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Purpose:Lung metastasis is an important cause of breast cancer–related deaths, in which SDF-1/CXCR4 signaling pathway plays a critical role. Single transmembrane protein LRP6 is viewed as an oncogene via activating the Wnt/β-catenin signaling pathway. Our work aims to investigate the relationship between SDF-1/CXCR4 and LRP6 in breast cancer lung metastasis.Experimental Design:We examined the expressions and functions of SDF-1/CXCR4 and LRP6 as well as their relationship in breast cancer in vitro and in vivo.Results:LRP6 ectodomain (LRP6N) directly bound to CXCR4 and competitively prevented SDF-1 binding to CXCR4. LRP6N prevented SDF-1/CXCR4-induced metastasis to lung and prolonged survival in mice bearing breast tumors, whereas LRP6 knockdown activated SDF-1/CXCR4 signal transduction and promoted lung metastasis and tumor death. Furthermore, patients with breast cancer with high CXCR4 expression had poor prognosis, which was exacerbated by low LRP6 expression but improved by high LRP6 expression. Interestingly, a secreted LRP6N was found in the serum of mice and humans, which was downregulated by the onset of cancer metastasis in both mice bearing breast cancer as well as in patients with breast cancer.Conclusions:LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis. LRP6N also provides an interesting link between Wnt signaling and SDF-1/CXCR4 signaling, the two key pathways involved in cancer development.

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Short text classification is a research focus for natural language processing (NLP), which is widely used in news classification, sentiment analysis, mail filtering and other fields. In recent years, deep learning techniques are applied to text classification and has made some progress. Different from ordinary text classification, short text has the problem of less vocabulary and feature sparsity, which raise higher request for text semantic feature representation. To address this issue, this paper propose a feature fusion framework based on the Bidirectional Encoder Representations from Transformers (BERT). In this hybrid method, BERT is used to train word vector representation. Convolutional neural network (CNN) capture static features. As a supplement, a bi-gated recurrent neural network (BiGRU) is adopted to capture contextual features. Furthermore, an attention mechanism is introduced to assign the weight of salient words. The experimental results confirmed that the proposed model significantly outperforms the other state-of-the-art baseline methods.

Myocardial infarction (MI) is one of the leading causes of death worldwide, and due to the widespread and irreversible damage caused, new therapeutic treatments are urgently needed in order to limit the degree of ischaemic damage following MI. Aberrant activation of Wnt/β‐catenin signalling pathway often occurs during cardiovascular diseases including MI, which results in excess production of reactive oxygen species (ROS) and further promotes myocardial dysfunction. Huoxin pill (HXP) is a Traditional Chinese Medicine formula that has been widely used in the treatment of coronary heart disease and angina; however, its mechanisms remain unclear. Here, we performed mouse models of MI and examined the effects and mechanisms of HXP in protecting against MI‐induced ischaemic damage. Our study showed that administration with HXP robustly protected against MI‐induced cardiac injuries, decreased infarct size and improved cardiac function. Moreover, HXP attenuated ischaemia‐induced DNA damage occurrence in vivo and H2O2‐induced DNA damage occurrence in vitro, via potent inhibition of adverse Wnt/β‑catenin signalling activation. Our study thus elucidated the role and mechanism of HXP in protecting against MI and oxidative stress‐induced injuries and suggests new therapeutic strategies in ischaemic heart disease via inhibition of Wnt/β‐catenin signalling pathway.

Obesity rates have rapidly increased worldwide and obesity-related diseases such as hypertension and cardiovascular diseases have become leading factors for global morbidity and mortality. Currently, there are no effective treatments that can prevent or reverse obesity long-term, and hence the prevention of obesity-related adverse effects such as hypertension is critical. Qingda granule (QDG) is a condensed Traditional Chinese Medicine (TCM) formula that has been used clinically for treating hypertension, however, its effectiveness in obesity-induced hypertension and cardiac dysfunction remains explored. Mouse models of obesity via long-term feeding of high-fat high-fructose diet (HFFD) were established to examine the effect and mechanism of QDG in protecting against obesity-induced hypertension and cardiac dysfunction. C57BL/6 mice were fed with either normal diet or HFFD over a period of 16 weeks and administered with either saline or QDG for assessment of obesity-induced blood pressure and cardiac function. QDG administration demonstrated robust anti-hypertensive effects and significantly attenuated HFFD-induced elevations in blood pressures. Moreover, QDG treatment also demonstrated robust cardioprotective effects during obesity-induced hypertension by markedly improving cardiac function and preventing cardiac hypertrophy. QDG protected against obesity-induced hypertension and cardiac dysfunction was due to its ability to prevent adverse chronic activation of Akt signaling pathway during long-term feeding of HFFD. Long-term usage of QDG treatments exhibited no observable side effects and also completely prevented obesity-induced organ damage, demonstrating the feasibility and safety of prolonged use. Our findings thus elucidated the role of QDG in preventing obesity-induced hypertension and cardiac hypertrophy via inhibiting adverse activation of Akt signaling activation. Therefore, our study provides the theoretical basis for the utilization of QDG as both a safe and effective drug in the therapeutic treatment of metabolic diseases such as obesity-induced hypertension.

Background: Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Methods: Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1st, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. Results: 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Conclusions: Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. Registration PROSPERO CRD42020218818.

Context Huoxin pill (HXP) is a commonly used TCM prescription for treatment of cardiovascular diseases. However, its mechanism in protecting against myocardial infarction (MI) remains unknown. Objective We performed a network pharmacology analysis to explore the bioactive ingredients, therapeutic effects, and mechanisms of HXP in protecting against MI. Materials and methods HPLC was used to identify major bioactive compounds, and overlap with MI target genes were visualised. 10-Week old C57BL/6 mice were randomly assigned as: Sham-operated control, MI + Phosphate buffered saline (PBS), and MI + HXP (3 mg/mL and 9 mg/mL) treatment groups, received oral gavage administration once every two-days starting from 1-week prior to MI, and subsequently MI models were established for one-week before sacrifice. Results AKT1, VEGFA, TNF and RELA were identified as core target proteins among eighty-five candidate bioactive compounds identified in HXP with overlapping MI-related genes. HXP protection against MI was mainly via regulation of inflammatory pathways, notably TNF signalling pathway. Mouse models of MI and cardiac myoblasts demonstrated that HXP improved MI-induced injury via improving regulation of inflammatory response. Discussion and conclusion Stellasterol, deoxycholic acid, kaempferol, and quercetin are important active compounds contained in HXP with anti-inflammatory properties in the therapeutic treatment of MI. Due to the straightforward nature and effectiveness of taking oral HXP medications, our findings provide a theoretical basis for the clinical application of HXP in treating patients with angina or myocardial ischaemia. Future research into the combination of surgical procedures or medications that restore blood flow together with HXP as supportive medication would be worthwhile.

Accurate positioning of fruit is a key issue that has attracted much attention in the field of harvest robots. The complex environment and close proximity make the perception of dense crops in greenhouses a challenging problem. Different from various solutions proposed involving special equipment or other auxiliary information, we propose a novel positioning approach based on instance segmentation using a monocular RGB camera. To achieve high position accuracy, we first design a deep convolutional neural network (CNN) in a multi-task framework to export a binary segmentation map and an embedded feature map. To solve the problem of performance degradation in the intersection-over-union (IoU) for the binary segmentation task caused by multi-task optimisation, the encoder part of our network is redesigned on the basis of a Visual Geometry Group network with 16 convolutional layers (VGG-16). Then, mean-shift clustering is used to achieve instance segmentation. Finally, a contour-finding algorithm is presented for outlining fruit without the help of any contextual information. Based on these contours, the five fruits with the largest contour areas are selected as the targets for positioning. We verify our method on a public sweet pepper dataset and achieve competitive results. Divided by the radius of the fruit, the average position error for the first target in the harvesting order is 0.18, which shows that our method outperforms the semantic segmentation method. For the first five targets in the harvesting order, this index is less than 0.3 on average, similar to that of the semantic segmentation method with only one target output.

Vascular endothelial growth factor (VEGF) is a well‐known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed to investigate whether dual treatment with insulin‐like growth factor binding protein‐4 (IGFBP‐4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP‐4 enhanced VEGF‐induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin‐1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen‐I and collagen‐III following MI. Importantly, while the protective action of IGFBP‐4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post‐ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease.

Background: Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved. Methods: Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy. Results: CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation. Conclusion: Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.

Myocardial infarction (MI) is the most common cause of cardiac injury, resulting in widespread and irreversible damage to the heart. The incidence of MI gives rise to the excessive production of inflammatory cytokines that further promotes myocardial dysfunction. Wnt/β-catenin signaling pathway is adversely activated during MI and plays an important role in the modulation of the inflammatory response following tissue injury. Huoxin pill (HXP) is a Traditional Chinese Medicine formulation that has been long used in the treatment of cardiovascular diseases, however its mechanisms of cardioprotection remain unclear.We performed murine models of MI in order to model myocardial ischemic damage and examine the effect and underlying mechanism of HXP in protecting against myocardial ischemic injury. We further constructed conditional cardiomyocyte-specific β-catenin knockout mice and induced surgical MI in order to better understand the role of Wnt/β-catenin signaling following myocardial infarction in the adult heart.HXP administration strongly protected against cardiac ischemic injury, improved cardiac function, and markedly decreased the expression of pro-inflammatory cytokines following MI. Nuclear activation of β‑catenin resulted in significantly increased nuclear translocation and activation of NF-κB. In contrast, cardiomyocyte-specific deletion of β-catenin decreased NF-κB activation and exhibited beneficial effects following ischemic injury. Hence, HXP protected against MI-induced ischemic injury and excessive inflammatory response via inhibiting Wnt/β‑catenin signaling.Our study elucidated the role of HXP in protecting against ischemic myocardial injury via preventing MI-induced inflammatory response, which was mediated by its ability to inhibit adverse Wnt/β‑catenin signaling activation. Thus, our study provides the basis for the implementation of HXP as an effective therapeutic strategy in protecting against myocardial ischemic diseases.

Purpose:Lung metastasis is an important cause of breast cancer–related deaths, in which SDF-1/CXCR4 signaling pathway plays a critical role. Single transmembrane protein LRP6 is viewed as an oncogene via activating the Wnt/β-catenin signaling pathway. Our work aims to investigate the relationship between SDF-1/CXCR4 and LRP6 in breast cancer lung metastasis.Experimental Design:We examined the expressions and functions of SDF-1/CXCR4 and LRP6 as well as their relationship in breast cancer in vitro and in vivo.Results:LRP6 ectodomain (LRP6N) directly bound to CXCR4 and competitively prevented SDF-1 binding to CXCR4. LRP6N prevented SDF-1/CXCR4-induced metastasis to lung and prolonged survival in mice bearing breast tumors, whereas LRP6 knockdown activated SDF-1/CXCR4 signal transduction and promoted lung metastasis and tumor death. Furthermore, patients with breast cancer with high CXCR4 expression had poor prognosis, which was exacerbated by low LRP6 expression but improved by high LRP6 expression. Interestingly, a secreted LRP6N was found in the serum of mice and humans, which was downregulated by the onset of cancer metastasis in both mice bearing breast cancer as well as in patients with breast cancer.Conclusions:LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis. LRP6N also provides an interesting link between Wnt signaling and SDF-1/CXCR4 signaling, the two key pathways involved in cancer development.

Ethnopharmacological relevance Traditional Chinese Medicine (TCM) is being increasingly used worldwide due to its diverse efficacy and relatively low side effects. Babao Dan (BBD) is a well-known TCM formula that is currently used for the effective treatment of various cancers, however its underlying molecular mechanism remains unknown. Aim of the study Tumor growth and tumor recurrence are characterized by two distinct populations of cells, namely the well-differentiated cancer cells composing the majority of tumor bulk, and cancer stem cells (CSCs) involved in tumor relapse, which are both strongly associated with excessive activation of Wnt/β-catenin signaling. Our study aims to elucidate the underlying molecular mechanisms associated with the anti-tumor proliferative effects of Babao Dan (BBD). Materials and methods We used a hepatoblastoma cell line HepG2 with stem cell-like traits that harbors a constitutively active mutant of β-catenin in order to study the anti-tumor ability of BBD via targeting Wnt/β-catenin signaling. Results BBD robustly attenuated both the intrinsic and extrinsic activation of Wnt/β-catenin pathway in HepG2 hepatoblastoma cells, as well as Wnt target genes. Moreover, BBD significantly inhibited both the proliferation of well-differentiated cancer cells, as well as the stem-like property of CSCs as evidenced by EpCAM, a Wnt target gene and a novel marker of cancer cell stemness. In addition, mice administered with BBD using HepG2 cell line derived xenograft model had marked reductions in tumor size and weight, as well as significantly decreased expressions of Wnt target genes and cancer cell stemness. Conclusion Our findings elucidated the underlying molecular mechanisms associated with the robust anti-tumor effects of BBD via potent inhibition of Wnt/β-catenin signaling, and implicate its use in the clinical treatment of cancers.

Background: Poly Ether Ether Ketone (PEEK) has been considered as a potential alternative material for endosseous dental implants, for its low elastic modulus, biocompatibility, and low cost in customized device manufacture. Hydroxyapatite-incorporation is supposed to improve the poor osseointegration of PEEK. Methods: In the present study we analyzed the in vivo response of hydroxyapatite-incorporated PEEK (PEEK-HA) implants in canine tibia. PEEK-HA and PEEK implants were implanted and were examined 4 weeks and 12 weeks after implantation with radiology and histology. Commercial titanium dental implants served as controls. Results: The ratio of bone volume to tissue volume of PEEK-HA implants was higher than that of PEEK implants 4 weeks after implantation in the μ-CT analysis. The bone implant contact of PEEK and PEEK-HA implants showed no statistical difference in the histological examination, but newly-formed bone around PEEK-HA implants showed more signs of mineralization than that around PEEK implants. Conclusion: The study suggested that bone formation was improved with hydroxyapatite-incorporation in PEEK. Hydroxyapatite-incorporated PEEK implants may represent a potential material for endosseous dental implant.

Background LRP5/6 are co-receptors in Wnt/β-catenin pathway. Recently, we discovered multiple β-catenin independent functions of LRP5/6 in tumor cells and in the diseased heart. Nucleoporin 37 (NUP37) is an important component of the nuclear pore complex (NPC), whose elevated expression is associated with worsened prognosis in liver cancer. Previous studies have shown that NUP37 interacted with YAP and activated YAP/TEAD signaling in liver cancer. Our preliminary findings showed a nuclear location of LRP5. We thus tested the hypothesis that LRP5 may act as a genuine regulator of YAP/TEAD signaling via modulating NUP37 in a β-catenin-independent way. Methods We performed siRNA knockdown of LRP5, LRP6, or β-catenin in liver cancer HepG2 cells to determine the effect on tumor cell proliferation. Protein expressions and interaction between LRP5 and NUP37 were determined using immunoprecipitation and western blot analyses. Results HepG2 cell proliferation was markedly inhibited by knockdown of LRP5 but not LRP6 or β-catenin, suggesting that LRP5 has a specific, β-catenin-independent role in inhibiting HepG2 cell proliferation. Knockdown of NUP37 by siRNA inhibited the proliferation of HepG2 cells, whereas overexpression of NUP37 reversed the decrease in cell proliferation induced by LRP5 knockdown. Immunoprecipitation assays confirmed that LRP5 bound to NUP37. Furthermore, LRP5 overexpression restored NUP37 knockdown-induced downregulation of YAP/TEAD pathway. Conclusions LRP5 deletion attenuates cell proliferation via destabilization of NUP37, in a β-catenin-independent manner. LRP5 therefore acts as a genuine regulator of YAP/TEAD signaling via maintaining the integrity of the NPC, and implicates a therapeutic strategy in targeting LRP5 for inhibiting liver cancer cell proliferation.

According to the analysis of indetermination between completion rate and remuneration of photo tasks in crowd sourcing mode, this study proposes relation curves that completion rate varies with remuneration and ranking of remuneration in the unit area inferred by cubic-Hermite interpolation method based on task data in Guangzhou and Foshan. Then this study uses Simulated Annealing Algorithm to find the optimal remuneration scheme which means that the task completion rate significantly increases with the small increase in the remuneration. This study also compares the scheme obtained by Simulated Annealing Algorithm with the initial scheme and finds that the task completion rate increased by 13.65%, while the total task remuneration increased by 1.17%. The results show that this optimization scheme is beneficial and reasonable.

An artificial intelligence (AI) assisted hyperspectral microscopic imaging (HMI) method was successfully developed to differentiate five common foodborne pathogens simultaneously. HMI is extremely powerful for characterizing living cells, with every pixel of the cell region containing abundant spectral information. Three regions of interest (ROIs), including the whole-cell ROI, boundary ROI (outer membrane of cells), and center ROI (inner area of cells) were investigated to assess their classification performance. An artificial recurrent neural network named the long-short term memory (LSTM) network was proposed and optimized to directly process the spectra acquired from different ROIs. Compared to principal component analysis (PCA) based classifiers such as latent discriminant analysis (PCA-LDA, 66.0%), the k-nearest neighbors (PCA-KNN, 74.0%), and the support vector machine (PCA-SVM, 85.0%), our AI-based classifier achieved the highest accuracy of 92.9% for the center ROI dataset. Furthermore, AI-assisted HMI is capable of predicting spectra instantly, making it an efficient tool for foodborne pathogen identification.

Background: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation. However, their roles in the adult heart remain unexplored. Methods: To understand the role of LRP5/6 and β-catenin in the adult heart, we constructed conditional cardiomyocyte-specific LRP5/6 and β-catenin knockout mice and induced surgical myocardial infarction. We also directly injected recombinant proteins of insulin-like growth factor binding protein 4 and Dkk1 into the heart immediately following myocardial infarction to further examine the mechanisms through which these proteins regulate LRP5/6 and β-catenin. Results: Deletion of LRP5/6 promoted cardiac ischemic insults. Conversely, deficiency of β-catenin, a downstream target of LRP5/6, was beneficial in ischemic injury. It is interesting to note that although both insulin-like growth factor binding protein 4 and Dkk1 are secreted Wnt/β-catenin pathway inhibitors, insulin-like growth factor binding protein 4 protected the ischemic heart by inhibiting β-catenin, whereas Dkk1 enhanced the injury response mainly through inducing LRP5/6 endocytosis and degradation. Conclusions: Our findings reveal previously unidentified dual roles of LRP5/6 involved in the cardiomyocyte response to ischemic injury. These findings suggest new therapeutic strategies in ischemic heart disease by fine-tuning LRP5/6 and β-catenin signaling within the Wnt/β-catenin pathway.

Greenhouse cultivation consumes large volumes of freshwater, and excessive irrigation induces environmental problems, such as nutrient leaching and secondary salinization. Pyrochar (biochar from high-temperature pyrolysis) is an effective soil amendment, and researches have shown that pyrochar application could maintain soil nutrient and enhance carbon sequestration. In addition to pyrochar from pyrolysis, hydrochar from hydrothermic carbonization is considered as a new type of biochar and has the advantages of low energy consumption and a high productive rate. However, the effect of these two biochars on water evaporation in clayey soils under a greenhouse system has seldom been studied. The relationship between water evaporation and biochar properties is still unknown. Thus, in the present study, water evaporation under pyrochar and hydrochar application were recorded. Results showed that both pyrochar and hydrochar application could inhibit water evaporation in clayey soil under greenhouse cultivation. Pyrochar showed a better inhibition effect compared with hydrochar. Correlation analysis indicated that the water evaporation rate was significantly positively correlated with bulk density of biochar (p &lt, 0.05). Overall, application of pyrochar or hydrochar could both reduce soil bulk density and inhibit soil evaporation, and be available for greenhouse cultivation. However, the inhibition effect depends on the properties of the biochar.

This study proposes an objective methodology for identifying and computing the factors relevant to the assessment of information security risks for digital libraries that is also compliant with the ISO 27000 and the GB/T 20984 standards. By introducing a fuzzy comprehensive assessment method and an expert investigation method to the dimensions of assets and threats, this study proposes a model for computing the value of assets and the severity of threats. In the dimension of vulnerabilities, a vulnerability computation model based on the multi-channel weighted average method is proposed. By considering the digital library of a typical public library in China as the object of assessment, this study acquires assessment data by using a combination of a questionnaire survey, an on-site survey and vulnerability scanning. Research findings consisted of the following: (1) the digital library identified a total of 3111 information security risk items; (2) according to the assessment results attained using a combination of the factor identification and computational methodologies proposed here in conjunction with the multiplicative method specified in GB/T 20984, the high-risk (or higher risk) items accounted for 0.9% of all risky items, which is consistent with the status quo in information security risks faced by digital libraries. The analysis showed that the proposed methodology is more scientific than the currently prevailing direct value assignment method.

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 suppresses food intake and decreases body weight. However, the mediating site(s) of action of the anorectic effects induced by peripheral administration of GLP-1R agonists are not well known. The present study investigated the effects of bilateral lesions of the central nucleus of the amygdala (CeA) on the suppression of chow and high-sucrose food intake by exendin-4 in rats. Adult male Sprague-Dawley rats with bilateral sham or electrolytic lesions (400 μA; 25 s) of the CeA were used for this experiment. No significant difference was found in the daily chow intake and high-sucrose food intake in rats with CeA lesion compared to sham-operated rats. Bilateral lesions of the CeA significantly attenuated the suppression of high-sucrose food intake by i.p. exendin-4, but not the suppression of chow intake. These results suggest that a mediating role of the CeA on the peripheral effects of exendin-4.

A Human Activity Recognition (HAR) classification model is used to predict the class or predefined type of human activity. With the limited amount of available original features of human activity, the classification performance is usually mediocre. One solution is to enrich the information of the original data attributes. The objective of this study is to find a suitable feature transformation method for inducing an accurate classifier for HAR. A novel concept for enriching the feature information of HAR is called Shadow Feature. Two versions of Shadow Features are implemented here. They are being tested via RapidMiner to see which version is more suitable for HAR. The experiment results show that the four data pre-processing strategies could be ranked by their performance as follow: shadow feature 2 > shadow feature 1 > statistical features > original features. Algorithm-wise, ensemble algorithms are able to improve the HAR classification performance while a single decision tree is shown to be a weak classifier. Finally, it is observed that good performance can be achieved when shadow features are applied over datasets of drastic activity; in this case shadow feature 2 is better than shadow feature 1. For datasets of subtle activity shadow features do have advantages too, though slightly; in this case shadow feature 1 works better than shadow feature 2.

Laser etching process of aluminum thin film on polyimide substrate was simulated by the finite element analysis software ANSYS to study the etching results. Theoretical etching profiles of aluminum thin film with different laser parameters were obtained from the simulation, which is in good agreement with experimental results observed by SEM, it shows that a best etching result can be obtained and it corresponded to a set of reasonable parameters. By optimizing such laser etching parameters as laser power and beam scanning velocity, etc., aluminum thin film could be etched ideally without damaging the polyimide substrate. Therefore, the simulation results can be taken as a guide for determination of practical laser etching parameters in order to obtain ideal etching patterns.

Aims The aim of the study was to develop a multiplex real-time PCR method to identify Campylobacter jejuni containing mutations commonly associated with macrolide resistance. Methods and Results A multiplex fluorescence real-time PCR assay was developed based on TaqMan minor groove binder (MGB) probes. The VS1-MGB probe was designed based on the VS1 gene and was used to identify Camp. jejuni. The 23S rDNA-MGB probe was designed to distinguish macrolide resistance mutations in 23S rDNA, while 57D-MGB and 74D-MGB were designed to detect resistance mutations in ribosomal protein L4. The specificity and accuracy of our method were identical to the conventional biochemical tests, mapA PCR, minimum inhibitory concentration (MIC) determination and DNA sequencing. The linear detection limit of the method was 0·03 ng genomic DNA and three colony formation unit (CFU) per reaction. In 6 of 18 cases, the nature of Erythromycin resistance could be correctly determined from natural isolates; absence of the tested mutations was demonstrated in the remaining four resistant isolates. Conclusions A multiplex TaqMan MGB real-time PCR assay with high specificity and accuracy was developed to simultaneously identify Camp. jejuni and detect the gene mutations associated with macrolide resistance. Significance and Impact of the Study This multiplex method can potentially simplify the identification of Camp. jejuni and determine macrolide resistance due to mutations in 23S rDNA or ribosomal protein L4. This method has a potential for application in different research areas and molecular surveillance.

It is known that bacterial group II phosphopantetheinyl transferases (PPTases) usually phosphopantetheinylate acyl carrier proteins (ACPs) involved in the secondary metabolism. For example, a bacterial group II PPTase SchPPT has been known to phosphopantetheinylate only ACPs involved in secondary metabolism, such as scn ACP0-2 and scn ACP7. In this study, we found two bacterial group II PPTases, Hppt and Sppt, could phosphopantetheinylate not only scn ACP0-2 and scn ACP7, but also sch FAS ACP, an ACP involved in primary metabolism. Swapping of the N terminus and C terminus of PPTases showed that (i) both the hybrids Hppt-Sppt and Sppt-Hppt could phosphopantetheinylate sch FAS ACP but not scn ACP0-2; (ii) both the hybrids Sppt-SchPPT and SchPPT-Sppt lost abilities to phosphopantetheinylate sch FAS ACP and scn ACP0-2. Hppt and Sppt represent group II PPTases which phosphopantetheinylate both ACPs involved in primary metabolism and ACPs involved in secondary metabolism.

Daptomycin, a novel cyclic lipopeptide antibiotic against Gram-positive bacteria, is produced by Streptomyces roseosporus. Though its biosynthetic mechanism, structural shuffling and fermentation optimization have been extensively studied, little is understood about its production regulation at the transcriptional levels. Here we reported that dptR2, encoding a DeoR-type regulator located close to the daptomycin biosynthesis gene cluster in S. roseosporus SW0702, is required for daptomycin production, but not for the expression of daptomycin gene cluster, suggesting that DptR2 was not a pathway-specific regulator. Furthermore, EMSA and qRT-PCR analysis suggested that DptR2 was positively auto-regulated by binding to its own promoter. Meanwhile, the binding sites on the dptR2 promoter were determined by a DNase I footprinting assay, and the essentiality of the inverted complementary sequences in the protected region for DptR2 binding was assessed. Our results for the first time reported the regulation of daptomycin production at the transcriptional level in S. roseosporus.

Canonical Wnt/β-catenin signaling pathway plays important roles in multiple aspects of cellular responses in development and diseases. It is currently thought that Wnt receptor Frizzled (Frz) exists separately to Wnt coreceptors LRP5 and LRP6 (LRP5/6), and that Wnt-Frz-LRP5/6 triple complex formation bridged by Wnt ligand is needed for canonical pathway activation. We recently showed that Frz and LRP5/6 interact with each other in the absence of Wnt ligand binding and this interaction maintains the Frz-LRP5/6 complex in an inactive state. Here, we further show that Wnt ligand stimulation induces conformational change of the Frz-LRP6 complex and leads to hexamer formation containing the core LDLR domain-mediated LRP6 homodimer that is stabilized by two pairs of Wnt3a and Frz8, that is, Wnt3a-Frz8-LRP6-LRP6-Frz8-Wnt3a. This LDLR-mediated LRP6 dimerization is essential for robust canonical Wnt pathway activation. Our study thus suggests a previously unrecognized mode of receptor interaction in Wnt signal initiation.

The aim of this study was to reveal the molecular mechanism involved in multidrug resistance and virulence of Campylobacter jejuni isolated from broiler chickens. The virulence of six multidrug resistant C. jejuni was determined by in vitro and in vivo methods. The de novo whole genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the multidrug resistance and virulence of a selected isolate (C. jejuni 1655). The comparative genomic analyses revealed a large number of single nucleotide polymorphisms, deletions, rearrangements, and inversions in C. jejuni 1655 compared to reference C. jejuni genomes. The co-emergence of Thr-86-Ile mutation in gyrA gene, A2075G mutation in 23S rRNA gene, tetO, aphA and aadE genes and pTet plasmid in C. jejuni 1655 contributed its multidrug resistance to fluoroquinolones, macrolides, tetracycline, and aminoglycosides. The combination of multiple virulence genes may work together to confer the relative higher virulence in C. jejuni 1655. The co-existence of mobile gene elements (e.g., pTet) and CRISPR-Cas system in C. jejuni 1655 may play an important role in the gene transfer and immune defense. The present study provides basic information of phenotypic and genomic features of C. jejuni 1655, a strain recently isolated from a chicken displaying multidrug resistance and relatively high level of virulence.