Junction Architecture Research Articles

Graphene/SrTiO3 interface-based UV photodetectors with high responsivity* *Project supported by the National Key Research and Development Program of China (Grant Nos. 2017YFF0104801 and 2018YFB0406601) and the National Natural Science Foundation of China (Grant Nos. 61804012 and 11721404).

Strontium titanate (SrTiO3), which is a crucial perovskite oxide with a direct energy band gap of 3.2 eV, holds great promise for ultraviolet (UV) photodetection. However, the response performance of the conventional SrTiO3-based photodetectors is limited by the large relative dielectric constant of the material, which reduces the internal electric field for electron-hole pair separation to form a current collected by electrodes. Recently, graphene/semiconductor hybrid photodetectors by van-der-Waals heteroepitaxy method demonstrate ultrahigh sensitivity, which is benefit from the interface junction architecture and then prolonged lifetime of photoexcited carriers. Here, a graphene/SrTiO3 interface-based photodetector is demonstrated with an ultrahigh responsivity of 1.2 × 106 A/W at the wavelength of 325 nm and ∼ 2.4 × 104 A/W at 261 nm. The corresponding response time is in the order of ∼ ms. Compared with graphene/GaN interface junction-based hybrid photodetectors, ∼ 2 orders of magnitude improvement of the ultrahigh responsivity originates from a gain mechanism which correlates with the large work function difference induced long photo-carrier lifetime as well as the low background carrier density. The performance of high responsivity and fast response speed facilitates SrTiO3 material for further efforts seeking practical applications.

A topological Josephson junction platform for creating, manipulating, and braiding Majorana bound states

As part of the intense effort toward identifying platforms in which Majorana bound states can be realized and manipulated to perform qubit operations, we propose a topological Josephson junction architecture that achieves these capabilities and which can be experimentally implemented. The platform uses conventional superconducting electrodes deposited on a topological insulator film to form networks of proximity-coupled lateral Josephson junctions. Magnetic fields threading the network of junction barriers create Josephson vortices that host Majorana bound states localized in the junction where the local phase difference is an odd multiple of π, i.e. attached to the cores of the Josephson vortices. This enables us to manipulate the Majorana states by moving the Josephson vortices, achieving functionality exclusive to these systems in contrast to others, such as those composed of topological superconductor nanowires. We describe protocols for: (1) braiding localized Majorana states by exchange, (2) controlling the separation and hence the coupling of adjacent localized Majorana states to effect non-Abelian rotations via hybridization of the Majorana modes, and (3) reading out changes in the non-local parity correlations induced by such operations. These schemes utilize current pulses and local magnetic field pulses to control the location of vortices, and measurements of the Josephson current–phase relation to reveal the presence of the Majorana bound states. Finally, we present brief discussions of readout schemes and viable experimental settings for realizing the platform.

Theoretical and experimental investigations of barrier height inhomogeneities in poly-Si/4H-SiC heterojunction diodes

p-Si/4H-SiC heterojunction diodes are realized by sputter-deposition of the Si top contact and subsequent post-deposition annealing at either 900 °C or 1000 °C. The high Schottky barrier height (SBH) of this junction architecture of around 1.65 V is ideal to analyze SBH inhomogeneities present in most Schottky- and heterojunctions. Current-voltage-temperature (IVT) and capacitance-voltage-temperature (CVT) measurements are conducted in a wide temperature range from 60 K up to 460 K while applying standard techniques for SBH extraction. Strong deviations from ideal IV characteristics are present especially at lowest temperatures when assuming a homogenous SBH. Additionally, the extracted SBHs at low temperatures differ a lot between the two methods, indicating the presence of low barrier conduction paths. The presence of at least two distinct SBH inhomogeneities is found, which are labeled as ‘intrinsic’ and ‘extrinsic’. Next, the Tung model was applied to fit the measured IVT data using a discretized Gaussian distribution of patch parameters to account for spreading resistance effects. By using multiple Gaussian distributions, excellent fitting results were achieved, giving the density values of the different patches and a background barrier height from the IVT data, which are in excellent agreement with the CVT data over a wide temperature range of 400 K.

GPA Peptide-Induced Nur77 Localization at Mitochondria Inhibits Inflammation and Oxidative Stress through Activating Autophagy in the Intestine.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. Nur77, belongs to the NR4A subfamily of nuclear hormone receptors, plays a critical role in controlling the pathology of colitis. The aim of this study is to investigate the protection effect and mechanism of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate, in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and intestinal epithelial cells (IECs) stimulated by lipopolysaccharide (LPS). In vivo, GPA treatment alleviates DSS-induced weight loss, disease activity index (DAI) increase, colon length shortening, and colonic pathological damage. Production of proinflammatory cytokines, ROS, and MDA is significantly decreased by GPA treatment. In vitro, GPA significantly inhibits proinflammatory cytokine production, cytotoxicity, ROS, and MDA in IECs. Furthermore, GPA induces autophagy to suppress inflammation and oxidative stress. GPA promotes Nur77 translocation from the nucleus to mitochondria where it facilitates Nur77 interaction with TRAF6 and p62, leading to the induction of autophagy. In addition, GPA contributed to the maintenance of tight junction architecture in vivo and in vitro. Taken together, GPA, as a Nur77 modulator, could exert anti-inflammatory and antioxidant effects by inducing autophagy in IECs, suggesting that GPA may be promising for the prevention of colitis.

Integration of PbS Quantum Dot Photodiodes on Silicon for NIR Imaging

Colloidal quantum dots based on lead sulfide (PbS) are very attractive materials for the realization of novel image sensors. They offer low cost synthesis, compatibility with a variety of substrates and processing on large area. The tunable band gap enables selective light detection from the visible wavelengths up to the short-wave-infrared (SWIR). This work describes the roadmap towards the integration of quantum dot photodiodes (QDPD) on top of a Si based CMOS read-out circuit. Photodiodes using an n-p junction architecture are fabricated on Si substrates, showing a dark current of 30 nA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at -1 V reverse bias, EQE above 20% and specific detectivity above 1012 cm Hz <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> W <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> at the wavelength of 940 nm. Efficiency is improved by reducing absorption in the top contact through optical design. Furthermore, photolithographic patterning of the thin-film stack is introduced for the first time, showing the feasibility of pixel pitches down to 40 μm, opening the way towards high resolution monolithic infrared imagers and the incorporation of infrared and visible sensitive pixels side by side.

Mechanism of blood-brain barrier disruption by an Escherichia coli from lambs with severe diarrhea and meningoencephalitis

Escherichia coli (E. coli) is a common conditional pathogen that is associated with a variety of infections in humans and animals. Although there are increasing reports regarding the infection of E. coli to domestic animals and poultry, the infection of E. coli in lambs is relatively less reported, especially on meningoencephalitis. Here, we reported the isolation of an E. coli strain designated as NMGCF-19 from lambs characterized with severe diarrhea and neurological disorder, and demonstrated that NMGCF-19 as the causative agent has the ability to disrupt the blood-brain barrier (BBB) to cause the meningoencephalitis using a mouse model. Investigation on the mechanism regarding the NMGCF-19-related meningoencephalitis revealed a significant decreased expression of ZO-1 and occludin in mouse brain tissue in comparison with the control mice. Moreover, infection of NMGCF-19 increased the expression of proinflammatory cytokines TNF-α, IL-6, IL-1β and IL-18, up-regulated HMGB1 level, and activated TLR2/TLR4/MyD88 and NLRP3 inflammasome pathways. These findings indicated that NMGCF-19 likely invades the brain tissue by disrupting the tight junction (TJ) architecture and causes the meningoencephalitis via increasing inflammatory response and activating TLR2/TLR4/MyD88 and NLRP3 inflammasome pathways.

Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons

SUMMARYAdenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and fly mobility. Furthermore, Zn72D’s regulatory role in RNA editing is conserved because the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons. The broad and conserved regulation of ADAR editing by Zn72D in neurons sustains critically important editing events.

THE ROLE OF THE ARP2/3 INHIBITORY PROTEIN ARPIN IN THE REGULATION OF ENDOTHELIAL BARRIER FUNCTIONS

The endothelium forms a semi‐permeable barrier in the vasculature that separates blood from underlying tissues. During inflammation, this barrier is altered usually leading to increased permeability and leukocyte recruitment. Such alterations include endothelial actin remodeling regulated by actin‐binding proteins (ABP) and junction architecture modulation. An ABP critical for actin remodeling is the Arp2/3 complex, which induces formation of branched actin networks. The Arp2/3 complex needs to be tightly regulated which is achieved by activation via nuclear promoting factors (NPF) and inhibition via proteins that locally antagonize the activity of NPFs such as PICK1, gadkin and arpin. Arpin contains a COOH‐terminal acidic motif that binds directly to the Arp2/3 complex in competition with NPF to inhibit its activity. Arpin has been shown to localize at the lamellipodial edge, where it colocalizes with the WAVE2 complex and antagonizes WAVE2 to regulate Arp2/3 activity in this specific subcellular location. However, nothing is known about the role of arpin in endothelial barrier regulation.First, we analyzed expression of arpin in different endothelial cell types and found that it is expressed at high levels in Human vein endothelial cells (HUVEC), human dermal microvascular endothelial cells (HMEC‐1), brain‐derived Endothelial cells.3 (bEnd3) and primary murine lung endothelial cells (MLEC). To analyze arpin functions in endothelial barrier regulation, we generated arpin‐depleted HUVEC by transfecting them with lentiviruses encoding specific short hairpin RNA (shRNA) against arpin and a scrambled control sequence, and selecting stable clones using puromycin. Western blot analysis revealed arpin downregulation of more than 90%. Expression of the junctional proteins VE‐cadherin, claudin‐1, occludin, ZO‐1 and the apical adhesion molecule ICAM‐1 did not change in arpin‐depleted HUVECs. However, VE‐Cadherin staining revealed significant gaps at cell contacts and redistribution into the cytoplasm. Moreover, we consistently observed more actin filaments in arpin‐depleted HUVEC. As ROCK1 and ZIPK kinases were overexpressed in the absence of arpin, we conclude that these filaments are contractile stress fibers that destabilize junctions by generating pulling forces. In vitro filter‐based permeability assays showed that arpin‐depleted HUVEC are much more permeable compared to control cells transduced with lentivirus expressing scrambled shRNA. These data suggest that arpin regulates the endothelial barrier by two possible mechanisms: First, arpin may inhibit Arp2/3 to control junction protein internalization and vesicle trafficking; and second, arpin may inhibit Arp2/3 to control actin dynamics at junctions. Whether arpin additionally regulates Arp2/3‐independent processes is currently unknown, and will be investigated in the future. Our data reveal arpin as a new critical regulator of endothelial barrier integrity.Support or Funding InformationThis work was supported by a grant of the Mexican Council for Science and Technology (CONACyT, 284292 to MS).

Manipulations of DNA four-way junction architecture and DNA modified Fe3O4@Au nanomaterials for the detection of miRNA

miRNAs have attracted increased attention as biomarkers, which have strong associations with diseases like cancers. Herein, we have constructed DNA four-way junction architecture on the surface of electrode for ultrasensitive electrochemical detection of miRNA. Isothermal duplex-specific nuclease catalyzed reaction and nicking endonuclease catalyzed reaction are performed on the synthesized novel magnetic nanomaterials and the formed DNA junctions, respectively. Besides the enzymatic reaction cycles, TCEP mediated electrochemical amplification is integrated for improvement of the sensitivity. This method not only achieves attomolar sensitivity, high selectivity and practical utility have also been confirmed. Therefore, the proposed approach is supposed to provide a powerful tool for miRNA related biological researches and clinical applications.

Abstract A16: A GUCY2c-CD3 bispecific engages T cells to induce cytotoxicity in gastrointestinal tumors

Abstract Background: Guanylyl cyclase C (GUCY2C) is a regulator of intestinal homeostasis and is expressed in more than 90% of colorectal cancer (CRC), as well as in other gastrointestinal malignancies. Target expression in normal tissues is largely restricted to the apical side of intestinal epithelial tight junctions, which could allow for preferential uptake of GUCY2C-targeted biologics by tumors that have disrupted tight junction architecture. Here we demonstrate tumor-selective uptake and potent efficacy with a half-life extended, GUCY2C-CD3 bispecific molecule that recruits CD3-positive T cells to induce cytotoxicity of GUCY2C-expressing tumors in several CRC models in vivo. Additionally, to address immune evasion mechanisms, rational combinations of the bispecific are explored with immune checkpoint blockade agents, as well as by blocking angiogenesis, which has been reported to enhance T-cell infiltration into tumors. Methods: GUCY2C-CD3 mediated activity was evaluated in vivo in several cell line- and patient derived-xenograft models of CRC, using adoptive transfer of human T cells in established subcutaneous and orthotopic tumors. Immunohistochemistry was performed to demonstrate biodistribution of the drug and recruitment of activated T cells in GUCY2C-expressing tumors vs. normal tissues. We also performed CYTOF analyses on GUCY2C-CD3-treated tumors and tumor-infiltrating lymphocytes (TILs) to identify markers of immune evasion. Combination studies with anti PD-1/PD-L1 checkpoint blockade agents and with an anti VEGF-A antibody were performed using the adoptive transfer model. Results: GUCY2C-CD3 bispecific showed preferential biodistribution to GUCY2C-expressing xenograft tumors compared to normal tissue. The drug demonstrated potent dose-dependent efficacy in several CRC models with no signs of toxicity. Bispecific treated tumors not only showed recruitment of activated T cells to the tumor site, but also upregulated checkpoint mechanisms, such as PD-L1 on tumors and exhaustion markers on TILs. Consequently, anti PD-1/PD-L1 checkpoint blocking antibodies provided enhanced efficacy when combined with GUCY2C-CD3. Additionally, significant combination benefit was observed when GUCY2C-CD3 was combined with an anti VEGF-A blocking antibody. Conclusions: Our preclinical data demonstrate that a GUCY2C-CD3 bispecific can selectively target colorectal tumors, including those with KRAS or BRAF mutations, which are difficult to treat with currently approved therapies. This bispecific shows combination benefits with T-cell checkpoint blockade agents, as well as antiangiogenesis agents, indicating that single-agent activity with GUCY2C-CD3 can be further enhanced with mechanisms that address immune evasion. Citation Format: Divya Mathur, Adam Root, Bozena Bugaj-Gaweda, Xingzhi Tan, Wei Fang, Stephanie Bisulco, Jonathan Golas, Jessica Kearney, Eric Upeslacis, Johnny Yao, Edward Rosfjord, Chad Stevens, Lindsay King, Jatin Narula, Kerry Kelleher, Cynthia Rohde, Lioudmila Tchistiakova, Anhco Nguyen, Puja Sapra. A GUCY2c-CD3 bispecific engages T cells to induce cytotoxicity in gastrointestinal tumors [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A16.

Development of Physiologically Responsive Human iPSC-Derived Intestinal Epithelium to Study Barrier Dysfunction in IBD.

In inflammatory bowel disease (IBD), the intestinal epithelium is characterized by increased permeability both in active disease and remission states. The genetic underpinnings of this increased intestinal permeability are largely unstudied, in part due to a lack of appropriate modelling systems. Our aim is to develop an in vitro model of intestinal permeability using induced pluripotent stem cell (iPSC)-derived human intestinal organoids (HIOs) and human colonic organoids (HCOs) to study barrier dysfunction. iPSCs were generated from healthy controls, adult onset IBD, and very early onset IBD (VEO-IBD) patients and differentiated into HIOs and HCOs. EpCAM+ selected cells were seeded onto Transwell inserts and barrier integrity studies were carried out in the presence or absence of pro-inflammatory cytokines TNFα and IFNγ. Quantitative real-time PCR (qRT-PCR), transmission electron microscopy (TEM), and immunofluorescence were used to determine altered tight and adherens junction protein expression or localization. Differentiation to HCO indicated an increased gene expression of CDX2, CD147, and CA2, and increased basal transepithelial electrical resistance compared to HIO. Permeability studies were carried out in HIO- and HCO-derived epithelium, and permeability of FD4 was significantly increased when exposed to TNFα and IFNγ. TEM and immunofluorescence imaging indicated a mislocalization of E-cadherin and ZO-1 in TNFα and IFNγ challenged organoids with a corresponding decrease in mRNA expression. Comparisons between HIO- and HCO-epithelium show a difference in gene expression, electrophysiology, and morphology: both are responsive to TNFα and IFNγ stimulation resulting in enhanced permeability, and changes in tight and adherens junction architecture. This data indicate that iPSC-derived HIOs and HCOs constitute an appropriate physiologically responsive model to study barrier dysfunction and the role of the epithelium in IBD and VEO-IBD.

Quantitatively relating brain endothelial cell\u2013cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

BackgroundThe endothelial cell–cell junctions of the blood–brain barrier (BBB) play a pivotal role in the barrier’s function. Altered cell–cell junctions can lead to barrier dysfunction and have been implicated in several diseases. Despite this, the driving forces regulating junctional protein presentation remain relatively understudied, largely due to the lack of efficient techniques to quantify their presentation at sites of cell–cell adhesion. Here, we used our novel Junction Analyzer Program (JAnaP) to quantify junction phenotype (i.e., continuous, punctate, or perpendicular) in response to various substrate compositions, cell culture times, and cAMP treatments in human brain microvascular endothelial cells (HBMECs). We then quantitatively correlated junction presentation with barrier permeability on both a “global” and “local” scale.MethodsWe cultured HBMECs on collagen I, fibronectin, collagen IV, laminin, fibronectin/collagen IV/laminin, or hyaluronic acid/gelatin for 2, 4, and 7 days with varying cAMP treatment schedules. Images of immunostained ZO-1, VE-cadherin, and claudin-5 were analyzed using the JAnaP to calculate the percent of the cell perimeter presenting continuous, punctate, or perpendicular junctions. Transwell permeability assays and resistance measurements were used to measure bulk (“global”) barrier properties, and a “local” permeability assay was used to correlate junction presentation proximal to permeable monolayer regions.ResultsSubstrate composition was found to play little role in junction presentation, while cAMP supplements significantly increased the continuous junction architecture. Increased culture time required increased cAMP treatment time to reach similar ZO-1 and VE-cadherin coverage observed with shorter culture, though longer cultures were required for claudin-5 presentation. Prolonged cAMP treatment (6 days) disrupted junction integrity for all three junction proteins. Transwell permeability and TEER assays showed no correlation with junction phenotype, but a local permeability assay revealed a correlation between the number of discontinuous and no junction regions with barrier penetration.ConclusionsThese results suggest that cAMP signaling influences HBMEC junction architecture more than matrix composition. Our studies emphasized the need for local barrier measurement to mechanistically understand the role of junction phenotype and supported previous results that continuous junctions are indicative of a more mature/stable endothelial barrier. Understanding what conditions influence junction presentations, and how they, in turn, affect barrier integrity, could lead to the development of therapeutics for diseases associated with BBB dysfunction.

Large-area in plane molecular junctions by electrografting in 10 nm metallic nanotrenches

A key issue to push molecular devices toward a new range of applications is the ability to master large scale integration while preserving the device’s functionality. Furthermore, providing extra tunability of the device by external parameters, such as gating in a transistor-like configuration, is highly suited for molecular electronics. Large area molecular junctions in crossbar geometry have demonstrated high yields and compatible and compatible fabrication with Complementary Metal Oxide Semiconductor (CMOS) technology. However, such a device’s geometry favors diffusion of metallic atoms in the molecular layer and gives a very limited access to perform electrical or optical gating on molecules. In this work, we propose a new molecular junction architecture going behind these limits. We report a robust approach for the fabrication of molecular junctions based on the electrografting of a nanometer-thick molecular layer in high aspect ratio metallic nanotrenches. Nanotrenches are obtained by edge-mediated shadow deposition, resulting in laterally aligned electrodes with a 10.3 nm ± 3.3 nm average spacing along a 20 μm length. An in-solution electroreduction of diazonium salts is subsequently performed to fill the nanotrenches by a thin oligomeric layer of anthraquinone molecules. Electronic transport measurements performed at room temperature reveal the ability to produce stable molecular devices. Such a new junction’s engineering offers the key advantages of high fabrication yield, great amenability for compact assembly, and reduced leakage current. The proposed architecture opens interesting perspectives to investigate fundamental and applied questions in molecular electronics, in which coupling of the molecules with external stimuli is required.

Photodynamic Priming Modulates Endothelial Cell-Cell Junction Phenotype for Light-activated Remote Control of Drug Delivery.

The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion of various molecules from the bloodstream into the brain. Photodynamic priming (PDP) is a non-cytotoxic modality that involves light activation of photosensitizers to photochemically modulate nearby molecules without killing the cells. Here we investigate the effects of sub-lethal photochemistry on junction phenotype (i.e., continuous, punctate, or perpendicular), as well as the BBB permeability in a transwell model of human brain microvascular endothelial cells (HBMECs). We showed that PDP decreases the continuous junction architecture by ~20%, increases the perpendicular junction architecture by ~40%, and has minimal impact on cell morphology in HBMECs. Furthermore, transwell permeability assay revealed that PDP improves the HBMEC permeability to dextran or nanoliposomes by up to 30-fold for 6-9 days. These results suggest that PDP could safely reverse the mature brain endothelial junctions without killing the HBMECs. This study not only emphasizes the critical roles of PDP in the modulation junction phenotype, but also highlights the opportunity to further develop PDP-based combinations that opens the cerebrum endothelium for enhanced drug transporter across the BBB.

An intermolecular-split G-quadruplex DNAzyme sensor for dengue virus detection.

Nucleic acids have special ability to organize themselves into various non-canonical structures, including a four-stranded DNA structure termed G-quadruplex (G4) that has been utilized for diagnostic and therapeutic applications. Herein, we report the ability of G4 to distinguish dengue virus (DENV) based on its serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) using a split G4-hemin DNAzyme configuration. In this system, two separate G-rich oligonucleotides are brought together upon target DNA strand hybridization to form a three-way junction architecture, allowing the formation of a G4 structure. The G4 formation in complexation with hemin can thus provide a signal readout by generating a DNAzyme that is able to catalyze H2O2-mediated oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). This results in a change of color providing a sensing platform for the colorimetric detection of DENV. In our approach, betaine and dimethyl sulfoxide were utilized for better G4 generation by enhancing the target-probe hybridization. In addition to this serotype-specific assay, a multi-probe cocktail assay, which is an all-in-one assay was also examined for DENV detection. The system highlights the potential of split G-quadruplex configurations for the development of DNA-based detection and serotyping systems in the future.

All solution and ambient processable organic photovoltaic modules fabricated by slot-die coating and achieved a certified 7.56% power conversion efficiency

To accelerate the commercialization of organic photovoltaics (OPVs), researchers should use scalable coating approaches compatible with roll-to-roll production in understanding the performance for OPV module manufacturing. The performance of OPV module is strongly changed by the interfacial materials, thin film deposition methods, and processing atmosphere with the film-forming properties of the bulk heterojunction (BHJ) layer influenced intimately to the efficiency of the devices. Herein, we present a reliable process flow and module architecture to demonstrate an air-stable, large-area, and solution-processable OPV module, which the electron transporting layer (ETL), BHJ layer, and hole transporting layer (HTL) are all deposited by slot-die coating and processed in the ambient. Thus prepared module achieved a certified power conversion efficiency (PCE) of 7.56% with an active area of 23.7 cm2 and FF up to 65% under 100 mW/cm2 AM1.5G irradiation. The cell to module loss is found to be 5.5% only in PCE. The encapsulated module also performed superior stability, the performance remained almost unchanged, and PCE can still maintain about 91.7% of the initial value after 1000 h light soaking. We believe this module performed an extremely high PCE reported for OPV module fabricated by ambient slot-die coating in single junction architecture, inferring that the industrialization of OPVs is promising and expectable.

Mice with an autosomal dominant Charcot-Marie-Tooth type 2O disease mutation in both dynein alleles display severe moto-sensory phenotypes

Charcot-Marie-Tooth disease (CMT) is the most common peripheral neuromuscular disorder worldwide. The axonal degeneration in CMT causes distal muscle weakness and atrophy, resulting in gait problems and difficulties with basic motor coordination skills. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. We previously generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R) and examined the heterozygous H304R/+offspring in a variety of motor skills and histological assays. Here we report the initial characterization of the homozygous H304R/R mouse, which is the first homozygous mutant DHC mouse to survive past the neonatal stage. We show that H304R/R mice have significantly more severe disease symptoms than the heterozygous H304R/+mice. The H304R/R mice have significant defects in motor skills, including grip strength, motor coordination, and gait and also related defects in neuromuscular junction architecture. Furthermore, the mice have defects in sensation, another aspect of CMT disease. Our results show that the H304R/+ and H304R/R mice will be important models for studying the onset and progression of both heterozygous and homozygous CMT disease alleles.

A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system.

Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear. Here, we investigate the impact of excitotoxicity induced by depletion of Drosophila Eaat1, an astrocytic glutamate transporter, on locomotor central pattern generator (CPG) activity, neuromuscular junction architecture, and motor function. We show that glutamate excitotoxicity triggers a circuit-dependent ROS feedback loop to sculpt the motor system. Excitotoxicity initially elevates ROS, thereby inactivating cholinergic interneurons and consequently changing CPG output activity to overexcite motor neurons and muscles. Remarkably, tonic motor neuron stimulation boosts muscular ROS, gradually dampening muscle contractility to feedback-enhance ROS accumulation in the CPG circuit and subsequently exacerbate circuit dysfunction. Ultimately, excess premotor excitation of motor neurons promotes ROS-activated stress signaling that alters neuromuscular junction architecture. Collectively, our results reveal that excitotoxicity-induced ROS can perturb motor system integrity through a circuit-dependent mechanism.

Improved power conversion efficiency in radial junction thin film solar cells based on amorphous silicon germanium alloys

Advanced material combining with novel 3D radial junction design is an attractive strategy to fabricate low-cost high-efficiency thin film solar cells. For improving the power conversion efficiency of traditional a-Si:H thin film solar cells, a conceptually new method incorporating Ge doping technology with 3D radial junction architecture is proposed here. By doping Ge with the optimal amount, the eternal quantum efficiency response of a-Si:Ge alloy thin film solar cell is greatly improved in the near-infrared wavelength. This enhanced spectrum response contributes to the improved power conversion efficiency according to the experimental results and theoretical simulations. On the other hand, by introducing the 3D radial junction architecture, both the excellent light trapping effect and the fast carrier separation contribute to the significantly improved short current density. With the optimal Ge doping amount, the radial junction a-Si:Ge alloy thin film solar cell achieves an open circuit voltage of 0.58 V, short current density of 20.14 mA/cm2, and fill factor of 53.7%, which contributes to the high power conversion efficiency up to 6.26%. From beginning to end, the fabrication temperature is lower than 400 °C and the whole fabrication process shows remarkable compatibility with current photovoltaic industry application. All above results suggest a potential route to the next generation of stable and highly efficient a-Si:H thin film solar cells.

Disruption of blood-brain barrier by an Escherichia coli isolated from canine septicemia and meningoencephalitis.

Escherichia coli (E. coli) is one of the common pathogenic bacteria in veterinary clinical infection. As an opportunistic microorganism, E. coli normally does not cause diseases. However, it causes infections under certain circumstance to domesticated animal and poultry, resulting in severe diarrhea, septicemia, and respiratory infections. Although there are increasing reports regarding the infections of E. coli to domestic animals and poultry, the infection of E. coli in dogs is relatively less reported, especially on septicemia and meningoencephalitis. Here, we reported the isolation and identification of an E. coli isolate named CEC-GZL17 from dogs characterized by septicemia and sudden death, and found that CEC-GZL17 is able to cause meningoencephalitis. Exploration on the potential mechanism underlying meningoencephalitis demonstrated that CEC-GZL17 infection significantly increases TNF-α expression and inhibits ZO-1 and occludin expressions in brain tissue, indicating that the E coli likely use the mechanism to penetrate the blood-brain barrier via disrupting tight junction architecture, thus leading to the invasion to brain tissue.