Effects of tail nerve electrical stimulation on the activation and plasticity of the lumbar locomotor circuits and the prevention of skeletal muscle atrophy after spinal cord transection in rats.

INTRODUCTION: Severe spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological processes are significant obstacles for motor function reconstruction. OBJECTIVE: We performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function. METHODS: Eight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8. RESULTS: After 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles. CONCLUSION: The mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting-edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs.

The therapeutic mechanism of transcranial iTBS on nerve regeneration and functional recovery in rats with complete spinal cord transection.

Background: After spinal cord transection injury, the inflammatory microenvironment formed at the injury site, and the cascade of effects generated by secondary injury, results in limited regeneration of injured axons and the apoptosis of neurons in the sensorimotor cortex (SMC). It is crucial to reverse these adverse processes for the recovery of voluntary movement. The mechanism of transcranial intermittent theta-burst stimulation (iTBS) as a new non-invasive neural regulation paradigm in promoting axonal regeneration and motor function repair was explored by means of a severe spinal cord transection. Methods: Rats underwent spinal cord transection and 2 mm resection of spinal cord at T10 level. Four groups were studied: Normal (no lesion), Control (lesion with no treatment), sham iTBS (lesion and no functional treatment) and experimental, exposed to transcranial iTBS, 72 h after spinal lesion. Each rat received treatment once a day for 5 days a week; behavioral tests were administered one a week. Inflammation, neuronal apoptosis, neuroprotective effects, regeneration and synaptic plasticity after spinal cord injury (SCI) were determined by immunofluorescence staining, western blotting and mRNA sequencing. For each rat, anterograde tracings were acquired from the SMC or the long descending propriospinal neurons and tested for cortical motor evoked potentials (CMEPs). Regeneration of the corticospinal tract (CST) and 5-hydroxytryptamine (5-HT) nerve fibers were analyzed 10 weeks after SCI. Results: When compared to the Control group, the iTBS group showed a reduced inflammatory response and reduced levels of neuronal apoptosis in the SMC when tested 2 weeks after treatment. Four weeks after SCI, the neuroimmune microenvironment at the injury site had improved in the iTBS group, and neuroprotective effects were evident, including the promotion of axonal regeneration and synaptic plasticity. After 8 weeks of iTBS treatment, there was a significant increase in CST regeneration in the region rostral to the site of injury. Furthermore, there was a significant increase in the number of 5-HT nerve fibers at the center of the injury site and the long descending propriospinal tract (LDPT) fibers in the region caudal to the site of injury. Moreover, CMEPs and hindlimb motor function were significantly improved. Conclusion: Neuronal activation and neural tracing further verified that iTBS had the potential to provide neuroprotective effects during the early stages of SCI and induce regeneration effects related to the descending motor pathways (CST, 5-HT and LDPT). Furthermore, our results revealed key relationships between neural pathway activation, neuroimmune regulation, neuroprotection and axonal regeneration, as well as the interaction network of key genes.

Q-Learning-Based Hyperheuristic Evolutionary Algorithm for Dynamic Task Allocation of Crowdsensing.

Task allocation is a crucial issue of mobile crowdsensing. The existing crowdsensing systems normally select the optimal participants giving no consideration to the sudden departure of mobile users, which significantly affects the sensing quality of tasks with a long sensing period. Furthermore, the ability of a mobile user to collect high-precision data is commonly treated as the same for different types of tasks, causing the unqualified data for some tasks provided by a competitive user. To address the issue, a dynamic task allocation model of crowdsensing is constructed by considering mobile user availability and tasks changing over time. Moreover, a novel indicator for comprehensively evaluating the sensing ability of mobile users collecting high-quality data for different types of tasks at the target area is proposed. A new Q -learning-based hyperheuristic evolutionary algorithm is suggested to deal with the problem in a self-learning way. Specifically, a memory-based initialization strategy is developed to seed a promising population by reusing participants who are capable of completing a particular task with high quality in the historical optima. In addition, taking both sensing ability and cost of a mobile user into account, a novel comprehensive strength-based neighborhood search is introduced as a low-level heuristic (LLH) to select a substitute for a costly participant. Finally, based on a new definition of the state, a Q -learning-based high-level strategy is designed to find a suitable LLH for each state. Empirical results of 30 static and 20 dynamic experiments expose that this hyperheuristic achieves superior performance compared to other state-of-the-art algorithms.

Decoupling-based adaptive sliding-mode synchro-position control for a dual-cylinder driven hydraulic support with different pipelines.

Dual-cylinder driving columns of a hydraulic support are required to be synchronous, with the purpose of guaranteeing the support balance and providing the roof an enough force. In addition, pipelines connecting cylinders with electro-hydraulic servo-valve have a significance influence on synchronization. Taking the length of pipelines into account, the mathematical model of a dual-cylinder driven hydraulic support is built, and the displacement-force coupling characteristic caused by the shared pump is tackled by a decoupling compensator. Following that, an adaptive sliding-mode synchro-position control strategy (ASSC) is designed based on an improved sliding mode reaching law and an adaptive law is developed to restrain the uncertainties resulted from the sub-system after decoupling. The experimental results obtained from the joint simulation platform and practical system show that the proposed controller can effectively reduce the synchronization error between two column positions and has better control performance than the PI and fuzzy PID controllers.

Upregulation of microRNA miR-141-3p and its prospective targets in endometrial carcinoma: a comprehensive study.

The clinicopathological value of microRNA-141-3p (miR-141-3p) and its prospective target genes in endometrial carcinoma (EC) remains unclear. The present study determined the expression level of miR-141-3p in EC via quantitative real-time PCR (RT-qPCR). RT-qPCR showed a markedly higher expression level of miR-141-3p in EC tissues than in non-EC endometrium tissues (P < 0.0001). The microarray and miRNA-seq data revealed upregulation of miR-141-3p. Integrated analysis based on 675 cases of EC and 63 controls gave a standardized mean difference of 1.737, confirmed the upregulation of miR-141-3p. The Kaplan-Meier survival curve showed that a higher expression of miR-141-3p positively corelated with a poorer prognosis. Combining the predicted targets and downregulated genes in EC, we obtained 271 target genes for miR-141-3p in EC. Two potential targets, PPP1R12A and PPP1R12B, were downregulated at both the mRNA and protein levels. This study indicates that the overexpression of miR-141-3p may play an important part in the carcinogenesis of EC. The overexpression of miR-141-3p may be a risk factor for the prognosis of patients with EC.

Defining the relative impact of muscle versus Schwann cell denervation on functional recovery after delayed nerve repair.

Functional recovery following peripheral nerve injury worsens with increasing durations of delay prior to repair. From the time of injury until re-innervation occurs, denervated muscle undergoes progressive atrophy that limits the extent to which motor function can be restored. Similarly, Schwann cells (SC) in the distal nerve lacking axonal interaction progressively lose their capacity to proliferate and support regenerating axons. The relative contributions of these processes to diminished functional recovery is unclear. We developed a novel rat model to isolate the effects of SC vs. muscle denervation on functional recovery. Four different groups underwent the following interventions for 12 weeks prior to nerve transfer: 1) muscle denervation; 2) SC denervation; 3) muscle + SC denervation (negative control); 4) no denervation (positive control). Functional recovery was measured weekly using the stimulated grip strength testing (SGST). Animals were sacrificed 13 weeks post nerve transfer. Retrograde labeling was used to assess the number of motor neurons that regenerated their axons. Immunofluorescence was performed to evaluate target muscle re-innervation and atrophy, and to assess the phenotype of the SC within the distal nerve segment. Functional recovery in the muscle denervation and SC denervation groups mirrored that of the negative and positive control groups, respectively. The SC denervation group achieved better functional recovery, with a greater number of reinnervated motor endplates and less muscle atrophy, than the muscle denervation group. Retrograde labeling suggested a higher number of neurons contributing to muscle reinnervation in the muscle denervation group as compared to SC denervation (p > 0.05). The distal nerve segment in the muscle denervation group had a greater proportion of SCs expressing the proliferation marker Ki67 as compared to the SC denervation group (p < 0.05). Conversely, the SC denervation group had a higher percentage of senescent SCs expressing p16 as compared to the muscle denervation group (p < 0.05). The deleterious effects of muscle denervation are more consequential than the effects of SC denervation on functional recovery. The effects of 12 weeks of SC denervation on functional outcome were negligible. Future studies are needed to determine whether longer periods of SC denervation negatively impact functional recovery.

Dual antiplatelet therapy reduced stroke risk in transient ischemic attack with positive diffusion weighted imaging.

Dual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan-Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30-0.97; p = 0.037). However, the benefit didn't exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14-1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.

TNFSF14, a novel target of miR-326, facilitates airway remodeling in airway smooth muscle cells via inducing extracellular matrix protein deposition and proliferation.

As a common chronic respiratory disease, the incidence of asthma is increasing in recent years worldwide. Airway remodeling is the primary pathological basis of refractory asthma, but the studies about the underlying mechanism of airway remodeling was a lack. In the study, we aimed to investigate the effects and mechanisms of miR-326 on airway remodeling in airway smooth muscle cells (ASMCs). The results showed that transforming growth factor-ß1 (TGF-ß1) accelerated matrix protein deposition by increasing the expression levels of collagen I and fibronectin, and promoted proliferative ability of ASMCs. However, miR-326 was significantly downregulated in TGF-ß1-treated ASMCs. MiR-326 mimics robustly decreased the collagen I and fibronectin levels and inhibited cell proliferation of TGF-ß1-treated ASMCs. Luciferase assay investigated that tumor necrosis factor superfamily member 14 (TNFSF14) was a direct target of miR-326. The expression of TNFSF14 was negatively regulated by miR-326. Moreover, exogenous TNFSF14 effectively reversed the inhibitory effects of miR-326 overexpression on the expression levels of collagen I and fibronectin, and promoted cell proliferation of TGF-ß1-treated ASMCs. In conclusion, miR-326 suppressed matrix protein deposition and cell proliferation of TGF-ß1-treated ASMCs via inhibiting TNFSF14. MiR-326 might be a promising novel therapeutic target for asthma.

CD117 expression is correlated with poor survival of patients and progression of lung carcinoma:a meta-analysis with a panel of 2645 patients.

The aim of this research was to investigate the clinical role and prognostic value of CD117 expression assessed immunohistochemically in lung carcinoma through a comprehensive meta-analysis in which 27 publications were acquired and 2645 patients were ultimately analysed. Statistical analysis and corresponding plots were performed using STATA version 12.0. Publication bias was assessed by Begg's funnel plots and Egger's test. Pooled HR and its 95% CI (HR = 1.53, 95% CI: 1.13-2.07, p = 0.007) for overall survival of patients indicated a poor prognostic value for CD117 expression in lung carcinoma, which was accompanied by heterogeneity and publication bias. In the subgroup analysis, there was strong evidence that could support an association between CD117 expression and poor prognosis in NSCLC patients (HR = 2.03, 95% CI: 1.41-2.90, p < 0.001; heterogeneity: I2 = 41.9%, c2 = 15.49, p = 0.078). Multivariate analysis also revealed consistent results in high-quality studies with reported HRs (HR = 2.16, 95% CI: 1.67-2.79, p < 0.001), and Asian patients (HR = 2.12, 95% CI: 1.45-3.10, p < 0.001). The correlations between CD117 expression and age, clinical stage, TNM stage, lymph node metastasis, or histology were not statistically significant. In conclusion, CD117 expression might be a potential marker for predicting poor prognosis, faster tumour growth, and early lymph node metastasis in NSCLC.

Clinical value of microRNA-198-5p downregulation in lung adenocarcinoma and its potential pathways.

Lung adenocarcinoma (LUAD), the main subtype of non-small cell lung cancer, is known to be regulated by various microRNAs (miRs/miRNAs); however, the role of miR-198-5p in LUAD has not been clarified. In the present study, the clinical value of miR-198-5p in LUAD and its potential molecular mechanism was evaluated. miR-198-5p expression was examined by reverse transcription-quantitative PCR (RT-qPCR) in 101 paired LUAD and adjacent normal lung tissues. Subsequently, the miR-198-5p expression level was determined from microarray data from the Gene Expression Omnibus, ArrayExpress and by meta-analyses. Furthermore, the target mRNAs of miR-198-5p from 12 miRNA-mRNA predictive tools were intersected with The Cancer Genome Atlas (TCGA)-based differentially expressed genes. In addition, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to determine the possible mechanism of miR-198-5p in LUAD. The Search Tool for the Retrieval of Interacting Genes/Proteins database was employed to construct a protein-protein interaction network among the potential target genes of miR-198-5p. The results showed that miR-198-5p expression was lower in LUAD tissues than in adjacent non-cancerous lung tissues (4.469±2.495 vs. 5.301±2.502; P=0.015). Meta-analyses, including the data from the present study and online microarray data, also verified the downregulation of miR-198-5p in 584 cases of LUAD. The expression of miR-198-5p was associated with the age, blood vessel invasion, Tumor-Node-Metastasis stage, and lymph node metastasis of patients with LUAD and served as an independent prognostic factor for survival. The hub genes of miR-198-5p were upregulated in LUAD, according to TCGA and The Human Protein Atlas. For the KEGG pathway analysis, the most enriched KEGG pathway was the p53 signaling pathway (P=1.42×10-6). These findings indicated that the downregulation of miR-198-5p may play a pivotal role in the development of LUAD by targeting various signaling pathways.

Down-regulation of microRNA-144-3p and its clinical value in non-small cell lung cancer: a comprehensive analysis based on microarray, miRNA-sequencing, and quantitative real-time PCR data.

BACKGROUND: Previous studies have shown that miR-144-3p might be a potential biomarker in non-small cell lung cancer (NSCLC). Nevertheless, the comprehensive mechanism behind the effects of miR-144-3p on the origin, differentiation, and apoptosis of NSCLC, as well as the relationship between miR-144-3p and clinical parameters, has been rarely reported. METHODS: We investigated the correlations between miR-144-3p expression and clinical characteristics through data collected from Gene Expression Omnibus (GEO) microarrays, the relevant literature, The Cancer Genome Atlas (TCGA), and real-time quantitative real-time PCR (RT-qPCR) analyses to determine the clinical role of miR-144-3p in NSCLC. Furthermore, we investigated the biological function of miR-144-3p by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein-protein interaction (PPI) network was created to identify the hub genes. RESULTS: From the comprehensive meta-analysis, the combined SMD of miR-144-3p was - 0.95 with 95% CI of (- 1.37, - 0.52), indicating that less miR-144-3p was expressed in the NSCLC tissue than in the normal tissue. MiR-144-3p expression was significantly correlated with stage, lymph node metastasis and vascular invasion (all P <  0.05). As for the bioinformatics analyses, a total of 37 genes were chosen as the potential targets of miR-144-3p in NSCLC. These promising target genes were highly enriched in various key pathways such as the protein digestion and absorption and the thyroid hormone signaling pathways. Additionally, PPI revealed five genes-C12orf5, CEP55, E2F8, STIL, and TOP2A-as hub genes with the threshold value of 6. CONCLUSIONS: The current study validated that miR-144-3p was lowly expressed in NSCLC. More importantly, miR-144-3p might function as a latent tumor biomarker in the prognosis prediction for NSCLC. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of NSCLC.

The expression, significance and function of cancer susceptibility candidate 9 in lung squamous cell carcinoma: A bioinformatics and in vitro investigation.

The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non­cancer tissues by reverse transcription­quantitative polymerase chain reaction assays and by data mining of high­throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co­expressed genes, prediction of potential transcription factors, and inspection of adjacent protein­coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co­expressed genes indicated that these genes were significantly associated with terms, including 'cell­cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos­related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein­coding genes, cysteine­rich secretory protein LCCL domain­containing 1 and hepatocyte nuclear factor 4­Î³, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.

Comprehensive clinical implications of homeobox A10 in 3,199 cases of non-small cell lung cancer tissue samples combining qRT-PCR, RNA sequencing and microarray data.

In the current study, we proposed to explore the potential role and related signaling pathways of Homobox A10 (HOXA10) in non-small cell lung cancer (NSCLC). HOXA10 levels in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were detected by qRT-PCR and the expression of HOXA10 was significantly up-regulated in the NSCLC tissue of all 55 pairs (P = 0.037). Overexpression of HOXA10 was closely correlated with the clinical stage of LUSC (P = 0.011). HOXA10 expression in RNA sequencing data based on 1, 077 cases exhibited concordant significant up-regulation in NSCLC, LUAD and LUSC (P < 0.001). In NSCLC, HOXA10 expression was closely correlated to patient T stage (P = 0.006). In LUAD, HOXA10 expression was compactly correlated to patient N stage (P = 0.02). Some of the microarrays from Gene Expression Omnibus (GEO) and ArrayExpress showed consistent over-expression of HOXA10 levels in NSCLCs. More importantly, the combined SMD value was 0.052 (95% CI: 0.29-0.75, P < 0.001) generated by meta-analysis from 47 datasets based on 4, 616 cases of NSCLC. The area under the curve (AUC) of SROC supported the over-expression of HOXA10 in NSCLC as being 0.88 (95% CI: 0.81-0.93), with sensitivity and specificity of 0.88 (95% CI: 0.81-0.93) and 0.56 (95% CI: 0.44-0.66), respectively. In addition, 111 co-expressed genes were collected from cBioPortal and enriched in "cell cycle", "cell adhesion molecules", "p53 signaling", and "adherens junction". Interestingly, an up-regulation trend of HOXA10 protein expression was also observed in NSCLC through tissue chips and immunohistochemistry. In conclusion, the overexpression of HOXA10 may play a pivotal role in the tumorigenesis of NSCLC, and this effect is observed more obviously in LUSC than in LUAD.

Development of a prognostic index based on an immunogenomic landscape analysis of papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study. METHODS: We integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset. Differentially-expressed and survival-associated IRGs in PTC patients were estimated a computational difference algorithm and COX regression analysis. The potential molecular mechanisms and properties of these PTC-specific IRGs were also explored with the help of computational biology. A new prognostic index based on immune-related genes was developed by using multivariable COX analysis. RESULTS: A total of 46 differentially expressed immune-related genes were significantly correlated with clinical outcome of PTC patients. Functional enrichment analysis revealed that these genes were actively involved in a cytokine-cytokine receptor interaction KEGG pathway. A prognostic signature based on RGs (AGTR1, CTGF, FAM3B, IL11, IL17C, PTH2R and SPAG11A) performed moderately in prognostic predictions and correlated with age, tumor stage, metastasis, number of lesions, and tumor burden. Intriguingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. CONCLUSIONS: Together, our results screened several IRGs of clinical significance, revealed drivers of the immune repertoire, and demonstrated the importance of a personalized, IRG-based immune signature in the recognition, surveillance, and prognosis of PTC.

The clinicopathological significance of decreased miR-125b-5p in hepatocellular carcinoma: evidence based on RT-qPCR, microRNA-microarray, and microRNA-sequencing.

The aim of the study was to comprehensively evaluate the clinical value of miR-125b-5p in hepatocellular carcinoma (HCC) and its potential molecular mechanisms. MiR-125b-5p expression was remarkably lower as examined by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) in 95 paired HCC and nonmalignant liver tissues in house (P<0.001), which was in accord with the results from miRNA-sequencing data with 371 cases of HCC. miRNA-chips from Gene Expression Omnibus (GEO) and ArrayExpress were screened. Among the seven included miRNA-chips, the relative expression of miR-125b-5p expression levels showed decreasing trends in HCC tissue samples compared with non-cancerous liver tissue samples. Altogether, A total of 655 cases of HCC tissues and 334 non-HCC liver tissues were included in the final meta-analysis. We observed that the expression of miR-125b-5p indeed decreased markedly in HCC tissues compared with the non-HCC tissues (SMD: -1.414, 95% CI: -1.894 to -0.935, P<0.001). The area under the SROC curve of lower expression of miR-125b-5p was 0.91 (95% CI: 0.89 to 0.94). A Kaplan-Meier survival analysis indicated that the lower expression or the absence of miR-125b-5p may be a risk factor for the poor outcome of HCC patients. Furthermore, the potential target genes of miR-125b-5p from 11 miRNA target prediction databases were intersected with 1,486 differentially expressed genes (DEGs) as calculated by RNA-sequencing data. Finally, a total of 330 GEGs were collected and enriched in the pathways of lysosome, focal adhesion, and pathways in cancer. In conclusion, this study utilizes a variety of research methods to confirm the lower level of miR-125b-5p in HCC tissues. This lower expression level of miR-125b-5p is closely related to increased disease progression in HCC patients.

Overexpression of MiR-452-5p in hepatocellular carcinoma tissues and its prospective signaling pathways.

BACKGROUND: The implication of miR-452-5p and its prospective machinery in hepatocellular carcinoma (HCC) remains largely unknown. For this reason, this study aimed to inspect the clinical implication of miR-452-5p expression in HCC tissues with multiple detection approaches, to analyze its potential function via in silico methods, and to validate this using a dual-luciferase reporter assay. METHODS: The assessment of the expression level of miR-452-5p in HCC was conducted via four methods: 1) in-house real-time quantitative PCR (RT-qPCR), 2) miRNA-sequencing (miRNA-seq) from The Cancer Genome Atlas (TCGA), 3) miRNA microarrays from the Gene Expression Omnibus (GEO), and 4) comprehensive meta-analyses calculating the standard mean difference (SMD) and summary of receiver operator characteristic (sROC). Following the target prediction, one of the potential targets of miR-452-5p was validated through a dual-luciferase reporter assay. RESULTS: MiR-452-5p was consistently elevated in HCC tissues via various detection methods, including in-house RT-qPCR, miRNA-seq, and miRNA microarrays. The final SMD was 0.842 for 820 cases of HCC samples. Simultaneously, the area under curve (AUC) of the sROC was 0.80 (0.76-0.83). The 1,135 predicted targets of miR-452-5p were enriched in the pathways of cytokine-cytokine receptor interaction, carbon metabolism, and complement and coagulation cascades. Among these predicted targets, CDKN1B was verified to be a real target of miR-452-5p. CONCLUSION: The overexpression of miR-452-5p may play a pivotal role in the carcinogenesis of HCC via targeting multiple signaling pathways and genes. The function and molecular machinery of miR-452-5p in HCC requires further in-depth exploration.

Robust Dynamic Multi-Objective Vehicle Routing Optimization Method.

For dynamic multi-objective vehicle routing problems, the waiting time of vehicle, the number of serving vehicles, and the total distance of routes were normally considered as the optimization objectives. Except for the above objectives, fuel consumption that leads to the environmental pollution and energy consumption was focused on in this paper. Considering the vehicles' load and the driving distance, a corresponding carbon emission model was built and set as an optimization objective. Dynamic multi-objective vehicle routing problems with hard time windows and randomly appeared dynamic customers, subsequently, were modeled. In existing planning methods, when the new service demand came up, global vehicle routing optimization method was triggered to find the optimal routes for non-served customers, which was time-consuming. Therefore, a robust dynamic multi-objective vehicle routing method with two-phase is proposed . Three highlights of the novel method are: (i) After finding optimal robust virtual routes for all customers by adopting multi-objective particle swarm optimization in the first phase, static vehicle routes for static customers are formed by removing all dynamic customers from robust virtual routes in next phase. (ii) The dynamically appeared customers append to be served according to their service time and the vehicles' statues. Global vehicle routing optimization is triggered only when no suitable locations can be found for dynamic customers. (iii) A metric measuring the algorithms robustness is given. The statistical results indicated that the routes obtained by the proposed method have better stability and robustness, but may be sub-optimum. Moreover, time-consuming global vehicle routing optimization is avoided as dynamic customers appear.

A PSO-based multi-objective multi-label feature selection method in classification.

Feature selection is an important data preprocessing technique in multi-label classification. Although a large number of studies have been proposed to tackle feature selection problem, there are a few cases for multi-label data. This paper studies a multi-label feature selection algorithm using an improved multi-objective particle swarm optimization (PSO), with the purpose of searching for a Pareto set of non-dominated solutions (feature subsets). Two new operators are employed to improve the performance of the proposed PSO-based algorithm. One operator is adaptive uniform mutation with action range varying over time, which is used to extend the exploration capability of the swarm; another is a local learning strategy, which is designed to exploit the areas with sparse solutions in the search space. Moreover, the idea of the archive, and the crowding distance are applied to PSO for finding the Pareto set. Finally, experiments verify that the proposed algorithm is a useful approach of feature selection for multi-label classification problem.

The Effects of Dinner-to-Bed Time and Post-Dinner Walk on Gastric Cancer Across Different Age Groups: A Multicenter Case-Control Study in Southeast China.

Gastric cancer (GC) remains a major killer throughout the world. Despite the dramatic decrease in GC over the last century, its etiology has not yet been well characterized. This study investigated the possible independent and combined effects of the dinner-to-bed time and post-dinner walk on the risk for GC across different age groups. A population-based, case-control study was conducted in southeast China, including 452 patients with GC and 465 age-, race-, and gender-matched controls. A self-designed questionnaire was used to collect information on demographic characteristics, dinner-to-bed time, post-dinner walk, and other behavioral factors. Conditional logistic regression models were used to estimate the effects of the dinner-to-bed time and post-dinner walk as well as their joint effect on the risk for GC across different age groups. Individuals with dinner-to-bed time <3 hours were more prone to have GC (P < 0.001), and the shorter the dinner-to-bed time was, the higher was the risk for GC (Ptrend < 0.001). Post-dinner nonwalk was associated with a 2.9-fold increased risk for GC compared with post-dinner walk (adjusted odds ratio [AOR] = 2.942, 95% confidence intervals [95% CIs] = 2.072-4.179). The interaction effect of dinner-to-bed time and post-dinner walk on GC risk was detected (AOR = 1.862, 95% CIs = 1.584-3.885, synergy index [SI] = 2.654, 95% CIs = 2.27-3.912). Participants with dinner-to-bed time <3 hours who did not walk after dinner were 7.4 times likely to suffer from GC (AOR = 7.401, 95% CIs = 4.523-13.16) than those with dinner-to-bed time ≥4 hours who took such walk. The risk of GC due to dinner-to-bed time <3 hours, post-dinner nonwalk and their interaction was positively correlated with age. The strongest risk was observed among people ≥70 years old, but the effects were not significant for people ≤55 years old. Dinner-to-bed time <3 hours and post-dinner nonwalk are independent risk factors for GC; the synergistic interaction between the 2 factors was positively related to age, which might significantly increase the risk for GC among people >55 years old.

WITHDRAWN: Early enteral nutrition versus late enteral nutrition for burns patients: A systematic review and meta-analysis.

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