Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization

The molecular nature of tight junction architecture and permeability is a long-standing mystery. Here, by comprehensive biochemical, biophysical, genetic, and electron microscopic analyses of claudin-16 and -19 interactions—two claudins that play key polygenic roles in fatal human renal disease, FHHNC—we found that 1) claudin-16 and -19 form a stable dimer through cis association of transmembrane domains 3 and 4; 2) mutations disrupting the claudin-16 and -19 cis interaction increase tight junction ultrastructural complexity but reduce tight junction permeability; and 3) no claudin hemichannel or heterotypic channel made of claudin-16 and -19 trans interaction can exist. These principles can be used to artificially alter tight junction permeabilities in various epithelia by manipulating selective claudin interactions. Our study also emphasizes the use of a novel recording approach based on scanning ion conductance microscopy to resolve tight junction permeabilities with submicrometer precision

Bioavailability of Orally Administered rhGM-CSF: A Single-Dose, Randomized, Open-Label, Two-Period Crossover Trial

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF). METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg) and subcutaneously injected with rhGM-CSF (3.75 microg/kg) respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI) scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of rhGM-CSF protein in clinical settings. TRIAL REGISTRATION: www.chictr.orgChiCTR-TRC-00000107

Study on Ecological Risk of Land Use in Urbanization Watershed Based on RS and GIS:A Case Study of Songhua River Watershed in Harbin Section

By using RS and GIS technology, the ecological risk index (ERI) was constructed based on the analysis of land use change and structural characteristics in urbanization watershed of Songhua River in Harbin section. Afterwards, the spatial distribution and change characteristics maps of ERI obtained by using block Kriging were analyzed to reveal the spatial and temporal evolution characteristics, change rules and formation mechanisms of ecological risk based on land use under the background of urbanization, and to minimize land use risk during urbanization process. The results showed that during the past 18 years, moderate ecological risk level was major, while proportion of high ecological risk was the lowest, and the area of higher and lower ecological risk region changed most greatly; high and higher ecological risk were focused on urban region and the transition zone from urban to suburban region, while low and lower ecological risk mainly distributed in forestland with higher vegetation coverage, water bodies, grassland, shrub land and so on. Meanwhile, the transition zone from high to low ecological risk was very obvious. In addition, ecological risk became slightly worse in some region due to the transformation from cropland to residential and urban land, while it became slightly better in other regions because of the transformation from cropland to forestland; the center of gravity in lower ecological risk region shifted most greatly, while the shift was the smallest in high ecological risk region, namely 12.31 and 0.57 km respectively

Robust and easy-repairable superhydrophobic surfaces with multiple length-scale topography constructed by thermal spray route

This paper demonstrates a thermal spray route for making superhydrophobic surfaces with mechanically robust and easy-repairable performances. Cone-like geometry with multi-scale topographical structures was firstly achieved by plasma spray deposition of titania using stainless steel mesh as shielding plate, then polytetrafluoroethylene/nano-copper composites were deposited by suspension flame spray onto the patterned titania coating. The coatings exhibit superhydrophobicity with a water contact angle of 153 and a sliding angle of 2. Unlike the surfaces with normal structure, the coatings with multiple length-scale structure retain the superhydrophobicity even after severe mechanical abrasion. The superhydrophobicity can be further easily restored after it is damaged by abrasion. The thermal spray construction of superhydrophobic surfaces proposed in this research offers the advantages of precisely tailoring the surface textures and surface chemistry cost-efficiently over as large an area as desired, showing bright prospects for versatile applications. (C) 2015 Elsevier B.V. All rights reserved

Can Adaptive Governance Promote Coupling Social-Ecological Systems? Evidence from the Vulnerable Ecological Region of Northwestern China

Adaptive governance is increasingly considered a feasible approach to address the uncertainties and complexities of social-ecological system (SES), whereas its role on SES coupling has not been sufficiently testified. Empirical evidence is provided in this paper with the case of northwestern China, a region struggling with economic backwardness and ecological vulnerability. Given the ambiguities in scholarship on the causal relationship between adaptive governance and SES coupling, we develop a theoretical framework to outline the driving mechanism of adaptive governance by focusing on its impact on ecosystem service (ES) delivery. Within the framework, ecosystem governance and social system governance are identified as pathways of adaptive governance, which are estimated on their effects on SES coupling by FGLS. The results show that (1) only the synergy of them can positively promote SES coupling rather than isolated one of them, and (2) only social system governance presents a lustrous role in restraining the effect of resource-dependence on SES coupling as opposed to ecosystem governance. The practice of northwestern China again evidences its key leader’s role in seizing the opportunity window and social innovation. The results further uncover the necessity of synthesizing the social and ecological dimensions for shaping adaptive governance and the direction of targeted reforms for catalyzing the transition to adaptive governance

Autoclaving-induced in-situ grown alumina on arc-sprayed aluminum coatings: Multiscaled topography facilitates antifouling performances

Topographical morphologies of arc sprayed aluminum coatings were tailored by post-spray steam sterilization processing at 120 degrees C. The porous needle-like nanostructures show the oxide grains of 250 nm in length and 60 nm in width grown on the surface of the coatings. The in-situ growth of the top alumina layer with the unique nano-patterns on aluminum coatings together with the flattened topography of aluminum formed during the spraying gave rise to a unique micro-/nano- hybrid structure. The structure and the presence of alumina synergistically offer the coatings excellent capability to inhibit effectively the adhesion of marine alga Chlorella and Phaeodactylum tricornutum. Potentiodynamic polarization testing further evidenced significantly enhanced corrosion resistance of the aluminum coatings after the autoclaving treatment. The results would give insights into processing thermal sprayed metallic coatings for desired topological structures for versatile properties. (C) 2016 Elsevier B.V. All rights reserved

Superhydrophobic nanocoatings prepared by a novel vacuum cold spray process

A superhydrophobic TiO2-oleic acid (OA) nanocomposite coating was fabricated by a novel vacuum cold spray (VCS) process at room temperature. The content of OA immobilized on TiO2 nanoparticles could influence the deposition effect during the VCS process, in turn controlling the wettability of nanocoatings acquired. The wettability of the nanocoatings could be adjusted by altering the content of OA in the starting nanocomposite powder. The maximum static water contact angle and the minimum sliding angle were obtained at 151.2 degrees and 1.2 degrees, respectively, with the molar ratio of OA to TiO2 at 1:10. Additionally, it was observed that the newly constructed superhydrophobic coatings display mechanical durability. This study presents a promising approach for fabricating inorganic -organic nanocomposite superhydrophobic coatings for long-term functional applications. (C) 2017 Elsevier B.V. All rights reserved