Col4a3-/- Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds

Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3^-/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3^-/- mice from three different genetic backgrounds, 129x1/SvJ, C57Bl/6 and Balb/C. male Col4a3^-/- 129x1/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl/6 and Balb/C Col4a3^-/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl/6 Col4a3^-/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.     

Sensitivity to zinc of Mediterranean woody species important for restoration

Heavy metals have increased in natural woodlands and shrublands over the last several decades as a consequence of anthropogenic activities. However, our knowledge of the effects of these elements on woody species is scarce. In this study, we examined the responses of six Mediterranean woody species to increasing levels of zinc in hydroponic culture and discussed the possible implications for the restoration of contaminated sites. The species used, Pinus pinea L., Pinus pinaster Ait., Pinus halepensis Mill., Tetraclinis articulata (Vahl) Mast., Rhamnus alaternus L. and Quercus suber L. represent a climatic gradient from dry sub-humid to semi-arid conditions. Zinc concentrations in shoots ranged from 53 μg g^− 1 in Q. suber to 382 μg g^− 1 in T. articulata and were well below the levels found in roots. Zinc inhibited root elongation and root biomass and changed the root length distribution per diameter class, but the magnitude of the effects was species-specific. Only P. halepensis and Q. suber showed toxicity symptoms in aboveground parts. Species more characteristic from xeric environments (T. articulata, R. alaternus and P. halepensis) were more sensitive to zinc than species from mesic environments (Q. suber, P. pinaster and P. pinea). According to the Zn responses and bioaccumulation, Q. suber P. pinea and P. halepensis are the best candidates for field trials to test the value of woody species to restore contaminated sites. None of the species tested seemed suitable for phytoremediation.     

Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery

Effective screening of large compound libraries in ion channel drug discovery requires the development of new electrophysiological techniques with substantially increased throughputs compared to the conventional patch clamp technique. Sophion Bioscience is aiming to meet this challenge by developing two lines of automated patch clamp products, a traditional pipette-based system called Apatchi-1, and a silicon chip-based system QPatch. The degree of automation spans from semi-automation (Apatchi-1) where a trained technician interacts with the system in a limited way, to a complete automation (QPatch 96) where the system works continuously and unattended until screening of a full compound library is completed. The performance of the systems range from medium to high throughputs.     

Advanced Characterization and Optimization of NiOx:Cu-SAM Hole-Transporting Bi-Layer for 23.4% Efficient Monolithic Cu(In,Ga)Se2-Perovskite Tandem Solar Cells

The performance of five hole-transporting layers (HTLs) is investigated in both single-junction perovskite and Cu(In, Ga)Se₂ (CIGSe)-perovskite tandem solar cells: nickel oxide (NiO_x,), copper-doped nickel oxide (NiO_x:Cu), NiO_x+SAM, NiO_x:Cu+SAM, and SAM, where SAM is the [2-(3,-6Dimethoxy-9H-carbazol-9yl)ethyl]phosphonic acid (MeO-2PACz) self-assembled monolayer. The performance of the devices is correlated to the charge-carrier dynamics at the HTL/perovskite interface and the limiting factors of these HTLs are analyzed by performing time-resolved and absolute photoluminescence ((Tr)PL), transient surface photovoltage (tr-SPV), and X-ray/UV photoemission spectroscopy (XPS/UPS) measurements on indium tin oxide (ITO)/HTL/perovskite and CIGSe/HTL/perovskite stacks. A high quasi-Fermi level splitting to open-circuit (QFLS-V_oc) deficit is detected for the NiO_x-based devices, attributed to electron trapping and poor hole extraction at the NiO_x-perovskite interface and a low carrier effective lifetime in the bulk of the perovskite. Simultaneously, doping the NiO_x with 2% Cu and passivating its surface with MeO-2PACz suppresses the electron trapping, enhances the holes extraction, reduces the non-radiative interfacial recombination, and improves the band alignment. Due to this superior interfacial charge-carrier dynamics, NiO_x:Cu+SAM is found to be the most suitable HTL for the monolithic CIGSe-perovskite tandem devices, enabling a power-conversion efficiency (PCE) of 23.4%, V_oc of 1.72V, and a fill factor (FF) of 71%, while the remaining four HTLs suffer from prominent V_oc and FF losses.     

Automated off-line respiratory event detection for the study of postoperative apnea in infants

Previously, we presented automated methods for thoraco-abdominal asynchrony estimation and movement artifact detection in respiratory inductance plethysmography (RIP) signals. This paper combines and improves these methods to give a method for the automated, off-line detection of pause, movement artifact, and asynchrony. Simulation studies demonstrated that the new combined method is accurate and robust in the presence of noise. The new procedure was successfully applied to cardiorespiratory signals acquired postoperatively from infants in the recovery room. A comparison of the events detected with the automated method to those visually scored by an expert clinician demonstrated a higher agreement (κ = 0.52) than that amongst several human scorers (κ = 0.31) in a clinical study . The method provides the following advantages: first, it is fully automated; second, it is more efficient than visual scoring; third, the analysis is repeatable and standardized; fourth, it provides greater agreement with an expert scorer compared to the agreement between trained scorers; fifth, it is amenable to online detection; and lastly, it is applicable to uncalibrated RIP signals. Examples of applications include respiratory monitoring of postsurgical patients and sleep studies.     

Optimizing the Optoelectronic Properties of Face-On Oriented Poly(3,4-Ethylenedioxythiophene) via Water-Assisted Oxidative Chemical Vapor Deposition

Engineering the texture and nanostructure to improve the electrical conductivity of semicrystalline conjugated polymers must address the rate-limiting step for charge carrier transport. In highly face-on orientation, the charge transport between chains within a crystallite becomes rate-limiting, which is highly sensitive to the π–π stacking distance and interchain charge transfer integral. Here, face-on oriented semicrystalline poly(3,4-ethylenedioxythiophene) (PEDOT) thin films are grown via water-assisted (W-A) oxidative chemical vapor deposition (oCVD). Combining W-A with the volatile oxidant, antimony pentachloride, yields an optimized electrical conductivity of 7520  ±  240 S cm⁻¹, a record for PEDOT thin films. Systematic control of π–π stacking distance from 3.50 Å down to 3.43 Å yields an electrical conductivity enhancement of ≈ 1140%. The highest electrical conductivity also corresponds to minimum in Urbach energy of 205 meV, indicating superior morphological order. The figure of merit for transparent conductors, σ_dc/σ_op, reaches a maximum value of 94, which is 1.9 × and 6.7 × higher than oCVD PEDOT grown without W-A and utilizing vanadium oxytrichloride and iron chloride oxidizing agents, respectively. The W-A oCVD is single-step all-dry process and provides conformal coverage, allowing direct growth on mechanical flexible, rough, and structured surfaces without the need for complex and costly transfer steps.     

Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends

Vertical arrays of nanostructures (NSs) are emerging as promising platforms for probing and manipulating live mammalian cells. The broad range of applications requires different types of interfaces, but cell settling on NS arrays is not yet fully controlled and understood. Cells are both seen to deform completely into NS arrays and to stay suspended like tiny fakirs, which have hitherto been explained with differences in NS spacing or density. Here, a better understanding of this phenomenon is provided by using a model that takes into account the extreme membrane deformation needed for a cell to settle into a NS array. It is shown that, in addition to the NS density, cell settling depends strongly on the dimensions of the single NS, and that the settling can be predicted for a given NS array geometry. The predictive power of the model is confirmed by experiments and good agreement with cases from the literature. Furthermore, the influence of cell‐related parameters is evaluated theoretically and a generic method of tuning cell settling through surface coating is demonstrated experimentally. These findings allow a more rational design of NS arrays for the numerous exciting biological applications where the mode of cell settling is crucial.     

Synthetic Crystals of Silver with Carbon: 3D Epitaxy of Carbon Nanostructures in the Silver Lattice

Only minimum amounts of carbon can be incorporated into silver, gold, and copper in a thermodynamically stable form. Here, the structure of stable silver carbon alloys is described, which are produced by thermoelectrically charging molten silver with carbon ions. Transmission electron microscopy and Raman scattering are combined to establish that large amount of carbon is accommodated in the form of epitaxial graphene‐like sheets. The carbon bonds covalently to the silver matrix as predicted from density functional theory (DFT) calculations with bond energies in the range 1.1–2.2 eV per atom or vacancy. Graphitic‐like sheets embedded in the crystal lattice of silver form 3D epitaxial structures with the host metal with a strain of ≈13% compared to equilibrium graphene. The carbon nanostructures persist upon remelting and resolidification. A DFT‐based analysis of the phonon density of states confirms the presence of intense vibration modes related to the Ag? C bonds observed in the Raman spectra of the alloy. The solid silver–high carbon alloy, termed “Ag‐covetic,” displays room temperature electrical conductivity of 5.62 × 10⁷ S m^?1 even for carbon concentrations of up to ≈6 wt% (36 at%). This process of incorporation of carbon presents a new paradigm for electrocharging assisted bulk processing.