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.

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.

Moxibustion down-regulates colonic epithelial cell apoptosis and repairs tight junctions in rats with Crohn's disease

AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. Themicrostructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a shortcircuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining. RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was signifi-cantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced signifi-cantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occlu- din, claudin-1 and ZO-1 in the MWM and HPM groups was signifi cantly enhanced (0.48 ± 0.10, 0.64 ± 0.09 vs 0.18 ± 0.05 for occludin, 0.12 ± 0.02, 0.17 ± 0.03 vs 0.05 ± 0.01 for claudin-1, and 0.08 ± 0.01, 0.11 ± 0.01 vs 0.02 ± 0.01 for ZO-1). And in SASP group, the expression of occludin and ZO-1 was also signifi cantly increased (0.27 ± 0.04 vs 0.18 ± 0.05 for occludin and 0.05 ± 0.01 vs 0.02 ± 0.01 for ZO-1), but there was no significant difference for claudin-1. The HPM and MWM groups had higher expression of occludin, claudin-1 and ZO-1 than the SASP group. CONCLUSION: HPM and MWM treatment can down-regulate apoptosis of colonic epithelial cells, repair tight junctions and enhance colonic epithelial barrier function in rats with CD.

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.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

GaInP/GaAs tandem solar cells with highly Te- and Mg-doped GaAs tunnel junctions grown by MBE

We report a GaInP/GaAs tandem solar cell with a novel GaAs tunnel junction（TJ） with using tellurium（Te） and magnesium（Mg） as n- and p-type dopants via dual-filament low temperature effusion cells grown by molecular beam epitaxy（MBE） at low temperature. The test Te/Mg-doped GaAs TJ shows a peak current density of 21 A/cm2. The tandem solar cell by the Te/Mg TJ shows a short-circuit current density of 12 m A/cm2, but a low open-circuit voltage range of1.4 V^1.71 V under AM1.5 illumination. The secondary ion mass spectroscopy（SIMS） analysis reveals that the Te doping is unexpectedly high and its doping profile extends to the Mg doping region, thus possibly resulting in a less abrupt junction with no tunneling carriers effectively. Furthermore, the tunneling interface shifts from the intended Ga As n＋＋/p＋＋junction to the AlGaInP/GaAs junction with a higher bandgap AlGaInP tunneling layers, thereby reducing the tunneling peak. The Te concentration of ~ 2.5 × 1020 in GaAs could cause a lattice strain of 10-3 in magnitude and thus a surface roughening,which also negatively influences the subsequent growth of the top subcell and the GaAs contacting layers. The doping features of Te and Mg are discussed to understand the photovoltaic response of the studied tandem cell.

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.

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.

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.

Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.

Influence of the Magnetic Field on the Transient Decay of the Density of Charge Carriers in a Silicon Photocell with Vertical Multijunctions Connected in Series Placed in Open Circuit

This study investigates the effect of the magnetic field on the transient density of excess minority charge carriers in the base of a series-connected vertical junction silicon solar cell. The solar cell is presented in open circuit transient operation. The magnetic field through the Laplace force which deflects the photogenerated carriers from their initial trajectory towards the lateral surfaces reducing their mobility, diffusion and conduction, will certainly influence the decay time of the transient regime. The transient density of excess minority carriers in the base is a sum of infinite terms whose decay time of the different harmonics is studied.

In vitro and in vivo evaluation of effects of Mg-6Zn alloy on tight junction of intestinal epithelial cell

The effects of biodegradable Mg?6Zn alloy on tight junction of intestinal epithelial cells (IEC-6) were investigated. In the in vitro experiments, the cells were exposed to Mg?6Zn alloy extracts with different concentrations (0, 20% and 40%) for 1, 3 and 5 d. The real-time polymerase chain reaction (PCR) results show that when the cells are treated with 40% and 20% extracts, the expression of Zona Occludens 1 (ZO-1) and Occludin increase as compared with those in the control group. In the in vivo experiments, Mg?6Zn alloy and titanium staples were implanted into rabbits’ intestinal tract for 1, 2 and 3 weeks. By immunohistochemical staining of peri-implant intestinal tissue, increased expression of Occludin and ZO-1 are observed in the Mg?6Zn alloy groups as compared with those in the titanium and control groups. The results show that Mg?6Zn alloy in intestine may promote the regeneration of tight junction, and the extract with a certain concentration can induce the expression of tight junction related genes in IEC-6 cells.

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.

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.

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.

The study of a new n/p tunnel recombination junction and its application in a-Si:H/μc-Si:H tandem solar cells

This paper reports that a double N layer （a-Si：H/μc-Si：H） is used to substitute the single microcrystalline silicon n layer （n-μc-Si：H） in n/p tunnel recombination junction between subcells in a-Si：H/μc-Si：H tandem solar cells. The electrical transport and optical properties of these tunnel recombination junctions are investigated by current voltage measurement and transmission measurement. The new n/p tunnel recombination junction shows a better ohmic contact. In addition, the n/p interface is exposed to the air to examine the effect of oxidation on the tunnel recombination junction performance. The open circuit voltage and FF of a-Si：H/μc-Si：H tandem solar cell are all improved and the current leakage of the subcells can be effectively prevented efficiently when the new n/p junction is implemented as tunnel recombination junction.

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.

Remnant neuromuscular junctions in denervated muscles contribute to functional recovery in delayed peripheral nerve repair

Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively.

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/).