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.

Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy

Lingyun Liu,Wei Wang,Yi Zhang,Jianting Long,Zhaohui Zhang,Qiao Li,Bin Chen,Shaoqiang Li,Yunpeng Hua,Shunli Shen,Baogang Peng 대한암학회 2018 Cancer Research and Treatment Vol.50 No.2

Purpose Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. Materials and Methods Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. Results The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigennegative and preoperative elevated carbohydrate antigen 19-9 patients. Conclusion Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.

Crashworthiness design of bionic-shell thin-walled tube under axial impact

Lingyun Qin,Shuyi Yang,Hongzhou Li,Juchuan Dai,Guosheng Wang,Qihui Ling,Zhewu Chen 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.7

Bionic structures have been widely utilized in the crashworthiness design of thin-walled structures due to their superior energy absorption capabilities. This study constructed a bionic-shell thin-walled tube (BST) with excellent crashworthiness based on the structural bionic principle using the shell shape cross-section as the prototype. First, the theoretical model of the mean crushing force (MCF) for BST under axial compression was developed. An experiment was conducted and the reliability of the finite element model was verified. Then, the effects of structural parameters, such as the number of ribs, wall thickness, and inner tube diameter on the crashworthiness of the BST were investigated using the finite element method. Finally, to obtain the ideal configuration of structural parameters, the BST was optimized using the response surface method (RSM) with specific energy absorption (SEA) and crushing force efficiency (CFE) as the optimization objectives and peak crushing force (PCF) as the constraint condition. The results showed that the BST with six ribs exhibited the best crashworthiness under the same mass. The optimized BST-6 was found to have better energy absorption performance than the double circular tube (DCT) and the bionic-horsetail thin-walled tube (BHT). Compared with the DCT, the SEA and CFE increased by 35.15 % and 32.23 %, respectively.

Promoting the modernization of community governance based on emotional management of network media in public events

Zhao Lingyun,Chen Xi 한중경제문화학회 2021 한중경제문화연구 Vol.16 No.-

A real-time sorting algorithm for in-beam PET of heavy-ion cancer therapy device

Ke, Lingyun,Yan, Junwei,Chen, Jinda,Wang, Changxin,Zhang, Xiuling,Du, Chengming,Hu, Minchi,Yang, Zuoqiao,Xu, Jiapeng,Qian, Yi,She, Qianshun,Yang, Haibo,Zhao, Hongyun,Pu, Tianlei,Pei, Changxu,Su, Hong Korean Nuclear Society 2021 Nuclear Engineering and Technology Vol.53 No.10

A real-time digital time-stamp sorting algorithm used in the In-Beam positron emission tomography (In-Beam PET) is presented. The algorithm is operated in the field programmable gate array (FPGA) and a small amount of registers, MUX and memory cells are used. It is developed for sorting the data of annihilation event from front-end circuits, so as to identify the coincidence events efficiently in a large amount of data. In the In-Beam PET, each annihilation event is detected by the detector array and digitized by the analog to digital converter (ADC) in Data Acquisition Unit (DAQU), with a resolution of 14 bits and sampling rate of 50 MS/s. Test and preliminary operation have been implemented, it can perform a sorting operation under the event count rate up to 1 MHz per channel, and support four channels in total, count rate up to 4 MHz. The performance of this algorithm has been verified by pulse generator and ²²Na radiation source, which can sort the events with chaotic order into chronological order completely. The application of this algorithm provides not only an efficient solution for selection of coincidence events, but also a design of electronic circuit with a small-scale structure.

Characterization and utilization of a cytoplasmic male sterility line of Wucai (Brassica campestris L.)

Guohu Chen,Xinyu Ye,Fanli Zeng,Jian Wang,Lingyun Yuan,Shidong Zhu,Jinfeng Hou,Yuan Cheng,Chenggang Wang 한국원예학회 2019 Horticulture, Environment, and Biotechnology Vol.60 No.3

The novel male sterility line 12-14A of Wucai ( Brassica campestris ) was generated by backcrossing. In this study, morphological,molecular, and cytological analyses were performed to characterize this line. The phenotypes of fl ower organsof 12-14A were diff erent from those of its maintainer line 12-14B, as the fl owers of 12-14A were completely infertile. Molecular analysis confi rmed that the male sterility line 12-14A was classifi ed as the ogu CMS type. An analysis of antherdevelopment in the CMS line demonstrated that two types of abortion occur simultaneously: pollen mother cell abortionand tetrad-to-mononuclear microspore abortion. In addition, the mature anthers of 12-14A showed typical abortive features,such as appearing dry, shrunken, and scaly. A heterosis test of hybrids from CMS 12-14A and four inbred lines was carriedout, and the F 1 hybrids exhibited clear heterosis in plant weight, as well as in the protein, soluble sugar, and vitamin C content,suggesting high yields and high quality potential. These results indicate that this novel CMS line may have powerfulpotential in Wucai hybrid breeding.

Effects of inulin diet supplementation on production performance, gut traits, and incidence of ascites in Haidong chicks under hypoxic conditions

Ding Baoan,Chen Lingyun,Lin Hao,Wang Xiezhong,Zhang Licheng,Ni Xiaoming,Pirone Andrea,Madigosky Stephen R.,Fronte Baldassare 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.3

Objective: Effects of inulin supplementation in diet of Haidong chicks under hypoxic conditions on production performance, intestinal morphologic change, microflora contents and the incidence of ascites were studied. Methods: Commercial male chicks (360) were randomly divided into 6 groups and were fed diets supplemented with 0, 0.05, 0.075, 0.1, 0.125, and 0.15 g/kg of inulin, respectively. Results: The body weight gain and feed intake were improved in chicks fed the diets supplemented with 0.1 and 0.125 g/kg of inulin, from d 1 to d 42 (p<0.05); moreover, blood parameters were positively affected when inulin was included in the diets and the thickness of the intestinal wall and muscle tissue in duodenum, jejunum, and ileum tended to increase (p<0.05), and the villi height and crypt depth in duodenum, jejunum, and ileum (p<0.05). Regarding the number of goblet cells in duodenum, jejunum and ileum tended to increase when chicks were fed the diets supplemented with 0.075, 0.1, 0.125, and 0.15 g/kg (p<0.05) of inulin. When chicks were fed diets supplemented with 0.75 or 0.1 g/kg of inulin, a significant reduction of Escherichia coli counts in the cecum was observed; for a contrary, a significant increment of Bifidobacterium and Lactobacillus was observed in cecum and ileum. Finally, supplementing the feed with inulin determined an overall reduction of ascites incidences in comparison to the control group. Conclusion: Thus, the results observed in the present study clearly suggest that the diet supplementation with a quantity of inulin ranging between 0.1 and 0.125 g/kg, can improve growth performances, intestinal morphology, internal microbial balance and ascites incidence, in broiler chicks raised at high altitude area. Even though these findings may be of interest for the poultry industry, they may particularly be relevant in those areas characterized by high altitude such as Northwest China regions. Objective: Effects of inulin supplementation in diet of Haidong chicks under hypoxic conditions on production performance, intestinal morphologic change, microflora contents and the incidence of ascites were studied.Methods: Commercial male chicks (360) were randomly divided into 6 groups and were fed diets supplemented with 0, 0.05, 0.075, 0.1, 0.125, and 0.15 g/kg of inulin, respectively.Results: The body weight gain and feed intake were improved in chicks fed the diets supplemented with 0.1 and 0.125 g/kg of inulin, from d 1 to d 42 (p<0.05); moreover, blood parameters were positively affected when inulin was included in the diets and the thickness of the intestinal wall and muscle tissue in duodenum, jejunum, and ileum tended to increase (p<0.05), and the villi height and crypt depth in duodenum, jejunum, and ileum (p<0.05). Regarding the number of goblet cells in duodenum, jejunum and ileum tended to increase when chicks were fed the diets supplemented with 0.075, 0.1, 0.125, and 0.15 g/kg (p<0.05) of inulin. When chicks were fed diets supplemented with 0.75 or 0.1 g/kg of inulin, a significant reduction of <i>Escherichia coli</i> counts in the cecum was observed; for a contrary, a significant increment of <i>Bifidobacterium</i> and <i>Lactobacillus</i> was observed in cecum and ileum. Finally, supplementing the feed with inulin determined an overall reduction of ascites incidences in comparison to the control group.Conclusion: Thus, the results observed in the present study clearly suggest that the diet supplementation with a quantity of inulin ranging between 0.1 and 0.125 g/kg, can improve growth performances, intestinal morphology, internal microbial balance and ascites incidence, in broiler chicks raised at high altitude area. Even though these findings may be of interest for the poultry industry, they may particularly be relevant in those areas characterized by high altitude such as Northwest China regions.

N₂O Emissions from a Solar Greenhouse Soil as Affected by Nutrient Management

Su Liu,Lingyun Kang,Qing Chen,Jingguo Wang 한국토양비료학회 2014 한국토양비료학회 학술발표회 초록집 Vol.2014 No.6

TFPI inhibits breast cancer progression by suppressing ERK/p38 MAPK signaling pathway

Xing Mengying,Yang Ying,Huang Jiaxue,Fang Yaqun,Jin Yucui,Li Lingyun,Chen Xiang,Zhu Xiaoxia,Ma Changyan 한국유전학회 2022 Genes & Genomics Vol.44 No.7

Background: Tissue factor pathway inhibitor-1 (TFPI) is a serine protease inhibitor, which is responsible for inactivating TF-induced coagulation. Recently, increasing studies revealed that TFPI was lowly expressed in tumor cells and exhibited the antitumor activity. Objective: The aim of this study was to explore the role and underlying molecular mechanisms of TFPI in breast cancer. Methods: The expression and prognostic value of TFPI were analyzed using UALCAN and Kaplan-Meier plotter website. The expression level of TFPI in breast cancer tissues and cells was examined by immunohistochemistry (IHC) and western blot analysis, respectively. Cellular proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were determined by transwell assay. The methylation level of TFPI promoter was determined by methylation-specific PCR. Results: TFPI expression was significantly lower in breast cancer tissues and cells compared to normal breast tissues and normal breast cells. Patients with low TFPI levels showed worse overall survival (OS). Furthermore, overexpression of TFPI significantly inhibited the proliferation, migration and invasion of breast cancer cells. Conversely, knockdown of TFPI promoted the proliferation, migration and invasion of breast cancer cells. Mechanistically, TFPI inhibited the ERK/p38 MAPK signaling pathway in breast cancer. Moreover, DNA hypermethylation of TFPI promoter was responsible for the downregulation of TFPI in breast cancer cells. Conclusion: TFPI inhibited breast cancer cell proliferation, migration and invasion through inhibition of the ERK/p38 MAPK signaling pathway, suggesting that TFPI may serve as a novel prognostic biomarker and therapeutic target for breast cancer.

Evaluation of energy correction algorithm for signals of PET in heavy-ion cancer therapy device

Niu, Xiaoyang,Yan, Junwei,Wang, Xiaohui,Yang, Haibo,Ke, Lingyun,Chen, Jinda,Du, Chengming,Zhang, Xiuling,Zhao, Chengxin,Kong, Jie,Su, Hong Korean Nuclear Society 2020 Nuclear Engineering and Technology Vol.52 No.1

In order to solve the contradiction between requirements of high sampling rate for acquiring accurate energy information of pulses and large amount of data to be processed timely, the method with an algorithm to correct errors caused by reducing the sampling rate is normally used in front-end read-out system, which is conductive to extract accurate energy information from digitized waveform of pulse. The functions and effects of algorithms, which mainly include polynomial fitting with different fitting times, double exponential function fitting under different sampling modes, and integral area algorithm, are analyzed and evaluated, and some meaningful results is presented in this paper. The algorithm described in the paper has been used preliminarily in a prototype system of Positron Emission Tomography (PET) for heavy-ion cancer therapy facility.