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Abstract Objective Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR‐223‐3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. Methods Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co‐culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. Results Compared with the control group, the expressions of miR‐223‐3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF‐β1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL‐6, IL‐17, and IL‐23 were significantly increased, and the levels of IL‐10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR‐223‐3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR‐223‐3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF‐β1 and IL‐10 in cells, and upregulated the expression of caspase3, Bax, IL‐17, IL‐6, and IL‐23. The opposite results were obtained with IVIG‐treated sera. Conclusion miR‐223‐3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.

Abstract Background Circular RNAs (circRNAs) act pivotal roles in the progression of multiple malignancies. However, the underlying mechanisms by which hsa_circ_0007031 (circTUBGCP3) contributes to lung adenocarcinoma (LAC) remain largely unknown. Methods The association of circTUBGCP3 expression with clinicopathological characteristics and prognosis in patients with LAC was determined by RT-qPCR and fluorescence in situ hybridization. The in vitro functional experiments as well as a subcutaneous tumorigenesis model were executed to estimate the role of circTUBGCP3 in LAC cells. The interaction between circTUBGCP3 and miR-885-3p was confirmed by RNA immunoprecipitation, luciferase gene report and RT-qPCR assays. The effects of circTUBGCP3 on miR-885-3p-mediated Wnt10b/β-catenin signaling were evaluated by Western blot. Results The upregulation of circTUBGCP3 or downregulation of miR-885-3p was associated with the pathological stage and poor survival in patients with LAC. Restored expression of circTUBGCP3 facilitated the growth and invasion of LAC cells, but knockdown of circTUBGCP3 harbored the opposite effects. In mechanism, circTUBGCP3 could act as a sponge of miR-885-3p, which suppressed the cell proliferation and colony formation and attenuated the tumor-promoting effects of circTUBGCP3. Wnt10b as a target of miR-885-3p could be upregulated be circTUBGCP3 and indicate poor survival in patient with LAC. Conclusions Our findings demonstrated that circTUBGCP3 promoted LAC progression by sponging miR-885-3p, and might represent a prognostic factor for LAC.

In this study, the rheological properties and physical significations of an incompressible viscoelastic (inCVE) the inCVE model was investigated by employing molecular dynamics calculations. Polypropylene (PP) and polystyrene (PS) polymers were selected as candidate materials, the corresponding cell models consisting of five chains of 80 (PP) and 30 (PS) units were built successively. The energy minimization and anneal treatment were launched to optimize the unfavorable structures. The periodic boundary condition, COMPASS force field and the Velocity-Verlet algorithm were employed to calculate the shear flow behavior of chains. The sample data were collected and fitted based on the Matlab platform, and the analysis of the variance (ANOVA) method was performed to determine the validity of the model. Experimental results reveal that the inCVE model matches well with the pseudo-plastic fluids. Compared with the Ostwald-de Waele power law model and Cross model, it is effective and robust, and exhibits a three-stage rheological characteristic. Moreover, it characterizes the stress yield, activation energy, temperature dependence and viscoelastic response of polymers.

Abstract Background Esophageal carcinogenesis is a multifactorial process in which genetic and environmental factors interact to activate intracellular signals, leading to the uncontrolled survival and growth of esophageal squamous cell carcinoma (ESCC) cells. The intracellular pathways of ESCC cells could be regulated by proteinase activated-receptors (PARs), which are comprised of four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4). Therefore, the function and possible mechanism of PAR1 and PAR4 in the progression of ECSS were explored in our study. Methods First, we detected the expression levels of PAR1 and PAR4 in 27 cases of ESCC specimens and cell lines by RT-qPCR, IHC and western blot. Meanwhile, the correlation between PAR1/PAR4 expression levels, clinicopathological characteristics, and disease free survival was analyzed. Then, we constructed PAR1/PAR4 knockdown cell models and investigated the role of PAR1/PAR4 knockdown on the proliferation, apoptosis, changes of calcium flow, and metastasis of ESCC cells via MTT, flow cytometry, transwell and wound healing assays in vitro. Further, an experimental metastasis model in vivo was established to explore the role of stable PAR1/PAR4 knockdown on the growth and metastasis of ESCC cells. Finally, the role of nSMase2 in the activation of NF-κB induced by PAR4 and the role of NF-κB and STAT3 signaling pathways in the PAR1/PAR4-mediated tumor promoting or suppressive functions were measured by immunoprecipitation, western blot and immunofluorescence assays. Results First, the integrated results demonstrated the expression levels of PAR1 and PAR4 are inversely proportional in ESCC. PAR1 potently enhanced tumor growth and metastasis, while PAR4 had an inhibitory effect. Further, the co-activation of STAT3 and NF-κB was involved in the PAR1 activation-induced tumor promoting effect, while only NF-κB participated in the PAR4 activation-induced tumor inhibitory effect in ESCC. To be specific, FAK/PI3K/AKT/STAT3/NF-κB signaling mediated PAR1 activation-induced tumor promoting effect and nSMase2/MAPK/NF-κB signaling mediated PAR4 activation-induced tumor inhibitory effect. Conclusions Overall, the study has provided new insights into the potential implication of PAR1 and PAR4 in the pathogenesis of ESCC. Besides, FAK/PI3K/AKT/STAT3/NF-κB and nSMase2/MAPK/NF-κB pathways may be novel targets for regulating tumor growth and metastasis in ESCC patients.

Cartilage tissue engineering technology provides a solution for treating osteoarthritis. Based on the viscoelastic nature of articular cartilage, many viscoelastic hydrogel scaffolds have been developed for investigating the effects on chondrocyte behaviors. However, cellulose nanocrystal/collagen (CNC/COL) hydrogels have not been used as a viscoelastic microenvironment to study chondrocyte growth. Here, we prepared CNC/COL hydrogels with tunable viscoelastic properties and investigated their influences on chondrocyte behaviors. The results showed that CNC and COL within the hydrogels are bonded by hydrogen bonds. The hydrogels had a microporous structure, and the viscoelastic properties were enhanced by increasing the concentration of CNC. Moreover, enhancing the hydrogel viscoelastic properties, including stress relaxation, creep, storage modulus, and loss modulus, promoted the cell shape change, proliferation, and matrix deposition and reduced the IL-1β level. Using a principal component analysis (PCA), stress relaxation was assessed to have the strongest correlation with chondrocytes behaviors, with an authority weight value of 62.547%. More importantly, FAK and YAP were involved in the chondrocytes’ response to the rapid relaxing hydrogel by immunofluorescence staining.

Esophageal cancer (EC) is a highly aggressive disease, and its progression involves a complex gene regulation network. Transcription factor SOX2 is amplified in various cancers including EC. A pathway involving SOX2 regulation of microRNAs (miRNAs) and their target genes has been previously revealed. This study aims to delineate the ability of SOX2 to influence the EC progression, with the involvement of miR-30e/USP4/SMAD4/CK2 axis. SOX2 expression was first examined in the clinical tissue samples from 30 EC patients. Effects of SOX2 on proliferation, migration, and invasion alongside tumorigenicity of transfected cells were examined by means of gain- and loss-of-function experiments. EC tissues and cells exhibited high expression of SOX2, miR-30e, and CK2 and poor expression of USP4 and SMAD4. Mechanistically, SOX2 was positively correlated with miR-30e and upregulated the expression of miR-30e. miR-30e specifically targeted USP4, which induced deubiquitination of SMAD4 and promoted its expression. Meanwhile, SMAD4 was enriched in the CK2 promoter region and thus inhibited its expression. SOX2 stimulated EC cell proliferative, invasive, and migratory capacities in vitro and tumor growth in vivo by regulating the miR-30e/USP4/SMAD4/CK2 axis. Collectively, our work reveals a novel SOX2-mediated regulatory network in EC that may be a viable target for EC treatment.

Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.

Abstract Background Exosomal microRNAs (miRNAs or miRs) from bone marrow-derived mesenchymal stem cells (UCMSCs) have emerged as promising therapeutic strategies for cancer treatment. The current study aimed to elucidate the underlying mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomal miR-375 in esophageal squamous cell carcinoma (ESCC). Methods After determining the expression of miR-375 and its putative target enabled homolog (ENAH) in ESCC tissues and cells, we tested effects of their altered expression on ESCC proliferation, invasion, migration, and tumorsphere formation was subsequently measured. Transfected hUCMSCs-derived exosomes (hUCMSCs-exo) were isolated and co-cultured with ESCC cells to measure the effects of miR-375 delivered by hUCMSCs-exo on ESCC development. Finally, we investigated the effect of miR-375 on tumor growth in vivo. Results The expression of miR-375 was reduced, while the expression of ENAH was elevated in ESCC. ENAH was identified as a target gene of miR-375. Elevated miR-375 or depleted ENAH expression inhibited ESCC cell proliferation, invasion, migration, tumorsphere formation, and promoted apoptosis. Moreover, miR-375 delivered by hUCMSCs-exo could suppress ESCC cell proliferation, invasion, migration, tumorsphere formation, but promoted apoptosis in vitro, as well as inhibiting tumor growth in vivo. Conclusions Taken together, hUCMSCs-exo can deliver miR-375 to suppress ENAH expression and subsequently inhibit the initiation and progression of ESCC.

Abstract Non‐small cell lung cancer (NSCLC), the major type of lung cancer, becomes the greatest threat to the life of people. Growing evidence shows prostate androgen‐regulated transcript 1 (PART1) is considered as effective markers for prostate cancer, and has been shown to be associated with poor prognosis of NSCLC. However, the tumorigenic mechanism of PART1 in NSCLC remains to be investigated. In this study, we found that the expression of PART1 was robustly induced in NSCLC tissues and cell lines. Functional studies established that overexpression of PART1 could promote NSCLC cell proliferation, migration, and invasion, while interference of PART1 inhibited NSCLC progression. Our results also identified miR‐635 as a novel target of PART1, whose expression was inhibited by PART1 in NSCLC cell lines. Moreover, gain‐ and loss‐of‐function studies revealed that PART1 could sponge miR‐635 and increase the expression of Janus kinase (JAK) and signal transducer and activator of transcription proteins (STATs). Finally, we deciphered the molecular mechanism by which PART1 contributed to promotion of NSCLC cell progression via phosphorylation and activation of JAK‐STAT signaling pathway. The animal experiment further confirmed that interference of NSCLC could suppress in vivo tumorigenic ability of NSCLC with favorable pharmacological activity via inactivation of JAK‐STAT signaling pathway. In conclusion, our findings clarified the biologic significance of PART1/miR‐635/JAK‐STAT axis in NSCLC progression and provided novel evidence that PART1 may be a new potential therapeutic target for the treatment of NSCLC.

The answer selection task is one of the most important issues within the automatic question answering system, and it aims to automatically find accurate answers to questions. Traditional methods for this task use manually generated features based on tf-idf and n-gram models to represent texts, and then select the right answers according to the similarity between the representations of questions and the candidate answers. Nowadays, many question answering systems adopt deep neural networks such as convolutional neural network (CNN) to generate the text features automatically, and obtained better performance than traditional methods. CNN can extract consecutive n-gram features with fixed length by sliding fixed-length convolutional kernels over the whole word sequence. However, due to the complex semantic compositionality of the natural language, there are many phrases with variable lengths and be composed of non-consecutive words in natural language, such as these phrases whose constituents are separated by other words within the same sentences. But the traditional CNN is unable to extract the variable length n-gram features and non-consecutive n-gram features. In this paper, we propose a multi-scale deformable convolutional neural network to capture the non-consecutive n-gram features by adding offset to the convolutional kernel, and also propose to stack multiple deformable convolutional layers to mine multi-scale n-gram features by the means of generating longer n-gram in higher layer. Furthermore, we apply the proposed model into the task of answer selection. Experimental results on public dataset demonstrate the effectiveness of our proposed model in answer selection.

Accurate prediction of the remaining useful life (RUL) of lithium–ion batteries is the focus of lithium–ion battery health management. To achieve high–precision RUL estimation of lithium–ion batteries, a novel RUL prediction model is proposed by combining the extraction of health indicators based on incremental capacity curve (IC) and the method of improved adaptive relevance vector machine (RVM). First, the IC curve is extracted based on the charging current and voltage data. To attenuate the noise effects on the IC curve, Gaussian filtering is used and the optimal filtering window is determined to remove the noise interference. Based on this, the peak characteristics of the IC curve are analyzed and four groups of health indicators are extracted, and the strong correlation between health indicators and capacity degradation is determined using Pearson correlation analysis. Then, to optimize the traditional fixed kernel parameter RVM model, an RVM regression model whose kernel parameters are optimized by the Bayesian algorithm is established. Finally, four sets of datasets under CS2 battery in the public dataset of the University of Maryland are carried out for experimental validation. The validation results show that the improved RVM model has better short–term prediction performance and long–term prediction stability, the RUL prediction error is less than 20 cycles, and the mean absolute error is less than 0.02. The performance of the improved RVM model is better than that of the traditional RVM model.

The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance (1HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been widely used as a first-line agent in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the development of chemoresistance ultimately limited the curative effect of anti-cancer drugs. The present study aims to investigate the functions of SNHG14 in gefitinib resistance and gain insight into the underlying molecular mechanisms. In the present study, we found that SNHG14 expression was elevated and miR-206-3p expression was decreased in gefitinib-resistant NSCLC tumor tissues and cells. Functionally, SNHG14 overexpression increased gefitinib resistance by promoting cell viability, lowering apoptosis and enhancing colony forming ability, while SNHG14 knockdown reduced gefitinib resistance in NSCLC cells. Mechanistically, SNHG14 induced ABCB1 expression via interaction with miR-206-3p. Moreover, depletion of SNHG14 enhanced the sensitivity of NSCLC cells to gefitinib in vivo. Together, SNHG14 confers gefitinib resistance in NSCLC by regulating miR-206-3p/ABCB1 pathway, contributing to a better understanding of SNHG14 in acquired resistance and elucidating a candidate target to improve treatment response of NSCLC patients.

Background: Long non-coding RNA CASC2 (lncRNA CASC2) has been found to be down-regulated in esophageal squamous cell carcinoma (ESCC). However, the effect of CASC2 on cisplatin-treated ESCC was unclear. The present study aimed to evaluate the role of CASC2 in cisplatin-treated ESCC cells.Methods: The expression levels of CASC2 and miR-181a were detected by qRT-PCR. Cell viability was measured by MTT assay. The cytotoxicity effect was detected by lactate dehydrogenase (LDH) release assay. Cell apoptosis was tested by flow cytometry. The protein levels of protein kinase B (Akt) and p-Akt were detected by western blotting.Results: The results showed that CASC2 was low-expressed in ESCC cell lines. Overexpression of CASC2 enhanced the inhibitory effect of cisplatin on cell viability and promoted cisplatin-induced LDH release and apoptosis. We also found that miR-181a expression levels were increased in ESCC cell lines. MiR-181a inhibitor enhanced the antitumor activity of cisplatin, which was similar with the effect of CASC2. CASC2 directly interacted with miR-181a and inhibited the miR-181a expression. MiR-181a reversed the effects of CASC2 on antitumor activity of cisplatin. In addition, we also found that CASC2 suppressed the Akt pathway by inhibiting miR-181a.Conclusions: CASC2 promoted the antitumor activity of cisplatin through inhibiting Akt pathway via negatively regulating miR-181a in ESCC cells. The results provide a new insight for ESCC therapy.

In this article, a feasible mathematical method was proposed to describe the instantaneous shear flow behavior of the incompressible and isothermal thermoplastic materials. Based on the molecular kinetics, thermodynamics, and continuum mechanics method, a viscoelastic model was presented about the intricate rheological phenomena of polymer macromolecules, which is simplified as the generalized Newton’s law. The rheological experiments were carried out with the isotactic polypropylene material. The analysis of variance method was performed to determine the fitness of the model. By comparing with the Ostwald–de Waele power law model and Cross model, the theoretical model was studied. The experimental results reveal that the theoretical model is more accurate than the Ostwald–de Waele power law model and shows a roughly equivalent fitness with the Cross model, which indicates that the theoretical model is effective and robust. Moreover, the results of this study may have potential industrial applications and benefit the users of certain plastic components.

Long non-coding RNAs (LncRNAs) have been found to be associated with the biological behaviors of human cancers. LINC00152 is reported as an oncogene in many kinds of malignancies. However, the functions and mechanisms of LINC00152 involved in esophageal squamous cell carcinoma (ESCC) remain elusive. Our results revealed that LINC00152 expression was up-regulated in ESCC, and correlated with advanced TNM stage, lymph node metastasis, and poor prognosis of ESCC patients. Functionally, LINC00152 knockdown suppressed proliferation, decreased colony forming ability, and induced apoptosis in ESCC cells. Mechanically, LINC00152 functioned as a competing endogenous RNA (ceRNA) to sponge miR-153-3p, thereby facilitating its downstream target FYN. Moreover, miR-153-3p-mediated tumor-suppressive effects were partly reversed following LINC00152 overexpression. Also, FYN knockdown displayed a similar anti-cancerous role in ESCC cells. Taken together, LINC00152 contributed to ESCC progression by down-regulating miR-153-3p and promoting FYN expression, uncovering a novel LINC00152/miR-153-3p/FYN regulatory pathway in ESCC.

In 2013, a resurgence of measles occurred in Beijing, China. The outbreaks occurred among adults and were associated with endemic genotype H1 and imported genotype D8 viruses. Migrant workers were disproportionately represented in the outbreaks; thus, vaccinating such workers against measles may be an effective strategy toward the elimination of this disease.

Adenovirus is one of the most common causes of viral acute respiratory infections. To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011.Through the surveillance project, 4617 cases of respiratory infections were identified during 2011-2013. Throat swabs (pharynx and tonsil secretions) were collected from all the patients, and 15 different respiratory viruses were screened by multiplex one-step PCR method. 45 were identified as adenovirus-positive from sporadic and outbreak cases of respiratory infection by a multiplex one-step RT-PCR method, and a total of 21 adenovirus isolates were obtained. Five HAdV types among three species, including HAdV-3 (species HAdV-B), HAdV-4 (species HAdV-E), HAdV-7 (species HAdV-B), HAdV-55 (species HAdV-B), and an undefined HAdV type (species HAdV-C) were identified. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination.This study confirmed that at least 5 HAdV types including HAdV-3, HAdV-4, HAdV-7, HAdV-55 and an undefined HAdV type were co-circulating and were the causative agents of respiratory tract infections in recent years in Beijing. HAdV-3, HAdV-4, HAdV-7, and HAdV-55 showed the apparent stability of the genomes, while intraspecies recombination was identified in strain BJ04 and BJ09. The recombinants carrying penton base gene of HAdV-1 as well as hexon and fiber genes of HAdV-2 might be a novel type of HAdV worthy of further study.