A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Anhai Chen,Chufeng He,Yong Feng,Jie Ling,Xin Peng,Xianlin Liu,Shuang Mao,Yongjia Chen,Mengyao Qin,Shuai Zhang,Yijiang Bai,Jian Song,Zhili Feng,Lu Ma,Dinghua He,Lingyun Mei1 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However,few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenicfactors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in thesepatients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the ge-netic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individualswithin the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis andclassified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing wasverified through a minigene assay. The predicted three-dimensional protein structure and biochemical experimentswere used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was fol-lowed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A >C) was identified and classified as pathogenic (PVS1(RNA),PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation mayimpair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellularmislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improvedhearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molec-ular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgeryprovides a reference for auditory rehabilitation in similar patients.

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps

Kun Chen,Miaomiao Han,Mengyao Tang,Yadong Xie,Yuting Lai,Xianting Hu,Jia Zhang,Jun Yang,Huabin Li 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.6

Purpose: Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP. Methods: Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and protein expression in nasal tissue extracts. Cells isolated from nasal tissues and peripheral blood mononuclear cells were characterized by flow cytometry. Local antibody production was measured in tissue extracts with a Bio-Plex assay. Additionally, changes in Hrd1 expression in response to specific inflammatory stimuli were measured in cultured dispersed polyp cells. Results: Nasal polyps (NPs) from patients with eosinophilic CRSwNP (ECRS) had increased levels of Hrd1, B-cells and plasma cells compared with NPs from patients with non-eosinophilic CRSwNP (non-ECRS) or other control subjects (P < 0.05). The average Hrd1 levels in B-cells in NPs from ECRS patients were significantly higher than those from non-ECRS patients and control subjects (P < 0.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal controls (P < 0.05). Interestingly, Hrd1 expression in cultured polyp cells from ECRS patients, but not non-ECRS patients, was significantly increased by interleukin-1β, lipopolysaccharide and Poly(I:C) stimulation, and inhibited by dexamethasone treatment (P < 0.05). Conclusions: Differential Hrd1 expression and B-cell accumulation between the ECRS and non-ECRS subsets suggests that they can exhibit distinct pathogenic mechanisms and play important roles in NP.

IL-17A Secreted by Th17 Cells Is Essential for the Host against Streptococcus agalactiae Infections

( Jing Chen ),( Siyu Yang ),( Wanyu Li ),( Wei Yu ),( Zhaowei Fan ),( Mengyao Wang ),( Zhenyue Feng ),( Chunyu Tong ),( Baifen Song ),( Jinzhu Ma ),( Yudong Cui ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.5

Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4⁺ T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4⁺ T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4⁺ T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4⁺ T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae. Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

未成年人犯罪低龄化之预防和教育路径探索

马玉梅 ( Ma-yumei ),陈梦瑶 ( Chen-mengyao ) 경상대학교 교육연구원 2022 중등교육연구 Vol.34 No.2

未成年人犯罪案件频发, 其犯罪的恶性程度已经远超出大众的想象, 并且已日渐成为一个世界性的难题。种种迹象表明, 未成年人犯罪日趋严重且未成年人犯罪年龄低龄化已然是一种现状, 虽然中国通过实施《刑法修正案(十一)》降低了刑事责任年龄以期进行减少犯罪和改善环境, 但这并不能从根本上解决未成年人犯罪低龄化的问题。本文通过分析未成年人犯罪的特点、低龄化趋势及成因, 认为家庭教育缺失、学校教育不足、社会风气不良、法律规制不完善等外部因素是导致低龄未成年人犯罪的主要客观原因, 未成年人自身方面心智不成熟和失衡也是犯罪的主要内因。想要从根本上预防低龄未成年人犯罪, 仅靠降低刑事责任年龄是难以达到理想治理效果的, 需要通过个人、家庭、学校、社会各界的共同推动, 同时司法方面也要积极推进, 学习借鉴各国优秀的有关未成年人犯罪的制度完善法律规制, 全面探索新时期低龄未成年人犯罪的预防和教育路径。只有依靠全社会的共同努力, 才能有效预防低龄未成年人犯罪, 保障社会秩序。 Article Abstract:Juvenile crimes occur frequently, and the malignant degree of their crimes has far exceeded the imagination of the public, and has increasingly become a worldwide problem. There are indications that juvenile delinquency is becoming more and more serious and the younger age of juvenile delinquency is already a status quo. Although China has lowered the age of criminal responsibility through the implementation of the Criminal Law Amendment (11) in order to reduce crime and improve the environment, this cannot fundamentally solve the problem of younger age of juvenile delinquency. By analyzing the characteristics, the trend and the causes of juvenile delinquency, this paper holds that the external factors, such as the lack of family education, the inadequate school education, the bad social atmosphere and the imperfect legal regulations, are the main objective causes of juvenile delinquency, and the immature and imbalance of minors' own minds are also the main internal cause of the crime. In order to fundamentally prevent juvenile delinquency, it is difficult to achieve the ideal governance effect only by lowering the age of criminal responsibility. It requires the joint efforts of individuals, families, schools and all sectors of society. And at the same time, the judiciary should actively promote, learn from the excellent systems of various countries on juvenile delinquency, improve the legal regulations, and comprehensively explore the path of prevention and education of juvenile delinquency in the new era. Only relying on the joint efforts of the whole society can we effectively prevent juvenile delinquency and ensure social order.

Backbone Coplanarity Tuning of 1,4-Di(3-alkoxy-2-thienyl)-2,5-difluorophenylene-Based Wide Bandgap Polymers for Efficient Organic Solar Cells Processed from Nonhalogenated Solvent

Liao, Qiaogan,Yang, Kun,Chen, Jianhua,Koh, Chang Woo,Tang, Yumin,Su, Mengyao,Wang, Yang,Yang, Yinhua,Feng, Xiyuan,He, Zhubing,Woo, Han Young,Guo, Xugang American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.34

<P>Halogenated solvents are prevailingly used in the fabrication of nonfullerene organic solar cells (NF-OSCs) at the current stage, imposing significant restraints on their practical applications. By copolymerizing phthalimide or thieno[3,4-<I>c</I>]pyrrole-4,6-dione (TPD) with 1,4-di(3-alkoxy-2-thienyl)-2,5-difluorophenylene (DOTFP), which features intramolecular noncovalent interactions, the backbone planarity of the resulting DOTFP-based polymers can be effectively tuned, yielding distinct solubilities, aggregation characters, and chain packing properties. Polymer DOTFP-PhI with a more twisted backbone showed a lower degree of aggregation in solution but an increased film crystallinity than polymer DOTFP-TPD. An organic thin-film transistor and NF-OSC based on DOTFP-PhI, processed with a nonhalogenated solvent, exhibited a high hole mobility up to 1.20 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP> and a promising power conversion efficiency up to 10.65%, respectively. The results demonstrate that DOTFP is a promising building block for constructing wide bandgap polymers and backbone coplanarity tuning is an effective strategy to develop high-performance organic semiconductors processable with a nonhalogenated solvent.</P> [FIG OMISSION]</BR>

Genome‑wide identification of GMP genes in Rosaceae and functional characterization of FaGMP4 in strawberry (Fragaria × ananassa)

Yuanxiu Lin,Jiahao Zhang,Lintai Wu,Yunting Zhang,Qing Chen,Mengyao Li,Yong Zhang,Ya Luo,Yan Wang,Xiaorong Wang,Haoru Tang 한국유전학회 2021 Genes & Genomics Vol.43 No.6

Background GDP-D-mannose pyrophosphorylase (GMP) is one of the key enzymes determining ascorbic acid (AsA) biosynthesis. However, little information about GMP genes is currently available for the Rosaceae species, especially in the AsA-riched cultivated octoploid strawberry (Fragaria × ananassa). Objective To identify the all the GMP genes in Rosaceae, as well as the predominant homologues and the role of GMP genes in strawberry AsA accumulation. Methods In the present study, we performed genome-wide identifcation and comprehensive analysis of the duplicated GMP genes in strawberry and other Rosaceae species by bioinformatics methods, the expression of the GMP genes from cultivated strawberry (Fragaria × ananassa, FaGMP) was specifcally analyzed by qPCR. Finally, the FaGMP4 was transiently overexpressed in strawberry to estimate the role of GMP in regulating AsA accumulation in strawberry. Results As results, a total of 28 GMP genes were identifed in the fve Rosaceae species. The origins of duplication events analysis suggested that most GMP duplications in Rosaceae species were generated from whole genome duplication (WGD). The Ka/Ks ratio suggested that FaGMP genes underwent a stabilization selection. qPCR based expression analysis showed diferent patterns of FaGMP paralogs during fruit ripening, while FaGMP4 expressed higher in the variety containing higher AsA. Overexpression of FaGMP4 in strawberry signifcantly enhanced AsA accumulation. Furthermore, the expression of FaGMP4 under the treatment of blue and red light was largely increased in leaves while signifcantly inhibited in fruit. These results revealed the vital role of FaGMP4 in regulating AsA in strawberry.

간호대생과 비보건계열 여대생의 미세먼지 위험에 대한 인식과 지식, 건강 관리행위 비교 연구

김선미,김슬기,김진선,박주형,배다희,유수빈,유영주,임지향,최유진,Chen Mengyao,양숙자,손지희 이화여자대학교 간호과학대학 2019 이화간호학회지 Vol.- No.53

Purpose: This study aimed to know whether there is a comparison of perception, knowledge and health promoting behaviors about particular matter between nursing students and non-health departments college students. Methods: A quantitative research is used. Data were collected from August 1 to 19. The study sample was nursing students and non-health departments students. For the similar condition of samples, this study excluded whose first language is not Korean. Independent T-test and pearson’s correlation was used for this study. Results: A significant positive correlation did not existed between difference of major and perception(t=0.017, p=0.986), knwledge(t=0.652, p=.516) and health promoting behaviors(t=-0.114, p=.910) about particular matters. Conclusion: Based on the study results, there is no significant correlation of perception and actions about particular matters between nursing students and non-health department college students.

Head-to-Head Linked Dialkylbifuran-Based Polymer Semiconductors for High-Performance Organic Thin-Film Transistors with Tunable Charge Carrier Polarity

Shi, Shengbin,Wang, Hang,Uddin, Mohammad Afsar,Yang, Kun,Su, Mengyao,Bianchi, Luca,Chen, Peng,Cheng, Xing,Guo, Han,Zhang, Shiming,Woo, Han Young,Guo, Xugang American Chemical Society 2019 Chemistry of materials Vol.31 No.5

<P>A planar backbone conformation is essential for enabling polymer semiconductors with high charge carrier mobility in organic thin-film transistors. Benefiting from the smaller van der Waals radius of the O atom in furan (versus the S atom in thiophene), alkylated furan exerts a reduced steric hindrance on neighboring arene, and it was found that the head-to-head (HH)-linked 3,3′-dialkyl-2,2′-bifuran (<B>BFR</B>) can attain a high degree of backbone planarity. Hence, <B>BFR</B> should be a promising building block for constructing polymer semiconductors with a planar backbone conformation and hold distinctive advantages over a dialkylbithiophene-based analogue, which is typically highly twisted. The alkyl chains on the 3 and 3′ positions offer good solubility to the resulting polymers, which in combination with its planar backbone yields an improved molecular design window for developing high-performance polymer semiconductors, particularly those with a simple molecular structure and based on the acceptor co-unit without any solubilizing chains. When incorporated into polymer semiconductors, remarkably high hole and electron mobilities of 1.50 and 0.31 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP> are obtained for <B>BFR</B>-based polymers <B>FBFR-BO</B> and <B>CNBFR-C18</B> containing fluorinated and cyano-functionalized benzothiadiazole as the acceptor co-unit, respectively. Such mobilities are the highest values for HH-linked polymers and also among the best for furan-containing polymers. The results demonstrate that HH-linked dialkylbifuran is a highly promising building block for constructing organic and polymeric semiconductors, and this new approach by incorporating HH <B>BFR</B> offers several distinctive advantages for developing high-performance polymer semiconductors, including effective optoelectronic property tuning using a minimal number of aromatic rings, reduced structural complexity, facile material synthesis, good material solubility, and enriching the material library. In addition, the study offers important guidelines for future development of furan-based polymers and head-to-head linkage containing organic semiconductors.</P> [FIG OMISSION]</BR>