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Identification of LRRC46 as a novel candidate gene for high myopia

Science China Life Sciences 2024年第9期67卷 1941-1956页

作者： Lingxi Jiang Chao Dai Yao Wei Bo Zhao Qi Li Zhengzheng Wu Liang Zou Zimeng Ye Zhenglin Yang Lulin Huang Yi Shi sichuan Provincial Key Laboratory for Human disease Gene Study and the center for Medical Genetics Department of Laboratory Medicine Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Department of Ophthalmology Sichuan Provincial People's Hospital University of Electronic Science and Technology of China School of Food and bioengineering Chengdu University School of Medicine University of Sydney research Unit for Blindness prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Jinfeng Laboratory

High myopia(HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues. In a previously reported myopic linkage region,MYP5(17q21–22), a potential candidate gene, LRRC46(c.C235T, p.Q79X), was identified in a large Han Chinese pedigree. LRRC46 is expressed in various eye tissues in humans and mice, including the retina, cornea, and sclera. In subsequent cell experiments, the mutation(c.C235T) decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T). Further investigation revealed that Lrrc46–/–mice(KO) exhibited a classical myopia phenotype. The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age, the activity of limbal stem cells decreased, and microstructural changes were observed in the fibroblasts of the sclera and cornea. We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT) mice, which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix, ECM) in KO mice. Subsequent in vitro studies further indicated that LRRC46, a member of the important LRR protein family, primarily affected the formation of collagens. This study suggested that LRRC46 is a novel candidate gene for HM, influencing collagen protein VⅢ(Col8a1) formation in the eye and gradually altering the biomechanical structure of the cornea and sclera, thereby promoting the occurrence and development of HM.

关键词： high myopia LRRC46 biomechanics collagen protein VIII

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Non-proteolytic ubiquitination of HBx controls HBV replication

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Virologica Sinica 2024年第2期39卷 338-342页

作者： Xiangpeng Sheng Yi Yang Min Zhu Linlin Zhou Fang Zhu Yuanfei Zhu Siying Dong Hui Kong Honghua Wang Ji Jiang Mingyue Wan Mingyang Feng Qiang Deng Yumin Xu Qing You Ronggui Hu State Key Laboratory for animal disease control and prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Thoracic Surgery Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Shanghai Key Laboratory of Plant Molecular Sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China Department of Pathogenic Biology West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China School of Medicine Guizhou UniversityGuiyang 550025China Key Laboratory of Medical Molecular Virology(MOE&MOH) School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Hospital Infection Management Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Dear Editor,Although effective vaccines and antiviral therapies are available,hepatitis B virus(HBV)infection is still a serious global health *** HBV infection remains the principal cause of liver cirrhosis and hepatocellular carcinoma(HCC).HBV is a small DNA virus,owning a~3.2 kb genome that encodes several proteins:viral DNA polymerase,core antigen(HBcAg),E antigen(HBeAg),three surface antigens(PreS1/PreS2/HBsAg),and a regulatory X protein(HBx)(Lamontagne et al.,2016).X protein,named for its lack of homology with any known proteins,is a 154 aa protein that plays an essential role in HBV biology and regulates the development of HCC(Yang et al.,2022).Although previous studies have strongly expanded our understanding of HBx,the regulation of HBx is not completely elucidated.

关键词： infection cirrhosis

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Characteristics of the multiple replicon plasmid IncX1-X1 in multidrug-resistant Escherichia coli from Malayan pangolin(Manis javanica)

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Integrative Zoology 2023年第2期18卷 289-298页

作者： Fang JI Shelan LIU Xue WANG Jianan ZHAO Jiayue ZHU Jianchun YANG Chenglin ZHANG Zhongxin JIA Ruili ZHAO Guocheng HU Jing WANG Jianhua QIN Gang LI Bin WU Chengmin WANG Guangdong Key Laboratory of animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and UtilizationInstitute of ZoologyGuangdong Academy of ScienceGuangzhouChina Department of Infectious diseases Zhejiang Center of Disease Control and PreventionHangzhouZhejiangChina School of bioengineering East China University of Science and TechnologyShanghaiChina Beijing Key Laboratory of Captive Wildlife Technologies Beijing ZooBeijingChina College of animal Science and Veterinary Medicine Tianjin Agricultural UniversityTianjinChina South China Institute of Environmental Sciences Ministry of Ecology and EnvironmentGuangzhouChina Department of Infectious diseases Hangzhou Center of Disease Control and PreventionHangzhouChina College of Veterinary Medicine Agricultural University of HebeiBaodingChina

Potential zoonotic pathogens may be transmitted from wildlife to humans through the illegal wild meat trade,which has become a pressing ***,research on the antimicrobial resistance genes(ARGs)of Malayan pangolin(Manis javanica)intestinal bacteria is ***,multidrug-resistant Escherichia coli M172-1(ST354)isolated from Malayan pangolin feces in 2019 was found to be resistant to 13 *** analysis revealed 4 plas-mids,namely,pM172-1.1,pM172-1.2,pM172-1.3,and pM172-1.4,in the *** pM172-1.2,pM172-1.3,and pM172-1.4 plasmids carried ARGs,namely,IncHI2-HI2A,IncX1-X1,and IncX1,***172-1.3 and pM172-1.4 contained intact IntI1 integrons(Is26/IntI1/arr2/cmlA5/blaOXA-10/ant(3′′)-IIA/dfrA14/Is26).No-tably,pM172-1.3 resulted from the fusion of 2 pM172-1.4 copies and carried many more *** addition to pM172-1.3 from the same host,other drug-resistant bacteria(*** M159-1(ST48),*** S171-1(ST206),and Klebsiella pneumoniae S174-1(ST2354))in the same Malayan pangolin fecal samples also carried 3 plasmids with 100%gene coverage of pM172-1.4 and 99.98%***,ARGs in IncX1 might spread in the intestinalﬂora of Malayan pangolin and between species via the illegal food chain,posing a potential threat to public health and safety.

关键词： ARG Manis javanica multiple-replicon plasmid IncX1-X1 plasmid IncX1

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Design and Expression of a Synthetic phyC Gene Encoding the Neutral Phytase in Pichia pastoris

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Acta Biochimica et Biophysica Sinica 2006年第11期38卷 803-811页

作者： Li-Kou ZOU~(1,3) Hong-Ning WANG~(2,1*) Xin PAN~4 Tao XIE~1 Qi WU~5 Zi-Wen XIE~1 Wan-Rong ZHOU~1 1 Laboratory of Veterinary and Biotechnology,sichuan Agricultural university,Ya'an 625014,China 2 sichuan university bioengineering research center for animal disease prevention and control,Chengdu 610065,China 3 Faculty of Environment and Resource of Dujiangyan Campus,sichuan Agricultural university,Dujiangyan 611830,China 4 College of Earth Science,Chengd university of Technology,Chengdu 610059,China 5 College of Life Science,sichuan Agricultural university,Ya'an 625014,China Laboratory of Veterinary and Biotechnology Sichuan Agricultural UniversityYa'an 625014 China Faculty of Environment and Resource of Dujiangyan Campus Sichuan Agricultural UniversityDujiangyan 611830 China sichuan university bioengineering research center for animal disease prevention and control Chengdu 610065 China College of Earth Science Chengdu University of TechnologyChengdu 610059 China College of Life Science Sichuan Agricultural UniversityYa'an 625014 China

The 1074-bp phyCs gene （optimized phyC gene） encoding neutral phytase was designed andsynthesized according to the methylotrophic yeast Pichia pastoris codon usage bias without altering theprotein *** expression vector,pP9K-phyCs,was linearized and transformed in *** of total extracellular phytase activity was 17.6 U/ml induced in Buffered Methanol-complex Medium（BMMY） and 18.5 U/ml in Wheat Bran Extract Induction （WBEI） medium at the flask scale,respectively,improving over 90 folds compared with the wild-type *** enzyme showed temperature optimumof 70℃ and pH optimum of *** enzyme activity retained 97% of the relative activity afterincubation at 80℃ for 5 *** of the heavy glycosylation the expressed phytase had a molecularsize of approximately 51 *** deglycosylation by endoglycosylase H （EndoH_f）,the enzyme had anapparent molecular size of 42 *** property and thermostability was affected by the glycosylation.

关键词： design expression synthetic phyC gene neutral phytase Pichia pastoris

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Expression, purification and characterization of a phyA^m-phyCs fusion phytase

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2008年第7期9卷 536-545页

作者： Li-kou ZOU Hong-ning WANG Xin PAN Guo-bao TIAN Zi-wen XIE Qi WE Hui CHEN Tao XIE Zhi-rong YANG College of Life Science Bioengineering Research Center for Animal Disease Prevention and Control Sichuan University Chengdu 610065 China Faculty of Biotechnology of Dujiangyan Campus Sichuan Agricultural University Dujiangyan 611830 China College of Earth Science Chengdu University of Technology Chengdu 610059 China College of Life Science Sichuan Agricultural University Ya ＇an 625014 China

The phyAm gene encoding acid phytase and optimized neutral phytase phyCs gene were inserted into expression vector pPIC9K in correct orientation and transformed into Pichia pastoris in order to expand the pH profile of phytase and decrease the cost of production. The fusion phytase phyAm-phyCs gene was successfully overexpressed in P. pastoris as an active and ex-tracellular phytase. The yield of total extracellular fusion phytase activity is (25.4±0.53) U/ml at the flask scale and (159.1±2.92) U/ml for high cell-density fermentation, respectively. Purified fusion phytase exhibits an optimal temperature at 55 °C and an optimal pH at 5.5~6.0 and its relative activity remains at a relatively high level of above 70% in the range of pH 2.0 to 7.0. About 51% to 63% of its original activity remains after incubation at 75 °C to 95 °C for 10 min. Due to heavy glycosylation, the expressed fusion phytase shows a broad and diffuse band in SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). After deglycosylation by endoglycosidase H (EndoHf), the enzyme has an apparent molecular size of 95 kDa. The characterization of the fusion phytase was compared with those of phyCs and phyAm.

关键词：基因表达 PhvCs PhvA^m 肌醇六磷酸酶

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Effects of exogenous enzymes and dietary energy on performance and digestive physiology of broilers

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Journal of animal Science and Biotechnology 2013年第4期4卷 294-302页

作者： Jialing Zou Ping Zheng Keying Zhang Xuemei Ding Shiping Bai Institute of animal Nutrition Engineering Research Center for Animal Disease-Resistance Nutrition of China Ministry of Education Sichuan Agricultural University

The study was conducted to compare the effects of XG with AG and BM at different metabolizable energy diets on growth performance, digestive physiology and energy utilization of broilers fed with corn-SBM diet. A 2 x 4 factoria design was used with two basal diets （the positive control group, PC; negative control with ME reduction 100 kcal/ kg, NC） and with or without the addition of three exogenous enzymes （0.02% BM; 0.01% AG; 0.05% XG） respectively. 1,200 one-day-old broilers were randomly allocated to 8 treatments with 10 pens of 1_5 broilers. There was no significant difference on BW, BWG, and FI at 0-21d, 21-42d or 0-42d for diet, enzymes or their interactions, but FI at 22-42d and 0-42d were tend to be decreased with the addition of enzymes. The F/G was significantly improved by the addition of enzymes especially in NC diet. The dietary AME and TME in PC or NC diet were significantly increased by XG or AG in NC diet. The villus length and V/C of ileum were significantly increased by the addition of BM or XG. XG improved the activities of trypsin, chymotrypsin and amylase, BM improved the activity of trypsin at 21d, and AG improved the activity of chymotrypsin at 21d. Comparing to PC diet, the addition of enzymes in PC or NC diet decreased feed cost per kg body weight gain especially in NC diet （except AG in PC diet） with the highest profits for XG in NC diet. In conclusion, supplementation of 0.02% BM or 0.01% AG or 0.0.5% XG could improve feed conversion of broilers in corn-soybean meal diet by improving energy utilization and digestive physiology, and also supplementation of 0.05% XG had a preferable efficacy in low energy diet.

关键词： Broilers Digestive physiology Exogenous enzymes Growth performance

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Genomic Characterization of a Streptococcus suis Serotype 2 Isolated from a Human Patient

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Biomedical and Environmental Sciences 2022年第8期35卷 760-763页

作者： GUO Geng Lin GAO Hua Sheng WANG Zhuo Hao TAN Zhong Ming HAN Ming Xiao CHEN Qi DU Hong ZHANG Wei ZHANG Hai Fang College of Veterinary Medicine Nanjing Agricultural UniversityNanjing 210095JiangsuChina Key Lab of animal Bacteriology Ministry of AgricultureNanjing 210095JiangsuChina OIE Reference Lab'for Swine Streptococcosis Nanjing 210095JiangsuChina Department of Clinical Laboratory The Second Affliated Hospital of Soochow UniversitySuzhou 215004JiangsuChina NHC Key Laboratory of Enteric Pathogenic Microbiology Jjiangsu Provincial Center for Disease Control and PreventionNanjng 210009JiangsuChina

Streptococcus suis(S. suis) is a Gram-positive zoonotic pathogen. S. suis infection in humans commonly causes meningitis, septicemia, arthritis,and streptococcal toxic shock-like syndrome(STSLS). S. suis has 29 serotypes, of which S. suis serotype 2(SS2) has the highest clinical isolation rate and strongest pathogenicity and causes most S. suis human *** 1,000 different sequence types(STs)were identified in *** based on multilocus sequence typing(MLST).Among these,STs,ST1,and ST7 belong to serotype 2 and are the major hazards of *** 1998 and 2005,two cases of SS2 human infection outbreak were reported in Jiangsu and sichuan,China,causing 14 deaths and 38 deaths,respectively.

关键词： suis Streptococcus Human

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MicroRNA transcriptome analysis of chicken embryo fibroblast cells infected with Newcastle disease virus variants

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animal diseases 2023年第3期3卷 166-177页

作者： Weiwei Liul Zejun Xu Siyuan Wang Cuiping Song Xusheng Qiu Lei Tan Yingjie Sun Ying Liaol Gujun Wang Xiufan Liu Chan Ding Shanghai Veterinary research Institute Chinese Academy of Agricultural SciencesShanghaiChina School of Food and bioengineering Wuhu Institute of TechnologyWuhuChina School of Veterinary Medicine South China Agricultural UniversityGuangzhouChina School of Veterinary Medicine Anhui Agricultural UniversityHefeiChina School of Veterinary Medicine Yangzhou UniversityYangzhouChina Jjangsu Coinnovation center for prevention and control flmportant animal Infectious diseases and Zoonoses Yangzhou UniversityYangzhouChina

Variations in the pathogenicity of Newcastle disease virus(NDV),the agent causing Newcastle disease,are associated with variants of different virulence.A few studies have characterized the expression of microRNAs(miRNAs)in NDV-infected avian ***,the expression of miRNAs in chicken embryo fibroblasts(CEFs)infected with Herts/33 and LaSota NDV strains(highly virulent and nonvirulent,respectively)was determined using RNA *** involved in NDV infection included 562 previously documented and 184 novel *** target genes involved transcription factors,cell apoptosis,ubiquitin-mediated proteolysis,and protein processing in the endoplasmic *** target genes associated with autophagy were verified by *** studies have documented the miRNA profles of CEFs infected with NDVs *** study adds to our knowledge of the cellular miRNAs involved in NDV infection and the complex molecular mechanisms mediating virus-host *** results of this study will aid the development of strategies against the chicken virus.

关键词： CEF Chicken microRNA Newcastle disease virus RNA-seq

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A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans： part 1. What have we learnt on the distribution of the disease and on its parasitic agent？

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Chinese Medical Journal 2011年第18期124卷 2943-2953页

作者： Dominique Angele Vuitton WANG Qian ZHOU Hong-xia Francis Raoul Jenny Knapp Solange Bresson-Hadni WEN Hao Patrick Giraudoux WHO Collaborating center for prevention and Treatment of Human Echinococcosis University Hospital and University of Francbe-Comte 25030 Besancon France sichuan center for disease control and prevention Chengdu Sichuan 610031 China Guangxi Medical university Nanning Guangxi 530021 China Chrono-Environnement Joint research Unit UMR 6249 University of Franche-Comte CNRS and INRA 25030 Besancon France Xinjiang Key Laboratory for Echinococcosis research 1st Teaching Hospital of Xinjiang Medical University Urumqi Xiniianz 830000. China

Since the first 2 cases observed in southern Germany and the correct identification of a parasite at the origin of the disease by the famous scientist Rudolf Virchow in 1855, the borders of the endemic area of alveolar echinococcosis （AE） have never stopped to expand. The parasite was successively recognized in Switzerland, then in Russia, Austria and France which were long considered as the only endemic areas for the disease. Cases were disclosed in Turkey in 1939; then much attention was paid to Alaska and to Hokkaido, in Japan. The situation totally changed in 1991 after the recognition of the Chinese endemic areas by the international community of scientists. The world map was completed in the beginning of the 21st century by the identification of AE in most of the countries of central/eastern Europe and Baltic States, and by the recognition of cases in central Asia. Up to now, the disease has however never been reported in the South hemisphere and in the United Kingdom. In the mid-1950s, demonstration by Rausch and Schiller in Alaska, and by Vogel in Germany, of the distinction between 2 parasite species responsible respectively for cystic echinococcosis （＂hydatid disease＂） and AE put an end to the long-lasting debate between the ＂dualists＂, who believed in that theory which eventually proved to be true, and the ＂unicists＂, who believed in a single species responsible for both diseases. At the end of the 20th century, molecular biology fully confirmed the ＂dualist＂ theory while adding several new species to the initially described E. granulosus; within the past decade, it also confirmed that little variation existed within Echinococcus （E.） multilocularis species, and that AE-Iooking infection in some intermediate animal hosts on the Tibetan plateau was indeed due to a new species, distinct from E. multilocularis, named E. shiquicus. Since the 1970s, the unique ecological interactions between the landscape, the hosts, and E. multilocularis have progressively be

关键词： alveolar echinococcosis Echinococcus species epidemiology history Rudolf Virchow western China

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Construction of an Infectious Clone for Mosquito-Derived Tembusu Virus Prototypical Strain

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Virologica Sinica 2021年第6期36卷 1678-1681页

作者： Xiaoli Wang Yu He Jiaqi Guo Bowen Jiang Mingshu Wang Renyong Jia Dekang Zhu Mafeng Liu Xinxin Zhao Qiao Yang Ying Wu Shaqiu Zhang Yunya Liu Ling Zhang Yanling Yu Anchun Cheng Shun Chen research center of Avian disease College of Veterinary MedicineSichuan Agricultural UniversityChengdu 611130China Institute of Preventive Veterinary Medicine College of Veterinary MedicineSichuan Agricultural UniversityChengdu 611130China Key Laboratory of animal disease and Human Health of sichuan Province Chengdu 611130China

Dear Editor,Duck Tembusu virus(DTMUV),a member of the Flavivirus genus within the Flaviviridae family,has caused huge economic losses to the poultry industry in China and even in Asia since 2010(Zhang et al.2017).The first strain of Tembusu virus(TMUV)MM_1775 was isolated from mosquitoes in 1955 in Malaysia(Platt et al.1975).DTMUV CQW1 strain(GenBank:KM233707.1)was isolated from the liver tissue of Cherry Valley ducks in southwest China in 2015(Zhu et al.2015).The positive control rCQW1 was rescued from an infectious clone that contained the full-length cDNA of *** the complete cDNA was positioned under the control of the T7 promoter elements for in vitro transcription(Chen et al.2018).The relationship between TMUV evolution and pathogenic variants has not been *** fundamental reason is the lack of the in vitro operation platform for the prototypical strain genome.

关键词： poultry Infectious Clone

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