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Abstract Background Elevation of soluble major histocompatibility complex class I chain-related gene A (sMICA) products in serum has been linked to tissue/organ transplantation, autoimmune diseases and some malignant disorders. Cells infected by microbiological pathogens may release sMICA, whereas less is known whether and to what extent serum sMICA levels may change in infectious diseases. Methods The present study determined serum sMICA levels by enzyme-linked immunosorbent assay (ELISA) in a southern China population, including patients (n = 1041) suffering from several types of malignant and infectious diseases and healthy controls (n = 141). Results Relative to controls, serum sMICA elevation was significant in patients of hepatic cancer, and was approaching statistical significance in patients with lung, gastric and nasopharyngeal cancers. sMICA elevation was also associated with some bacterial (Enterobacteriaceae, Mycobacterium tuberculosis, non-fermenting Gram-negative bacteria and Gram-positive cocci), viral (hepatitis B and C) and the Microspironema pallidum infections. Conclusion Serum sMICA levels may be informative for the diagnosis of some malignant and infectious diseases. The results also indicate that microbiological infections should be considered as a potential confounding clinical condition causing serum sMICA elevation while using this test to evaluate the status of other disorders, such as cancers, host-graft response and autoimmune diseases.

The larvae of the insect Galleria mellonella , have recently been established as a non-mammalian infection model for the Mycobacterium tuberculosis complex (MTBC). To gain further insight into the potential of this model, we applied proteomic (label-free quantification) and transcriptomic (gene expression) approaches to characterise the innate immune response of G. mellonella to infection with Mycobacterium bovis BCG lux over a 168 h time course. Proteomic analysis of the haemolymph from infected larvae revealed distinct changes in the proteome at all time points (4, 48, 168 h). Reverse transcriptase quantitative PCR confirmed induction of five genes (gloverin , cecropin , IMPI , hemolin , and Hdd11), which encoded proteins found to be differentially abundant from the proteomic analysis. However, the trend between gene expression and protein abundance were largely inconsistent (20%). Overall, the data are in agreement with previous phenotypic observations such as haemocyte internalization of mycobacterial bacilli (hemolin/β-actin), formation of granuloma-like structures (Hdd11), and melanization (phenoloxidase activating enzyme 3 and serpins). Furthermore, similarities in immune expression in G. mellonella , mouse, zebrafish and in vitro cell-line models of tuberculosis infection were also identified for the mechanism of phagocytosis (β-actin). Cecropins (antimicrobial peptides), which share the same α-helical motif as a highly potent peptide expressed in humans (h-CAP-18), were induced in G. mellonella in response to infection, giving insight into a potential starting point for novel antimycobacterial agents. We believe that these novel insights into the innate immune response further contribute to the validation of this cost-effective and ethically acceptable insect model to study members of the MTBC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a kind of malignancy generated from the nasopharyngeal epithelium. Recently, long noncoding RNA (lncRNA) has been shown to be involved in the regulation of many signaling pathways and is closely associated with carcinogenesis and tumor progression. However, the precise role of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in NPC is not well understood. Here, we find that OIP5-AS1 is overexpressed in NPC patient specimens and NPC cell lines. Further investigations reveal that knockdown of OIP5-AS1 significantly inhibits the proliferation, migration, and invasion and accelerates the apoptosis of NPC cells in vitro. Consistent with these findings, NPC progression is significantly slowed in mice when OIP5-AS1 is knocked down. Interestingly, there is a functional link between OIP5-AS1 and microRNA-203 (miR-203), a tumor suppressor, in NPC cells. In conclusion, our data demonstrate that OIP5-AS1 plays an important role in the development and progression of NPC by targeting miR-203 and therefore provide a promising target for the treatment of NPC. [ABSTRACT FROM AUTHOR]

Sound source localization in noisy and reverberant rooms using microphone arrays remains a challenging task, especially for small-sized arrays. Recent years have seen promising advances on deep learning assisted approaches by reformulating the sound localization problem as a classification one. A key to the deep learning-based approaches lies in extracting sound location features effectively in noisy and reverberant conditions. The popularly adopted features are based on the well-established generalized cross correlation phase transform (GCC-PHAT), which is known to be helpful in combating room reverberation. However, the GCC-PHAT features may not be applicable to small-sized arrays. This paper proposes a deep learning assisted sound localization method using a small-sized microphone array constructed by two orthogonal first-order differential microphone arrays. An improved feature extraction scheme based on sound intensity estimation is also proposed by decoupling the correlation between sound pressure and particle velocity components in the whitening weighting construction to enhance the robustness of the time-frequency bin-wise sound intensity features. Simulation and real-world experimental results show that the proposed deep learning assisted approach can achieve higher spatial resolution and is superior to its state-of-the-art counterparts using the GCC-PHAT or sound intensity features for small-sized arrays in noisy and reverberant environments. [ABSTRACT FROM AUTHOR]

The RNA chaperone Hfq regulates diverse processes in numerous bacteria. In this study, we compared phenotypes (growth rate, adherence, response to different stress conditions and virulence in Galleria mellonella) of wild-type (WT) and isogenic hfq mutants of three serovars (1, 8 and 15) of the porcine pathogen Actinobacillus pleuropneumoniae. Similar growth in rich broth was seen for all strains except Ap1∆ hfq , which showed slightly reduced growth throughout the 24 h time course, and the complemented Ap8∆ hfq C mutant had a prolonged lag phase. Differences were seen between the three serovar WT strains regarding adherence, stress response and virulence in G. mellonella , and deletion of hfq affected some, but not all of these phenotypes, depending on serovar. Complementation by expression of cloned hfq from an endogenous promoter only restored some WT phenotypes, indicating that complex regulatory networks may be involved, and that levels of Hfq may be as important as presence/absence of the protein regarding its contribution to gene regulation. Our results support that Hfq is a pleiotropic global regulator in A. pleuropneumoniae , but serovar-related differences exist. These results highlight the importance of testing multiple strains/serovars within a given species when determining contributions of global regulators, such as Hfq, to expression of complex phenotypes. [ABSTRACT FROM AUTHOR]

Heat shock transcription factor (HSF) is ubiquitous in the whole biological world and plays an important role in regulating growth and development and responses to environment stress. In this study, a total of 60 HSF transcription factors in Brassica juncea genome were identified and analyzed. Phylogenetic analysis showed that HSF genes were divided into three groups namely: A, B, and C, of which group A was further divided into nine subgroups (A1–A9). The analysis of gene structure and conserved motifs showed that some homologous genes are highly conserved. There was strong conservative microcollinearity among Brassica rapa, B. juncea, and Brassica oleracea, which provides a basis for studying the replication of gene families. Moreover, the results revealed that the promoter regions of BjuHSF genes were rich in cis-elements related to growth and development, hormone signal, and stress response. The prediction of protein interaction results showed that HSFs could interact with multiple transcription factors and proteins in the genome, while functional annotation revealed that BjuHSF genes were involved in many biological processes. The expression patterns of BjuHSF genes were analyzed by qPCR, and the results showed that these genes were closely linked to stress response, hormones, and development process. These results are a foundation for further analysis of the regulation mechanism of HSF gene family. [ABSTRACT FROM AUTHOR]

Guaranteeing safety is always a prerequisite in the process of realizing various automotive applications. However, the automotive functional safety design has been challenged by multiple factors, such as the complexity of the new generation automotive electrical and electronic (E/E) architecture, the continuous release and update of automotive functional safety standard International Standardization Organization (ISO) 26262, the release of new AUTOSAR adaptive platform standard, and the increase in different types of costs. In this article, we summarize the recent advances of automotive functional safety design methodologies through analysis, design, optimization, and runtime phases, respectively: 1) functional safety analysis; 2) functional safety guarantee; 3) safety-aware cost optimization; and 4) safety-critical multifunctional scheduling. Then, we provide the future trends in functional safety design methodologies that will be directly oriented to autonomous vehicles and adapt to the next generation functional safety standard ISO 21448. [ABSTRACT FROM AUTHOR]

The understanding of the microstructures is critical to the design of SiC fibers with excellent thermal stability and mechanical properties. We introduce a density-sensitive electron microscopy method, high-angle annular dark field (HAADF) imaging to study the microstructure of SiC fibers processed at a variety of temperatures ranging from 1200 to 1800 °C. It is revealed that, irrespective of their processing temperatures, SiC grains form the skeleton of SiC fibers that are surrounded by a multiple of zones with low HAADF contrast (low-density zones, LDZs). LDZs mainly consist of amorphous SiOC phases and turbostratic graphite. As a result, three important interfaces that dictate grain growth, namely, the SiC/amorphous SiOC interface, the SiC/turbostratic graphite phase boundary and the SiC high angle grain boundary (HAGBs) emerge. We find that, the SiC/turbostratic graphite interfaces and the SiC HAGBs are more effective in suppressing the growth of SiC grains than the SiC/a-SiOC interfaces on a basis of extensive TEM characterization. Aberration corrected TEM reveals marked differences in the atomic structures of those three interfaces, shedding light on how the interfacial structures affect grain growth of SiC fibers. [ABSTRACT FROM AUTHOR]

Evidence of plasmids carrying the tetracycline resistance gene, tet (B), was found in the previously reported whole genome sequences of 14 United Kingdom, and 4 Brazilian, isolates of Actinobacillus pleuropneumoniae. Isolation and sequencing of selected plasmids, combined with comparative sequence analysis, indicated that the four Brazilian isolates all harbor plasmids that are nearly identical to pB1001, a plasmid previously found in Pasteurella multocida isolates from Spain. Of the United Kingdom isolates, 13/14 harbor plasmids that are (almost) identical to pTetHS016 from Haemophilus parasuis. The remaining United Kingdom isolate, MIDG3362, harbors a 12666 bp plasmid that shares extensive regions of similarity with pOV from P. multocida (which carries blaROB-1 , sul2 , and strAB genes), as well as with pTetHS016. The newly identified multi-resistance plasmid, pM3362MDR, appears to have arisen through illegitimate recombination of pTetHS016 into the stop codon of the truncated strB gene in a pOV-like plasmid. All of the tet (B)-carrying plasmids studied were capable of replicating in Escherichia coli , and predicted origins of replication were identified. A putative origin of transfer (oriT) sequence with similar secondary structure and a nic -site almost identical to that of RP4 was also identified in these plasmids, however, attempts to mobilize them from an RP4-encoding E. coli donor strain were not successful, indicating that specific conjugation machinery may be required. [ABSTRACT FROM AUTHOR]

Problems with serological cross-reactivity have led to development of a number of PCRs (individual and multiplex) for molecular typing of Actinobacillus pleuropneumoniae , the causative agent of porcine pleuropneumonia. Most of these assays were developed for detection of specific amplicons within capsule biosynthetic genes before the availability of complete sequences for the different serovars. Here we describe comparative analysis of the complete capsular loci for all 18 serovars of A. pleuropneumoniae , and development of two multiplex PCRs for comprehensive capsule typing of this important pig pathogen. [ABSTRACT FROM AUTHOR]

Summary: LiFePo4 battery is widely used in electric vehicles; however, its flatness and hysteresis of the open‐circuit voltage curve pose a big challenge to precise state of charge (SOC) estimation. The issue is discussed and addressed in this paper. First, a cell model with hysteresis is built to describe real‐time dynamic characteristics of the LiFePo4 battery. Second, the model parameters and SOC are estimated independently to avoid the possibility of cross interference between them. For model identification, an adaptive unscented Kalman filter (AUKF) algorithm is used to identify the cell parameters as they change slowly. While SOC could change rapidly, wavelet transform AUKF algorithm is put forward to estimate SOC. In the novel algorithm, the measurement noise can be estimated and updated online. Finally, the performance of the proposed method is verified under dynamic current condition. The experimental results show that estimated value based on the proposed method is more accurate than unscented Kalman filter‐based method and AUKF‐based algorithm. Meanwhile, the proposed estimator also has the merits of fast convergence and good robustness against the initialization uncertainty. [ABSTRACT FROM AUTHOR]

Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative in vivo models. The insect larvae, Galleria mellonella has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections. Here we report for the first time that G. mellonella can be used as an infection model for members of the Mycobacterium tuberculosis complex. We demonstrate a dose-response for G. mellonella survival infected with different inocula of bioluminescent Mycobacterium bovis BCG lux, and demonstrate suppression of mycobacterial luminesence over 14 days. Histopathology staining and transmission electron microscopy of infected G. mellonella phagocytic haemocytes show internalization and aggregation of M. bovis BCG lux in granuloma-like structures, and increasing accumulation of lipid bodies within M. bovis BCG lux over time, characteristic of latent tuberculosis infection. Our results demonstrate that G. mellonella can act as a surrogate host to study the pathogenesis of mycobacterial infection and shed light on host-mycobacteria interactions, including latent tuberculosis infection. [ABSTRACT FROM AUTHOR]

Aim This study was designed to determine the risk factors of lymph node metastasis in non-small cell lung cancer (NSCLC) patients with tumors ≤ 2 cm, using the Shanghai Chest Hospital Lung Cancer Database. Methods Five hundred and eighteen patients with NSCLC ≤ 2 cm were included in this study, and were classified into lymph node-positive and lymph node-negative groups. Univariate and multivariate logistic regression analyses were performed to select the independent risk factors for lymph node metastasis in NSCLC patients. Results No evidence of metastasis was found in tumors ≤ 1 cm, all positive results were in tumors sized 1-2 cm. Imaging characteristics, including solid and part-solid nodules, were strongly associated with lymph node metastasis (odds ratio [ OR] 24.959, 95% confidence interval [ CI] 5.999-103.835, P < 0.001; OR 12.559, 95% CI 3.564-44.259, P < 0.001) and subgroup logistic analysis ( OR 21.384, 95% CI 5.058-90.407, P < 0.001; OR 11.632, 95% CI 3.290-41.126, P < 0.001). Greater lymph node metastasis was observed in non-adeno non-squamous carcinoma. The presence of pleural invasion and carcinoembryonic antigen levels indicated lymph node dissection. Similar results were revealed in subgroup analysis in tumors ≤ 2 to > 1 cm. Conclusion Size had a great impact on lymph node metastasis, especially tumors of 1-2 cm. Preoperative imaging, non-adeno non-squamous carcinoma, pleural invasion, and carcinoembryonic antigen all indicated lymph node dissection. There was no discrepancy between N1 and N2 positive lymph nodes. [ABSTRACT FROM AUTHOR]

Objectives: To characterize ICEApl2, an SXT-related integrative and conjugative element (ICE) found in a clinical isolate of the porcine pathogen Actinobacillus pleuropneumoniae, and analyse the functional nature of the encoded FloR.Methods: ICEApl2 was identified in the genome of A. pleuropneumoniae MIDG3553. Functional analysis was done using conjugal transfer experiments. MIDG3553 was tested for susceptibility to the antimicrobials for which resistance genes are present in ICEApl2. Lack of florfenicol/chloramphenicol resistance conferred by the encoded FloR protein was investigated by cloning and site-directed mutagenesis experiments in Escherichia coli.Results: ICEApl2 is 92660 bp and contains 89 genes. Comparative sequence analysis indicated that ICEApl2 is a member of the SXT/R391 ICE family. Conjugation experiments showed that, although ICEApl2 is capable of excision from the chromosome, it is not self-transmissible. ICEApl2 encodes the antimicrobial resistance genes floR, strAB, sul2 and dfrA1, and MIDG3553 is resistant to streptomycin, sulfisoxazole and trimethoprim, but not florfenicol or chloramphenicol. Cloning and site-directed mutagenesis of the floR gene revealed the importance of the nature of the hydrophobic amino acid residues at positions 160 and 228 in FloR for determining resistance to florfenicol and chloramphenicol.Conclusions: Our results indicate that the nature of hydrophobic residues at positions 160 and 228 of FloR contribute dynamically to specific efflux of florfenicol and chloramphenicol, although some differences in resistance levels may depend on the bacterial host species. This is also, to our knowledge, the first description of an SXT/R391 ICE in A. pleuropneumoniae or any member of the Pasteurellaceae. [ABSTRACT FROM AUTHOR]

This paper is concerned with input-to-state stability (ISS) of coupled retarded systems on networks (CRSNs). By incorporating Razumikhin method with generalized Kirchhoff’s Matrix Tree Theorem, sufficient conditions are established to guarantee ISS of CRSNs. For the convenience of application, sufficient conditions in the form of coefficients are also obtained. What is more, a sufficient criterion on ISS of the coupled retarded oscillators system on networks is derived. Finally, as an illustration, a numerical example is given to demonstrate the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Conventional methods for sound source localization using microphone arrays are usually addressed from the signal processing viewpoint, where the sound source location is treated as a continuous parameter to be estimated over some spatial space. Actually, in some practical scenarios, such as in conference rooms and cars, sound source locations are only confined to some predefined areas. Therefore, it is more reasonable to deal with the problem from a machine learning point of view. By incorporating the prior information available about sound environments, machine learning-based methods have the potential to better deal with sound source localization in the presence of room reverberation. The key to machine learning-based sound source localization methods is how to extract effective source location features. The existing feature extraction schemes, such as the popular time-difference-of-arrival features, however, are not suitable for small-sized sensor arrays, due to the fact that sound source localization in reverberant environments become much challenging for small-sized arrays. To combat the problem, in this paper, we propose a reverberation robust feature extraction method for sound source localization based on sound intensity (SI) estimation using a small-sized microphone array. In particular, three robust feature extraction procedures have been employed in the proposed features, including normalization, phase transform weighting, and fully incorporating the redundancies in SI estimation. Simulation and real-world experimental results both show that the proposed sound source location features are more effective for small-sized arrays in reverberant environments when compared with the existing features. [ABSTRACT FROM PUBLISHER]

Objective: The prognostic significance of CD147 expression in esophageal cancer patients remains controversial. Using a meta-analysis, we investigated the prognostic and clinicopathologic characteristics of CD147 in esophageal cancer. Methods: A comprehensive literature search of the PubMed (1966–2016), EMBASE (1980–2016), Cochrane Library (1996–2016), Web of Science (1945–2016), China National Knowledge Infrastructure (1982–2016), and Wanfang databases (1988–2016) was performed to identify studies of all esophageal cancer subtypes. Correlations between CD147 expression and survival outcomes and clinicopathological features were analyzed using meta-analysis methods. Results: Seventeen studies were included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95% CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13, 8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147 expression was detected in esophageal cancer tissues than noncancerous tissues (OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95% CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI = (6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95% CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38), p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p = 0.0005), but not with tumor differentiation, age, or sex. Conclusion: Our meta-analysis suggests that CD147 is an efficient prognostic factor in esophageal cancer. High CD147 expression in patients with esophageal cancer was associated with worse survival outcomes and common clinicopathological indicators of poor prognosis. [ABSTRACT FROM AUTHOR]

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a leading cause of infectious disease mortality. Animal infection models have contributed substantially to our understanding of TB, yet their biological and non-biological limitations are a research bottleneck. There is a need for more ethically acceptable, economical, and reproducible TB infection models capable of mimicking key aspects of disease. Here we demonstrate and present a basic description of how Galleria mellonella (the greater wax moth, Gm) larvae can be used as a low cost, rapid and ethically more acceptable model for TB research. This is the first study to infect Gm with the fully virulent MTB H37Rv, the most widely used strain in research. Infection of Gm with MTB resulted in a symptomatic lethal infection, the virulence of which differed from both attenuated Mycobacterium bovis BCG and auxotrophic MTB strains. The Gm-MTB model can also be used for anti-TB drug screening, although CFU enumeration from Gm is necessary for confirmation of mycobacterial load reducing activity of the tested compound. Furthermore, comparative virulence of MTB isogenic mutants can be determined in Gm. However, comparison of mutant phenotypes in Gm against conventional models must consider the limitations of innate immunity. Our findings indicate that Gm will be a practical, valuable and advantageous additional model to be used alongside existing models to advance tuberculosis research. [ABSTRACT FROM AUTHOR]

Identification of bioactive components is an important area of research in traditional Chinese medicine (TCM) formula. The reported identification methods only consider the interaction between the components and the target proteins, which is not sufficient to explain the influence of TCM on the gene expression. Here, we propose the Initial Transcription Process-based Identification (ITPI) method for the discovery of bioactive components that influence transcription factors (TFs). In this method, genome-wide chip detection technology was used to identify differentially expressed genes (DEGs). The TFs of DEGs were derived from GeneCards. The components influencing the TFs were derived from STITCH. The bioactive components in the formula were identified by evaluating the molecular similarity between the components in formula and the components that influence the TF of DEGs. Using the formula of Tian-Zhu-San (TZS) as an example, the reliability and limitation of ITPI were examined and 16 bioactive components that influence TFs were identified. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor 2 (HER2) has been established as an important target of HER2-positive lung cancer, but somatic mutations in HER2 kinase domain are frequently observed that may cause drug resistance and sensitivity for tyrosine kinase inhibitors (TKIs). In this study, the response profile of 14 small-molecule TKIs upon 11 clinical HER2 mutations was investigated systematically using a synthetic strategy that integrated in silico analysis and in vitro assay to explore the structural basis, energetic property and biological implication underlying the intermolecular interactions of TKIs with wild-type and variant HER2. It is found that most clinical mutations are far away from HER2 active site and thus can only address modest or moderate effect on inhibitor binding. However, few single-point substations such as D769H and D769Y as well as the gatekeeper mutation T798 M were predicted to cause strong resistance for an array of TKIs by reshaping the geometric feature and physiochemical property of the active site. Furthermore, inhibitor response to the most common insertion mutation in HER2 exion 20 (HER2YVMA) was examined in detail; the response can be grouped into three classes: sensitization, resistance and insusceptibility. The Bcr-Abl inhibitor bosutinib and EGFR inhibitor gefitinib were selected as the representatives of, respectively, sensitization and insusceptibility to perform kinase assay against the GST-tagged, recombinant kinase domains of wild-type HER2WT and HER2YVMA variant. As expected, the biological activity of bosutinib was improved by ∼160-fold due to the insertion, while gefitinib exhibited low inhibitory potency on both HER2WT and HER2YVMA (IC50>100 μM). Structural analysis revealed an intensive network of hydrogen bonds and hydrophobic interactions in HER2YVMAbosutinib complex, whereas only few nonspecific van der Waals contacts were observed at the complex interface of HER2YVMA with gefitinib. [ABSTRACT FROM AUTHOR]