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In the past decade, more and more attention has been paid to the fire performance of concrete-filled double-skin steel tubular (CFDST) columns. The columns in actual structures are not isolated members and are affected by the adjacent structural members. However, little research has been conducted on the behaviour of restrained CFDST columns under fire. In this paper finite element models were developed to analyse the fire performance of axially and rotationally restrained circular CFDST columns. The predicted temperature–time curves, internal axial force–time curves and fire resistance agreed well with the related test results. Based on the verified models, a parametric study was performed to investigate the effect on the internal axial force–time curves and fire resistance. The parameters included axial load level, axial restraint ratio, diameter of the outer tube, slenderness ratio, diameter-to-thickness ratios of the outer and inner steel tubes, dimension ratio of the inner tube to the outer tube, load eccentricity, yield strengths of the outer and inner tubes, compressive strength of the concrete, fire protection thickness and rotational restraint ratio. Through regression analysis, a design formula was proposed to calculate the fire resistance of restrained circular CFDST columns.

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Additional file 1: Figure S1. Diagram for pathways in the mediation analysis. Figure S2. Flowchart for population selection from the UK Biobank. Figure S3. Sex differences in the incidence of all-cause dementia mediated by individual chronic diseases. Figure S4. Sex differences in the incidence of young-onset dementia mediated by individual chronic diseases. Figure S5. Sex differences in the incidence of late-onset dementia mediated by individual chronic diseases. Figure S6. Mediators of sex differences in the incidence of dementia among individuals by excluding those who were diagnosed with dementia in the first five years of follow-up. Figure S7. Mediators of sex differences in the incidence of dementia among individuals with complete data. Table S1. Codes for international classification disease and self-reported fields for dementia. Table S2. Chronic conditions used to create the multimorbidity score for dementia. Table S3. Potential mediators tested in the analysis. Table S4. Other baseline characteristics in women and men. Table S5. Categorical variables in imputed and non-imputed data. Table S6. Continuous variables in imputed and non-imputed data. Table S7. Risk for incident dementia associated with mediators.

Additional file 1: Figure S1. Bioinformation analysis of TIM. Figure S2. The expression level of TIM in different metastatic sites. Figure S3. The protocol and detection using mouse breast cancer cell line 4T1 co-cultured with their specific CTLs or CD8+ T cells in the siNC group and siTIM group. Figure S4. The correlation between PD-L1 and TIMELESS in different breast cancer subtypes. Table S1. RNA sequences used in this study. Table S2. Stable cell line sequences. Table S3. DNA Oligo Sequences used in this study.

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Floods are one of the most dangerous disasters that affect human beings. Timely and accurate flood forecasting can effectively reduce losses to human life and property as well as improve the utilization rate of flood resources. In this study, an F-K++ real-time flood classification forecasting framework based on k-means++, principal component analysis, and backpropagation (BP) neural network was constructed using the Jingle sub-basin, a tributary of the Yellow River Basin, as the study area. The model parameters of different flood types were obtained, and a flood classification and predictions were made based on the mature M-EIES model applied in the study area. The relationship between the hydrological model parameters and hydrological characteristics of the different flood types was analyzed. The results show that the flood real-time classification framework established in this study can be used for flood classifications and predictions in real time. The parameters of the flood classification and prediction model were consistent with the characteristics of the flood events. Compared with unclassified predictions, the accuracy of the classification and prediction models significantly improved. The Nash coefficient increased by 5%–11.62%, the relative error of the average flood peak was reduced by 6.08%–12.7%, the relative error of average flood volume was reduced by 5.74%–8.07%, and the time difference of the average peak was reduced by 43%–66%. The methodology proposed in this study can identify extreme flood events and provide scientific support for flood classifications and predictions, flood control and disaster reduction in river basins, and the efficient utilization of water resources.

L-shaped concrete-filled steel hollow-section (CFSHS) columns have the potential to be widely used as corner columns, and have the advantage of creating larger usable areas in buildings. However, few experimental tests of this kind of column under diagonal cyclic loading have been reported. Tests on eight L-shaped CFSHS columns with equal legs were conducted to study their hysteretic behaviour; the test variables were: loading angle, concrete compressive strength, axial load level and presence or absence of stiffeners. The failure process and modes, stiffness degradation, ductility and energy dissipation were observed, and lateral load–displacement hysteretic curves and envelope curves were plotted. The results show that L-shaped CFSHS columns have generally good hysteretic behaviour and that the displacement ductility coefficients are in excess of 3 in most cases. Columns with a loading angle of 45° have >10% decrease in ultimate strength but a slightly higher ductility than columns with a loading angle of 0°. The ultimate strength, ductility and energy dissipation of columns all decrease with increasing axial load levels. Discontinuously welded stiffeners can improve the ultimate strength and ductility, but the amplitude is limited. Finally, a finite-element model was developed; the predicted results agree well with the test results.

Highlights • Slit dual-frequency ultrasonic was used to emulsify walnut emulsions. • Oil droplets and protein particles were decreased by ultrasonic emulsification. • The stability of walnut emulsions was improved by slit dual-frequency ultrasonic., A highly hygienic walnut emulsion beverage was prepared by using a slit dual-frequency emulsification technique. The optimal ultrasonic parameters were studied as a model system: the ultrasonic time of 50 min, the ultrasonic power density of 260 W/L, and a dual-frequency ultrasonic combination of 28/68 kHz. Walnut emulsion with an average mean volume diameter of 2.05 µm, a Zeta potential absolute value of 40 mV was obtained after ultrasonic treatment, and the emulsion stability could be maintained for more than 14 days without phase separation. At the lowest ultrasonic energy input, the vibrating emulsion could promote droplet aggregation. However, excessive energy input could result in sample overtreatment and reduced emulsion activity. The laser scanning confocal microscope (LSCM) and transmission electron microscope (TEM) confirmed that walnut emulsion processed by slit dual-frequency ultrasonic had pretty high stability. Therefore, the slit dual-frequency ultrasonic emulsification technique was found to be well suited for the preparation of complex and fine oil-in-water food emulsions.

Additional file 1: Table S1. Field codes for diseases of interest. Table S2. ICD codes for diseases of interest. Table S3. Matching analysis for diseases that were inversely associated with incident mortality. Table S4. Classification of diseases. Table S5. Death and the number of diseases. Table S6. Baseline characteristics of participants by mortality. Table S7. Disease contribution among individuals who were diagnosed with one disease only in life-course. Table S8. Risk for mortality associated with individual diseases of interest at baseline among individuals with complete data. Table S9. Prevalence of individual diseases by a number of diseases in life-course. Table S10. Number of events at baseline captured by self-reported and inpatient data.

Additional file 1: Table S1. Plasmids and E. coli stains used in this study. Table S2. Primers used in this study. Table S3. The schematic and sequences of the editing cassette used in this study. Table S4. The sequences of clone PCR products used to identity the E. coli variants. Figure S1. Stability of the chromosomal organization of E. coli0.10/4.54 and E. coli2.28/2.36. (A) Colony PCR analysis of the E. coli0.10/4.54 cells after culturing for more than 100 generations using the primer pairs f1/r1, f2/r2, f1/r2 and f2/r1. (B) Colony PCR analysis of E. coli2.28/2.36 after culturing for more than 100 generations using the primer pairs f3/r3, f4/r4, f3/r4 and f4/r3. Figure S2. Stability of the chromosomal organization of E. coli2.28/2.36 (mix with E. coliMut). A total of 11 rounds of inoculation were conducted, corresponding to approximately 100 generations. The culture of the first (0 generation), third (about 30 generations), fifth (about 50 generations), seventh (about 70 generations), ninth (about 90 generations) and last (about 100 generations) round of E. coli2.28/2.36 (mix with E. coliMut) was spread on LB agar plates, 24 single colonies of each strain were selected and four pairs of primers f5/r5, f6/r6, f5/f6 and r5/r6 were used to investigate the speed of transition of genomic instability with the passage of generations.

Additional file 2: Figure S1. Proportional hazards assumption test for cardiometabolic disorders and incident mortality. Figure S2. Proportional hazards assumption test for cardiometabolic disorders and incident mortality. Figure S3. Proportional hazards assumption test for cancers and incident mortality. Figure S4. Proportional hazards assumption test for musculoskeletal disorders, digestive disorders and incident mortality. Figure S5. Proportional hazards assumption test for other diseases and incident mortality.

Additional file 1: Table S1. Baseline characteristics of study participants stratified by discovery or replication dataset. Table S2. β coefficient of adjusted HR (95% CI) and P values of Incident Dementia for All 249 Metabolites in Cox Proportional Hazards Model. Table S3. Coefficients of selected 24 metabolites in elastic net regularized logistic regression model after 10-fold cross validation, their coefficients in e-net regression model in training dataset, and their VIFs in testing dataset.

Additional file 2: Supplemental Tables 2-6.

Additional file 3: Figure S6. Risk for mortality associated with individual diseases of interest in life-course. Figure S7. Disease trajectory in life-course among individuals who were diagnosed with two diseases before dying from any reasons. Figure S8. Disease trajectory in life-course among individuals who were diagnosed with three diseases before dying from any reasons. Figure S9. Disease trajectory in life-course among individuals who were diagnosed with four diseases before dying from any reasons. Figure S10. Disease trajectory in life-course among individuals who were diagnosed with five diseases before dying from any reasons. Figure S11. Disease trajectory in life-course among individuals who were diagnosed with six or more diseases before dying from any reasons.

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Additional file 4: Figure S12. Disease trajectory in the whole life-course among individuals who were diagnosed with two diseases before dying from cancer. Figure S13. Disease trajectory in the whole life-course among individuals who were diagnosed with three diseases before dying from cancer. Figure S14. Disease trajectory in the whole life-course among individuals who were diagnosed with four diseases before dying from cancer. Figure S15. Disease trajectory in the whole life-course among individuals who were diagnosed with five diseases before dying from cancer. Figure S16. Disease trajectory in the whole life-course among individuals who were diagnosed with six or more diseases before dying from cancer. Figure S17. Disease trajectory in the whole life-course among individuals who were diagnosed with two diseases before dying from cardiovascular disease. Figure S18. Disease trajectory in the whole life-course among individuals who were diagnosed with three diseases before dying from cardiovascular disease. Figure S19. Disease trajectory in the whole life-course among individuals who were diagnosed with four diseases before dying from cardiovascular disease. Figure S20. Disease trajectory in the whole life-course among individuals who were diagnosed with five diseases before dying from cardiovascular disease. Figure S21. Disease trajectory in the whole life-course among individuals who were diagnosed with six or more diseases before dying from cardiovascular disease.

Additional file : Text S1 Construction of plasmids for the chromosomal integration of heterologous genes. Text S2 The amino acid sequences of PCcrtZ. Text S3 The amino acid sequences of PacrtZ. Table S1. Primers used in this study. Table S2. Plasmids used in this study. Table S3. Caretenoids production by strains producing Zeaxanthin in shake flasks. Fig. S1. Flowchart illustrating the construction of the main strains used in this study Fig. S2. Carotenoids production of antxanthin producing strains. Fig. S3. Fed-batch fermentation results for canthaxanthin production by strains Can004 Fig. S4. Fed-batch fermentation results for astaxanthin production by strains Ast019.

Additional file 2: Supplemental Tables 2-6.

Objective To understand the current prevalence of cervical and breast cancers and their influencing factors in women aged 30-64 years in Xiangyang city. Methods A questionnaire survey was conducted to collect information of demographic characteristics, past medical history, family tumor history, menstrual and reproductive history and the prevalence of common gynecological diseases among married women aged 30-64 years in Xiangyang. Cervical cancer screening was performed primarily by high-risk HPV typing detection, followed by Thinprep cytologic test, colposcopy and pathological examination. Breast cancer screening was performed through visual inspection, palpation and color Doppler ultrasonography, followed by X-ray mammography and pathological examination. Results A total of 318067 women participated in the screening in 2017, among which 91143(28.66%) cases had non-HPV genital tract infection and 91143(28.66%) cases had benign uterine disease; 826(259.69/105) cases had cervical precancerous lesions, including 385 cases of CINⅡ, 425 cases of CINⅢ and 16 cases of adenocarcinoma in situ; 79(24.84/105) cases were cervical cancer, including 18 cases of microinvasive carcinoma and 61 cases of invasive cancer; 44097(13.86%) cases had benign breast disease and 80(25.27/105) cases were breast cancer. Multivariate regression analysis indicated that age, family history of cervical cancer, multiple pregnancies, delayed menopause and reproductive tract infection may be risk factors for cervical cancer, while age, high level of education and family history may be risk factors for breast cancer. Conclusion The incidence of cervical and breast cancers in Xiangyang city is at a moderate level. Regular screening and active control of high-risk factors are of great significance to the prevention and treatment of cervical and breast cancers.

Objective: We develop a computer-aided diagnosis (CAD) system using deep learning approaches for lesion detection and classification on whole-slide images (WSIs) with breast cancer. The deep features being distinguishing in classification from the convolutional neural networks (CNN) are demonstrated in this study to provide comprehensive interpretability for the proposed CAD system using pathological knowledge. Methods: In the experiment, a total of 186 slides of WSIs were collected and classified into three categories: Non-Carcinoma, Ductal Carcinoma in Situ (DCIS), and Invasive Ductal Carcinoma (IDC). Instead of conducting pixel-wise classification into three classes directly, we designed a hierarchical framework with the multi-view scheme that performs lesion detection for region proposal at higher magnification first and then conducts lesion classification at lower magnification for each detected lesion. Results: The slide-level accuracy rate for three-category classification reaches 90.8% (99/109) through 5-fold cross-validation and achieves 94.8% (73/77) on the testing set. The experimental results show that the morphological characteristics and co-occurrence properties learned by the deep learning models for lesion classification are accordant with the clinical rules in diagnosis. Conclusion: The pathological interpretability of the deep features not only enhances the reliability of the proposed CAD system to gain acceptance from medical specialists, but also facilitates the development of deep learning frameworks for various tasks in pathology. Significance: This paper presents a CAD system for pathological image analysis, which fills the clinical requirements and can be accepted by medical specialists with providing its interpretability from the pathological perspective.

Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and play crucial regulatory roles in human cancer biology. The purpose of the present study was to explore the expression pattern and biological role of circular RNA PVT1 (circPVT1) in non-small cell lung cancer (NSCLC). We firstly found that circPVT1 was overexpressed in clinical NSCLC tissues and cell lines. NSCLC patients with high expression of circPVT1 exhibited aggressive clinicopathological characteristics and poor prognosis. In vitro assays of the NSCLC cell lines (H1299 and A549 cells) demonstrated that knockdown of circPVT1 inhibited NSCLC cell proliferation and induced NSCLC cell apoptosis. We further found that circPVT1 served as a competing endogenous RNA of miR-497 and indirectly regulated Bcl-2 expression in NSCLC cells. Finally, inhibition of miR-497 abrogated the effects of circPVT1 knockdown in NSCLC cells. Taken together, the results from our study indicated circPVT1 acts as an oncogene in NSCLC, and may serve as a promising therapeutic target for NSCLC patients.

Additional file 8: Table S1. The sequences of primers and oligonucleotides used in this study.

Additional file 1: Primer and chimeric promoter sequences.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Early diagnosis and better therapy response have been believed to be associated with better prognosis. CRC biomarkers are considered as precise indicators for the early diagnosis and better therapy response. It is, therefore, of importance to find out, analyze and evaluate the CRC biomarkers to further provide the more precis evidence for predicting novel potential biomarkers and eventually to improve early diagnosis, personalized therapy and prognosis for CRC. In this study, we started with creating and establishing a CRC biomarker database. (CBD: http://sysbio.suda.edu.cn/CBD/index.html) In the CBD database, there were 870 reported CRC biomarkers collected from the published articles in PubMed. In this version of the CBD, CRC biomarker data was carefully collected, sorted, displayed, and analyzed. The major applications of the CBD are to provide 1) the records of CRC biomarkers (DNA, RNA, protein and others) concerning diagnosis, treatment and prognosis; 2) the basic and clinical research information concerning the CRC biomarkers; 3) the primary results for bioinformatics and biostatics analysis of the CRC biomarkers; 4) downloading/uploading the biomedicine information for CRC biomarkers. Based on our CBD and other public databases, we further analyzed the presented CRC biomarkers (DNAs, RNAs, proteins) and predicted novel potential multiple biomarkers (the combination of single biomarkers) with biological networks and pathways analysis for diagnosis, therapy response and prognosis in CRC. We found several hub biomarkers and key pathways for the diagnosis, treatment and prognosis in CRC. Receiver operating characteristic (ROC) test and survival analysis by microarray data revealed that multiple biomarkers could be better biomarkers than the single biomarkers for the diagnosis and prognosis of CRC. There are 62 diagnosis biomarkers for colon cancer in our CBD. In the previous studies, we found these present biomarkers were not enough to improve significantly the diagnosis of colon cancer. In order to find out novel biomarkers for the colon cancer diagnosis, we have performed /machine learning (ML) techniques such as support vector machine (SVM) and regression tree to predict candidate to discover diagnostic biomarkers for colon cancer. Based on the protein-protein interaction (PPI) network topology features of the identified biomarkers, we found 12 protein biomarkers which were considered as the candidate colon cancer diagnosis biomarkers. Among these protein biomarkers Chromogranin-A (CHGA) was the most powerful biomarker, which showed good performance in bioinformatics test and Immunohistochemistry(IHC). We are now expanding this study to CRC. Expression of CHGA protein in colon cancer was further verified with a novel logistic regressionbased meta-analysis, and convinced as a valuable diagnostic biomarker as compared with the typical diagnostic biomarkers, such as TP53, KRAS and MKI67. microRNAs (miRNAs/miRs) have been considered as potential biomarkers. A novel miRNA-mRNA interaction network-based model was used to predict miRNA biomarkers for CRC and found that miRNA-186-5p, miRNA-10b-5p and miRNA-30e-5p might be the novel biomarkers for CRC diagnosis. In conclusion, we have created a useful CBD database for CRC biomarkers and provided detailed information for how to use the CBD in CRC biomarker investigations. Our studies have been focusing on the biomarkers in diagnosis, therapy and prognosis. Based on our CBD and other powerful cancer associated databases, ML has been used to analyze the characteristics of the CRC biomarkers and predict novel potential CRC biomarkers. The predicted potential biomarkers were further confirmed at biomedical laboratory.

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P= 0.042) and non-RT patients (P= 0.003) and was associated with mucinous histological type (P= 0.004), COX-2 (P= 0.042), and p73 expression (P= 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P= 0.033) and with WRAP53 expression (P= 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P= 0.015), AEG-1 (astrocyte elevated gene-1) (P= 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P= 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA-gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P= 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival,P= 0.001; disease-free survival,P= 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer. Funding Agencies|Swedish Cancer Foundation; Swedish Research CouncilSwedish Research Council; Health Research Council in the South-East of Sweden [1921-B91-08XBC]

Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis. Funding Agencies|Swedish Cancer Foundation [CAN 2016/341]; Svenska Forskningsradet FormasSwedish Research Council Formas [2016-01098]

Purpose This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). Method We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. Result A total of 43 randomized clinical trials were included in our NMA. With regard to efficacy outcomes, including 6 min walking distance (6MWD), functional class amelioration (FCA), death, clinical worsening (CW), pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), cardiac index (CI), and mean right atrial pressure (mRAP), endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitor (PDE-5Is), ERA combined with PDE-5Is (EAP), and prostacyclin analogs (PGI) combined with ERA (PAE) performed better than others. Meanwhile PAP and PGE demonstrated better than others in tolerability. Overall, EAP and PAE showed good efficacy and were well-tolerated among all therapies. Conclusion Overall, we recommend EAP as the optimal choice for patients with PAH in clinical practice and PAE as suboptimal in view of their desirable performance in efficacy. Most of the combination therapies performed better than monotherapies.

Aiming at the high embankment section of heavy-load Railway, a finite element model of dynamic response of subgrade structure under train load is established, and ZL-TNTLM program is used to apply load excitation. The results show that the dynamic stress on the top of the roadbed is a single peak curve under heavy train load, and the peak value of the vertical acceleration vibration changes obviously under heavy train load, and presents a periodic change With the increase of the train speed, the dynamic pressure stress of the track bed and the foundation bed does not increase obviously with the increase of the train speed, but fluctuates and changes slowly; the dynamic stress and the vertical acceleration in the roadbed attenuate non-linearly along the depth direction The attenuation of acceleration is greater than dynamic stress along the direction of subgrade depth. The results are of theoretical and engineering significance for revealing the dynamic stress and vertical acceleration mechanism of heavy-haul railway subgrade under the change of high-speed train speed.

The cleavage of amyloid beta induced by copper(ii) in the presence of anti-oxidants is discussed., The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer’s disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(ii) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology.

The computer-aided detection (CADe) systems are developed to assist pathologists in slide assessment, increasing diagnosis efficiency and reducing missing inspections. Many studies have shown such a CADe system with deep learning approaches outperforms the one using conventional methods that rely on hand-crafted features based on field-knowledge. However, most developers who adopted deep learning models directly focused on the efficacy of outcomes, without providing comprehensive explanations on why their proposed frameworks can work effectively. In this study, we designed four experiments to verify the consecutive concepts, showing that the deep features learned from pathological patches are interpretable by domain knowledge of pathology and enlightening for clinical diagnosis in the task of lesion detection. The experimental results show the activation features work as morphological descriptors for specific cells or tissues, which agree with the clinical rules in classification. That is, the deep learning framework not only detects the distribution of tumor cells but also recognizes lymphocytes, collagen fibers, and some other non-cell structural tissues. Most of the characteristics learned by the deep learning models have summarized the detection rules that can be recognized by the experienced pathologists, whereas there are still some features may not be intuitive to domain experts but discriminative in classification for machines. Those features are worthy to be further studied in order to find out the reasonable correlations to pathological knowledge, from which pathological experts may draw inspirations for exploring new characteristics in diagnosis., Comment: v1

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy-hemoglobin (Hb) dependent drug (RRx-001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC-biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx-001 in hypoxic RBC. Herein, RRx-001 and Hb are introduced into RBC membrane camouflaged TiO2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx-001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.

Objectives: The goal of the present study is to investigate the status of alexithymia and social support among ICU nurses，and to investigate the correlation between the alexithymia and social support of ICU nurses. Methods: From June to November 2016，400 ICU nurses were sampled from 7 general hospitals in Changchun with convenient sampling method， there were 375 valid questionnaires. The efficiency was 93.75%. The questionnaire includes the self-designed general situation questionnaire，Toronto Alexithymia Scale (TAS-20) and Social Support Rating Scale (SSRS). Results: 1. The total score of the alexithymia of ICU nurses was 55.07± 7.85，and the mean score of alexithymia was 2.75±0.39. 2. The total score of social support of ICU nurses was 37.14± 6.75，and the mean score of social support was 2.86±0.52. 3. The total score of the alexithymia was negatively correlated with the subjective support，objective support，supportive utilization and the total score of social support(P Conclusions: 1. ICU nurses generally have a certain degree of empathy， and at a moderate level. The job title，working years，with or without children， marital status were the factors that affect the ICU nurses9 alexithymia. 2. The social support of ICU nurses was at the middle level. Gender，age， job title，working years，with or without children and marital status were the factors affecting the social support of ICU nurses. 3. The alexithymia of ICU nurses was negatively correlated with the subjective support.

Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD. Funding Agencies|Swedish Cancer Foundation; Swedish Research Council

This paper analyzes an indoor positioning system using white lighting LEDs. The performance of the positioning system is determined by the layout of LEDs, the receiver circuit, incidence angle of light, LED light source, and the photodiode. The Cramer–Rao bound as the theoretical accuracy limitation of received signal strength indicator algorithm is derived. The influences to positioning accuracy of multipath reflections and unparallel optical axis of LEDs and receivers are analyzed in certain scenarios. It is concluded that if the diffuse channel gain is measured previously in a certain environment and the modulation speed is far less than the channel cutoff frequency, the theoretical accuracy limit is not affected by multipath link. Multiple noises of system are analyzed in detail. The influence to positioning accuracy of indoor uniform illumination is also discussed. The result proves that the theoretical estimated accuracy of triangular LEDs array is higher than square LEDs array. With typical parameter values, the simulated theoretical accuracy of system is up to the level of centimeter.

Rehmannia is a commonly used Chinese herb, which improves learning and memory. However, the crucial components of the signal transduction pathway associated with this effect remain elusive. Pri-mary hippocampal neurons were cultured in vitro, insulted with high-concentration (1 × 10(-4) mol/L) cor-ticosterone, and treated with 1 × 10(-4) mol/L mannotriose. Thiazolyl blue tetrazolium bromide assay and western blot analysis showed that hippocampal neuron survival rates and protein levels of glucocorti-coid receptor, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor were all dramatically decreased after high-concentration corticosterone-induced injury. This effect was reversed by mannotriose, to a similar level as RU38486 and donepezil. Our findings indicate that mannotriose could protect hippocampal neurons from high-concentration corticosterone-induced injury. The mechanism by which this occurred was associated with levels of glucocorticoid receptor protein, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor.

Objective: clinical use atomization inhalation as adjuvant therapy, monitoring of exhaled NO content in patients with bronchial asthma airway, study of atomization inhalation effect about the existence of the NO content in the airway. Methods: select a 3 armour hospital respiratory asthma history for more than five years, no smoking, no patients with other diseases, 100 randomly selected as the research object. Experimental group in addition to the given routine therapy, randomly selected from 50 people, given budesonide suspension 2 mg and 0.48 mg salbutamol sulfate aerosol inhalation,; Physiological saline control group given conventional treatment, the use of placebo atomization inhalation, atomization inhalation once every seven hours, 2 times a day, at 0, 4, 8, respectively the NO concentration monitoring in the airway. Results: the experimental group was NO content in the airway in patients with bronchial asthma fall faster. Conclusion: use of budesonide suspension and salbutamol sulfate atomization can decrease the NO content in patients with bronchial asthma airway faster, make earlier control of the inflammation, which can be taken as reference to clinical treatment.

Objective: To investigate the effectiveness of airway clearance by utilizing different inhalation methods in moderate and severe AECOPD patients. Methods: According to the GOLD(2013) totle 92 moderate and severe AECOPD patients (range 65-73 years old, mean age 67.3+2.1,65.3% male) who were treated in our department from January 2014 to January 2015 were enrolled with a first episode of thick and tenacious sputum discharge. Patients were randomized into two groups(control group and experimental group) and each group included 46 cases. Mucosolvin as the nebulizing drug was given to both groups. Patients in control group using the ultrasonic atomizing inhalation while the experimental group using the high flow oxygen(6-8L/Min) driven atomization inhalation therapy. After 1 week of treatment, SPO2, PaCO2, clinical symptoms and pulmonary function examinations were compared before and after treatments. Results: After the treatment comparing the control group, SPO2 in the experimental group were (97.03+3.31)% higher than that of the control group (92.10+2.67)% ( p Conclusion: In the process of aiding sputum discharge for the moderate and severe AECOPD patients high flow oxygen(6-8L/Min) driven atomization inhalation was more effective than ultrasonic atomization inhalation therapy in improving the aspects of Spo2, PCO2, lung functions and clinical symptoms.

This paper reflects the outcome of several years of the IoT international cooperation between the EU and China and documents the state-of-the-art on IoT development in both regions and future cooperation avenues.

IoT deployments generate data of the real world in an automated fashion without direct user involvement. With increasing scale of these IoT deploy-ments the extraction of the right knowledge about the real world from a vast amount of IoT data and efficient decisions is a challenging endeavor. While so-lutions to deal with large amounts of IoT data are slowly emerging, potential users of IoT solutions or policy makers find it difficult to assess the actual use-fulness of investing in IoT deployments or selecting adequate deployment strat-egies for a particular business domain. Despite the recent hype generated by consultancy companies and IoT ven-dors about the IoT, there is still a lack of experience in assessing the utility and benefits of IoT deployments as many IoT deployments are still in their early stages. In order to capture such experience quicker and derive best practices for IoT deployments, systematic tools or methodologies are required in order to al-low the assessment of the goodness or usefulness of IoT deployments and a comparison between emerging IoT deployments to be performed. This paper addresses this existing gap and proposes a novel benchmarking framework for IoT deployments. The proposed framework is complementary to the emerging tools for the analysis of big data as it allows various stakeholders to develop a deeper understanding of the surrounding IoT business eco-system in a respective problem domain and the value proposition that the deployment of an IoT infrastructure may bring. It also allows a better decision making for policy makers for regulatory frameworks.

In order to rule overload and oversize transportation, regulate the produce of vehicles, mandatory standard GB 1589-2004 “Limits of dimensions, axle load and masses for road vehicles” was promulgated and implemented in China. With the implement of standard GB 1589-2004, it achieved the expected result. However, with the improvement of vehicle technology, road and the facilities, related technical regulations should more closely conform to international regulations. Besides, some factors which didn’t meet actual situations were found after the implement of this standard. A comparative analysis was discussed in this paper about the dimensions, axle load and masses of vehicle in order to make the standard more suitable for road transport’s actual needs, road facilities’ requirements at home and abroad. Finally, this paper puts forward opinions and suggestions which will be useful for the revision of the standard.

The development of an IoT deployment benchmarking framework is proposed. The framework, aimed at supporting policy decision process, expresses visions from 4 different stakeholders and proposes a comprehensive approach including 7 dimensions within a taxonomy to be used as a basis for the selection of benchmarking indicators. A consultative approach based on web survey and stakeholders interviews is proposed to evaluate robustness of the proposed benchmark.