Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant

Background A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant. Methods We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10-14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Results Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome. Conclusions An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant

High-Endurance Long-Term Potentiation in Neuromorphic Organic Electrochemical Transistors by PEDOT:PSS Electrochemical Polymerization on the Gate Electrode

The brain exhibits extraordinary information processing capabilities thanks to neural networks that can operate in parallel with minimal energy consumption. Memory and learning require the creation of new neural networks through the long-term modification of the structure of the synapses, a phenomenon called long-term plasticity. Here, we use an organic electrochemical transistor to simulate long-term potentiation and depotentiation processes. Similarly to what happens in a synapse, the polymerization of the 3,4-ethylenedioxythiophene (EDOT) on the gate electrode modifies the structure of the device and boosts the ability of the gate potential to modify the conductivity of the channel. Operando AFM measurements were carried out to demonstrate the correlation between neuromorphic behavior and modification of the gate electrode. Long-term enhancement depends on both the number of pulses used and the gate potential, which generates long-term potentiation when a threshold of +0.7 V is overcome. Long-term depotentiation occurs by applying a +3.0 V potential and exploits the overoxidation of the deposited PEDOT:PSS. The induced states are stable for at least 2 months. The developed device shows very interesting characteristics in the field of neuromorphic electronics

Organic Electrochemical Transistors for Oxygen Sensing in Water with Battery Free, Near Field Communication Readout

Organic Electrochemical Transistors (OECTs) are investigated as electrochemical sensors due to their amplification behaviour, stability in aqueous environments and compatibility with low-cost processing on flexible plastic substrates. For widespread, sustainable application in sensor-networks, OECTs must be compatible with wireless, battery free sensor readout schemes. Although OECTs operate at low-voltages, high transistor channel currents and long response time-constants make the integration with low-power electronics difficult. To address the issue, we investigate hydrogel based OECTs for oxygen sensing in liquid and gas and their power consumption. To achieve stable, interference-free O2 sensors with miniaturized OECTs we introduce a silicone based O2 permeable membrane. Our results show how the membrane enables fast and stable sensor readout in micrometric OECTs and reduces power consumption to be compatible with a commercial battery-free NFC chip readout. We also demonstrate stable O2 sensor operation in complex mixtures with several competing redox analytes. Our result opens the opportunity for developing bio-compatible, non-invasive and wireless OECTs sensors for wound healing monitoring or environmental monitoring

Neuromorphic organic electrochemical transistor with agarose hydrogel for high-endurance plasticity

With an increasing interest in information processing and the development of biocompatible technologies, the opportunities regarding neuromorphic structures have risen. Neural networks have the ability of storing information through irreversible chemical modifications, obtaining long-term plasticity. On the other hand, short-term plasticity, which is defined by the ability of temporarily store information, relates to an induced strengthening/weakening of the synaptic weight that is dissipated after a characteristic time constant. Both the processes can be emulated by different structures as memristors, transistors or capacitors. Considering organic electrochemical transistors (OECT) as suitable components for these applications, our research group has recently developed a method that induces long-term plasticity involving direct electropolymerization of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on the gate electrode, thanks to a series of voltage pulses. [1] Following the same direction, to enhance the compatibility with hardware electronics and durability of neuromorphic OECTs, the application of an agarose-based hydrogel as a solid electrolyte was investigated. The channel, connecting the source and drain electrodes, and the gate electrode are encapsulated in a hydrogel composed by agarose, EDOT and NaPSS. The hydrogel composition can be tuned to optimize the device performances, in terms of long-term plasticity emulation and transconductance. The device is prepared by drop casting the liquid gel precursor on the OECT, covering the channel and the gate electrode. Once the crosslinked network is physically formed, with the application of voltage pulses at the gate electrode between -0.5 and 1.3 V and of a fixed drain potential (Vd) of -0.3 V, the electropolymerization starts. Short-term plasticity was also investigated, observing an increase in characteristic time constant because of the presence of a porous 3D network, opposed to the previous aqueous solution. Future perspectives involve the optimization of the composition, to increase the device transconductance, and the study of neuromorphic OECTs as control devices

Silicon Meet Graphene for a New Family of Near-Infrared Resonant Cavity Enhanced Photodetectors

In this work we have investigated resonant cavity enhanced (RCE) photodetectors (PDs), exploiting the Internal Photoemission Effect (IPE) through a Single Layer Graphene (SLG) replacing metals in the Silicon (Si) Schottky junctions, operating at 1550 nm. The SLG/Si Schottky junction is incorporated into a Fabry-Perot (F-P) optical microcavity in order to enhance both the graphene absorption and the responsivity. These devices are provided of high spectral selectivity at the resonance wavelength which can be suitably tuned by changing the length of the cavity. We get a wavelength-dependent photoresponse with external responsivity similar to 20 mA/W in a planar F-P microcavity with finesse of 5.4. In addition, in order to increase the finesse of the cavity, and consequently its responsivity, a new device where the SLG has placed in the middle of a Si-based F-P microcavity has been proposed and theoretically investigated. We have demonstrated that, in a properly designed device, a SLG optical absorption, responsivity and finesse of 100%, 0.43 A/W and 172 can be obtained, respectively. Unfortunately, the estimated bandwidth is low due to the planarity of the structure where both Ohmic (Al) and Schottky (SLG) contacts are placed in the same plane. In order to improve the PD bandwidth, we have fabricated and characterized a prototype of a vertical RCE SLG/Si Schottky PD where two contacts are both placed at the edges of a high-finesse 200nm-thick Si-based microcavity Thanks to this innovative structure an increase of the responsivity-bandwidth product is expected. The insights included in this work can open the path for developing of a new family of high-performance photodetectors that can find application in silicon photonics

Longevity in Untreated Congenital Growth Hormone Deficiency Due to a Homozygous Mutation in the GHRH Receptor Gene

Context: Reduced longevity observed in hypopituitarism has been attributed to GH deficiency (GHD). It is, however, unclear whether GHD or other confounding factors cause this early mortality