Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

<p>Abstract</p> <p>Objective</p> <p>To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction.</p> <p>Methods</p> <p>Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls.</p> <p>Results</p> <p>The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.</p> <p>Conclusion</p> <p>There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue.</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here:</p> <p><url>http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998</url>.</p

Hydrogen isotope separation using graphene-based membranes in liquid water

Hydrogen isotope separation has been effectively achieved using gaseous H2/D2 filtered through graphene/Nafion composite membranes. Nevertheless, deuteron nearly does not exist in the form of gaseous D2 in nature but in liquid water. Thus, it is a more feasible way to separate and enrich deuterium from water. Herein we have successfully transferred monolayer graphene to a rigid and porous polymer substrate PITEM (polyimide tracked film), which could avoid the swelling problem of the Nafion substrate, as well as keep the integrity of graphene. Meanwhile, defects in large area of CVD graphene could be successfully repaired by interfacial polymerization resulting in high separation factor. Moreover, a new model was proposed for the proton transport mechanism through monolayer graphene based on the kinetic isotope effect (KIE). In this model, graphene plays the significant role in the H/D separation process by completely breaking the O-H/O-D bond, which can maximize the KIE leading to prompted H/D separation performance. This work suggests a promising application of using monolayer graphene in industry and proposes a pronounced understanding of proton transport in grapheneComment: 10 pages, 4 figures (6pages, 6figures for SI

Delivery Efficiency of miR-21i-CPP-SWCNT and Its Inhibitory Effect on Fibrosis of the Renal Mesangial Cells

MicroRNA 21 (miR-21) was proved to cause renal fibrosis and the inhibition of miR-21 would improve the poor prognosis in renal cell carcinoma diseases. The complementary oligonucleotide of mature miR-21 was considered to be an effective intracellular miR-21 inhibitor (miR-21i). The directly effective delivery of miR-21i into fibrotic cell is a facile method for treatment of renal fibrosis. Herein, the miR-21i-CPP-SWCNT delivery system, synthesized via single-walled carbon nanotube (SWCNT) and cell-penetrating peptide (CPP), was taken as a novel fibrosis-targeting therapeutic carrier. The miR-21i and CPP firstly bind together via electrostatic forces, and subsequently miR-21i-CPP binds to the surface of SWCNTs via hydrophobic forces. CPP could endow the delivery system with targeting property, while SWCNT would enhance its penetrating ability. The exogenous miR-21i released from the designed miR-21i-CPP-SWCNTs had successfully inhibited the expression of fibrosis-related proteins in renal mesangial cells (RMCs). We found that the expression of TGF-β1 proteins was more sensitive to miR-21i-CPP-SWCNT than the expression of α-SMA proteins

In vivo coherent Raman imaging of the melanomagenesis-associated pigment pheomelanin

Melanoma is the most deadly form of skin cancer with a yearly global incidence over 232,000 patients. Individuals with fair skin and red hair exhibit the highest risk for developing melanoma, with evidence suggesting the red/blond pigment known as pheomelanin may elevate melanoma risk through both UV radiation-dependent and -independent mechanisms. Although the ability to identify, characterize, and monitor pheomelanin within skin is vital for improving our understanding of the underlying biology of these lesions, no tools exist for real-time, in vivo detection of the pigment. Here we show that the distribution of pheomelanin in cells and tissues can be visually characterized non-destructively and noninvasively in vivo with coherent anti-Stokes Raman scattering (CARS) microscopy, a label-free vibrational imaging technique. We validated our CARS imaging strategy in vitro to in vivo with synthetic pheomelanin, isolated melanocytes, and the Mc1re/e, red-haired mouse model. Nests of pheomelanotic melanocytes were observed in the red-haired animals, but not in the genetically matched Mc1re/e; Tyrc/c (“albino-red-haired”) mice. Importantly, samples from human amelanotic melanomas subjected to CARS imaging exhibited strong pheomelanotic signals. This is the first time, to our knowledge, that pheomelanin has been visualized and spatially localized in melanocytes, skin, and human amelanotic melanomas

Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data

This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure:activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances. Both diindolylmethane (DIM) and resveratrol are specifically-acting dietary anti-androgens. The EARs for several anti-androgens were therefore expressed relative to the EAR of DIM, and how this ‘dietary comparator ratio’ (DCR) approach may be used to make safety decisions was assessed using an exposure-led case study for an anti-androgenic botanical ingredient. This highlights a pragmatic approach which allows novel chemical exposures to be put into context against dietary exposures to natural anti-androgenic substances. The DCR approach may have utility for other modes of action where appropriate comparators can be identified

5G-PPP Technology Board:Delivery of 5G Services Indoors - the wireless wire challenge and solutions

The 5G Public Private Partnership (5G PPP) has focused its research and innovation activities mainly on outdoor use cases and supporting the user and its applications while on the move. However, many use cases inherently apply in indoor environments whereas their requirements are not always properly reflected by the requirements eminent for outdoor applications. The best example for indoor applications can be found is the Industry 4.0 vertical, in which most described use cases are occurring in a manufacturing hall. Other environments exhibit similar characteristics such as commercial spaces in offices, shopping malls and commercial buildings. We can find further similar environments in the media &amp; entertainment sector, culture sector with museums and the transportation sector with metro tunnels. Finally in the residential space we can observe a strong trend for wireless connectivity of appliances and devices in the home. Some of these spaces are exhibiting very high requirements among others in terms of device density, high-accuracy localisation, reliability, latency, time sensitivity, coverage and service continuity. The delivery of 5G services to these spaces has to consider the specificities of the indoor environments, in which the radio propagation characteristics are different and in the case of deep indoor scenarios, external radio signals cannot penetrate building construction materials. Furthermore, these spaces are usually “polluted” by existing wireless technologies, causing a multitude of interreference issues with 5G radio technologies. Nevertheless, there exist cases in which the co-existence of 5G new radio and other radio technologies may be sensible, such as for offloading local traffic. In any case the deployment of networks indoors is advised to consider and be planned along existing infrastructure, like powerlines and available shafts for other utilities. Finally indoor environments expose administrative cross-domain issues, and in some cases so called non-public networks, foreseen by 3GPP, could be an attractive deployment model for the owner/tenant of a private space and for the mobile network operators serving the area. Technology-wise there exist a number of solutions for indoor RAN deployment, ranging from small cell architectures, optical wireless/visual light communication, and THz communication utilising reconfigurable intelligent surfaces. For service delivery the concept of multi-access edge computing is well tailored to host virtual network functions needed in the indoor environment, including but not limited to functions supporting localisation, security, load balancing, video optimisation and multi-source streaming. Measurements of key performance indicators in indoor environments indicate that with proper planning and consideration of the environment characteristics, available solutions can deliver on the expectations. Measurements have been conducted regarding throughput and reliability in the mmWave and optical wireless communication cases, electric and magnetic field measurements, round trip latency measurements, as well as high-accuracy positioning in laboratory environment. Overall, the results so far are encouraging and indicate that 5G and beyond networks must advance further in order to meet the demands of future emerging intelligent automation systems in the next 10 years. Highly advanced industrial environments present challenges for 5G specifications, spanning congestion, interference, security and safety concerns, high power consumption, restricted propagation and poor location accuracy within the radio and core backbone communication networks for the massive IoT use cases, especially inside buildings. 6G and beyond 5G deployments for industrial networks will be increasingly denser, heterogeneous and dynamic, posing stricter performance requirements on the network. The large volume of data generated by future connected devices will put a strain on networks. It is therefore fundamental to discriminate the value of information to maximize the utility for the end users with limited network resources

Multimodality microscopy and micro-Raman spectroscopy for in vivo skin characterization and diagnosis

Accurate and early diagnosis of skin diseases will improve clinical outcomes. Visual inspection alone has limited diagnostic accuracy, while biopsy followed by histopathology examination is invasive and time-consuming. The objective is to design and develop a multimodal optical instrument that provides biochemical and morphological information on human skin in vivo. Raman spectroscopy (RS) is capable of providing biochemical information of tissues. Reflectance confocal microscopy (RCM), which generates micron-level resolution images with capability of optical sectioning, can provide refractive-index-based morphological information of the skin. Multiphoton microscopy (MPM) could simultaneously provide biochemistry-based morphological information from two-photon fluorescence (TPF) and second-harmonic-generation (SHG) images. The thesis hypothesis is that a multimodality instrument combining RS, RCM, and MPM could be developed and provide complementary information in real-time for in vivo skin evaluation and aiding non-invasive diagnosis. A confocal Raman spectroscopy system was initially developed and tested in a study on in vivo mouse skin. Spectral biomarkers (899 and 1325-1330 cm-¹) were found to differentiate tumor-bearing skin from normal skin. A RCM system was then integrated with the spectroscopy system to guide spectral measurements. Noninvasive morphological and biochemical analysis was performed on ex vivo and in vivo human skin. The system was further enhanced by adding an MPM module that can image cellular structures with TPF signals from keratin, NADH, and melanin, as well as image elastic and colla ii gen fibers via TPF and SHG signals, respectively. The finalized system was utilized to noninvasively measure a cherry angioma lesion and its surrounding structures on the skin of a volunteer. Confocal Raman spectra from various regions-of-interest acquired under the guidance of MPM and RCM imaging showed different spectral patterns for blood vessels, keratinocytes, and dermal fibers. The system was also successfully used to perform imaging directed two-photon absorption based photothermolysis on ex vivo mouse skin. All the results showed positive evidence, well supporting the overall hypothesis. The developed multimodality system, capable of acquiring co-registered RCM, TPF and SHG images simultaneously at video-rate, and performing image-guided region-of-interest Raman spectral measurements of human skin in vivo, is a powerful tool for non-invasive skin evaluation and diagnosis.Medicine, Faculty ofGraduat