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The bone lacunar-canalicular system (LCS) is an important microstructural basis for signaling and material transport in bone tissue, guaranteeing normal physiological processes in tissues. Spaceflight astronauts and elderly osteoporosis are related to its function, so it is necessary to reveal the mass transfer laws in bone microstructure under different gravity fields to provide insight for effective clinical treatment.Using the natural LCS structure of bovine tibial cortical bone as the object, the mass transfer experiments on cortical bone were conducted by using sodium fluorescein tracer through different frequency pulsating pressure provided by dynamic perfusion loading device and different high G environments provided by high-speed centrifuge to analyze the mass transfer laws under different gravity fields and different pulsating pressures.The fluorescence intensity of lacunae within the osteon was lower the farther away from the Haversian canal. As the gravity field magnitude increased, the fluorescence intensity within each lacuna enhanced, and the more distant the lacunae from the Haversian canal, the greater the fluorescence intensity enhancement. High-frequency pulsating pressure simulated high-intensity exercise in humans can improve mass transfer efficiency in the LCS.High-intensity exercise may greatly increase solute molecules, nutrients, and signaling molecules in osteocytes and improve the activity of osteocytes. Hypergravity can enhance the transport of solute molecules, nutrients, and signaling molecules in the LCS, especially promoting mass transfer to deep layer lacunae. Conversely, mass transfer to deep layer lacunae may be inhibited under microgravity, causing bone loss and ultimately leading to osteoporosis.

The supplementary file contains the Supplementary Figure S1-S10, Table 1-3 and supplementary word-1. Figure S1 indicated the identification of three cases with low expression of miR-422a. Figure S2 suggested validation of microarray results by qRT-PCR analysis of six randomly selected lncRNAs and six randomly selected circRNAs in three cases. Figure S3 was identification of differentially expressed lncRNAs in GBM tumour and adjacent normal tissues. Figure S4 was Identification of differentially expressed circRNAs in GBM tumour and adjacent normal tissues. Figure S5 was the screen of possible interaction between lncRNA/circRNAs and miR-422a in glioblastoma. Figure S6 indicated circNT5E affects the cell apoptosis of glioblastoma. Figure S7 was CRISPR/Cas9 system targeting Alusq and Alusg. Figure S8 indicated ADARB2 directly interacts with the Alusq region of NT5E pre-mRNA. Figure S9 demonstrated circNT5E regulates cell apoptosis by miR-422a in glioblastoma. Figure S10 suggested circNT5E functions as an efficient miRNA sponge in glioblastoma. Supplementary Table 1 was the detailed clinical patients information. Supplementary Table 2 was the summary of primers and RNA sequences used in this study. Supplementary Table 3 was the summary of GBM-related tumor suppressor miRNAs extracted from the literature. Supplementary Word-1 indicated the sequences of Alu elements of circNT5E analysis.

Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a–downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor–like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis.Significance: Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. Cancer Res; 78(17); 4812–25. ©2018 AACR.

Background: Excessive use of fossil energy has exacerbated global warming, and the goal of carbon neutralization has been put on the agenda. In order to make full use of renewable energy and reduce greenhouse gas emissions, it is urgent to develop environment-friendly energy storage devices. We previously reported metal sulfides/ graphene nanocomposites for the applications in supercapacitors (I. NiS/graphene). Recent work was presented as the paper in the series (II. Ni-Mn-S/Mn-Cu-O/graphene). Objective: To synthesize graphene-supported multi-metal sulfides for electrochemical capacitance storage. Method: The materials were prepared with a two-step hydrothermal method. Samples were characterized by field emission scanning electron microscopy, X-ray powder diffraction, and electrochemical measurements. Results: The as-fabricated electrode exhibited a specific capacitance of 566 F g–1 at the current density of 1 A g–1 and a rate of 68% at 10 A g–1. The materials retained 75.8% of the initial capacitance after 1000 charge-discharge cycles at 5 A g–1. The results suggest optimum Ni-Mn-S/Mn-Cu-O/graphene composites for supercapacitor applications. Conclusion: The Ni-Mn-S/Mn-Cu-O/graphene composites with nanosheet structures were prepared with a two-step hydrothermal method. The materials showed enhanced electrochemical capacitance performances superior to the individual components.

Current prosthetic hands remain challenging to use in water conditions for amputees, such as bathing, swimming, and washing. In order to improve the living conditions of amputees, we developed a waterproof conductive silicone electrode and proposed a corresponding signal recognition method. To evaluate the signal acquisition performance of the electrode, we designed two experiments to compare the conductive silicone electrode with the Ag/AgCl electrode according to acquired surface electromyography (sEMG) signals. For the first experiment, we acquired sEMG signals simultaneously by two kinds of the electrode on flexor carpi radialis, and the correlation coefficient of signals is 0.8752. In the second experiment, we used two kinds of electrodes to record sEMG signals, and the recognition accuracy has no significant difference. The results of the two experiments can show that the proposed electrode can be used for sEMG signal acquisition. Further, we developed an experiment to prove the feasibility of underwater signal acquisition by the proposed electrode. We acquired two-channel signals using the conductive silicone electrode in the water condition, and the recognition accuracy can still reach 93.41%. After sEMG signals were performed high-pass filtering, the accuracy is 94.44%. The experimental results demonstrate that we can use the electrode to acquire sEMG signals in the water condition. Based on the developed waterproof sEMG electrode and signal recognition system, it is now possible for amputees to use prosthetic hands in water conditions.

Hypoxia induces a series of cellular adaptive responses that enable promotion of inflammation and cancer development. Hypoxia-inducible factor-1α (HIF-1α) is involved in the hypoxia response and cancer promotion, and it accumulates in hypoxia and is degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxia-inducible long non-coding RNA (lncRNA) that regulates HIF-1α stability, crucial for cancer progression. Extensive analyses of clinical data indicate that PCAT-1 is elevated in breast cancer patients and is associated with pathological grade, tumor size, and poor clinical outcomes. Through gain- and loss-of-function experiments, we find that PCAT-1 promotes hypoxia-associated breast cancer progression including growth, migration, invasion, colony formation, and metabolic regulation. Mechanistically, PCAT-1 directly interacts with the receptor of activated protein C kinase-1 (RACK1) protein and prevents RACK1 from binding to HIF-1α, thus protecting HIF-1α from RACK1-induced oxygen-independent degradation. These findings provide new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest a novel role of PCAT-1 as a potential therapeutic target for breast cancer., Graphical abstract, Hypoxia induces a series of cellular adaptive responses that enable promotion of inflammation and cancer development. Liu and colleagues reveal that PCAT-1 is critical for maintaining the stability of HIF-1α in hypoxic breast cancer cells, which is related to advanced disease progression and poor prognosis.

The objective of this study was to evaluate the therapy effects of a novel biological scaffold containing heparin, collagen and vascular endothelial growth factor (VEGF) in treating traumatic brain injury (TBI). In our research, a functional composite scaffold constituted by collagen, heparin and vascular endothelial growth factor was used to stimulate angiogenesis and improve nerve-tissue regeneration in a rat model of TBI. The composite scaffold possessed excellent mechanical properties and good porosity, and could effectively control the release rate of VEGF. Motor and cognitive functions such as motor evoked potential, Morris water maze test and modified neurological severity score were evidently improved after the scaffold was grafted onto the injury site in the rat TBI model. There was clearly improved restoration of damaged nerve tissue at the injured site. Furthermore, brain edema and inflammatory reactions were significantly alleviated. Newly formed neurons with associated synaptic structures, nerve fibers, myelin sheaths and functional angiogenesis with intact endothelium at the injury site were observed. In conclusion, our data revealed that the collagen/heparin scaffold combined with VEGF could create excellent microenvironment stimuli for damaged nerve-tissue regeneration, providing a potential strategy for treating TBI.

Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM).A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124.In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM.Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM.

Objective: Curcumin possesses extensive therapeutic effects on several diseases and tumor cells, which has inhibitory effects on mammalian target of rapamycin (mTOR)-STAT3 signaling. Our study aims to explore the influences of curcumin on promoting the recovery of motor function after spinal cord injury (SCI) in rats through the mTOR-STAT3 signaling pathway. Methods : SCI rats were treated with rapamycin and curcumin followed by establishing rat models of SCI. The influences of rapamycin and curcumin on the protein expressions of PTEN, Akt, phosphorylated S6 and chondroitin sulphate proteoglycans (CSPGs) were measured by western blot. Means of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was used to assess motor function. Results: After SCI, curcumin promoted the expression of PTEN, reduced the proliferation of neuroglia cells, affected the expressions of CSPGs and improved the motor function. Conclusion: Curcumin can promote motor function recovery after SCI which is possibly by up-regulating the PTEN expression via the mTOR-STAT3 signaling pathway.

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury (TBI). We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds (3D-CC-ST) on the injured tissue regeneration process. 3D-CC-ST was performed using 3D printing technology at a low temperature (−20°C), and the physical properties and degeneration rate were measured. The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells. Immediately after the establishment of the canine TBI model, 3D-CC-ST and 3D-CC (3D-printed collagen/chitosan scaffolds) were implanted into the cavity of TBI. Following implantation of scaffolds, neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery. Histological and immunofluorescence staining were performed to evaluate neuro-regeneration. The group treated with 3D-CC-ST had good performance of behavior functions. Implanting 3D-CC-ST significantly reduced the cavity area, facilitated the regeneration of nerve fibers and vessel reconstruction, and promoted endogenous neuronal differentiation and synapse formation after TBI. The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.

With the rapid development of the energy industry, the scale of gas stations continues to expand, and gas station equipment has become sophisticated and complex. Once the gas station equipment fails, it will affect the service of the gas station and even cause serious safety accidents. Aiming at the complex and dangerous environment of gas stations, a gas station IoT data collection method based on MQTT is proposed. Gas station equipment is connected to the cloud through the IoT technology, the system collects and analyzes data, visualizes the analysis results, and finally saves the data in the database. Through this data collection method, coupled with the improvement of gas station data observability, gas station fault detection and maintenance will be more efficient.

Background: Due to endogenous neuronal deficiency and glial scar formation, spinal cord injury (SCI) often leads to irreversible neurological loss. Accumulating evidence has shown that a suitable scaffold has important value for promoting nerve regeneration after SCI. Collagen/heparin sulfate scaffold (CHSS) has shown effect for guiding axonal regeneration and decreasing glial scar deposition after SCI. The current research aimed to evaluate the utility of the CHSSs adsorbed with mesenchymal stem cells (MSCs) on nerve regeneration, and functional recovery after acute complete SCI. Methods: CHSSs were prepared, and evaluated for biocompatibility. The CHSSs adsorbed with MSCs were transplanted into these canines with complete SCI. Results: We observed that MSCs had good biocompatibility with CHSSs. In complete transverse SCI models, the implantation of CHSS co-cultured with MSCs exhibited significant improvement in locomotion, motor evoked potential, magnetic resonance imaging, diffusion tensor imaging, and urodynamic parameters. Meanwhile, nerve fibers were markedly improved in the CHSS adsorbed with MSCs group. Moreover, we observed that the implantation of CHSS combined with MSCs modulated inflammatory cytokine levels. Conclusions: The results preliminarily demonstrated that the transplantation of MSCs on a CHSS could improve the recovery of motor function after SCI. Thus, implanting the MSCs-laden CHSS is a promising combinatorial therapy for treatment in acute SCI.

Episodic memory allows a person to recall and mentally reexperience specific episodes from one’s personal past. Studies of episodic memory are of great significance for the diagnosis and the exploration of the mechanism of memory generation. Most of the current studies focus on certain brain regions and pay less attention to the interrelationship between multiple brain regions. To explore the interrelationship in the brain network, we use an open fMRI dataset to construct the brain functional connectivity and effective connectivity network. We establish a binary directed network of the memory when it is reactivated. The binary directed network shows that the occipital lobe and parietal lobe have the most causal connections. The number of edges starting from the superior parietal lobule is the highest, with 49 edges, and 31 of which are connected to the occipital cortex. This means that the interaction between the superior parietal lobule and the occipital lobe plays the most important role in episodic memory, and the superior parietal lobule plays a more causal role in causality. In addition, memory regions such as the precuneus and fusiform also have some edges. The results show that the posterior parietal cortex plays an important role of hub node in the episodic memory network. From the brain network model, more information can be obtained, which is conducive to exploring the brain’s changing pattern in the whole memory process.

This paper describes our system participated in Task 7 of SemEval-2021: Detecting and Rating Humor and Offense. The task is designed to detect and score humor and offense which are influenced by subjective factors. In order to obtain semantic information from a large amount of unlabeled data, we applied unsupervised pre-trained language models. By conducting research and experiments, we found that the ERNIE 2.0 and DeBERTa pre-trained models achieved impressive performance in various subtasks. Therefore, we applied the above pre-trained models to fine-tune the downstream neural network. In the process of fine-tuning the model, we adopted multi-task training strategy and ensemble learning method. Based on the above strategy and method, we achieved RMSE of 0.4959 for subtask 1b, and finally won the first place.

Tissue engineering is considered highly promising for the repair of traumatic brain injury (TBI), and accumulating evidence has proved the efficacy of biomaterials and 3D printing. Although collagen is famous for its natural properties, some defects still restrict its potential applications in tissue repair. In this experimental study, we fabricated a kind of scaffold with collagen and heparin sulfate via 3D printing, which possesses favorable physical properties and suitable degradation rate along with satisfactory cytocompatibility. After implantation, the results of motor evoked potentials (MEPs) showed that the latency and amplitude can both be improved in hemiplegic limbs, and the structural integrity of the cerebral cortex and corticospinal tract can be enhanced significantly under magnetic resonance imaging (MRI) evaluation. Additionally, the results of in situ hybridization (ISH) and immunofluorescence staining also revealed the facilitating role of 3D printing collagen/heparin sulfate scaffolds on vascular and neural regeneration. Moreover, the individuals implanted with this kind of scaffold present better gait characteristics and preferable electromyography and myodynamia. In general, 3D printed collagen/heparin sulfate scaffolds have superb performance in both structural repair and functional improvement and may offer a new strategy for the repair of TBI.

Background: Hypoxia induces a series of cellular adaptive responses that enable to promote inflammation and cancer development. However, only few have been fully characterized about the roles of long noncoding RNAs (lncRNAs) in hypoxia-associated cancer progression. Methods: The involvement of lncRNAs in hypoxia-related cancer progression was screened by qRT-PCR. Based on the public databases and integrating bioinformatics analysis, the alteration of prostate cancer associated transcript-1 (PCAT-1) in breast cancer tissues was detected and validated in a cohort of breast cancer tissues. Overexpression and knocking down experiments were performed to uncover the biological roles of PCAT-1 on cell hypoxia-associated phenotypes and biological behaviors. RNA immunoprecipitation (RIP) and RNA pull-down were carried out to reveal the physical interaction between PCAT-1 and receptor of activated protein-C kinase-1 (RACK1). Moreover, xenograft mouse models were used to evaluate the influence of PCAT-1 on cancer progression and metastasis in vivo.Results: We identified PCAT-1 as a hypoxia-inducible lncRNA that regulated the hypoxia-inducible factor-1α (HIF-1α) stability, crucial for cancer progression. Extensive analyses of clinical data indicated that PCAT-1 was elevated in breast cancer patients and was associated with pathological grade, tumor size and poor clinical outcomes. Through gain and loss of function experiments, we found that PCAT-1 promoted hypoxia-associated breast cancer progression including growth, migration, invasion, colony formation, and metabolic regulation. Mechanistically, PCAT-1 directly interacted with RACK1 protein and prevented RACK1 from binding to HIF-1α, thus protecting HIF-1α from RACK1-induced oxygen-independent degradation.Conclusions: These findings provide a new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest that a novel role of PCAT-1 as a potential therapeutic target for breast cancer.

This paper describes the system designed by ERNIE Team which achieved the first place in SemEval-2020 Task 10: Emphasis Selection For Written Text in Visual Media. Given a sentence, we are asked to find out the most important words as the suggestion for automated design. We leverage the unsupervised pre-training model and finetune these models on our task. After our investigation, we found that the following models achieved an excellent performance in this task: ERNIE 2.0, XLM-ROBERTA, ROBERTA and ALBERT. We combine a pointwise regression loss and a pairwise ranking loss which is more close to the final Match m metric to finetune our models. And we also find that additional feature engineering and data augmentation can help improve the performance. Our best model achieves the highest score of 0.823 and ranks first for all kinds of metrics.

BACKGROUND Driven by the increasing demand for potential patients to monitor their own heart health, wearable technology is increasingly helping people to better monitor their heart health status at a medical level. OBJECTIVE The aim of this study was to develop a flexible and non-contact wearable electrocardiogram system, which can achieve real-time monitoring and primary diagnosis. METHODS A flexible electrocardiogram (ECG) acquisition device (wearable ECG) is designed based on flexible front-end circuit and textile capacitive electrodes, which are based on a conductive textile instead of rigid metal plates. The multi-domain feature space consists of time-domain features and frequency-domain statistical features, which can be used for classification via a back-propagation neural network (BPNN) and a support vector machine (SVM), both of which are optimized using a genetic algorithm. RESULTS The BPNN classifier exhibits good performance, with an accuracy of 98.33%, a sensitivity of 98.33%, a specificity of 99.63% and a positive predictive value of 97.85%. The SVM classifier achieves a higher classification accuracy of 98.89% and also performs better than the BPNN classifier in terms of the sensitivity, specificity and positive predictive value, achieving values of 98.89%, 99.81% and 98.89%, respectively. CONCLUSIONS The experimental results reveal that there is a better classification effect of SVM when classifying normal heart rhythms and 8 types of arrhythmia. The proposed wearable ECG monitoring can aid in the primary diagnosis of certain heart diseases.

Code switching is a linguistic phenomenon which may occur within a multilingual setting where speakers share more than one language. With the increasing communication between groups with different languages, this phenomenon is more and more popular. However, there are little research and data in this area, especially in code-mixing sentiment classification. In this work, the domain transfer learning from state-of-the-art uni-language model ERNIE is tested on the code-mixing dataset, and surprisingly, a strong baseline is achieved. And further more, the adversarial training with a multi-lingual model is used to achieved 1st place of SemEval-2020 Task9 Hindi-English sentiment classification competition.

Additional file 1 : Table S1. The primers used in this study

Immunosuppression is an important mechanism for the development of sepsis pathology, and is the key to the high mortality of sepsis. However, patients appear to be immunocompromised before sepsis onset due to lack of enough attention. Present sepsis models cannot fully mimic the onset of sepsis in patients. Hence, effective treatments in animal experiments could not be transformed into clinical application. In the present study, we improved the animal model of sepsis and used cyclosporine A immunosuppressive mice to make it closer to immune status before the onset of sepsis, followed by the intraperitoneal injection of Escherichia coli (E. coli) CMCC (B) 44,102 standard strain to produce the immunocompromised sepsis model. This trial systematically evaluates the new immunosuppressive sepsis model. Compared with routine sepsis models, the release of inflammatory factors in the new sepsis model was insufficient, blood bacteria were more cultured, diffuse intravascular coagulation (DIC) was more severe, lung, liver and kidney damage were heavier, and mortality rate was higher. In conclusion, the new sepsis model can mimic the patient's pre-onset immunocompromised state, is suitable for the development and evaluation of new methods of sepsis, and solves the controversy of sepsis treatment, providing new ideas and direction.

Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. Results: We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. Conclusion: The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer.

Background Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). Methods A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. Results In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. Conclusions Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM. Graphical abstract

To study the utility of neurophysiological monitoring in the micro-surgical treatments on children with Tethered Cord Syndrome (TCS). A total of 100 patients were included in this study. 51 children underwent micro-surgical treatments without neurophysiological monitoring (no monitoring group) from 2004 to 2009, whereas 49 children with neurophysiological monitoring (monitoring group) from 2010 to 2016. Postoperative evaluations demonstrated that more children in monitoring group (39, 80%) achieved total release than no monitoring group (36, 71%). Fewer new complications (9, 18%) were found in children of monitoring group than that of no monitoring group (19, 37%) (χ2 = 4.422, P 0.05). Additionally, more children in monitoring group (34, 76%) achieved complete recovery or significant improvement than that of no monitoring group (24, 54%) (χ2 = 4.326, P 0.05). This retrospective study provided the evidence supporting the hypothesis that intra-operative neurophysiological monitoring may better guide the surgical process, reduce the risk of post-operative complications, and improve the recovery of children with TCS.

Table S1. Primers used in this study. (DOCX 15â kb)

Figure S1. Top 30 gene ontology (GO) enrichment and pathway enrichment results and identification of circMMP9. (A) GO analysis indicated the top 30 Enrichment Score results. The GO domains included biological process, cellular components and molecular function. The top 30 GO enrichment results are shown. (B) Pathway enrichment analysis demonstrated the significant pathways of differentially expressed circRNAs. The top 30 enrichment pathways are shown. (C) cDNA and gDNA expression was measured by PCR using divergent and convergent primers in 3 GBM tissues, U87 cells and U251 cells. (D) circMMP9 and MMP9 mRNA expression was analyzed by qRT-PCR using RNA from U87 and U251 cells treated with RNase R (***P