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.

이광수의 '무정'과 장한수의 '제소인연' 비교연구

장춘매(Zhang, Chun-Mei) 한국문학회 2010 韓國文學論叢 Vol.56 No.-

20세기 초에 유가사상에 젖어 있었던 중한 양국은 서구문화의 영향으로 근대화로 진입하기 시작했다. 중한 양국 근대과도기의 연애와 혼인에 관한 인식을 밝히기 위해 본고는 한국 작가 이광수의 <무정>과 중국 작가 장한수의 <제소인연>을 비교했다. 두 작품은 모두 당대 사람들에게 익숙하지 않은 자유연애 이야기를 서술하고 있다. 본고는 이 두 작품을 주제, 인물, 서사법 등 여러 측면에서 비교하여 그 공통점과 차이점을 찾아낼 뿐만 아니라 작가 이광수와 장한수가 자유연애에 대해 주장하는 관점도 규명했다. 그리고 주제와 문체의 차원에서 두 작품이 전통문학을 계승하면서 개혁해 나아가는 측면도 고찰하였다. As the twentieth century began, both Korea and China featured with the traditional Confucianism started towards modern societies thanks to the influence of western culture. To expound the general viewpoints of the two countries on marriage at the transitional time, the paper is intended to make a comparative study of two works--Mu Jeong by Korean writer Lee Kwang-soo and Ti xiao yin yuan by Chinese writer Zhang Hen-shui. The two works both tell stories about people’s freedom to choose their spouses--a new concept unfamiliar to peoples at that time in both countries. The paper is designed to seek out the differences and similarities between the two novels from the aspects of themes, characterizations, and narrative methods and is an attempt to make a study of the propositions of both Lee Kwang-soo and Zhang Hen-shui on the freedom to choose one's spouse. Besides, the paper is also an effort to study what the two writers inherit from their respective traditional literatures and what is invented by the two.

Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome

Xi-Mei Zhang,Yun-Bo Zhang,Mei-Hua Chi 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.3

Purpose: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). Materials and Methods: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. Results: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessmentfor insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reducedFPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. Conclusion: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.

Different genomic DNA methylation patterns between male and female adults of white-backed planthoppers Sogatella furcifera

Mei Zhang,Jia-Lin Chen,Xiao-Sui Zhou,Shi-Ke Liang,Guang-Hong Li,Fang-Hai Wang 한국응용곤충학회 2014 Journal of Asia-Pacific Entomology Vol.17 No.4

DNAmethylation plays a key role in gene regulation and phenotype variation in many organisms. The aimof thisstudy was to survey the frequency and variation of cytosine methylation at CCGG sequences in adult male andfemale planthoppers Sogatella furcifera, a major rice pest in Asia, and to determine the occurrence ofmethylationchanges associatedwith sexual dimorphismusingmethylation-sensitive amplification polymorphism. 1131DNAfragments including CCGG siteswere amplified using 36 pairs of selective primers: about 191methylated bandswere identified. Inmale planthoppers,we got a total of 581 bands, including 40 fully-methylated bands, 65 hemimethylatedbands and 476 none-methylated bands, so the fully-methylated ratio, hemi-methylated ratio andtotal methylated ratio were 6.88%, 11.19% and 18.07%, respectively. In the female planthopper, there were atotal of 550 bands, including 44 fully-methylated bands, 42 hemi-methylated bands and 464 none-methylatedbands. The fully-methylated ratio was 7.64% in female planthoppers, which was slightly higher than in themale planthoppers, however, the hemi-methylated ratio was lower (8.00%) in the female compared with themale planthopper. Altogether, 46 DNA bands displayed variable cytosine methylation patterns between maleand female samples: 20 of themoccurred only inmale samples and 26 only in female samples. Thus, the genomemethylation patterns are different between male and female adults. The results suggest that DNA methylationmight be related to sexual differentiation and development in S. furcifera.

Genotoxicity of Zizyphi Spinosi Semen in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

Zhang, Mei-Shu,Bang, In-Seok,Kang, Chang-Su,Park, Cheol-Beom The Korean Society of Food Hygiene and Safety 2012 한국식품위생안전성학회지 Vol.27 No.2

Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alkaloids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucleated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spinosi does not have mutagenic potential under the conditions examined in each study.

Comparisons of Curative and Side Effects of Chemoradiotherapy among Xinjiang Han, Uigur and Kazakh Esophageal Carcinoma Patients

Zhang, Li,Ma, Li-Li,Zhang, Jian-Qing,Yang, Mei,Xun, Tu-Er,Li, Ai Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Objective: This study aimed to explore the differences in the curative and side effects of chemoradiotherapy on esophageal cancer (EC) among Xinjiang Han, Uigur and Kazakh patients. Methods: 170 patients with IIA stage-IV of esophageal squamous cell carcinoma were analyzed retrospectively. Based on different nationalities, they were divided into the Han, Uigur and Kazakh groups. The 1-, 2- and 3-year survival rates, incidence of the side effects (including hematological toxicities, radioactive esophagitis and percutaneous reactions) and application of antibiotics and harmonics were compared among the groups. There was no significant difference in the short-term curative effects among the Han, Uigur and Kazakh groups. The 1- 2- and 3-year survival rates of the three groups were 84%, 40%, 26%; 78%, 27%, 18%; and 60%, 21%, 12% ($x^2$=14.497, P<0.05). The incidence rate of hamatological toxicity ${\geq}$Grade 2 in the Kazakh group was significantly lower than that in the Han or Uigur group. Results: The incidence rates of radioactive esophagitis and percutaneous reactions Grade 2 in the Han group were significantly higher than those in the Uigur or Kazakh group. There was no significant difference in the types of applied antibiotics among the groups, but there were significant differences in the days of antibiotic application and proportion of patients receiving harmonics between the Hans and either of other groups. Conclusion: Chemoradiotherapy shows a better effect in the long-term survival rate among Han EC patients compared with Uigur or Kazakh EC patients. Uigur and Kazakh patients show a better tolerance to the side effects of chemoradiotherapy compared with Hans.

Efficient Production and Molecular Identification of Tetraploid Watermelons Using Colchicine and Oryzaline in Vitro

Zhang Ming-Fang,Zhang Quan-Mei,Yang Jing-Hua,Yang Jia-Fu,Lin Yi,Rao Li-Bing 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

The Effect of Transformation on the Virulence of Streptococcus pneumoniae

Zhang Xue-Mei,Yin Yi-Bing,Zhu Dan,Chen Bao-De,Luo Jin-Yong,Deng Vi-Ping,Liu Ming-Fang,Chen Shu-Hui,Meng Jiang-Ping,Lan Kai,Huang Yuan-Shuai,Kang Ge-Fei The Microbiological Society of Korea 2005 The journal of microbiology Vol.43 No.4

Although pneumococcus is one of the most frequently encountered opportunistic pathogen in the world, the mechanisms responsible for its infectiveness have not yet been fully understood. In this paper, we have attempted to characterize the effects of pneumococcal transformation on the pathogenesis of the organism. We constructed three transformation-deficient pneumococcal strains, which were designated as Nos. 1d, 2d, and 22d. The construction of these altered strains was achieved via the insertion of the inactivated gene, comE, to strains 1, 2 and 22. We then conducted a comparison between the virulence of the transformation-deficient strains and that of the wild-type strains, via an evaluation of the ability of each strain to adhere to endothelial cells, and also assessed psaA mRNA expression, and the survival of hosts after bacterial challenge. Compared to what was observed with the wild-type strains, our results indicated that the ability of all of the transformation-deficient strains to adhere to the ECV304 cells had been significantly reduced (p < 0.05), the expression of psaA mRNA was reduced significantly (p < 0.05) in strains 2d and 22d, and the median survival time of mice infected with strains Id and 2d was increased significantly after intraperitoneal bacterial challenge (p < 0.05). The results of our study also clearly indicated that transformation exerts significant effects on the virulence characteristics of S. pneumoniae, although the degree to which this effect is noted appears to depend primarily on the genetic background of the bacteria.

Overexpressed Ostepontin-c as a Potential Biomarker for Esophageal Squamous Cell Carcinoma

Zhang, Mei-Xiang,Xu, Yi-Jun,Zhu, Ming-Chen,Yan, Feng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

Diversity and composition of microbiota during fermentation of traditional Nuodeng ham

Zhang Xiao-mei,Dang Xi-jun,Wang Yuan-bing,Sun Tao,Wang Yao,Yu Hong,Yang Wu-song 한국미생물학회 2021 The journal of microbiology Vol.59 No.1

The microbial community is one of the most important factors in shaping the characteristics of fermented food. Nuodeng ham, traditionally produced and subjected to 1–4 years of fermentation, is a dry fermented food product with cultural and economic significance to locals in southwestern China. In this study, we aimed to characterize the microbiota and physicochemical profiles of Nuodeng ham across different stages of fermentation. Ham samples from each of the four years were analyzed by sequencing bacterial 16S rRNA gene and fungal internal transcribed spacer sequence, in order to characterize the diversity and composition of their microflora. A total of 2,679,483 bacterial and 2,983,234 fungal sequences of high quality were obtained and assigned to 514 and 57 genera, respectively. Among these microbes, Staphylococcus and Candida were the most abundant genera observed in the ham samples, though samples from different years showed differences in their microbial abundance. Results of physicochemical properties (pH, water, amino acid, NaCl, nitrate and nitrite contents, and the composition of volatile compounds) revealed differences among the ham samples in the composition of volatile compounds, especially in the third year samples, in which no nitrite was detected. These results suggest that the structure and diversity of microbial communities significantly differed across different stages of fermentation. Moreover, the third year hams exhibits a unique and balanced microbial community, which might contribute to the special flavor in the green and safe food products. Thus, our study lends insights into the production of high quality Nuodeng ham.