Stable Zinc Electrode Reaction Enabled by Combined Cationic and Anionic Electrolyte Additives for Non-Flow Aqueous Zn─Br2 Batteries.

Aqueous zinc-bromine batteries hold immense promise for large-scale energy storage systems due to their inherent safety and high energy density. However, achieving a reliable zinc metal electrode reaction is challenging because zinc metal in the aqueous electrolyte inevitably leads to dendrite growth and related side reactions, resulting in rapid capacity fading. Here, it is reported that combined cationic and anionic additives in the electrolytes using CeCl3 can simultaneously address the multiple chronic issues of the zinc metal electrode. Trivalent Ce3+ forms an electrostatic shielding layer to prevent Zn2+ from concentrating at zinc metal protrusions, while the high electron-donating nature of Cl- mitigates H2O decomposition on the zinc metal surface by reducing the interaction between Zn2+ and H2O. These combined cationic and anionic effects significantly enhance the reversibility of the zinc metal reaction, allowing the non-flow aqueous Zn─Br2 full-cell to reliably cycle with exceptionally high capacity (>400 mAh after 5000 cycles) even in a large-scale battery configuration of 15 × 15 cm2.

Novel Mg- and Ga-doped ZnO/Li-Doped Graphene Oxide Transparent Electrode/Electron-Transporting Layer Combinations for High-Performance Thin-Film Solar Cells.

Herein, a novel combination of Mg- and Ga-co-doped ZnO (MGZO)/Li-doped graphene oxide (LGO) transparent electrode (TE)/electron-transporting layer (ETL) has been applied for the first time in Cu2 ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs). MGZO has a wide optical spectrum with high transmittance compared to that with conventional Al-doped ZnO (AZO), enabling additional photon harvesting, and has a low electrical resistance that increases electron collection rate. These excellent optoelectronic properties significantly improved the short-circuit current density and fill factor of the TFSCs. Additionally, the solution-processable alternative LGO ETL prevented plasma-induced damage to chemical bath deposited cadmium sulfide (CdS) buffer, thereby enabling the maintenance of high-quality junctions using a thin CdS buffer layer (≈30 nm). Interfacial engineering with LGO improved the Voc of the CZTSSe TFSCs from 466 to 502 mV. Furthermore, the tunable work function obtained through Li doping generated a more favorable band offset in CdS/LGO/MGZO interfaces, thereby, improving the electron collection. The MGZO/LGO TE/ETL combination achieved a power conversion efficiency of 10.67%, which is considerably higher than that of conventional AZO/intrinsic ZnO (8.33%).

Effect of Polymer Chain Length on the Superlattice Assembly of Functionalized Gold Nanoparticles.

We report on the assembly of gold nanoparticle (AuNPs) superlattices at the liquid/vapor interface and in the bulk of their suspensions. Interparticle distances in the assemblies are achieved on multiple length scales by varying chain lengths of surface grafted AuNPs by polyethylene glycol (PEG) with molecular weights in the range 2000-40,000 Da. Crystal structures and lattice constants in both 2D and 3D assemblies are determined by synchrotron-based surface-sensitive and small-angle X-ray scattering. Assuming knowledge of grafting density, we show that experimentally determined interparticle distances are adequately modeled by spherical brushes close to the θ point (Flory-Huggins parameter, χ≈12) for 2D superlattices at a liquid interface and a nonsolvent (χ = ∞) for the 3D dry superlattices.

Unusual Effect of Iodine Ions on the Self-Assembly of Poly(ethylene glycol)-Capped Gold Nanoparticles.

We use synchrotron X-ray reflectivity and grazing incidence small-angle X-ray scattering to investigate the surface assembly of the poly(ethylene glycol) (PEG)-grafted gold nanoparticles (PEG-AuNPs) induced by different salts. We find that NaCl and CsCl behave as many other electrolytes, namely, drive the PEG-AuNPs to the vapor/suspension interface to form a layer of single-particle depth and organize them into very high-quality two-dimensional (2D) hexagonal crystals. By contrast, NaI induces the migration of PEG-AuNPs to the aqueous surface at much higher surface densities than the other salts (at similar concentrations). The resulting 2D ordering at moderate NaI concentrations is very short ranged, and at a higher NaI concentration, the high-density monolayer is amorphous. Considering NaCl, CsCl and the majority of salts behave similarly, this implicates the anomaly of iodine ion (I-) in this unusual surface population. We argue that the influence of most electrolytes on the PEG corona preserves the polymer in the θ-point with sufficient flexibility to settle into a highly ordered state, whereas I- has a much more severe effect on the corona by collapsing it. The collapsed PEG renders the grafted AuNP a nonspherical shaped complex that, although packs at high density, cannot organize into a 2D ordered arrangement.

Enhancement of the Surface Roughness by Powder Spray Coating on Zirconia Substrate.

Highly surface-roughened zirconia substrates were obtained from additive zirconia powder coating by room temperature spray processing. Homogeneous and dense zirconia coatings were deposited on sintered zirconia substrates with strong bonding by a powder spray coating method. The thickness and surface roughness of the coating layers on zirconia substrates increased with increasing coating cycles, which was confirmed from atomic force microscopy (AFM) and roughness analyses. The tetragonal phase and chemical composition of the zirconia coating layers were similar to those of the raw 3Y-TZP powder used as a raw material, indicating that no phase or composition changes occurred during the spray process.

Use of Physcion to Improve Atopic Dermatitis-Like Skin Lesions through Blocking of Thymic Stromal Lymphopoietin.

Physcion is well known for the treatment of carcinoma. However, the therapeutic effect of physcion on atopic dermatitis (AD) through the inhibition of thymic stromal lymphopoietin (TSLP) level remains largely unknown. In this study, we investigated the anti-AD effect of physcion using HMC-1 cells, splenocytes, and a murine model. Treatment with physcion decreased production and mRNA expression levels of TSLP, IL-6, TNF-ɑ, and IL-1ß in activated HMC-1 cells. Physcion reduced the expression levels of RIP2/caspase-1 and phospho (p)ERK/pJNK/pp38 in activated HMC-1 cells. Physcion suppressed the expression levels of pIKKß/NF-κB/pIkB in activated HMC-1 cells. Moreover, physcion attenuated the production levels of TSLP, IL-4, IL-6, TNF-, and IFN-γ from activated splenocytes. Oral administration of physcion improved the severity of 2,4-dinitrochlorobenzene-induced AD-like lesional skin through reducing infiltration of inflammatory cells and mast cells, and the protein and mRNA levels of TSLP, IL-4, and IL-6 in the lesional skin tissues. Physcion attenuated histamine, IgE, TSLP, IL-4, IL-6, and TNF- levels in serum. In addition, physcion inhibited caspase-1 activation in the lesional skin tissues. These findings indicate that physcion could ameliorate AD-like skin lesions by inhibiting TSLP levels via caspase-1/MAPKs/NF-kB signalings, which would provide experimental evidence of the therapeutic potential of physcion for AD.

Imaging DNA single-strand breaks generated by reactive oxygen species using a liquid crystal-based sensor.

DNA single-strand breaks (SSBs) have attracted much interest since they are highly related to carcinogenesis and ageing. Herein, we report a new liquid crystal (LC)-based sensor for the detection of DNA SSBs generated by reactive oxygen species (ROS) created from the Fenton reaction. The adsorption of single-stranded DNA (ssDNA) onto the cationic surfactant-laden aqueous/LC interface interferes with the surfactant layer, inducing a planar orientation of the LCs. However, the DNA SSBs generated by the Fenton reaction-produced ROS result in a decrease of the electrostatic interactions between the ssDNA and cationic surfactant molecules, causing rearrangement of the surfactant layer and reorientation of the LCs back to a homeotropic alignment. The changes in orientation of the LCs caused by the DNA SSBs are simply converted and observed as a shift from a bright optical image of the LCs to a dark one under a polarized light microscope. With this simple LC-based approach, the DNA SSBs could be detected more effectively and rapidly without any complex instrumentation or intricate processes. Therefore, our research provides a novel strategy for the detection of DNA damage as well as better insight into the DNA-damaging process.

Improved Heat Dissipation of High-Power LED Lighting by a Lens Plate with Thermally-Conductive Plastics.

The junction temperature of high-power LED lighting was reduced effectively using a lens plate made from a thermally-conductive plastics (TCP). TCP has an excellent thermal conductivity, approximately 5 times that of polymethylmethacrylate (PMMA). Two sets of high-power LED lighting were designed using a multi array LED package with a lens plate for thermal simulation. The difference between two models was the materials of the lens plate. The lens plates of first and second models were fabricated by PMMA (PMMA lighting) and TCP (TCP lighting), respectively. At the lens plate, the simulated temperature of the TCP lighting was higher than that of the PMMA lighting. Near the LED package, the temperature of the TCP lighting was 2 °C lower than that of the PMMA lighting. This was well matched with the measured temperature of the fabricated lighting with TCP and PMMA.

Influence of the Thermal Conductivity of Thermally Conductive Plastics on the Thermal Distribution of an Light-Emitting Diode Headlight for Vehicles.

This paper investigates the thermal distribution of an LED headlight for vehicles based on the thermal conductivity of thermally conductive plastics (TCP). In general, heat dissipation structures used for LED headlights are made from metallic materials. However, headlight structures made from TCP have not been investigated. The headlights made from TCP having a various thermal conductivity were fabricated by injection molding with and without a metal plate insert. The temperature characteristics were compared and analyzed using thermal simulations and measurement. The inserted metal in TCP greatly reduced the temperature at solder point, indicating that the fast heat dissipation from the high power LED package to TCP though the inserted metal is essential. The measured temperature at solder points decreased as the thermal conductivity of TCP increased, which is well matched to the simulation results. The measured temperature at the solder point was lower than 150 °C when the thermal conductivity of the TCP was 10 W/mK.

A Novel and Facile Route to Synthesize Atomic-Layered MoS2 Film for Large-Area Electronics.

High-quality and large-area molybdenum disulfide (MoS2 ) thin film is highly desirable for applications in large-area electronics. However, there remains a challenge in attaining MoS2 film of reasonable crystallinity due to the absence of appropriate choice and control of precursors, as well as choice of suitable growth substrates. Herein, a novel and facile route is reported for synthesizing few-layered MoS2 film with new precursors via chemical vapor deposition. Prior to growth, an aqueous solution of sodium molybdate as the molybdenum precursor is spun onto the growth substrate and dimethyl disulfide as the liquid sulfur precursor is supplied with a bubbling system during growth. To supplement the limiting effect of Mo (sodium molybdate), a supplementary Mo is supplied by dissolving molybdenum hexacarbonyl (Mo(CO)6 ) in the liquid sulfur precursor delivered by the bubbler. By precisely controlling the amounts of precursors and hydrogen flow, full coverage of MoS2 film is readily achievable in 20 min. Large-area MoS2 field effect transistors (FETs) fabricated with a conventional photolithography have a carrier mobility as high as 18.9 cm2 V-1 s-1 , which is the highest reported for bottom-gated MoS2 -FETs fabricated via photolithography with an on/off ratio of ≈105 at room temperature.

What Injury Mechanism and Patterns of Ligament Status Are Associated With Isolated Coronoid, Isolated Radial Head, and Combined Fractures?

BACKGROUND: Isolated coronoid, isolated radial head, and combined coronoid and radial head fractures are common elbow fractures, and specific ligamentous injury of each fracture configuration has been reported. However, the osseous injury mechanism related to ligament status remains unclear. QUESTIONS/PURPOSES: The objectives of this study were: (1) to determine what ligamentous injury patterns (medial or lateral collateral) and bone contusion patterns (medial or lateral) are associated with isolated coronoid, isolated radial head, and combined coronoid and radial head fractures; (2) to correlate the osseous injury mechanism based on these findings with isolated coronoid, isolated radial head, and combined coronoid and radial head fractures; and (3) to determine whether isolated and combined coronoid fractures have different fracture lines through the coronoid (tip or anteromedial facet), speculated to be caused by different injury mechanisms. METHODS: Between June 2007 and June 2012, 100 patients with elbow fractures were included in the cohort, with 46 of these patients being excluded owing to incongruity for our surgical indication. Finally, 54 patients with surgically treated elbow fractures who had MRI preoperatively were assessed retrospectively. There were 17 elbows with isolated coronoid fractures, 22 with isolated radial head fractures, and 15 with combined coronoid and radial head fractures. Collateral ligament injury pattern and existence of distal humerus bone contusion were reviewed on MR images. RESULTS: Patients with isolated radial head fractures were at greater risk of medial collateral ligament rupture compared with patients with isolated coronoid fractures (radial head only: 15 of 22 [68%]; coronoid only: three of 17 [18%]; odds ratio [OR], 10.0; 95% CI, 2.2-46.5; p = 0.002). Patients with isolated coronoid fractures had greater risk of lateral ulnar collateral ligament ruptures (coronoid: 16 of 17 [94%]; radial head: seven of 22 [32%]; OR, 3.5; 95% CI, 3.8-333.3; p < 0.001). The presence of radial head fractures was associated with the risk of lateral bone bruising (isolated radial head fracture: 32 of 37 [86%], isolated coronoid fracture: four of 17 [24%]; OR, 29.6; 95% CI, 5.2-168.9; p < 0.001). Medial bone bruising was only detected in isolated coronoid fractures (isolated coronoid fracture: 12 of 17 [71%], others: zero of 37 [0%]). All isolated coronoid fractures involved the anteromedial facet of the coronoid (17 of 17; 100%). However, combined coronoid and radial head fractures often involved the tip (13 of 15; 87%). CONCLUSIONS: Isolated coronoid fractures mostly involved the anteromedial facet of the coronoid process associated with lateral ulnar collateral ligament rupture and medial bone bruising. However, isolated radial head fractures were associated with medial collateral ligament rupture and lateral bone bruising. Combined coronoid and radial head fractures mostly involved a tip fracture of the coronoid with lateral ulnar collateral ligament rupture and lateral bone bruising. Thus surgeons may predict which ligament they should be aware of in the surgical field. LEVEL OF EVIDENCE: Level III, prognostic study.

Ixeris dentata (Thunb. Ex Thunb.) Nakai Extract Inhibits Proliferation and Induces Apoptosis in Breast Cancer Cells through Akt/NF-κB Pathways.

Ixeris dentata (Thunb. Ex Thunb.) Nakai (ID) exhibits various physiological activities, and its related plant derived-products are expected to represent promising cancer therapeutic agents. However, the anticancer effects of ID extract on breast cancer cells classified as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are still unknown. In this study, we investigated the anti-cancer effects and analyzed the molecular mechanism of ID extract in T47D, MCF-7 (ER-, PR-positive, HER2-negative), SK-BR-3(ER-, PR-negative, HER2-positive), and MDA-MB-231 (Triple-negative) through in vitro studies. Additionally, we examined its anti-tumor effects through in vivo studies. Our findings indicated that ID extract-induced apoptosis was mediated via various survival pathways on four breast cancer cells by identifying the factors including Bcl-2 family, phospho-Akt and phospho-nuclear factor-κB (NF-κB). Based on in vitro findings that induced apoptosis via Akt-NF-κB signaling, we investigated the effects of ID extract on mice bearing MDA-MB-231 cells. The results showed that ID extract significantly decreased MDA-MB-231 tumor volume and weight via inducing apoptosis by suppressing phospho-Akt. Overall, these results indicate that ID extract induces apoptosis through the Akt-NFκB signaling pathway in MDA-MB-231 breast cancer cells and tumors, and it may serve as a therapeutic agent for triple-negative human breast cancer.

Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression.

In this study, we showed that PI3K/Akt signaling mediates fucoidan's anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The drug also significantly increased chromatin condensation, which indicates apoptosis, in a concentration-dependent manner as shown by DAPI (4',6-diamidino-2-phenylindole) staining. Fucoidan increased expression of Bax, cleaved poly-ADP ribose polymerase and cleaved caspase-9, and decreased of the Bcl-2, p-Akt, p-PI3K, p-P38, and p-ERK in a concentration-dependent manner. In vivo, fucoidan (at 5 and 10 mg/kg) significantly decreased tumor volume, and increased apoptosis as assessed by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, confirming the tumor inhibitory effect. The drug also increased expression of p-Akt and p-ERK as shown by immunohistochemistry staining. Therefore, fucoidan may be a promising cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human prostate cancer cells.

Vascular Complications Arising from Hemostasis with Manual Compression Following Extracorporeal Membrane Oxygenation Decannulation.

BACKGROUND: We evaluated the vascular complications and success rate of manual compression in achieving hemostasis and access site closure after transfemoral arterial extracorporeal membrane oxygenation (ECMO) decannulation. METHODS: Between February 2010 and July 2014, 63 patients who underwent veno-arterial ECMO were retrospectively studied. Patients who developed postprocedural vascular complications after manual compression were identified, and the hemostasis success rate was evaluated. RESULTS: The overall manual compression success rate was 95.2%. Eleven patients (17.5%) developed vascular complications: hematoma (more than 5 cm) occurred in six patients (9.5%) who were treated with repeat manual compression. Retroperitoneal bleeding occurred in one patient, requiring abdominal hematoma evacuation surgery. One patient (1.6%) developed access site bleeding, requiring suturing. One patient (1.6%) developed an arteriovenous fistula (AVF). Two patients (3.2%) had a pseudoaneurysm, of whom one was treated with sclerotherapy in the femoral artery; the other patient and the AVF patient were treated with repeat manual compression. The hematoma rate was significantly higher in patients with an activated partial thromboplastin time (aPTT) >56, and in whom dual antiplatelet drugs were used (OR: 11.55, 95% CI: 1.32-100.92, p = 0.027; OR: 8.17, CI: 1.61-41.46, p = 0.011, respectively). CONCLUSION: The use of dual antiplatelet drugs and a higher aPTT can lead to an increased risk of post-procedural vascular complications. Therefore, manual compression should be applied cautiously after the correction of coagulopathy factors such as activated clotting time (ACT), aPTT, and platelets.

Spatially Organized Films from Bdellovibrio bacteriovorus Prey Lysates.

Bdellovibrio bacteriovorus is a Gram-negative predator of other Gram-negative bacteria. Interestingly, Bdellovibrio bacteriovorus 109J cells grown in coculture with Escherichia coli ML-35 prey develop into a spatially organized two-dimensional film when located on a nutrient-rich surface. From deposition of 10 µl of a routine cleared coculture of B. bacteriovorus and E. coli cells, the cells multiply into a macroscopic community and segregate into an inner, yellow circular region and an outer, off-white region. Fluorescence in situ hybridization and atomic force microscopy measurements confirm that the mature film is spatially organized into two morphologically distinct Bdellovibrio populations, with primarily small, vibroid cells in the center and a complex mixture of pleomorphic cells in the outer radii. The interior region cell population exhibits the hunting phenotype while the outer region cell subpopulation does not. Crowding and high nutrient availability with limited prey appear to favor diversification of the B. bacteriovorus population into two distinct, thriving subpopulations and may be beneficial to the persistence of B. bacteriovorus in biofilms.

Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthritic mice.

OBJECTIVE: Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is one of the active components present in the root and rhizome of Rheum palmatum. It has been shown to contain biological activity (antitumour, antibacterial, diuretic and vasorelaxant effects). However, the mechanisms underlying the anti-arthritic effect of emodin have not been elucidated. Here we investigated whether emodin treatment would modulate the severity of the disease in an experimental arthritis model. METHODS: We evaluated the effects of emodin on CIA mice in vivo. RESULTS: The pathological processes of RA are mediated by a number of cytokines and MMPs. Expression of these proinflammatory mediators is controlled by nuclear factor-κB (NF-κB). This study was performed to explore the effect of emodin on control of the NF-κB activation pathway and to investigate whether emodin has anti-inflammatory effects in CIA mice in vivo. Emodin inhibited the nuclear translocation and DNA binding of NF-κB subunits, which were correlated with its inhibitory effect on cytoplasmic IκBα degradation in CIA mice. These events further suppressed chemokine production and MMP expression. In addition, emodin inhibited the osteoclast differentiation induced by M-CSF and receptor activation of NF-κB ligand in bone marrow macrophages. CONCLUSION: These findings suggest that emodin exerts anti-inflammatory effects in CIA mice through inhibition of the NF-κB pathway and therefore may have therapeutic value for the treatment of RA.

Apoptotic effect of tolfenamic acid on MDA-MB-231 breast cancer cells and xenograft tumors.

Recent studies have indicated that non-steroidal anti-inflammatory drug (NSAID), particularly tolfenamic acid, can inhibit proliferation and induce apoptosis invarious cancer cells. Breast cancer represents one-third of all cancers diagnosed in women and is the second leading cause of cancer death in Western European and North American women. In the present study, we investigated the apoptotic effect of tolfenamic acid in MDA-MB-231 estrogen receptor-negative human breast carcinoma cells and in a xenograft tumor model. Treatment of cells with tolfenamic acid significantly decreased cell viability in a concentration-dependent manner. Notably, tolfenamic acid increased apoptosis-related proteins, such as p53 and p21, within 48 h. Furthermore, in vivo experiments showed that tolfenamic acid treatment resulted in a significant reduction in tumor volume over 5 weeks. Immunohistochemistry results showed that apoptosis-related protein induction by tolfenamic acid was significantly higher in the 50 mg/kg-treated group compared to the control group. Together, these results indicate that tolfenamic acid induces apoptosis in MDA-MB-231 breast cancer cells and tumor xenograft model and it may be a potential chemotherapeutic agent against breast cancer.

Requirements for anti-aquaporin 5 autoantibody production in a mouse model.

Several oral bacteria, including Prevotella melaninogenica (Pm), have aquaporin (AQP) proteins homologous to human AQP5, a major water channel protein targeted in Sjogren's syndrome. This study aimed to understand the antigenic characteristics that induce autoantibodies against an AQP5 "E" epitope (AQP5E) in a mouse model using C57BL/6 mice. Immunization with a PmE-L peptide derived from Pm AQP, which contains amino acid mismatches both at the B- and T-cell epitopes, efficiently induced anti-AQP5E autoantibodies accompanied by increased germinal center (GC) B and follicular helper T cells in the draining lymph nodes. However, PmE, a peptide lacking a T-cell epitope, and AQP5E-L, an AQP5-derived self-peptide, hardly induced either anti-AQP5E autoantibodies or GC responses. Surprisingly, OTII-AQP5E, a peptide that replaced the self T-cell epitope of AQP5E-L with an ovalbumin-derived foreign T-cell epitope, was not any better than AQP5E-L in the induction of anti-AQP5E autoantibodies and GC response, despite the substantial expansion of CD4+ T cells and production of anti-OTII-AQP5E antibodies. The complex of biotinylated PmE-L peptide and highly immunogenic streptavidin (SA) induced a strong extrafollicular B-cell response skewed toward the expansion of SA-specific B cells. However, the expansion of AQP5E-specific GC B cells was limited, resulting in the inefficient induction of anti-AQP5E autoantibodies. Collectively, our results have demonstrated that anti-AQP5E autoantibody production is only allowed when foreign B- and T-cell epitopes drive a strong GC response of AQP5E-specific B cells for affinity maturation. This study helps explain why cross-reactive anti-AQP5 autoantibodies are not produced during the immune response to Pm in most healthy people.