Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

Expression Patterns of the Cell Junction-associated Genes During Rat Liver Regeneration

To study actions of the genes associated with tight junction, adherent junction, focal adhesion, and gap junction during liver regeneration （LR）, these genes were obtained by collecting data from databases and thesis, and their expression profiles in rat regenerating liver were detected employing Rat Genome 230 2.0 array. Next the LR-associated genes were identified by comparing the difference between sham operation （SO） and partial hepatectomy （PH） groups. 79, 53, 109, 53 genes involved in the above four junctions were found to be LR-associated. The initial and total expression numbers of these genes occurring in the initial phase of LR, G0/G1, cell proliferation, cell differentiation, and structure-functional rebuilding were 124, 43, 122, 10, and 249, 145, 957, 306, respectively, illustrating that genes were initi^ly expressed mainly in the initiation stage, and functioned in different phases. Up-regulation-and down-regulation to a total of 972 and 540 times, as well as, 41 types of expression patterns showed that the physiological and biochemical activities were diverse and complicated in LR. According to the data, there was an increase in the forepart and prophase, but a decrease in late-metaphase and anaphase for gap junction assembly. Focal adhesion formation displayed an enhancement in forepart, prophase, and anaphase; and formation of tight junctions and adherent junctions last throughout the LR.

Cell junction proteins within the cochlea: A review of recent research

Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Substrate Stiffness Affects Endothelial Cell Junctions and MAPK Signaling Pathway

Vascular homeostasis is critical for maintaining normal vascular structure and function. Aging is an irreversible trigger of vascular sclerosis, which causes structural and functional damage to blood vessels, leading to severe atherosclerosis. Endothelial cells (ECs) can respond to mechanical stimuli from the extracellular matrix, causing disruption of endothelial barrier function and activating signaling pathways to regulate cellular behavior under pathological conditions. In this paper, we investigated the effect of substrate stiffness on endothelial cell junctions, and the activation of mitogen-activated protein kinase (MAPK) signaling pathways. An in vitro stiffness model was established using polyacrylamide hydrogels of 1 kPa, 20 kPa and 100 kPa. By transcriptome analysis, we found that the cell-cell junction, cadherin binding, cytoskeleton and classical signaling pathways such as MAPK and Rho GTPase of endothelial cells were regulated by substrate stiffness. The expression of cell junction-related molecules TJP1, TJP2, JAM3 and JCAD was also found to be reduced at higher stiffness. The MAPK signaling pathway-related molecules MAP2K3, MAP2K7, MAP3K3, MAP3K6, MAPK3, MAPK7 were upregulated with increased stiffness. qRT-PCR analysis showed that the gene expression of JCAD was reduced with increased stiffness. Immunofluorescence staining of VE-cadherin indicated that the total fluorescence level of VE-cadherin decreased significantly with increased stiffness, and stiffness impaired the cell-cell junction with increased punctuation and discontinuity. Western blotting analysis confirmed that the protein expression ratio of pp38MAPK/p38MAPK increased with stiffness. Our research suggested that substrate stiffness played an important role in regulating endothelial cell integrity and MAPK signaling pathway.

Determination of the Series Resistance of a Series Vertical-Junction Silicon (N+/P/P+) Solar Cell under Polychromatic Illumination and Magnetic Field: Effect of Optimum Thickness

By solving the magneto-transport equation for excess minority charge carriers in the base of the series vertical-junction silicon cell, the phenomenological parameters of the cell can be determined from the boundary conditions. Photocurrent density and photovoltage are determined for each value of applied magnetic field and corresponding optimum thickness, to establish the current-voltage characteristic (Jph(Sf, Sb, z, B, Hop)-Vph(Sf, Sb, z, B, Hop) of the silicon cell under polychromatic illumination. This study will make it possible to reduce the material used (by reducing the optimum thickness), which will help to lower prices. It will also enable us to reduce betting effects (lower series resistance), thereby boosting solar cell efficiency.

Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

Background:Burn wound healing is a complex process and the role of Wnt ligands varies in this process.Whether and how Wnt4 functions in burn wound healing is not well understood.In this study,we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.Methods:First,the expression of Wnt4 during burn wound healing was determined by immunoflu-orescence,Western blotting and qPCR.Then,Wnt4 was overexpressed in burn wounds.The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining.Collagen secretion was observed by Masson staining.Vessel formation and fibroblast distribution were observed by immunostaining.Next,Wnt4 was knocked down in HaCaT cells.The migration of HaCaT cells was analysed by scratch healing and transwell assays.Next,the expression ofβ-catenin was detected by Western blotting and immunofluorescence.The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence.Finally,the molecular changes induced by Wnt4 were analysed by RNA sequencing,immunofluorescence,Western blotting and qPCR in HaCaT cells and burn wound healing tissues.Results:The expression of Wnt4 was enhanced in burn wound skin.Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis.Collagen secretion,vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression.When Wnt4 was knocked down in HaCaT cells,the ratio of proliferating cells decreased,the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased.The nuclear translocation ofβ-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells.RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown.The expression of the cell junction proteins was decreased by the overexpression of Wnt4.Conclusions:Wnt4 promoted the migration of epidermal cells.Overexpression of Wnt4 increased the thickness of the burn wound.A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation ofβ-catenin,thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.

Numerical Simulation for Enhancing Performance of MoS2 Hetero-Junction Solar Cell Employing Cu2O as Hole Transport Layer

The paper reported the design and thorough analysis of a thin-film solar cell (TFSC) based on molybdenum disulfide (MoS2) with an integrated Copper(I) Oxide (Cu2O) hole transport layer (HTL), employing the one-dimensional Solar Cell Capacitance Simulator (SCAPS-1D) software. By varying crucial parameters such as absorber layer thickness, doping density, and bulk defect density, as well as HTL thickness, doping concentration, and electron affinity, defect density at ZnO/absorber and absorber/Cu2O interfaces, and operating temperature, we explored key photovoltaic measures including open circuit voltage (Voc), short-circuit current density (Jsc), fill-factor (FF), and power conversion efficiency (PCE) of the hetero-junction solar cell. The study demonstrated an efficiency of 18.87% for the MoS2 solar cell without HTL, while the proposed solar cell (SC) utilizing Cu2O HTL and optimized device structure exhibited a remarkable PCE of 26.70%. The outcomes derived from the present study offer valuable insights for the progress of a highly efficient and economically viable MoS2 hetero-junction TFSC.

Microscopic Structure of the Sigmoido-Jugular Junction in the Third-Trimester Fetus

Context and Justification: The sigmoido-jugular junction connects two structures of different compositions and has a complex organization. The sinusoidal portion of its endothelium contains muscle cells in adults. Is this the same presentation observed in fetuses? Objective: To describe the sigmoido-jugular junction in fetuses. Materials and Methods: Over a period of seven months, a histochemical and immunohistochemical study was conducted on 30 sigmoido-jugular junctions taken from 15 fetuses aged at least 32 weeks of gestation. These fetuses were obtained following expulsion due to intrauterine death, after informed consent from the parents. Results: Three portions can be identified: sigmoid, junctional, and jugular. Histochemical preparations revealed the existence of two constant layers and a third layer present only at the jugular level. From the inside out, the layers are as follows: 1) Inner Layer (Endothelium): This layer is clearer from the junction and reveals the presence of smooth muscle cells at the sigmoid level in immunohistochemistry. 2) Outer Layer: At the sigmoid and junctional levels, this layer consists of collagen fibers and becomes median at the jugular level, where it is composed of elastic and muscular collagen fibers. 3) Third Layer: Present only at the jugular level, this layer corresponds to the adventitia. Conclusion: The architecture of the sigmoido-jugular junction in fetuses, which is identical to that in adults, excludes the metaplastic hypothesis regarding endothelial smooth muscle cells in the sigmoid portion. Instead, it favors their role in regulating encephalic venous drainage.

The role of ubiquitination and deubiquitination in the regulation of cell junctions

Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, recep- tor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiq- uitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on inves- tigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases＇ biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.

Cinnamicaldehyde regulates the expression of tight junction proteins and amino acid transporters in intestinal porcine epithelial cells

Background： Cinnamicaldehyde（CA） is a key flavor compound in cinnamon essential oil possessing various bioactivities. Tight junction（TJ） proteins are vital for the maintenance of intestinal epithelial barrier function,transport, absorption and utilization of dietary amino acids and other nutrients. In this study, we tested the hypothesis that CA may regulate the expression of TJ proteins and amino acid transporters in intestinal porcine epithelial cells（IPEC-1） isolated from neonatal pigs.Results： Compared with the control, cells incubated with 25 μmol/L CA had increased transepithelial electrical resistance（TEER） and decreased paracellular intestinal permeability. The beneficial effect of CA on mucosal barrier function was associated with enhanced protein abundance for claudin-4, zonula occludens（ZO）-1, ZO-2, and ZO-3. Immunofluorescence staining showed that 25 μmol/L CA promoted the localization of claudin-1 and claudin-3 to the plasma membrane without affecting the localization of other TJ proteins, including claudin-4, occludin,ZO-1, ZO-2, and ZO-3, compared with the control cells. Moreover, protein abundances for rBAT, xCT and LAT2 in IPEC-1 cells were enhanced by 25 μmol/L CA, while that for EAAT3 was not affected.Conclusions： CA improves intestinal mucosal barrier function by regulating the distribution of claudin-1 and claudin-3 in enterocytes, as well as enhancing protein abundance for amino acid transporters rBAT, xCT and LAT2 in enterocytes. Supplementation with CA may provide an effective nutritional strategy to improve intestinal integrity and amino acid transport and absorption in piglets.

Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Bifacial Silicon Solar Cell Steady Photoconductivity under Constant Magnetic Field and Junction Recombination Velocity Effects

The paper reported a theoretical study on the photoconductivity of a bifacial silicon solar cell under polychromatic illumination and a constant magnetic field effect. By use of the continuity equation in the base of the solar cell maintained in a constant temperature at 300 K, an expression of the excess minority carriers’ density was determined according to the applied magnetic field, the base depth and the junction recombination velocity. From the expression of the minority carriers’ density, the photoconductivity of the solar cell was deduced and which allowed us to predict some recombination phenomena, the use of such solar cell in optoelectronics. The profile of the photoconductivity also permitted us to utilize a linear model in order to determine an electrical capacitance that varied with magnetic field.

Enhanced Efficiency of Metamorphic Triple Junction Solar Cells for Space Applications

Metamorphic In0.55Ga0.45P/In0.06Ga0.94As/Ge triple-junction （3J-MM） solar cells are grown on Ge （100） sub- strates via metal organic chemical vapor deposition. Epi-structural analyses such as high resolution x-ray diffrac- tion, photoluminence, cathodoluminescence and HRTEM are employed and the results show that the high crystal quality of 3J-MM solar cells is obtained with low threading dislocation density of graded buffer （an average value of 6.8× 10^4/cm2）. Benefitting from the optimized bandgap combination, under one sun, AM0 spectrum, 25℃ conditions, the conversion efficiency is achieved about 32%, 5% higher compared with the lattice-matched In0.49Ga0.51P/In0.01Ga0.99As/Ge triple junction （3J-LM） solar cell. Under 1-MeV electron irradiation test, the degradation of the EQE and I-V characteristics of 3J-MM solar cells is at the same level as the 33-LM solar cell. The end-of-life efficiency is -27.1%. Therefore, the metamorphic triple-junction solar cell may be a promising candidate for next-generation space multi-junction solar cells.

Junction Surface Recombination Concept as Applied to Silicon Solar Cell Maximum Power Point Determination Using Matlab/Simulink: Effect of Temperature

In this work, we study the method for determining the maximum of the minority carrier recombination velocity at the junction Sfmax, corresponding to the maximum power delivered by the photovoltaic generator. For this, we study the temperature influence on the behavior of the front white biased solar cell in steady state. By solving the continuity equation of excess minority carrier in the base, we have established the expressions of the photocurrent density, the recombination velocity on the back side of the base Sb, and the photovoltage. The photocurrent density and the photovoltage are plotted as a function of Sf, called, minority carrier recombination velocity at the junction surface, for different temperature values. The illuminated I-V characteristic curves of the solar cell are then derived. To better characterize the solar cell, we study the electrical power delivered by the base of the solar cell to the external charge circuit as either junction surface recombination velocity or photovoltage dependent. From the output power versus junction surface recombination velocity Sf, we have deduced an eigenvalue equation depending on junction recombination velocity. This equation allows to obtain the maximum junction recombination velocity Sfmax corresponding to the maximum power delivered by the photovoltaic generator, throughout simulink model. Finally, we deduce the conversion efficiency of the solar cell.

Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line

Our previous study has proven that tea polyphenol has a role in lung neoplasms. The present communication was to investage the anti-proliferation effect of tea polyphenol on the PG cells, which was a high metastatic human lung carcinoma cell line, by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) cell viability assay, and to study the change of intracellular calcium concentration, connexin43 (Cx43) expression, gap junctional intercellular communication (GJIC) and cell cycle distribution after the tea polyphenol treatment by laser scanning confocal microscopy and flow cytometry. The results showed that 1) tea polyphenol could kill the PG cells in a dose-depent manner via inhibiting the PG cell proliferation and blocking the PG cell cycle progression staying in G0/G1 phase and not transfering in S and G2/M phases to reduce the PG cell proliferation index;2) the increases of intracellular calcium concentration, GJIC and Cx43 expression were related with the tea polyphenol doses. The data suggested that tea polyphenol could inhibit the growth of PG cells, which mechanism was associated with the up-regulation of GJIC.

A New Method for Fitting Current–Voltage Curves of Planar Heterojunction Perovskite Solar Cells

Herein we propose a new equivalent circuit including double heterojunctions in series to simulate the current–voltage characteristic of P–I–N planar structure perovskite solar cells. This new method can theoretically solve the dilemma of the parameter diode ideal factor being larger than2 from an ideal single heterojunction equivalent circuit,which usually is in the range from 1 to 2. The diode ideal factor reflects PN junction quality, which influences the recombination at electron transport layer/perovskite and perovskite/hole transport layer interface. Based on the double PN junction equivalent circuit, we can also simulate the dark current–voltage curve for analyzing recombination current(Shockley–Read–Hall recombination) and diffusion current(including direct recombination), and thus carrier recombination and transportation characteristics. This new model offers an efficacious and simple method to investigate interfaces condition, film quality of perovskite absorbing layer and performance of transport layer, helping us furtherimprove the device efficiency and analyze the working mechanism.

Numerical simulation of a triple-junction thin-film solar cell based on μc-Si_(1-x)Ge_x :H

In this paper, a-Si：H/a-SiGe：H/μc-SiGe：H triple-junction solar cell structure is proposed. By the analyses of mi- croelectronic and photonic structures （AMPS-1D） and our TRJ-F/TRJ-M/TRJ-B tunneling-recombination junction （TRJ） model, the most preferably combined bandgap for this structure is found to be 1.85 eV/1.50 eV/1.0 eV. Using more realistic material properties, optimized thickness combination is investigated. Along this direction, a-Si：H/a-SiGe：H/μc-SiGe：H triple cell with an initial efficiency of 12.09% （Voc = 2.03 V, FF = 0.69, Jsc = 8.63 mA/cm^2, area = 1 cm^2） is achieved in our laboratory.

Delta-doped quantum wire tunnel junction for highly concentrated solar cells

We propose a novel structure for tunnel junction based on delta-doped AlGaAs/GaAs quantum wires. Higher spatial confinement of quantum wires alongside the increased effective doping concentration in the delta-doped regions extremely increase the peak tunneling current and enhance the performance of tunnel junction. The proposed structure can be used as tunnel junction in the multijunction solar cells under the highest possible thermodynamically limited solar concentration.The combination of the quantum wire with the delta-doped structure can be of benefit to the solar cells' advantages including higher number of sub-bands and high degeneracy. Simulation results show a voltage drop of 40 mV due to the proposed tunnel junction used in a multijunction solar cell which presents an extremely low resistance to the achieved peak tunneling current.

The p recombination layer in tunnel junctions for micromorph tandem solar cells

A new tunnel recombination junction is fabricated for n-i-p type micromorph tandem solar cells. We insert a thin heavily doped hydrogenated amorphous silicon （a-Si：H） p^＋ recombination layer between the n a-Si：H and the p hydrogenated nanocrystalline silicon （nc-Si：H） layers to improve the performance of the n-i-p tandem solar cells. The effects of the boron doping gas ratio and the deposition time of the p-a-Si：H recombination layer on the tunnel recombination junctions have been investigated. The current-voltage characteristic of the tunnel recombination junction shows a nearly ohmic characteristic, and the resistance of the tunnel recombination junction can be as low as 1.5 Ω-cm^2 by using the optimized p-a-Si：H recombination layer. We obtain tandem solar cells with open circuit voltage Voc = 1.4 V, which is nearly the sum of the Vocs of the two corresponding single cells, indicating no Voc losses at the tunnel recombination junction.

Cell cycle dependent regulation of gap junction coupling and apoptosis in GFSHR-17 granulosa cells

Recent results have shown that the level of gap junction coupling could modulate the induction of apoptotic reactions. We previously observed that 1H-[1,2, 4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a block- er of guanylyl cyclase, inhibited gap junction coupling and thereby promoted activation of characteristic apoptotic reactions such as chromatin condensation, DNA strand breaking, and formation of blebs in GFSHR-17 granulosa cells, the in vitro model for granulosa cells of the maturing ovular follicle. In the present report, we focus on the effects of ODQ with respect to the cell cycle in GFSHR-17 granulosa cells. In synchronised GFSHR-17 granulosa cells, the double whole-cell patch-clamp technique revealed that gap junction conductance in mitotic cells was reduced in comparison to cells in interphase. This reduction of gap junction conductance correlated with a reduction of non-phosphorylated Cx43 in mitotic cells. We compared the stimulation of apoptotic reactions by ODQ between cells in mitosis and in interphase. We observed that the induction of both chromatin condensation and DNA strand breaking by ODQ was increased in mitotic cells, as compared to cells in interphase. The effects of ODQ were not observed in He-La cells that do not express connexins. The results in- dicate that reduction of gap junction coupling in mitotic GFSHR-17 granulosa cells depends on phosphor- rylation of Cx43 and raises the sensitivity to stimulation of apoptosis. We propose that gap junction coupling is involved in regulation of apoptosis of granulosa cells in maturing ovular follicle.