Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation

Background: Recently, aptamers have been extensively researched for therapy and diagnostic applications. Thrombin-binding aptamer is a 15 nt deoxyribonucleic acid screened by SELEX, it can specifically bind to thrombin and inhibit blood coagulation. Since it is also endowed with excellent antitumor activity, the intrinsic anticoagulation advantage converted to a main potential side effect for its further application in antiproliferative therapy. Methods: Site-specific alkylation was conducted through nucleophilic reaction of phosphorothioated TBAs using bromide reagents. Circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) measurements were used to evaluate anticoagulation activity, and a CCK-8 assay was used to determine cell proliferation activity. Results: The CD spectra of the modified TBAs were weakened, and their affinity for thrombin was dramatically reduced, as reflected by the K-D values. On the other hand, their inhibition of A549 cells was retained. Conclusions: Incorporation of different alkyls apparently disrupted the binding of TBA to thrombin while maintaining the antitumor activity. General significance: A new modification strategy was established for the use of TBA as a more selective antitumor agent.National Natural Science Foundation of China [21332010, 21572013]; Ministry of Science and Technology of the People's Republic of China [2012CB720604]SCI(E)ARTICLE71864-1869186

A micromachined flow shear-stress sensor based on thermal transfer principles

Microhot-film shear-stress sensors have been developed by using surface micromachining techniques. The sensor consists of a suspended silicon-nitride diaphragm located on top of a vacuum-sealed cavity. A heating and heat-sensing element, made of polycrystalline silicon material, resides on top of the diaphragm. The underlying vacuum cavity greatly reduces conductive heat loss to the substrate and therefore increases the sensitivity of the sensor. Testing of the sensor has been conducted in a wind tunnel under three operation modes-constant current, constant voltage, and constant temperature. Under the constant-temperature mode, a typical shear-stress sensor exhibits a time constant of 72 μs

Expression of peroxiredoxins in the human testis, epididymis and spermatozoa and their role in preventing H2O2-induced damage to spermatozoa

Introduction. High levels of reactive oxygen species (ROS) have potential toxic effects on testicular function and sperm quality. Peroxiredoxins (PRDXs) are enzymes with a role as ROS scavenger. The aim of the study was to reveal the presence and localization of PRDXs in human testis, epididymis and spermatozoa, and the protective roles of PRDX2 and PRDX6 in sperm motility. Material and methods. The presence and localization of PRDXs in the human testis, epididymis and spermatozoa were detected by immunohistochemistry, western blot and immunofluorescence. The effect of anti-peroxidative damage to spermatozoa was examined by adding H2O2 to the recombinant protein-treated spermatozoa. Results. There were strong signals of PRDX1 in spermatogonia and round spermatids; PRDX2 in the round spermatids; PRDX4 and 5 in spermatogonia; PRDX6 in Sertoli cells. PRDXs were also found in epididymal epithelial cells where the expression of PRDX1, 4, 5, 6 in the cauda was higher than in the caput of epididymis. PRDX1-6 immunoreactivity was found throughout acrosome, post-acrosomal region, equatorial segment, neck and cytoplasmic droplet, midpiece and principal piece. The H2O2-induced reduction in sperm motility was reversed by recombinant PRDX2 or PRDX6 in a dose-dependent manner. Conclusions. PRDX1-6 in the human testis and epididymis presented cell-specificity. PRDX2 and 6 are potential antioxidant protectors for human spermatozoa

Route Design Model of Feeder Bus Service for Urban Rail Transit Stations

As an important part of urban public transportation systems, the feeder bus fills a service gap left by rail transit, effectively extending the range of rail transit’s service and solving the problem of short-distance travel and interchanges. By defining the potential demand of feeder bus services and considering its relationship with the traffic demands of corresponding staging areas, the distance between road and rail transit, and the repetition factor of road bus lines, this paper established a potential demand model of roads by opening feeder bus services and applying a logit model for passenger flow distribution. Based on a circular route model, a route starting and ending at urban rail transit stations was generated, and a genetic algorithm was then applied to solve it. The Wei-Fang community of Shanghai was selected as the test area. Per the model and algorithm, the feeder route length was conformed to a functional orientation of short-distance travel and the feeder service of a feeder bus; the route mostly covered where conventional bus lines were fewer, which is a finding that is in agreement with the actual situation; the feasibility of the model and algorithm was verified

Optimization of natural gas transport pipeline network layout: a new methodology based on dominance degree model

At the phase of 13-th five-year plan in China, natural gas will play an important role in energy revolution. With the growth of consumption, natural gas infrastructures will become hot spots of future investment and pipeline network construction will also usher in a period of rapid development. Therefore, it is of great theoretical and practical significance to study layout methods of transport pipeline network. This paper takes natural gas transport pipeline network as a research object, introduces dominance degree to analyse benefits of pipeline projects. Then, this paper proposes Dominance Degree Model (DDM) of transport pipeline projects based on Potential Model (PM) and Economic Potential Theory (EPT). According to DDM of gas transport pipeline projects, layout methods of pipeline network are put forward, which is simple and easy to obtain the overall optimal solution and ensure maximum comprehensive benefits. What’s more, construction sequences of gas transport pipeline projects can be also determined. Finally, the model is applied to a real case of natural gas transport pipeline projects in Zhejiang Province, China. The calculation results suggest that the model should deal with the transport pipeline network layout problem well, which have important implications for other potential pipeline networks not only in the Zhejiang Province but also throughout China and beyond

Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

BACKGROUND: We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function. METHODS: The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 10(5) B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured. RESULTS: The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased. CONCLUSION: LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma

Sustainable Layout Planning Methods for Taxi Service Centres: A Case Study of Jiangning District, Nanjing

Taxi fleet size has undergone a continuous rapid growth in Chinese cities, while the service facility layout planning has relatively lagged behind, causing a decrease in the service quality. Therefore, it is crucial to carry out taxi service centre layout planning. This study analyses the functional orientation and hierarchical layout mode of taxi service centres, and then proposes stepwise layout planning methods combining existing transportation facilities. Considering the demand for integrated service centres is relatively low and convenient service centres are highly flexible, their layout can be determined by qualitative analysis. The constrained layout model of functional service centres is established by optimizing the layout scheme among various alternative taxi service centres. The study finds the model is a mixed 0–1 integer programming problem, genetic algorithms are applied to solve it. Finally, the proposed methods are applied to a real case of Jiangning district, Nanjing. The results show that one integrated service centre, four functional service centres, and twenty-three convenient service centres could satisfy taxi drivers’ demand, which suggests that the proposed methods should effectively address the layout planning problem of taxi service centres, thus have important implications for other cities’ downtown areas in China and beyond

Optimization of urban mini-bus stop spacing: a case study of Shanghai (China)

U posljednjih se nekoliko godina služba mini-autobusa brzo razvija, a odgovarajući razmak između stajališta značajno poboljšava učinkovitost putovanja stanovnika. Kako bi mini-bus stajališta bila praktično locirana, u ovom se radu najprije predlaže matematički model temeljen na Voronoi dijagramima u svrhu smanjenja ukupnog vremena putovanja putnika. Za rješenje tog modela primijenjena je poboljšana tehnika Wilson-Han-Powell sekvencionalno kvadratno programiranje (SQP). Na temelju geografskih informacijskih sustava (GIS) korišten je Kartezijanski koordinatni sustav za izračunavanje pješačke udaljenosti između mini-bus stanica i početnih ili odredišta, koja se ne mogu izravno izmjeriti. Drugo, u skladu sa stvarnim stanjem, u radu se predlažu metode modifikacije za podešavanje stajališta mini-autobusa. Valjanost i korisnost metodologije ispitana je njenom primjenom na stvarnom slučaju u Šangaju (Kina). Rezultati proračuna pokazuje da se modelom dobro rješava problem određivanja razmaka između stajališta mini autobusa.In recent years, the mini-bus service has gained a rapid development, while the reasonable stop spacing is significant to improve residents’ travel efficiency. In order to locate the mini-bus stops practically, this paper firstly proposes a mathematical model based on Voronoi Diagrams to minimize residents’ total travel time. Improved Wilson-Han-Powell Sequential Quadratic Programming (SQP) technique is employed to solve the model. Based on Geographic Information Systems (GIS), the Cartesian coordinate system is used to calculate the walking distance between mini-bus stops and origins or destinations, which cannot be directly measured. Secondly, based on the actual situation, this paper proposes modification methods for adjusting mini-bus stops. The validity and usefulness of the methodology is tested through applying it to a real case in Shanghai (China). The calculation results suggest that the model deals well with the mini-bus stop spacing problem

Annealing novel nucleobase-lipids with oligonucleotides or plasmid DNA based on H-bonding or π-π interaction:Assemblies and transfections

Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo. Several kinds of nucleic acid drugs including aptamer, ssRNA, antisense oligonucleotide, and plasmid DNAs can be delivered by DXBAs, especially DNCA. In particular, G4-aptamer AS1411 encapsulated by DNCA exhibits cellular uptake enhancement, lysosome degradation reduction, cell apoptosis promotion, cell cycle phase alteration in vitro and duration prolongation in vivo, resulting in significant anti-proliferative activity. Our results demonstrate that DNCA is a promising transfection agent for G4-aptamers and exhibites bright application prospects in the permeation improvement of single-stranded oligonucleotides or plasmid DNAs

VisANT 3.5: multi-scale network visualization, analysis and inference based on the gene ontology

Despite its wide usage in biological databases and applications, the role of the gene ontology (GO) in network analysis is usually limited to functional annotation of genes or gene sets with auxiliary information on correlations ignored. Here, we report on new capabilities of VisANT—an integrative software platform for the visualization, mining, analysis and modeling of the biological networks—which extend the application of GO in network visualization, analysis and inference. The new VisANT functions can be classified into three categories. (i) Visualization: a new tree-based browser allows visualization of GO hierarchies. GO terms can be easily dropped into the network to group genes annotated under the term, thereby integrating the hierarchical ontology with the network. This facilitates multi-scale visualization and analysis. (ii) Flexible annotation schema: in addition to conventional methods for annotating network nodes with the most specific functional descriptions available, VisANT also provides functions to annotate genes at any customized level of abstraction. (iii) Finding over-represented GO terms and expression-enriched GO modules: two new algorithms have been implemented as VisANT plugins. One detects over-represented GO annotations in any given sub-network and the other finds the GO categories that are enriched in a specified phenotype or perturbed dataset. Both algorithms take account of network topology (i.e. correlations between genes based on various sources of evidence). VisANT is freely available at http://visant.bu.edu