Junction Barrier Research Articles

Design of Ion-Implanted Junction Termination Extension for Vertical GaN Pin Rectifiers

Gallium-nitride and related materials have become suitable semiconductor platforms for next-generation power electronic devices. This materials system leverages unique properties of wider energy bandgap, higher carrier mobility, and ultrashort carrier recombination lifetime to achieve much improved bipolar switching characteristics when compared to Si- or SiC-based counterparts. In recent years, vertical GaN switches such as PIN rectifiers, junction barrier Schottky (JBS) diodes, and junction field-effect transistors (JFETs) have been actively sought in hopes to achieve low-loss device performance at kilo-volt (kV) operation range. Over the years, significant progresses in low-defect-density substrate preparation and high-quality epitaxial growth using metalorganic chemical vapor deposition (MOCVD) reactors, along with robust fabrication processing techniques helped achieve many impressive GaN-based power device demonstrations. As vertical GaN devices operate at the kV ranges, proper engineering of the electric field is a key to exploiting the ultimate device performance. To this end, several device-level design strategies such as field plates, beveled sidewalls, and junction termination extensions have been studied. In the context of realizing a planar device topology in GaN materials systems, ion implantation into GaN materials systems offer new opportunities to provide precise control of inhomogeneous carrier distribution for the creation of versatile doping profiles and geometries such as selectively doped regions or highly resistive regions at arbitrary locations in GaN devices.In this presentation, we will discuss a study of the floating guard rings (FGRs) designs that utilize a nitrogen-ion implantation isolation technique. The designs can effectively mitigate the electric field crowding effect and enable robust avalanching capability in vertical GaN PIN rectifiers. Using 1.2-kV GaN PIN rectifiers as design examples, a set of numerical simulation study was performed using a TCAD-Sentaurus software package. The results showed that a closely packed FGRs with a gap of adjacent FGRs in the range of 1-3 microns, a width of the FGRs in the range of 4 to 6 microns, along with a variable-width FGR design toward the outer rings can effectively suppress the peak electric field distribution at edge of the main junction and the surface of junction termination extensions. For example, consider a GaN PIN rectifier structure with a drift layer that consists of 6 microns of unintentionally doped (UID) GaN (n= 5×1015 cm-3) and a 4-micron-thick lightly doped GaN (n = 2×1016 cm-3). The FGR structures can be formed by creating highly resistive GaN regions in the epitaxially grown p-GaN layer using an ion implantation technique. In this design, five of the FGRs have 1-micron-wide undoped GaN and a 6-micron-wide p-GaN region in the p-GaN layer. The outermost FGR (the 6th FGR) is designed to have a 2-micron-wide undoped GaN and 5-micron-wide p-GaN extension. The resulting field distribution showed an effective suppression of the field crowding effect at the edge of the main junction (Figure 1(a)) and a smooth electric potential drop along the lateral direction can be achieved (Figure 1(b)). As shown in Figure 2, the electric field distribution at the vertical junction was plotted for two FGR designs with and without a metal plate on top of the p-GaN region. The electric field distribution of the main junction was also plotted for comparison. It is clearly shown that the peak electric field at the vertical junction is effectively reduced with the metal-plated FGRs by >10% when compared to a non-plated FGRs. Reduced peak electric field in typically high-electric-field regions can safeguard the device from experiencing premature breakdown for robust switching operations. We found that 6 FGRs with a total lateral extension of <45 microns from the main pn junction are sufficient to provide effective junction termination for 1.2 kV devices. Such designs could also support for devices with a blocking voltage up to 1.6 kV.FGR designs were implemented in GaN PIN rectifiers for experimental validation. The fabrication processing of vertical GaN PIN rectifiers was grown on n-type free-standing or bulk GaN substrates using a MOCVD reactor. The cathode was formed by depositing Ti/Al-based ohmic contact on the backside of the wafer, and the anode electrode was formed on the topside p-type GaN layer. Nitrogen-ion implantation was employed to create FGR structures and served as a mean of inter-device isolation. Detailed design strategies of the FGRs, device processing and device characterizations will be discussed in the conference. Figure 1

Chicory ameliorates hyperuricemia via modulating gut microbiota and alleviating LPS/TLR4 axis in quail

BackgroundHigh-purine diet can cause gut microbiota disorder, which is closely related to the occurrence of hyperuricemia (HUA). At the same time, the development of HUA is often accompanied by renal impairment. Chicory, a natural medicine, has a significant effect on lowering uric acid. However, whether its concrete mechanism is associated with the regulation of gut microbiota and renal damage is still unclear. MethodsHyperuricemic quails induced by high-purine diet were used, and quails were divided into control (CON), model (MOD), and model plus high, middle, low doses of chicory. The uricosuric effect was evaluated by detecting the uric acid levels in serum and feces. Meanwhile, the morphology of intestine and kidney were observed by hematoxylin and eosin (HE) staining, and the expression of intestinal barrier junction proteins Occludin, Claudin-1 were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Furthermore, the latent mechanism was clarified by analyzing 16S rRNA amplicon of gut microbiota and measuring the changes of LPS/TLR4 axis inflammatory response of the kidney by western blotting and enzyme-linked immunosorbent assay (ELISA). ResultsThe results showed that serum uric acid levels were significantly decreased, and the feces uric acid levels were noticeably increased after the intervention of chicory. In addition, chicory could repair the damage of intestinal mucosa and improve the permeability of intestinal barrier. Moreover, the 16S rRNA sequencing analysis uncovered that chicory restored gut microbiota by increasing the probiotics flora (Bifidobacterium, Erysipelotrichaceae) and reducing the pathogenic bacteria group (Helicobacteraceae). Furthermore, it was found that chicory reduced the LPS/TLR4 axis inflammatory response by down regulating the serum LPS and TLR4/NF-κB inflammatory pathway in kidney, thus promoting the excretion of uric acid in kidney. ConclusionChicory intervention ameliorated HUA via modulating the imbalance of gut microbiota and suppressing LPS/TLR4 axis inflammatory reaction in quail model, which may be a promising candidate for hyperuricemia-relieving properties.

Insights on the structural and electrical transport of sodium titanate nanotubes decorated with CuInS2 quantum dots heterostructures

In this work we present the synthesis of nanoscale heterostructures comprising sodium titanate nanotubes Na2Ti2O5·H2O (NaNT) decorated with CuInS2 (CIS) quantum dots with different sizes and weight fractions. Our study focused on the structural, microstructural, electrical and optical characterization of the nanoscale heterostructure by means of high-resolution transmission electron microscopy, atomic force microscopy, grazing incidence small angle X-ray scattering, confocal Raman microscopy, UV–Vis and impedance spectroscopy analyses. In most cases, these nanoscale heterostructures exhibited considerable enhancement on the electrical conductivity explained in terms of efficient interconnections between the titanate nanotubes and CIS quantum dots. UV–Vis spectroscopy characterization showed a decrease in the optical band gap in comparison to the pure NaNT from 3.68 to 3.45 eV. Impedance spectroscopy analysis confirmed the efficient electrical interconnections between titanate nanotubes, yielding not only to a decrease in the titanate junction resistance but also to an apparent decrease in the junction barrier voltage. All these features could postulate these nanoscale heterostructures as good candidates as photoelectrodes in solar cell applications.

Effect of High Glucose on Ocular Surface Epithelial Cell Barrier and Tight Junction Proteins.

PurposePatients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.MethodsHuman corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay. The cells were harvested for protein extraction and mRNA isolation. Gene and protein expression of claudins, zonula occludens (ZOs), and occludin was quantified using real-time PCR and Western blot.ResultsGlucose caused a significant decrease in TEER after 72 hours of exposure in both corneal and conjunctival epithelial cells. Glucose did not cause any notable change in migration of either corneal or conjunctival epithelial cells. Glucose exposure did not cause any notable change in protein expression of claudin-1, ZO-1, ZO-2, ZO-3, or occludin. On the other hand, 15 mM glucose caused an increase in gene expression of claudin-1, claudin-3, ZO-2, ZO-3, and occludin, a likely response to osmotic stress since 15 mM mannitol also caused consistently similar increase in gene expression of these proteins.ConclusionsHigh glucose exposure causes impairment of corneal and conjunctival epithelial cell barrier function, but this detrimental effect is not caused by a decrease in expression of tight junction proteins: claudin-1, ZO-1, ZO-2, ZO-3, and occludin.

NC1-Peptide From Collagen α3 (IV) Chains in the Basement Membrane of Testes Regulates Spermatogenesis via p-FAK-Y407.

The blood-testis barrier (BTB) in the testis is an important ultrastructure to support spermatogenesis. This blood-tissue barrier undergoes remodeling at late stage VII to early stage IX of the epithelial cycle to support the transport of preleptotene spermatocytes across the BTB to prepare for meiosis I/II at the apical compartment through a mechanism that remains to be delineated. Studies have shown that NC1-peptide-derived collagen α3 (IV) chain in the basement membrane is a bioactive peptide that induces BTB remodeling. It also promotes the release of fully developed spermatids into the tubule lumen. Thus, this endogenously produced peptide coordinates these 2 cellular events across the seminiferous epithelium. Using an NC1-peptide complementary deoxyribonucleic acid (cDNA) construct to transfect adult rat testes for overexpression, NC1-peptide was found to effectively induce germ cell exfoliation and BTB remodeling, which was associated with a surge and activation of p-rpS6, the downstream signaling protein of mTORC1 and the concomitant downregulation of p-FAK-Y407 in the testis. In order to define the functional relationship between p-rpS6 and p-FAK-Y407 signaling to confer the ability of NC1-peptide to regulate testis function, a phosphomimetic (and thus constitutively active) mutant of p-FAK-Y407 (p-FAK-Y407E-MT) was used for its co-transfection, utilizing Sertoli cells cultured in vitro with a functional tight junction (TJ) barrier that mimicked the BTB in vivo. Overexpression of p-FAK-Y407E-MT blocked the effects of NC1-peptide to perturb Sertoli cell BTB function by promoting F-actin and microtubule cytoskeleton function, and downregulated the NC1-peptide-mediated induction of p-rpS6 activation. In brief, NC1-peptide is an important endogenously produced biomolecule that regulates BTB dynamics.

Enhanced Photovoltaic and Photosensing Performances in Gadolinium-Doped Bismuth Ferrite

Recent emerging developments have demonstrated that bismuth ferrite is one of the promising lead-free perovskite materials for solar-energy harvesting, photoelectrochemical conversion, and photodetector. This work reports high short-circuit photocurrent densities ~1.2×1033 µA/cm2 in p-type gadolinium (Gd)-doped BiFeO3 ceramic with n-type indium-tin-oxide under 405 nm irradiation and sunlight at 102 mW/cm2 intensity, respectively. A polarization-enhanced photosensing responsivity (R) of ~5.4×10-2 A/W and detectivity (D*) of ~1.5×1011 Jones were achieved at low 405 nm irradiation. Enhanced photovoltaic conversion via a prior electric-field poling can be attributed to the p-n junction and field-modulated Schottky barrier in conjunction with domain nucleation, ordered polar nano-regions (PNRs), and increased O 2p-Fe 3d orbital hybridization. The network of domain walls and grain boundaries serves as conduction pathways for the photo-generated charge carriers. The remarkable improvement of photocurrent in polycrystalline Gd-doped BiFeO3 opens a window for using bismuth ferrite materials in self-powered UV-visible photodetector.

1200-V 4H-SiC Merged p-i-n Schottky Diodes With High Avalanche Capability

In this article, the avalanche capability of the 1.2-kV 4H-SiC junction barrier Schottky (JBS) and merged p-i-n Schottky (MPS) diodes is investigated through simulation and experiments. For MPS diodes, the width of the wide P+ region (W) is found to have great effects on the device avalanche capability. MPS diodes with varied W-values (3-20 μm) and JBS diode are designed and fabricated, and their avalanche energy/current capability is tested with unclamped inductive switching tests. The experimental results show that the MPS diode has an optimized avalanche capability at W = 8-μm design. Simulation study reveals that the avalanche current is mainly distributed at the edges of the P+ regions in the JBS/MPS diodes as a result of the curvature-effect-induced electric field crowding. The localized current crowding and unbalanced current distribution in the avalanche mode contribute to a reduced effective power dissipation area and a weaker avalanche capability. The current nonuniformity coefficient (k) is used to characterize the severity of the current unbalance, and it is found that kdeclines as Wincreases when W = 3-8 μm and then gets increased when W exceeds 8 μm. Both the experimental and simulation results indicate that the MPS diode is superior to the JBS diode in avalanche capability, and the width of the wide P+ region in the MPS diode has an optimal design (8 μm in this article) which corresponds to the alleviated current crowding issue and 9%-19% improvement of the avalanche capability.

Investigation of Dislocations Inducing Leakage Current on SiC Junction Barrier Schottky Diode by Two-Photon-Excited Band-Edge Photoluminescence

Tilt angles of threading dislocations (TDs) which induce leakage of current on SiC junction barrier schottky diodes (SiC-JBSs) were investigated by two-photon-excited photoluminescence (2PPL) and transmission electron microscopy (TEM). Observation of leakage spots measured by atomic force microscopy (AFM) revealed that pit-like structures were certainly formed but the depths were considerably shallow, indicating that influence of local electric field due to the structures was negligible on our SiC-JBSs. It became clear that tilt angles of the TDs inducing leakage were relatively larger than about 11° by 2PPL and that the TD was the threading mixed dislocation by TEM.

Dynamic Switching of 3kV 4H-SiC Charge-Balanced Junction Barrier Schottky (JBS) Diodes

We have performed detailed dynamic switching measurements for 3kV 4H-SiC Charge-Balanced (CB) junction barrier Schottky (JBS) diodes [1,2] and studied their dependence on device design parameters. We have done forward and reverse recovery characterizations and found unusual switching characteristics in these CB-JBS diodes. These switching characteristics are explained based on the design and layout of the devices.

Half-Metal–Spin-Gapless-Semiconductor Junctions as a Route to the Ideal Diode

The ideal diode is a theoretical concept that completely conducts the electric current under forward bias without any loss and that behaves like a perfect insulator under reverse bias. However, real diodes have a junction barrier that electrons have to overcome and thus they have a threshold voltage $V_T$, which must be supplied to the diode to turn it on. This threshold voltage gives rise to power dissipation in the form of heat and hence is an undesirable feature. In this work, based on half-metallic magnets and spin-gapless semiconductors we propose a diode concept that does not have a junction barrier and the operation principle of which relies on the spin-dependent transport properties of the HMM and SGS materials. We show that the HMM and SGS materials form an Ohmic contact under any finite forward bias, while for a reverse bias the current is blocked due to spin-dependent filtering of the electrons. Thus, the HMM-SGS junctions act as a diode with zero threshold voltage $V_T$, and linear $I-V$ characteristics as well as an infinite on:off ratio at zero temperature. However, at finite temperatures, non-spin-flip thermally excited high-energy electrons as well as low-energy spin-flip excitations can give rise to a leakage current and thus reduce the on:off ratio under a reverse bias. Furthermore, a zero threshold voltage allows one to detect extremely weak signals and due to the Ohmic HMM-SGS contact, the proposed diode has a much higher current drive capability and low resistance, which is advantageous compared to conventional semiconductor diodes. We employ the NEGF method combined with DFT to demonstrate the linear $I-V$ characteristics of the proposed diode based on two-dimensional half-metallic Fe/MoS$_2$ and spin-gapless semiconducting VS$_2$ planar heterojunctions.

Role of Tight Junctions and Their Protein Expression in Atopic Dermatitis

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.

Cell membrane-related toxic responses and disruption of intercellular communication in PCB mechanisms of toxicity: A review.

An understanding of polychlorinated biphenyl (PCB) congener-specific effects on cell membrane and intercellular communication is important within the studies of PCB absorption, organ-related PCB accumulation and exertion of toxic responses. Toxic potential of PCBs is linked to various deleterious effects on human health, including neurotoxicity, immunotoxicity, reproductive toxicity and genotoxicity and, recently in 2016 International Agency for Research on Cancer (IARC) has upgraded the classification of PCBs to Group 1 "Carcinogenic to humans." Proposed mechanisms of aforementioned PCBs adverse effects at cellular membrane level are: (i) downregulation of gap junction intercellular communication and/or connexins; (ii) compromised membrane integrity; and (iii) altered tight junction barrier function. This study, based on an extensive literature survey, shows the progress in scientific research of each of these three levels with the aim of pointing out the earliest toxic events of PCBs, which can result in serious cell/tissue/organ damage.

On the design of the channel region in 4H-SiC JBS diode through an analytical model of the potential barrier

In this paper, we propose a tool for the design of 4H-polytype Silicon Carbide Junction Barrier Schottky, JBS, diodes, which are promising devices for their low on-state resistance and their high blocking voltage. Our tool calculates the width of the channel region in terms of the geometrical and physical parameters and of the doping concentration in order that the device shows forward electrical characteristics similar to that of Schottky Barrier Diode. Their operating principle is defined by the control of the flow of electron carriers through a potential barrier, which is located in the n-type region under the Schottky metal contact surrounded by the p+-type regions. Indeed, if the electric fields of the p+-n junctions extend for the whole channel region under equilibrium conditions, the height of the induced potential barrier can be higher than that of the conventional Schottky built-in potential and can affect the electrical characteristics of the device, for example increasing the turn-on voltage. Although they have been firstly developed in Silicon technology, 4H-SiC JBS diodes are easier to fabricate because the electric fields of 4H-SiC p–n junctions have a wider space charge region for the same values of the doping concentrations with respect to Si JBS devices, resulting in a more relaxed design constrain of the channel geometry. Our analytical model can calculate the potential barrier height as function of the geometrical and physical parameters of the device and can evaluate the maximum channel width for which the potential barrier is higher than Schottky built-in voltage. The analytical results are compared through numerical simulations obtained from ATLAS Silvaco software.

Schottky enabled enhanced UV detection by graphene oxide composited transparent ZnO thin films

Transparent optoelectronics devices have recently drawn considerable research attentions for the next generation electronic technologies. Here, we fabricate highly transparent (87 to 90% under visible light) composite films of graphene oxide (GO) and zinc oxide (ZnO) by all-solution process. The non-linear current–voltage characteristics at room temperature resemble Schottky barrier junction formation between ZnO-GO film surface and Ag dot. Under UV irradiation (λ ~ 375 nm and power density ~1 mW/cm2) the ideality factor increases from 7.82 to 8.72 but the potential barrier height reduces from 0.66 to 0.50 eV in ZnO and ZnO-GO 25% films which are favorable for advancing optoelectronic technologies. This is demonstrated by excellent UV photoresponsivity of 5.3 A/W at low bias (+1 V) for ZnO-GO 25% along with low UV response (15.8 s) and recovery times (36.6 s). While at −1 V bias the photoresponsivity reaches to 1.25 A/W. Such distinct characteristics as compared to other reports on all-solution processed ZnO-GO composites could be attributed to the reduction of GO to form rGO within ZnO matrix to develop conducting channels in the composite films, the formation of excellent Schottky barriers with Ag, the modulation in excitonic characteristics by defect distributions at the interfacial regions among rGO flakes and ZnO matrix, and the facilitated charge transport through the junctions.

Straight leg raise metrics on high‐resolution manometry associate with esophageal reflux burden

Straight leg raise (SLR) is a provocative maneuver that assesses esophagogastric junction (EGJ) barrier function during high-resolution manometry (HRM). We evaluated the value of SLR in symptomatic reflux patients undergoing ambulatory reflux monitoring. Adult patients being evaluated for reflux symptoms with esophageal physiologic testing off antisecretory therapy over a 12month period were studied. Demographics, clinical presentation, HRM studies, and reflux monitoring studies were analyzed. Intra-abdominal and intra-esophageal pressures were extracted at baseline and during SLR from HRM studies. Acid exposure time (AET) was derived from reflux monitoring studies, and EGJ morphology and tone from HRM studies. SLR pressure metrics predicting abnormal AET were evaluated. Of 122 patients, 70 (57.4%) had ≥50% peak intra-abdominal pressure increase during SLR (58.0±1.4years, 75.7% female). Peak intra-esophageal pressure gradient between baseline and SLR predicted pathologic AET when ≥100% (AUC 0.78, sensitivity 71%, specificity 75%, P<.001), seen in 60.7% with AET>6%, but only 23.7% with AET<4% (P=.01). Peak intra-esophageal pressure gradient ≥100% was most discriminative in identifying abnormal acid burden in type 1 EGJ morphology (P=.005) but trended toward significance in type 2 and type 3 morphology (P=.1). Normal and abnormal EGJ contractile integral did not associate with peak intra-esophageal pressure gradient either collectively or when subdivided by EGJ morphology (P≥.2). Analysis of intra-esophageal pressure gradients during SLR, a simple HRM maneuver, may augment evaluation of symptomatic GERD, and provide adjunctive evidence supporting GERD.

Basement Membrane Remodeling Controls Endothelial Function in Idiopathic Pulmonary Arterial Hypertension.

The extracellular matrix (ECM) increasingly emerges as an active driver in several diseases, including idiopathic pulmonary arterial hypertension (IPAH). The basement membrane (BM) is a specialized class of ECM proteins. In pulmonary arteries, the BM is in close contact and direct proximity to vascular cells, including endothelial cells. So far, the role of the BM has remained underinvestigated in IPAH. Here, we aimed to shed light on the involvement of the BM in IPAH, by addressing its structure, composition, and function. On an ultrastructural level, we observed a marked increase in BM thickness in IPAH pulmonary vessels. BM composition was distinct in small and large vessels and altered in IPAH. Proteoglycans were mostly responsible for distinction between smaller and larger vessels, whereas BM collagens and laminins were more abundantly expressed in IPAH. Type IV collagen and laminin both strengthened endothelial barrier integrity. However, only type IV collagen concentration dependently increased cell adhesion of both donor and IPAH-derived pulmonary arterial endothelial cells (PAECs) and induced nuclear translocation of mechanosensitive transcriptional coactivator of the hippo pathway YAP (Yes-activated protein). On the other hand, laminin caused cytoplasmic retention of YAP in IPAH PAECs. Accordingly, silencing of COL4A5 and LAMC1, respectively, differentially affected tight junction formation and barrier integrity in both donor and IPAH PAECs. Collectively, our results highlight the importance of a well-maintained BM homeostasis. By linking changes in BM structure and composition to altered endothelial cell function, we here suggest an active involvement of the BM in IPAH pathogenesis.

The Role of Ferroelectric Polarization in Resistive Memory Properties of Metal/Insulator/Semiconductor Tunnel Junctions: A Comparative Study.

Recently, tunnel junction devices adopting semiconducting Nb:SrTiO3 electrodes have attracted considerable attention for their potential applications in resistive data storage and neuromorphic computing. In this work, we report on a comparative study of Pt/insulator/Nb:SrTiO3 tunnel junctions between ferroelectric BaTiO3 and nonferroelectric SrTiO3 and LaAlO3 barriers to reveal the role of polarization in resistance switching properties. Although hysteretic behaviors appear in current-voltage measurements of all devices regardless of the barrier character, significantly improved current ratios by more than three orders of magnitude are observed in the Pt/BaTiO3/Nb:SrTiO3 tunnel junctions due to the dominance of polarization in modulation of junction barrier profiles between the low and high resistance states. The switchable polarization also gives rise to enhanced resistance retention since the electron diffusion that smears the barrier contrast of the bistable resistance states is suppressed by the polar BaTiO3/Nb:SrTiO3 interface associated with the ferroelectric bound charges. These polarization-induced effects are absent in the nonferroelectric Pt/SrTiO3/Nb:SrTiO3 and Pt/LaAlO3/Nb:SrTiO3 devices in which serious resistance state decay, described by Fick's second law, is observed since there are no switchable interface charges on SrTiO3/Nb:SrTiO3 and LaAlO3/Nb:SrTiO3 to block the electron diffusion. In addition, the Pt/BaTiO3/Nb:SrTiO3 device also exhibits an excellent switching endurance up to ∼4.0 × 106 bipolar cycles. These enhancements indicate the importance of ferroelectric polarization for achieving high-performance resistance switching and suggest that metal/ferroelectric/Nb:SrTiO3 tunnel junctions are promising candidates for nonvolatile memory applications.

IL1B Increases Intestinal Tight Junction Permeability by Up-regulation of MIR200C-3p, Which Degrades Occludin mRNA

Defects in the epithelial tight junction (TJ) barrier contribute to development of intestinal inflammation associated with diseases. Interleukin 1 beta (IL1B) increases intestinal permeability in mice. We investigated microRNAs that are regulated by IL1B and their effects on expression of TJ proteins and intestinal permeability. We used Targetscan to identify microRNAs that would bind the 3' untranslated region (3'UTR) of occludin mRNA; regions that interacted with microRNAs were predicted using the V-fold server and Assemble2, and 3-dimensional models were created using UCSF Chimera linked with Assemble2. Caco-2 cells were transfected with vectors that express microRNAs, analyzed by immunoblots and real-time polymerase chain reaction (PCR), and grown as monolayers; permeability in response to IL1B was assessed with the marker inulin. Male C57BL/6 mice were given intraperitoneal injections of IL1B and intestinal recycling perfusion was measured; some mice were given dextran sodium sulfate to induce colitis and/or gavage with an antagonist to MIR200C-3p (antagomiR-200C) or the nonspecific antagomiR (control). Intestinal tissues were collected from mice and analyzed by histology and real-time PCR; enterocytes were isolated by laser capture microdissection. We also analyzed colon tissues and organoids from patients with and without ulcerative colitis. Incubation of Caco-2 monolayers with IL1B increased TJ permeability and reduced levels of occludin protein and mRNA without affecting the expression of other transmembrane TJ proteins. Targetscan identified MIR122, MIR200B-3p, and MIR200C-3p, as miRNAs that might bind to the occludin 3'UTR. MIR200C-3p was rapidly increased in Caco-2 cells incubated with IL1B; the antagomiR-200c prevented the IL1B-induced decrease in occludin mRNA and protein and reduced TJ permeability. Administration of IL1B to mice increased small intestinal TJ permeability, compared with mice given vehicle; enterocytes isolated from mice given IL1B had increased expression of MIR200C-3p and decreased levels of occludin messenger RNA (mRNA) and protein. Intestinal tissues from mice with colitis had increased levels of IL1B mRNA and MIR200C-3p and decreased levels of occludin mRNA; gavage of mice with antagomiR-200C reduced levels of MIR200C-3p and prevented the decrease in occludin mRNA and the increase in colonic permeability. Colon tissues and organoids from patients with ulcerative colitis had increased levels of IL1B mRNA and MIR200C-3p compared with healthy controls. Using 3-dimensional molecular modeling and mutational analyses, we identified the nucleotide bases in the occluding mRNA 3'UTR that interact with MIR200C-3p. Intestine tissues from patients with ulcerative colitis and mice with colitis have increased levels of IL1B mRNA and MIR200C-3p, which reduces expression of occludin by enterocytes and thereby increases TJ permeability. Three-dimensional modeling of the interaction between MIR200C-3p and the occludin mRNA 3'UTR identified sites of interaction. The antagomiR-200C prevents the decrease in occludin in enterocytes and intestine tissues of mice with colitis, maintaining the TJ barrier.

Proanthocyanidin-Rich Grape Seed Extract Reduces Inflammation and Oxidative Stress and Restores Tight Junction Barrier Function in Caco-2 Colon Cells.

Grape polyphenols have previously been shown to improve gut health and attenuate the symptoms of metabolic syndrome; however, the mechanism of these beneficial effects is still debated. In this study, we investigated the protective effect of proanthocyanidin-rich grape seed extract (GSE) on bacterial lipopolysaccharide (LPS)-induced oxidative stress, inflammation, and barrier integrity of human Caco-2 colon cells. GSE significantly reduced the LPS-induced intracellular reactive oxygen species (ROS) production and mitochondrial superoxide production, and upregulated the expression of antioxidant enzyme genes. GSE also restored the LPS-damaged mitochondrial function by increasing mitochondrial membrane potential. In addition, GSE increased the expression of tight junction proteins in the LPS-treated Caco-2 cells, increased the expression of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine gene expression. Our findings suggest that GSE exerts its beneficial effects on metabolic syndrome by scavenging intestinal ROS, thus reducing oxidative stress, increasing epithelial barrier integrity, and decreasing intestinal inflammation.

Eucalyptol Blocks Diabetes-Associated Disruption of Tight Junction and Blood Retinal Barrier in Retinal Pigment Epithelial Cells and Diabetic Eyes

Abstract Objectives Diabetes-associated retinal impairment has been implicated in diabetic retinopathy. Chronic hyperglycemia leads to disruption of tight junction and breakdown of blood retinal barrier. Eucalyptol is a natural organic essential oil and a monoterpenoid present in eucalyptus oil with anti-inflammatory, anti-diabetic and antioxidant properties. Methods Primary human retinal pigment epithelial cells (HRPEC) were cultured in media containing 33 mM glucose for 4 days in the presence of 1–20 μM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Cell lysates and mouse eye tissue extracts were prepared for Western blotting, in which antibodies of ZO-1, occludin, matrix metalloproteinase (MMP)-2 and MMP-9 were used. Results Eucalyptol enhanced epithelial induction of the tight junction proteins of ZO-1 and occludin reduced by glucose loading. Consistently, oral administration of eucalyptol to db/db mice augmented the eye tissue levels of these tight junction proteins. In addition, the induction of MMP-2 and MMP-9 involved in the degradation of extracellular matrix, was elevated by exposure of glucose to HRPEC, which was encumbered by eucalyptol in a dose-dependent manner. Conclusions These results demonstrated that eucalyptol maintained transepithelial cells integrity and blood retinal barrier in diabetic eyes. Therefore, eucalyptol may be a potent retinoprotective agent combating diabetes-associated retinal malfunction. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (2017R1A6A3A04011473).