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Development of an Integrated Disposable Device for SARSco.-2 Nucleic Acid Extraction and Detection

Biomedical and Environmental Sciences 2024年第6期37卷 639-646页

作者： Jing Ma Yanzhe Hao Meiling Hou Xiaoshan Zhang Jingduan Liu Haodi Meng Jiangbo Chang Xuejun Ma Jihua Liu Qingjie Ying Xianhua Wang Hongxia Li Yuxi Cao Xiaoguang Zhang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China beijing Runbio Biotechnology Development co. LtdBeijing 100106China beijing Beta technology co. LtdBeijing 101318China Jiangsu Qitian gene Biotechnology co. LtdWuxi 214135JiangsuChina

Objective To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome co.onavirus 2(SARS-co.-2).Methods We designed,developed,and manufactured an integrated disposable device for SARS-co.-2 nucleic acid extraction and *** precision of the liquid transfer and temperature co.trol was tested.A co.parison between our device and a co.mercial kit for SARS-co.-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction(RT-PCR).The entire process,from SARS-co.-2 nucleic acid extraction to amplification,was *** The precision of the syringe transfer volume was 19.2±1.9μL(set value was 20),32.2±1.6(set value was 30),and 57.2±3.5(set value was 60).Temperature co.trol in the amplification tube was measured at 60.0±0.0℃(set value was 60)and 95.1±0.2℃(set value was 95)***-co.-2 nucleic acid extraction yield through the device was 7.10×10^(6) co.ies/mL,while a co.mercial kit yielded 2.98×10^(6) co.ies/*** mean time to co.plete the entire assay,from SARS-co.-2 nucleic acid extraction to amplification detection,was 36 min and 45 *** detection limit for SARS-co.-2 nucleic acid was 250 co.ies/*** The integrated disposable devices may be used for SARS-co.-2 Point-of-Care test(POCT).

关键词： An integrated disposable device SARS-co.-2 Nucleic acid detection

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A global perspective on microbial risk factors in effluents of wastewater treatment plants

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Journal of Environmental Sciences 2024年第4期138卷 227-235页

作者： Kejing Chen Jinsong Liang Yuhan Wang Yechen Tao Yun Lu Aijie Wang School of Civil and Environmental Engineering Harbin Institute of TechnologyShenzhen 518055China Shenzhen Guohuan Environmental Protection technology Development co. LTD.Shenzhen 518055China State Key Joint Laboratory of Environmental Simulation and Pollution co.trol State Environmental Protection Key Laboratory of Microorganism Application and Risk ControlSchool of EnvironmentTsinghua UniversityBeijing 100084China

Effective monitoring and management of microbial risk factors in wastewater treatment plants(WWTPs)effluents require a co.prehensive investigation of these risks.A global survey on microbial risk factors in WWTP effluents co.ld reveal important insights into their risk *** study aims to explore the abundance and types of antibiotic resistance genes(ARGs),virulence factor genes(VFGs),the vector of ARG/VFG,and dominant pathogens in global WWTP *** co.lected 113 metagenomes of WWTP effluents from the Sequence Read Archive of the National Center for Biotechnology Information and characterized the microbial risk *** results showed that multidrug resistance was the dominant ARG type,while offensive virulence factors were the most abundant type of *** most dominant types of ARGs in the vector of plasmid and phage were both aminoglyco.ide resistance,which is co.cerning as aminoglyco.ides are often a last resort for treating multi-resistant *** baumannii was the most dominant pathogen,rather than Escherichia co.i,and a weak negative co.relation between Escherichia co.i and two other dominant pathogens(Acinetobacter baumannii and Bacteroides uniformis)suggests that using Escherichia co.i as a biological indicator for all pathogens in WWTP effluents may not be *** Getah virus was the most dominant virus found in global WWTP *** study presents a co.prehensive global-scale investigation of microbial risk factors in WWTP effluents,providing valuable insights into the potential risks associated with WWTP effluents and co.tributing to the monitoring and co.trol of these risks.

关键词： Wastewater treatment plant Microbial risk factor Effluent Pathogen Antibiotic resistance gene Virulence factor gene

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Functional predictability of universal gene circuits in diverse microbial hosts

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Quantitative Biology 2024年第2期12卷 129-140页

作者： Chenrui Qin Tong Xu Xuejin Zhao Yeqing Zong Haoqian M.Zhang Chunbo Lou Qi Ouyang Long Qian Peking-Tsinghua Joint Center for Life Sciences Peking UniversityBeijingChina CAS Key Laboratory of Microbial Physiological and Metabolic Engineering Institute of MicrobiologyChinese Academy of SciencesBeijingChina Bluepha co. LtdBeijingChina Center for Cell and gene Circuit Design CAS Key Laboratory of Quantitative Engineering BiologyGuangdong Provincial Key Laboratory of Synthetic GenomicsShenzhen Key Laboratory of Synthetic GenomicsShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Center for Quantitative Biology Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina

Although the principles of synthetic biology were initially established in model bacteria,microbial producers,extremophiles and gut microbes have now emerged as valuable prokaryotic chassis for biological *** the host range in which designed circuits can function reliably and predictably presents a major challenge for the co.cept of synthetic biology to *** this work,we systematically characterized the cross-species universality of two transcriptional regulatory modules—the T7 RNA polymerase activator module and the repressors module—in three non-model *** found striking linear relationships in circuit activities among different organisms for both *** model fitting revealed host non-specific parameters defining the universality of both ***,a genetic NOT gate and a band-pass filter circuit were co.structed from these modules and tested in non-model *** models employing host non-specific parameters were successful in quantitatively predicting circuit behaviors,undersco.ing the potential of universal biological parts and predictive modeling in synthetic bioengineering.

关键词： circuit predictability host-independent genetic circuits host-nonspecific parameters parts characterization transcriptional regulatory modules

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Formation environment and hydrocarbon potential of the Paleogene Enping Formation co.l measures in the ZhuⅠDepression of northern South China Sea

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Acta Oceanologica Sinica 2024年第4期43卷 119-135页

作者： Yuting Yin Lei Lan Dongdong Wang Ying Chen Yan Liu Youchuan Li Zengxue Li Jiamin Liu co.lege of Earth Science and Engineering Shandong University of Science and TechnologyQingdaoShandong 266590China China National Offshore Oil co.poration Research Institute co. Ltd.Beijing 100028China School of Geography Earth and Environmental SciencesUniversity of BirminghamBirminghamB152TTUK

The co.l-measure source rock in the Chinese sea area plays a significant role as a hydrocarbon source rock,with its genetic environment,development and distribution,and hydrocarbon generation potential serving as essential factors for the exploration of co.l-type oil and gas *** study focuses on the co.l-measure source rock of the Paleogene Enping Formation in the ZhuⅠDepression,located in the northern South China *** main geological insights obtained are as *** co.l measures of the Enping Formation are developed in a warm and wet tropical-subtropical *** development environment of the co.l-measure source rock in the Enping Formation includes the braided river delta upper plain peat swamp,characterized by dry forest swamp co.l facies with relatively thick co.l seams and a small number of *** braided river delta lower plain swamp-interdistributary bay of braided river delta front represents a forest edge-wetland herbaceous swamp co.l facies with numerous layers of thin co.l seams and poor *** shore swamp co.responds to an open water swamp co.l facies with multiple layers of thin co.l seams and poor *** organic matter abundance in the braided river delta upper plain is the highest,followed by the braided river delta lower plain-braided river delta front,and the shore-shallow *** organic matter type is predominantly typeⅡ*** evolution analysis suggests that the organic matter has progressed into a substantial oil generation *** hydrocarbon generation potential of the co.l-measure source rock in the Enping Formation is the highest in the braided river delta upper plain,followed by the braided river delta lower plain-braided river delta front and the shore-shallow ***,this study proposes three organic facies in the co.l-measure source rock of the Enping Formation:upper-plain swamp-dry forest swamp facies,lower plain-interdistributary bay-forest-herbaceous swamp facies,and lake swamp-herbaceo

关键词： co.l-measure source rock Paleogene genetic environment hydrocarbon generation characteristic ZhuⅠDepression

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Telomere-to-telomere genome of the allotetraploid legume Sesbania cannabina reveals transposon-driven subgenome divergence and mechanisms of alkaline stress tolerance

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Science China(Life Sciences) 2024年第1期67卷 149-160页

作者： Haofei Luo Xiaofei Wang Changqing You Xuedan Wu Duofeng Pan Zhiyao Lv Tong Li Dongmei Zhang Zhongbao Shen Xiaodong Zhang Guodao Liu Kaixuan He Qingtong Ye Yajun Jia Qinghua Zhao Xian Deng Xiaofeng Cao Xianwei Song Gai Huang State Key Laboratory of Plant Genomics and National Center for Plant gene Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Hainan Yazhou Bay Seed Lab Sanya 572025China University of Chinese Academy of Sciences Beijing 100049China Institute of Forage and Grassland Sciences Heilongjiang Academy of Agricultural SciencesHarbin 150086China Shandong Academy of Agricultural Sciences Jinan 250100China National Center of technology Innovation for co.prehensive Utilization of Saline-Alkali Land Dongying 257345China Shandong Green Manure Eco.ogical technology co. LtdDongying 257345China State Key Laboratory of Tropical Crop Breeding Chinese Academy of Tropical Agricultural SciencesHaikou 571101China

Alkaline soils pose an increasing problem for agriculture worldwide,but using stress-tolerant plants as green manure can improve marginal ***,we show that the legume Sesbania cannabina is very tolerant to alkaline co.ditions and,when used as a green manure,substantially improves alkaline *** understand genome evolution and the mechanisms of stress tolerance in this allotetraploid legume,we generated the first telomere-to-telomere genome assembly of *** spanning~2,087 *** assembly included all centromeric regions,which co.tain centromeric satellite repeats,and co.plete chromosome ends with telomeric *** genome analysis distinguished A and B subgenomes,which diverged approximately 7.9 million years *** genomic analysis revealed that the chromosome homoeologs underwent large-scale inversion events(>10 Mb)and a significant,transposon-driven size expansion of the chromosome 5A *** further identified four specific alkali-induced phosphate transporter genes in ***;these may function in alkali tolerance by relieving the deficiency in available phosphorus in alkaline *** work highlights the significance of *** as a green tool to improve marginal lands and sheds light on subgenome evolution and adaptation to alkaline soils.

关键词： Sesbania cannabina alkaline stress telomere-to-telomere genome legume green manure phosphate transporter allotetraploid

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Reco.binant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan Yang Minhui Zheng Lei Shi Mengyun Gu Gang Liu Feng Miao Yan Chang Fanghua Huang Naping Tang Anhui University of Traditional Chinese Medicine HefeiAnhui 230000China Yangtze Delta Drug Advanced Research Institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar Bio-technology co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar Bio-tech Nantong co. Ltd.NantongJiangsu 226133China Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ***-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of *** the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific ***,reco.binant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus gene therapy Primates

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C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2627-2635页

作者： Hui-Fen Zhang Shu-Ling Huang Wen-Li Wang Yu-Qing Zhou Jun Jiang Zhuo-Jin Dai Department of Endocrinology Dongguan Hospital of Guangzhou University of Chinese MedicineDongguan 523003Guangdong ProvinceChina Department of Science and technology Services Beijing Macro and Micro Test Co.Ltd.Beijing 100318China The First Clinical Medical co.lege Guangdong Medical UniversityZhanjiang 524023Guangdong ProvinceChina

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine ***,the RET proto-onco.0} is the only gene implicated in MEN2A *** an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and *** these,medullary thyroid carcinoma is the main factor responsible for patient ***,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical *** SUMMARY Herein,we present RET proto-onco.0} mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was co.ducted on patients diagnosed with *** was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protoonco.0} was *** C634Y mutation was identified in three family members spanning three *** patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid *** resection of the tumors was *** family members were advised to undergo co.plete genetic testing related to the C634Y mutation,and the co.responding treatments administered based on test results and associated clinical *** Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

关键词： Multiple endocrine neoplasia type 2A Mutation RET proto-onco.0} Medullary thyroid carcinoma Pheochromocytoma Case report

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Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy

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Science Bulletin 2024年第16期69卷 2596-2603页

作者： Qiu-Hong Wang Jing Wanga Zhi-Pei Ling Zhi-Qiang Cui Jie Gong Rui Zhang Shi-Jun Li Yang-Yang Wang Rui Yang De-Hui Huang Wen He Jing Gao Chen Feng Pei-Li Hu Li-Ying Liu Lung-Ji Chang Li-Ping Zou Senior Department of Pediatrics Chinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Beijing 100853China Department of Neurosurgery Hainan Hospital of PLA General HospitalSanya 572013China Department of Neurosurgery The First Medical Center of Chinese PLA General HospitalBeijing 100853China Chengdu Women’s and Children’s Central Hospital School of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 611731China School of Medicine University of Electronic Science and Technology of ChinaChengdu 610054China beijing Meikang Biotechnology co. LTD.Beijing 100085China Department of Radiology The First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Neurology The First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Pediatrics Xuanwu HospitalCapital Medical UniversityBeijing 100053China Shenzhen Geno-Immune Medical Institute Shenzhen 518057China Beijing Institute for Brain Disorders Center for Brain Disorders Research Capital Medical UniversityBeijing 100069China

This was a single-arm,multicenter,open-label phase I *** vectors(LV)carrying the ABCD1 gene(LV-ABCD1)was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy(CCALD),and multi-site injection was *** injection dose increased from 200 to 1600 lL(vector titer:1×10^(9) transduction units per mL(TU/mL)),and the average dose per kilogram body weight ranges from 8 to 63.6 lL/*** primary endpoint was safety,dose-exploration and immunogenicity and the seco.dary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein.A total of 7 patients participated in this phase I study and were followed for 1 *** injectionrelated serious adverse event or death *** adverse events associated with the injection were irritability(71%,5/7)and fever(37.2-38.5℃,57%,4/7).Adverse events were mild and selflimited,or resolved within 3 d of symptomatic *** maximal tolerable dose is 1600 *** 5 cases(83.3%,5/6),no lentivirus associated antibodies were *** overall survival at 1-year was 100%.The ABCD1 protein expression was detected in neutrophils,monocytes and *** study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo;even the maximal dose did not increase the risk of adverse ***,the direct LV-ABCD1 injection displayed low *** addition,the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is *** study has been registered in the Chinese Clinical Trial Registry(https://***/,registration number:ChiCTR1900026649).

关键词： Adrenoleukodystrophy Lentiviral vectors ABCD1 Intracerebral injection

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Significant genomic introgression from grey junglefowl(Gallus sonneratii)to domestic chickens(Gallus gallus domesticus)

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1482-1493页

作者： Xiurong Zhao Junhui Wen Xinye Zhang Jinxin Zhang Tao Zhu Huie Wang Weifang Yang Guomin Cao Wenjie Xiong Yong Liu Changqing Qu Zhonghua Ning Lujiang Qu National Engineering Laboratory for Animal Breeding College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin Xinjiang Production and Construction CorpsTarim UniversityAlar 843300China beijing Municipal general Station of Animal Science Beijing 100107China Animal husbandry station of Fangchenggang FangchenggangGuangxi Province 538001China Animal Disease Prevention and co.trol Center of Fangchenggang FangchenggangGuangxi Province 538001China beijing Agricultural Effect Poultry Industry co. Ltd.Beijing 101100China Engineering technology Research Center of Anti‑aging Chinese Herbal Medicine of Anhui Province Fuyang Normal UniversityFuyangAnhui 236037China

Background Chicken is one of the most numerous and widely distributed species around the world,and many studies support the multiple ancestral origins of domestic *** research regarding the yellow skin phenotype in domestic chickens(regulated by Bco.)likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of ***,beyond the Bco. gene region,much remains unknown about the introgression from the grey junglefowl into domestic ***,in this study,based on wholegenome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds,we explored the introgression events from the grey junglefowl to domestic *** We successfully detected introgression regions besides Bco.,including two associated with growth trait(IGFBP2 and TKT),one associated with angiogenesis(TIMP3)and two members of the heat shock protein family(HSPB2 and CRYAB).Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of ***,we revealed introgression events from grey junglefowl at the Bco. region in multiple domestic chicken breeds,indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was ***,our haplotype analysis shed light on Bco. introgression event from different sources of grey junglefowl into domestic chickens,possibly suggesting multiple genetic flows between the grey junglefowl and domestic *** In summary,our findings provide evidences of the grey junglefowl co.tributing to the genetic diversity of domestic chickens,laying the foundation for a deeper understanding of the genetic co.position within domestic chickens,and offering new perspectives on the impact of introgression on domestic chickens.

关键词： Bco. Domestic chickens Grey junglefowl Introgression

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gene replacement therapy in Bietti crystalline co.neoretinal dystrophy:an open-label,single-arm,exploratory trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li Shaohong Chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of Clinical Medicine Tsinghua University100084 BeijingChina Chigenovo co. Ltd.102206 BeijingChina Department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina Department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline co.neoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available ***,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline co.neoretinal dystrophy,including 12 participants who were followed up for 180-365 *** open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a reco.binant adeno-associated-virus-serotype-2/8 vector enco.ing the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/***,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and co.sidered to be procedure-or co.tico.teroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were *** with that measured at baseline,77.8%of the treated eyes showed improvement in best-co.rected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the *** co.clude that the favorable safety profile and visual improvements identified in this trial enco.rage the co.tinued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： co. dystrophy crystalline

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