muscles, but not soleus, were highly stretched. Before and immediately after the heel drop exercise, elastic moduli of the AT, MG and LG were measured by shear wave elastography. RESULTS: After the heel drop exercise, the stiffness of AT increased significantly by 41.8 + 33.5% (P < 0.001), whereas the increases in the MG and LG stiffness were found to be more drastic by 75 + 47.7% (P < 0.001) and 71.7 + 51.8% (P < 0.001), respectively. Regarding the AT, MG and LG stiffness measurements, the inter-operator reliability was 0.940, 0.987 and 0.986, and the intra-operator reliability was 0.916 to 0.978, 0.801 to 0.961 and 0.889 to 0.985, respectively. DISCUSSION: The gastrocnemius muscles were shown to bear larger mechanical loads than the AT during an acute bout of eccentric heel drop exercise. The findings from this pilot study shed some light on how and to what extent the AT and gastrocnemius muscles mechanically responds to an isolated set of heel drop exercise. Taken together, appropriate eccentric load might potentially benefit mechanical adaptations of the AT and gastrocnemius muscles in the rehabilitation of patients with Achilles tendinopathy.

Diabetic nephropathy and endothelial dysfunction: Current and future therapies, and emerging of vascular imaging for preclinical renal-kinetic study.

An explosion in global epidemic of type 2 diabetes mellitus poses major rise in cases with vascular endothelial dysfunction ranging from micro- (retinopathy, nephropathy and neuropathy) to macro-vascular (atherosclerosis and cardiomyopathy) conditions. Functional destruction of endothelium is regarded as an early event that lays the groundwork for the development of renal microangiopathy and subsequent clinical manifestation of nephropathic symptoms. Recent research has shed some light on the molecular mechanisms of type 2 diabetes-associated comorbidity of endothelial dysfunction and nephropathy. Stemming from currently proposed endothelium-centered therapeutic strategies for diabetic nephropathy, this review highlighted some most exploited pathways that involve the intricate coordination of vasodilators, vasoconstrictors and vaso-modulatory molecules in the pathogenesis of diabetic nephropathy. We also emphasized the emerging roles of oxidative and epigenetic modifications of microvasculature as our prospective therapeutics for diabetic renal diseases. Finally, this review in particular addressed the potential use of multispectral optoacoustic tomography in real-time, minimally-invasive vascular imaging of small experimental animals for preclinical renal-kinetic drug trials.

Differential secretion pathways of proteins fused to the Escherichia coli maltose binding protein (MBP) in Pichia pastoris.

The Escherichia coli maltose binding protein (MBP) is an N-terminal fusion partner that was shown to enhance the secretion of some heterologous proteins from the yeast Pichia pastoris, a popular host for recombinant protein expression. The amount of increase in secretion was dependent on the identity of the cargo protein, and the fusions were proteolyzed prior to secretion, limiting its use as a purification tag. In order to overcome these obstacles, we used the MBP as C-terminal partner for several cargo peptides. While the Cargo-MBP proteins were no longer proteolyzed in between these two moieties when the MBP was in this relative position, the secretion efficiency of several fusions was lower than when MBP was located at the opposite end of the cargo protein (MBP-Cargo). Furthermore, fluorescence analysis suggested that the MBP-EGFP and EGFP-MBP proteins followed different routes within the cell. The effect of several Pichia pastoris beta-galactosidase supersecretion (bgs) strains, mutants showing enhanced secretion of select reporters, was also investigated on both MBP-EGFP and EGFP-MBP. While the secretion efficiency, proteolysis and localization of the MBP-EGFP was influenced by the modified function of Bgs13, EGFP-MBP behavior was not affected in the bgs strain. Taken together, these results indicate that the location of the MBP in a fusion affects the pathway and trans-acting factors regulating secretion in P. pastoris.

Targeting of P-Element Reporters to Heterochromatic Domains by Transposable Element 1360 in Drosophila melanogaster.

Heterochromatin is a common DNA packaging form employed by eukaryotes to constitutively silence transposable elements. Determining which sequences to package as heterochromatin is vital for an organism. Here, we use Drosophila melanogaster to study heterochromatin formation, exploiting position-effect variegation, a process whereby a transgene is silenced stochastically if inserted in proximity to heterochromatin, leading to a variegating phenotype. Previous studies identified the transposable element 1360 as a target for heterochromatin formation. We use transgene reporters with either one or four copies of 1360 to determine if increasing local repeat density can alter the fraction of the genome supporting heterochromatin formation. We find that including 1360 in the reporter increases the frequency with which variegating phenotypes are observed. This increase is due to a greater recovery of insertions at the telomere-associated sequences (∼50% of variegating inserts). In contrast to variegating insertions elsewhere, the phenotype of telomere-associated sequence insertions is largely independent of the presence of 1360 in the reporter. We find that variegating and fully expressed transgenes are located in different types of chromatin and that variegating reporters in the telomere-associated sequences differ from those in pericentric heterochromatin. Indeed, chromatin marks at the transgene insertion site can be used to predict the eye phenotype. Our analysis reveals that increasing the local repeat density (via the transgene reporter) does not enlarge the fraction of the genome supporting heterochromatin formation. Rather, additional copies of 1360 appear to target the reporter to the telomere-associated sequences with greater efficiency, thus leading to an increased recovery of variegating insertions.

Wnt/ß-Catenin activates MiR-183/96/182 expression in hepatocellular carcinoma that promotes cell invasion.

Nearly 50% of known miRNAs are found in clusters and transcribed as polycistronic transcripts. In this study, we showed that over-expression of miR-183/96/182 cluster is frequent in hepatocellular carcinoma (HCC), a highly aggressive malignancy that is commonly fatal. In a cohort of HCC patients (n = 81), miR-183/96/182 up-regulation correlated with metastatic features including presence of microvascular invasion, advanced tumor differentiation, and shorter recurrence-free survival. Univariate and multivariate analyses further showed miR-183/96/182 over-expression represented an independent prognostic factor (Relative Risk: 2.0471; P = 0.0289). Functional investigation using siRNA against miR-183/96/182 in two invasive HCC cells indicated significant inhibition on cell migration and invasion without affecting cell viability. Forkhead boxO1 (FOXO1) was further validated as a downstream target of these three miRNAs. In investigating the regulatory mechanism underlining miR-183/96/182 over-expression, a direct interaction of CTNNB1 on the promoter region was confirmed by ChIP-PCR and luciferase reporter validations. Knockdown of CTNNB1 also showed concordant down-regulations of miR-183, -96 and -182, and the re-expression of FOXO1. Our findings demonstrated that over-expression of miR-183/96/182 confers an oncogenic function in HCC cell dissemination, and could serve as an independent prognostic predictor for HCC patients.