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Supplemental Material, sj-pdf-1-ear-10.1177_01455613211042566 for Atrial Fibrillation Is Not Associated With Sudden Sensorineural Hearing Loss by Trong-Zong Chen, Bi-Hua Cheng, Hsiao-Yun Hu, Chia-Chi Chang, Shu-Yi Lin and Hung-Meng Huang in Ear, Nose & Throat Journal

Yueh-Hsia Luo,1 Hsien-Jen Cheng,2 Feng-Yuan Tsai,2 Tsui-Chun Tsou,2 Shu-Yi Lin,3 Pinpin Lin2 1Department of Life Sciences, National Central University, Taoyuan City 32001, Taiwan; 2National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County 35053, TaiwanCorrespondence: Yueh-Hsia LuoDepartment of Life Sciences, National Central University, No. 300, Zhongda Road, Zhongli District, Taoyuan City 32001, TaiwanTel +886-34227151Fax +886-34228482Email yhLuo@g.ncu.edu.twPinpin LinNational Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, TaiwanTel +886-37246166Fax +886-37587406Email pplin@nhri.edu.twBackground: Gold nanoparticles with high biocompatibility and immunomodulatory properties have potential applications in the development of new diagnostic and therapeutic strategies for nanomedicine. Nanoparticles targeting macrophages can manipulate or control immunological diseases. This study assessed the activity of dendrimer-encapsulated gold nanodots (AuNDs) with three surface modifications [ie, outfacing groups with primary amine (AuNDs-NH2), hydroxyl (AuNDs-OH), and quaternary ammonium ions (AuNDs-CH3)] regulated macrophage function and antioxidant response through Nrf2-dependent pathway.Methods: AuNDs were prepared and characterized. Intracellular distribution of AuNDs in human macrophages was observed through confocal microscopy. The activity of AuNDs was evaluated using macrophage functions and antioxidant response in the human macrophage cell line THP-1.Results: AuNDs-NH2 and AuNDs-CH3, but not AuNDs-OH, drove the obvious Nrf2-antioxidant response element pathway in THP-1 cells. Of the three, AuNDs-NH2 considerably increased mRNA levels and antioxidant activities of heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 in THP-1 cells. IL-6 mRNA and protein expression was mediated through Nrf2 activation in AuNDs-NH2-treated macrophages. Furthermore, Nrf2 activation by AuNDs-NH2 increased the phagocytic ability of THP-1 macrophages.Conclusion: AuNDs-NH2 had immunomodulatory activities in macrophages. The findings of the present work suggested that AuNDs have potential effects against chronic inflammatory diseases via the Nrf2 pathway.Keywords: gold nanodots, macrophage, antioxidant, inflammation

Shu-Yi Lin,1 Bing-Yu Yao,2 Che-Ming Jack Hu,2,3 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Research Center for Nanotechnology and Infectious Diseases, Taipei, TaiwanCorrespondence: Hui-Wen ChenDepartment of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei 10617, TaiwanTel +886 2 33669450Email winnichen@ntu.edu.twBackground: Poultry vaccine has limited choices of adjuvants and is facing severe threat of infectious diseases due to ineffective of widely used commercial vaccines. Thus, development of novel adjuvant that offers safe and effective immunity is of urgent need.Materials and Methods: The present research engineers a novel chicken adjuvant with potent immune-potentiating capability by incorporating avian toll-like receptor 21 (TLR21) agonist CpG ODN 2007 with a poly(lactic-co-glycolic acid) (PLGA)-based hollow nanoparticle platform (CpG-NP), which subsequently assessed ex vivo and in vivo.Results: CpG-NPs with an average diameter of 164 nm capable of sustained release of CpG for up to 96 hours were successfully prepared. With the ex vivo model of chicken bone marrow-derived dendritic cells (chBMDCs), CpG-NP was engulfed effectively and found to induce DC maturation, promoting dendrite formation and upregulation of CD40, CD80 and CCR7. In addition to enhanced expression of IL-1β, IL-6, IL-12 and IFN-γ, 53/84 immune-related genes were found to be stimulated in CpG-NP-treated chBMDCs, whereas only 39 of such genes were stimulated in free CpG-treated cells. These upregulated genes suggest immune skewing toward T helper cell 1 bias and evidence of improved mucosal immunity upon vaccination with the CpG-NP. The CpG-NP-treated chBMDCs showed protective effects to DF-1 cells against avian influenza virus H6N1 infection. Upon subsequent coupling with infectious bronchitis virus subunit antigen administration, chickens were immunostimulated to acquire higher humoral immune response and protective response against viral challenge.Conclustion: This work presents a novel hollow CpG-NP formulation, demonstrating effective and long-lasting immunostimulatory ability ex vivo and in vivo for chickens, as systemically compared to free CpG. This enhanced immune stimulation benefits from high stability and controlled release of internal component of nanoparticles that improve cellular delivery, lymphoid organ targeting and sustainable DC activation. CpG-NP has broad application potential in antiviral and vaccine development.Keywords: polymeric hollow nanoparticle, CpG, adjuvant, antiviral response, influenza virus, infectious bronchitis virus, vaccine

This article presents the first work to fundamentally study the effect of steric hindrance in Pdot systems., Semiconducting polymer dots (Pdots) have recently emerged as a new type of ultrabright fluorescent probe that has been proved to be very useful for biomedical imaging. However, Pdots often suffer from serious fluorescence aggregation-caused quenching (ACQ) especially for near-infrared (NIR) fluorescent Pdots. This article compared two strategies to overcome the ACQ effect in near-infrared emissive Pdot systems: aggregation-induced emission (AIE) and anti-aggregation-caused quenching (anti-ACQ). The results show that the anti-ACQ platform outperforms the AIE system. The fluorescence quantum yield of anti-ACQ-based Pdots can be over 50% and the average per-particle brightness of the Pdots is about 5 times higher than that of the commercially available quantum dots. To help understand why the monomer conformations could greatly affect the optical properties of Pdots, molecular dynamics simulations were performed for the first time in such complicated Pdot systems. To demonstrate applications for in vivo fluorescence imaging, both microangiography imaging on living zebrafish embryos and specific tumor targeting on mice were performed. We anticipate that these studies will pave the way for the design of new highly fluorescent Pdot systems.