A Reliable Web Services Selection Method for Concurrent Requests

Current methods of service selection based on quality of service (QoS) usually focus on a single service request at a time, or let the users in a waiting queue wait for Web services when the same functional Web service has more than one requests, and then choose the Web service with the best QoS for the current request according to its own needs. However, there are multiple service requests for the same functional web service at a time in practice and we cannot choose the best service for users every time because of the service’s load. This paper aims at solving the Web Services selection for concurrent requests and developing a global optimal selection method for multiple similar service requesters to optimize the system resources. It proposes the improved social cognitive (ISCO) algorithm which uses genetic algorithm for observational learning and uses deviating degree to evaluate the solution. Furthermore, to enhance the efficiency of ISCO, the elite strategy is used in ISCO algorithm. We evaluate performance of the ISCO algorithm and the selection method through simulations. The simulation results demonstrate that the ISCO is valid for optimization problems with discrete data and more effective than ACO and GA

HSAF-induced antifungal effects in Candida albicans through ROS-mediated apoptosis

Heat-stable antifungal factor (HSAF) belongs to polycyclic tetramate macrolactams (PTMs), which inhibits many fungal pathogens and is effective in inhibiting Candida albicans (C. albicans). In this study, we found that HSAF induced the apoptosis of C. albicans SC5314 through inducing the production of reactive oxygen species (ROS). Nevertheless, we validated the efficacy of HSAF against candidiasis caused by C. albicans in a murine model in vivo,and HSAF significantly improved survival and reduced fungal burden compared to vehicles. A molecular dynamics (MD) simulation was also investigated, revealing the theoretical binding mode of HSAF to the β-tubulin of C. albicans. This study first found PTMs-induced fungal apoptosis through ROS accumulation in C. albicans and its potential as a novel agent for fungicides

Improvements of nuclease and nickase gene modification techniques for the treatment of genetic diseases

Advancements in genome editing make possible to exploit the functions of enzymes for efficient DNA modifications with tremendous potential to treat human genetic diseases. Several nuclease genome editing strategies including Meganucleases (MNs), Zinc Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) have been developed for the correction of genetic mutations. CRISPR-Cas has further been engineered to create nickase genome editing tools including Base editors and Prime editors with much precision and efficacy. In this review, we summarized recent improvements in nuclease and nickase genome editing approaches for the treatment of genetic diseases. We also highlighted some limitations for the translation of these approaches into clinical applications

Psychological distress among women undergoing in vitro fertilization-embryo transfer: A cross-sectional and longitudinal network analysis

BackgroundWomen undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment were generally found to experience varying degrees of psychological distress across the treatment. Existing studies focused on total scores and diagnostic thresholds to characterize the symptoms’ severity, which might hinder scientific progress in understanding and treating psychological distress.AimsWe aimed to investigate (a) how depression and anxiety symptoms are interconnected within a network, and (b) the changes of the network (symptom connections and network centralities) over time, in women undergoing in vitro fertilization-embryo transfer.MethodsA 4-wave longitudinal study was designed with 343 eligible women recruited from the Reproductive Medicine Center of a tertiary hospital in China. The network models were created to explore the relationship and changes between psychopathology symptoms both within and across anxiety and depression, with anxiety measured by the Generalized Anxiety Disorder-7 and depression measured by the Patient Health Questionnaire-9. Symptom network analysis was conducted to evaluate network and network properties, network centrality, and bridge centrality, as well as change trajectory network.ResultsFor the strength centrality, “inability to control worry” and “worrying too much” were the most central symptoms at T1; however, these symptoms decreased. The centrality of “sadness” and “guilt” tended to increase steadily and became dominant symptoms. For bridge centrality indices, several bridge symptoms were identified separately from T1 to T4: “irritability,” “concentration difficulties,” “nervousness,” and “restlessness;” “guilt” exhibited increased bridge symptoms. Furthermore, the change trajectory network indicated that “suicide ideation” became more closely related to guilt but not to worrying too much over time.ConclusionThis study provides novel insights into the changes in central features, connections, and bridge symptoms during IVF-ET treatment and identified several bridge symptoms separately at different stages, which could activate the connection between psychopathology symptoms. The results revealed that sense of guilt was associated with worsening psychopathology symptoms, indicating that future psychological interventions should target guilt-related symptoms as a priority

Identification and characterization of mcr mediated colistin resistance in extraintestinal Escherichia coli from poultry and livestock in China

Antimicrobial resistance to colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of multidrug-resistant Enterobacteriaceae infection in humans. In this study, we investigated the presence of colistin resistance genes (mcr-1, mcr-2, mcr-3) in Escherichia coli strains isolated from poultry and livestock collected between 2004 and 2012 in China. Furthermore, we studied the maintenance and transfer of the mcr-1 gene in E. coli after serial passages. Overall, 2.7% (17/624) of the E. coli isolates were positive for the mcr-1 gene while none were positive for the mcr-2 and mcr-3 genes. The prevalences of mcr-1 were similar in E. coli isolates from chickens (3.2%; 13/404), pigs (0.9%; 1/113) and ducks (6.8%; 3/44) but were absent in isolates from cattle (0/63). The mcr-1 gene was maintained in the E. coli after six passages (equivalent to 60 generations). In vitro transfer of mcr-1 was evident even without colistin selection. Our data indicate the presence of mcr-1 in extraintestinal E. coli from food-producing animals in China, and suggest that high numbers of the mcr-1-positive bacteria in poultry and livestock do not appear to be readily lost after withdrawal of colistin as a food additive

Atrial natriuretic peptide and three-dimensional echocardiography after transcatheter closure of atrial septal defect

<p>Abstract</p> <p>Background</p> <p>Atrial septal defect (ASD) accounts for 10% of all congenital heart lesions and represent the third most congenital cardiac defect seen in adults. Atrial natriuretic peptide (ANP) is an important regulator of the sodium and volume homeostasis. This study was designed to investigate the changes in plasma ANP concentrations and three-dimensional echocardiography (3DE) measurements of cardiac volume in patients with ASD during transcatheter closure of defect.</p> <p>Methods</p> <p>Plasma ANP concentrations and transthoracic 3DE measurements of right ventricular volume were performed in 46 patients with ASD before closure, and at 3 days after closure. 22 healthy subjects matched for age, sex served as control subjects.</p> <p>Results</p> <p>The 46 patients (20 men, 26 women; mean age 26.32 ± 13.28, range 6 to 63 years) were diagnosed to secundum ASD (the stretched diameters of ASD were from 9~36(25.34 ± 7.80 mm), and had been successfully placed Amplatzer septal occluder (the sizes of occluder were from 11 to 40 mm). The results showed that compared with control subjects, plasma ANP concentrations were elevated in patients with ASD. Plasma ANP concentrations positively correlated significantly with pulmonary artery pressure (PAP) (r = 0.74, <it>p </it>< 0.05) and 3DE measurements of cardiac volumes (right ventricular end-diastolic (r = 0.50, <it>p </it>< 0.05) and end-systolic volume (r = 0.50, <it>p </it>< 0.05) and negatively correlated with RVEF (r = -0.38, <it>p </it>< 0.05). Transthoracic 3DE measurements of right ventricular volume and plasma ANP concentrations decreased significantly at 3 days after closure (<it>p </it>< 0.05) compared with it before closure.</p> <p>Conclusion</p> <p>Plasma ANP concentrations were markedly elevated in patients with pulmonary arterial hypertension and right ventricular volume overload and decreased significantly after closure of ASD. This study suggested that ANP may help to identify patients with ASD complicated by pulmonary arterial hypertension and right ventricular volume overload that demanded early intervention and may become effective marker for evaluating changes in cardiac load after transcatheter ASD closure.</p

The potential mechanism of Aidi injection against neuroblastoma—an investigation based on network pharmacology analysis

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP).Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein–protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells.Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug–compound–hub target gene–pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells.Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research

Epidemiology of anti-tuberculosis drug resistance in a chinese population: current situation and challenges ahead

<p>Abstract</p> <p>Background</p> <p>Drug resistance has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. Careful monitoring of the patterns and trends of drug resistance should remain a priority.</p> <p>Methods</p> <p>Strains were collected from 1824 diagnosed sputum smear positive pulmonary TB patients in Jiangsu province of China and then tested for drug susceptibility against rifampicin, isoniazid, ethambutol and streptomycin. The prevalence and patterns of drug resistance in mycobacterium tuberculosis (MTB) isolates were investigated. Multiple logistic regression analysis was performed to identify the risk factors for multidrug resistant (MDR) bacterial infection. The strength of association was estimated by odds ratio (OR) and 95% confidence interval (95% CI).</p> <p>Results</p> <p>The drug susceptibility tests showed that 1077(59.05%) MTB strains were sensitive to all the four antibiotics and the other 747(40.95%) strains were resistant to at least one drug. The proportions of mono-drug resistance were 28.73% for isoniazid, 19.41% for rifampicin, 29.33% for streptomycin, and 13.98% for ethambutol, respectively. The prevalence of MDR-TB was 16.61%, which was significantly different between new cases (7.63%) and those with previous treatment history (33.07%). Geographical variation of drug resistance was observed, where the proportion of MDR-TB among new cases was higher in the central (9.50%) or north part (9.57%) than that in the south area (4.91%) of Jiangsu province. The age of patients was significantly associated with the risk of drug resistance (P < 0.001) and the adjusted OR (95% CI) was 1.88(1.26-2.81) for patients aged 35-44 years when compared with those 65 years or older. Patients with previous treatment history had a more than 5-fold increased risk of MDR-TB (adjusted OR: 6.14, 95% CI: 4.61-8.17), compared with those previously not having been treated.</p> <p>Conclusions</p> <p>The high prevalence of drug resistance has been a major challenge for TB control. Prevention and control of drug-resistant TB should be emphasized by the revised DOTS (direct observed therapy, short course) program through prompt case detection, routine and quality-assured drug susceptibility test for patients at high risk of resistance, programmatic treatment with both first and second-line medicines, and systematic treatment observation, with priority for high MDR-TB settings.</p

Genome and secretome analysis of Pochonia chlamydosporia provide new insight into egg-parasitic mechanisms

Pochonia chlamydosporia infects eggs and females of economically important plant-parasitic nematodes. The fungal isolates parasitizing different nematodes are genetically distinct. To understand their intraspecific genetic differentiation, parasitic mechanisms, and adaptive evolution, we assembled seven putative chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs (~44 Mb, including 7.19% of transposable elements) and compared them with the genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode. We focus on secretomes of the fungus, which play important roles in pathogenicity and fungus-host/environment interactions, and identified 1,750 secreted proteins, with a high proportion of carboxypeptidases, subtilisins, and chitinases. We analyzed the phylogenies of these genes and predicted new pathogenic molecules. By comparative transcriptome analysis, we found that secreted proteins involved in responses to nutrient stress are mainly comprised of proteases and glycoside hydrolases. Moreover, 32 secreted proteins undergoing positive selection and 71 duplicated gene pairs encoding secreted proteins are identified. Two duplicated pairs encoding secreted glycosyl hydrolases (GH30), which may be related to fungal endophytic process and lost in many insect-pathogenic fungi but exist in nematophagous fungi, are putatively acquired from bacteria by horizontal gene transfer. The results help understanding genetic origins and evolution of parasitism-related genes.This work was supported by the National Key Research and Development (R&D) Plan of China (2016YFC1201100), and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IVFCAAS)