85 research outputs found

    Eosinophils downregulate lung alloimmunity by decreasing TCR signal transduction

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    Despite the accepted notion that granulocytes play a universally destructive role in organ and tissue grafts, it has been recently described that eosinophils can facilitate immunosuppression-mediated acceptance of murine lung allografts. The mechanism of eosinophil-mediated tolerance, or their role in regulating alloimmune responses in the absence of immunosuppression, remains unknown. Using lung transplants in a fully MHC-mismatched BALB/c (H2d) to C57BL/6 (H2b) strain combination, we demonstrate that eosinophils downregulate T cell-mediated immune responses and play a tolerogenic role even in the absence of immunosuppression. We further show that such downregulation depends on PD-L1/PD-1-mediated synapse formation between eosinophils and T cells. We also demonstrate that eosinophils suppress T lymphocyte responses through the inhibition of T cell receptor/CD3 (TCR/CD3) subunit association and signal transduction in an inducible NOS-dependent manner. Increasing local eosinophil concentration, through administration of intratracheal eotaxin and IL-5, can ameliorate alloimmune responses in the lung allograft. Thus, our data indicate that eosinophil mobilization may be utilized as a novel means of lung allograft-specific immunosuppression

    Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice

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    Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au110-PEI-PEG5000-AA.siRNA) illustrated favourable physicochemical characteristics, including particle size, surface charge, and stability. In vitro, anisamide-targeted AuNPs selectively bound to human prostate cancer PC-3 cells, inducing efficient endosomal escape of siRNA, and effective downregulation of the RelA gene. In vivo, prolonged systemic exposure of siRNA was achieved by anisamide-targeted AuNPs resulting in significant tumour growth suppression in a PC3 xenograft mouse model without an increase in toxicity. In addition, a combination of siRNA-mediated NF-κB knockdown using anisamide-targeted AuNPs with Paclitaxel produced a synergistic therapeutic response, thus providing a promising therapeutic strategy for the treatment of prostate cancer

    Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumour-bearing mice

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    Background: Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects. Methods: In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex. Results: The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice. Conclusion: These results demonstrate a promising strategy for clinical application of CPTT in cancer

    Quantum simulation of topological zero modes on a 41-qubit superconducting processor

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    Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named as Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-AndreËŠ\acute{\mathrm{e}}-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.Comment: Main text: 6 pages, 4 figures; Supplementary: 16 pages, 14 figure

    Fasting blood glucose level in oral squamous cell carcinoma: Analysis of 205 cases by histopathology and serological detection

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    Objective: The present study explored the correlation between FBG level with clinicopathological features and prognosis, a total of 205 OSCC patients were included retrospectively. Materials and methods: 205 patients who were admitted to the Department of Oral and Maxillofacial Oncology Surgery from January 2008 to December 2019, were enrolled. ROC curve analysis was used to obtain the optimal cutoff value for FBG; The Cox proportional hazard regression model for the risk factors affecting prognosis. Results: Cox proportional regression models univariate analysis showed that age, treatment, neck lymphatic dissection, surgical margin, FBG, BMI were positive predictors, while primary tumor size, differentiation, tumor recurrence, drinking were negative predictors; on multivariable Cox regression analysis, tumor recurrence, BMI, FBG, surgical margin and alcohol consumption were independently and significantly related to the outcome of OSCC. Conclusions: The FBG is an independent prognostic factor for patients with OSCC. To improve the overall survival of patients with OSCC, comprehensive treatment based on radical surgery should be considered as the major treatment modalities

    Asymmetric double-agents architecture for fast handoff and efficient routing

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    MIPv6 is one of the dominating protocols that enable a mobile node to maintain its connectivity to the Internet when moving from one access router to another. However, it suffers from long handoff latency and routing inefficiency. In this paper, we present a novel distributed mobility management scheme, ADA (Asymmetric Double-agents Architecture), which introduces two mobility agents to serve one end-to-end communication. One mobility agent is located close to the MN to limit the amount of MIPv6 signaling traffic outside the local domain. The other mobility agent is located close to the CN to minimize routing overheads. Quantitative analysis shows that ADA significantly outperforms the existing mobility management protocols.5 page(s

    Performance Analysis of Ship Exhaust Gas Temperature Differential Power Generation

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    In addition to the use of waste heat from the vessel’s exhaust gas to save energy onboard, reduce the carbon emissions of the ship, and combine the characteristics of ship waste heat, mathematical modeling and testing of ship waste heat temperature difference power generation were carried out in this study. Finally, an experimental platform for temperature differential power generation was established to assess the impact of influencing agents on the efficiency of temperature differential power generation. The results show that the effect of different thermally conductive greases on the efficiency of temperature differential power generation tablets is basically the same. In addition, the rate of flow of cooling water, the cooling plate area, and the heat source temperature have more significant effects on the open-circuit voltage and maximum output power. The results show that the maximum power output growth rate increases with increasing cooling water flow, reaching 8.26% at 4 L/min. Likewise, increasing the heat source temperature enhances the maximum output power growth rate by 15.25% at 220 °C. Conversely, the maximum output power of the temperature difference power generation device decreases as the cooling plate area increases, and the maximum output power reduction rate is 15.25% when the cooling plate area is 80 × 200 mm2 compared to the case of using a cooling plate area of 80 × 80 mm2. Moreover, the maximum output power of the temperature differential power generation device reaches 13.6 W under optimal conditions. Assuming that the temperature difference power generation plate is evenly distributed on the tailpipe of the 6260ZCD marine booster diesel engine, it could save approximately 5.44 kW·h electric power per hour and achieve a reduction in CO2 emissions of 0.3435 kg per hour

    Preparation Methods and Performance Analysis of Polyanthra-Quinone/Carbon Nanotube Composites for Capturing Carbon Dioxide

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    Carbon capture is one of the important methods to achieve carbon neutrality. In this paper, a simple and reliable method for the preparation of poly(anthraquinone)/multi-walled carbon nanotube composites (PAQ/MWCNTs) for capturing carbon dioxide is proposed. Using constant magnetic stirring, 1,4-anthraquinone (1,4-AQ) was allowed to accumulate on multi-walled carbon nanotube (MWCNTs) substrates via π–π. The poly(anthraquinone)/multi-walled carbon nanotube composites were produced by this continuous process. Besides, the carbon cloth electrode prepared from PAQ/MWCNTs composites was subjected to redox potentials for carbon dioxide capture. Results showed that PAQ/MWCNTs composites had good redox reversibility, their carbon dioxide capture capacity was 7.80 mmol·g−1 while the material utilization rate reaches reached 73.4%
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