夏海滨

一、个人简介

夏海滨，博士，生化与分子生物学教授，博士生导师。伟德bevictor中文版基因治疗重点实验室主任。陕西省细胞生物学会监事长；陕西省生物化学与分子生物学会副理事长；陕西省免疫学会常务理事；美国基因及细胞治疗学会（ASGCT）会员。

1994年9月至1997年7月在第四军医大学免疫学教研室攻读博士学位，1997年11月至2005年9月在美国University of Iowa基因治疗中心从事有关神经退行性疾病基因治疗研究，2005年10至2006年8月在美国University of Texas Southwest Medical Center任助理教授，从事骨骼肌干细胞方面的研究。2006年9月至今，任职伟德betvlctor体育官网教授，主要从事肿瘤基因治疗、肿瘤干细胞、基因定点靶向整合技术的研究与应用及老年痴呆分子机理的研究。2006年至今，主持国家科技部863项1项，国家自然科学基金6项，农业部农业部科技重大专项子课题1项，陕西省自然科学基金重点项目1项和面上项目2项。获得国际专利3项，国内专利20项。在Nature Medicine、Nature Biotechnology、PNAS、J. Virol 、Gene Ther 、Cancer Lett、STTT、Glia、Elife、Hum Gene Ther、Cancer Gene Ther等国内外学术刊物上发表论文160余篇。

二、承担的科研项目

1. 国家自然科学基金, “一种新的在体Aβ CAR-microglia制备方法的建立及其在阿尔茨海默 病动物模型中的实验治疗研究”（2026.01-2029.12）。课题编号：82571681

2. 国家自然科学基金,“基于双靶分子识别的Dox调控的增强型IL13 CAR-T在恶性脑胶质瘤动物模型中的实验治疗研究”(2018.1-2021.12)。课题编号：81773265。

3. 国家自然科学基金,“结合靶向基因组编辑技术构建用于单基因缺陷原位修复的新型高容量腺病毒载体”(2015.1-2018.12)。课题编号：81471772。

4. 陕西省自然科学基金重点项目，“新型溶瘤腺病毒载体靶向恶性脑胶质瘤的基因治疗研究” (2014.5-2017.4)。课题编号：2014JZ005。

5. 国家自然科学基金,“骨髓间充质干细胞装载新型药物诱导性溶瘤腺病毒Ad5/11-Ind-D24靶向脑胶质母细胞瘤的实验治疗研究”(2013.1-2016.12)。课题编号：81272543。

6. 国家自然科学基金,“腺病毒核心蛋白遗传标记方法的建立及其应用研究”(2011.1-2013.12)。课题编号：31070137。

7. 农业部科技重大专项子课题，“锌指核酸酶及同源重组腺病毒表达载体的构建” (2009.6 -2010.12)。课题编号：2009ZX08010-023B。

8. 国家自然科学基金，“新型靶向条件复制型溶瘤腺病毒载体Ad5/11 D24 在恶性脑胶质母细胞瘤中的实验治疗研究”(2009.1-2011.12)。课题编号：30872993。

9. 陕西省自然科学基金，“双表达VEGF siRNA 的新型靶向Ad5/3-RGD腺病毒载体在脑胶质母细胞瘤基因治疗中的实验研究”（2008.1.1-2010.12.31）。课题编号：2007C201。

10. 国家科技部863课题，“高效表达小干扰RNA 新型腺病毒载体的研究”（2006.12.1-2008.12.31）。课题编号：2006AA02Z163。

三、授权专利

1. Davidson, Anderson, Haskell and Xia. (2004) Rapid Generation of Recombinant Adenoviral Vectors. US Patent No. US 6830920.

2. Davidson, Xia and Mao. (2005) siRNA-mediated gene silencing with viral vectors. Issuance of Australian Patent No.2005200828.

3. Paulson, Harper, Miller, Davidson, Xia and Mao. (2005) Allele-Specific siRNA-Mediated Gene Silencing. Issuance of Australian Patent No.2005200827.

4. 夏海滨、张伟锋、郑晓晶、赵俊丽、王东阳。表达小干扰RNA的VA1缺失的腺病毒载体及构建方法和应用。授权公告日：2011年5月4日，专利号：ZL 2009 1 0022759.9，专利申请国：中国。

5. 夏海滨、张伟锋、王东阳、郑晓晶、赵俊丽。肿瘤特异嵌合启动子及其构建方法和应用。授权公告日：2011 年11 月30，专利号：ZL 2009 1 0023841.3，专利申请国：中国。

6. 夏海滨、赵俊丽。腺病毒核心蛋白遗传标记载体的构建方法。授权公告日：2012 年01 月11日，专利号：ZL 2010 1 0214774.6，专利申请国：中国。

7. 夏海滨、郑晓晶、王东阳、边晔、孙晓聪、冯真真、李婧。小干扰RNA 快速筛选的载体及其构建方法和应用。授权公告日：2012年11月7日，专利号：ZL 2009 1 0022909.6，专利申请国：中国。

8. 夏海滨，张伟锋。快速检测锌指核酸酶介导基因定点整合的方法。授权公告日：2013 年 6月12日，专利号：ZL 2011 1 0009773.2，专利申请国：中国。

9. 夏海滨，李星。一步法构建携带外源基因的D24纤维蛋白修饰的条件复制型腺病毒载体及其应用。授权公告日：2013 年 9月11日，专利号：ZL 2012 1 0014951.5，专利申请国：中国。

10. 夏海滨，刘世海。小肽修饰表达两个外源基因的条件复制型溶瘤腺病毒载体及构建方法和应用。授权公告日：2014年3月12日，专利号：ZL 2011 10139710.9，专利申请国：中国。

11. 夏海滨，李星。纤维蛋白修饰表达两个外源基因的溶瘤腺病毒载体及构建方法和应用。专授权公告日：2014 年 4月23日，专利号：ZL 201110139756.0，专利申请国：中国。

12. 夏海滨，陈皓。单载体双向启动的Tet-on诱导表达系统及其构建方法和应用。授权公告日：2014 年 9月10日，专利号：ZL 2012 1 0300572.2，专利申请国：中国。

13. 夏海滨，郑晓晶，邸炳艳。制备六联体蛋白经遗传修饰的腺病毒的载体及其构建方法。授权公告日：2014年10月22日，专利号：ZL 201110427860.X，专利申请国：中国。

14. 夏海滨，张伟锋，刘思也。携带锌指核酸酶表达元件和供体DNA的腺病毒及其构建方法和应用。授权公告日：2014年12月10日，专利号：ZL 201310076298.X，专利申请国：中国。

15. 夏海滨，张伟锋。锌指蛋白的快速筛选方法。授权公告日：2015年5月27日，专利号：ZL 201210207952.1，专利申请国：中国。

16. 夏海滨，张伟锋，刘思也。一种基因打靶系统。授权公告日：2015年06月10日，专利号：ZL 201310157216.4，专利申请国：中国。

17. 夏海滨，张伟锋，肖丹，单琳琳。一种抗凋亡细胞系及其建立方法和应用。授权公告日：2020年08月18日，专利号：ZL 201710202547.3，专利申请国：中国。

18. 夏海滨，李彦青。一种基于单克隆抗体检测人PGRN的双夹心ELISA试剂盒。授权公告日：2020年08月28日，专利号：ZL 201711367163.3，专利申请国：中国。

19. 夏海滨，陈皓。病毒复制受转录抑制型Tet-on系统调控的条件复制腺病毒载体及应用。授权公告日：2020年11月06日，专利号：ZL 201710547604.1，专利申请国：中国。

20. 夏海滨，李雅，张伟锋，朱久玲，李燕。基于CRISPR/Cas9多基因敲除低转染效率细胞系的方法。授权公告日：2021年02月05日，专利号：ZL 201710153605.8，专利申请国：中国。

21. 夏海滨，陈皓，郑晓晶，代鑫，李燕，陈芳。一种表达受茶碱调控的适体核酶修饰型sgRNA的载体及应用。授权公告日：2021年02月19日，专利号：ZL 201710184537.1，专利申请国：中国。

22. 夏海滨，单琳琳，朱贺，张伟锋。一种用于提高高容量腺病毒包装效率的辅助腺病毒。授权公告日：2021年03月26日，专利号：ZL 201711239774.X，专利申请国：中国。

23. 夏海滨，王玉芬。一种基于单克隆抗体检验人proGRP的双夹心ELISA试剂盒。授权公告日：2021年06月15日，专利号：ZL 201810727981.8，专利申请国：中国。

24. 夏海滨，单琳琳，张伟锋，赵俊丽。一种特异性靶向hDGKθ基因的荧光素酶报告系统。授权公告日：2022年03月15日，专利号：ZL 201810054844.2，专利申请国：中国。

四、代表性论文

1. Shan L, He Q, Zhang W, Zheng X, Zhao J, Yang P, Mao Q, Xia H. CRISPR/Cas9-mediated promoterless gene targeting reduces lysosome storage in MPS VII mice. Sci China Life Sci. 2025 Jul 2.

2. Li Y, He Q, Chen S, Dli H, Zhao J, Sun X, Yang P, Mao Q, Xia H. BI-7273, a BRD9 inhibitor, reduces lipid accumulation by downregulating the AKT/mTOR/SREBP1 signaling pathway. Biochem Pharmacol.2024 Aug;226:116412.

3. Zheng X, Wang M, He Q, Chen S, Simayi D, Ma X, Zhao J, Sun X, Yang P, Mao Q, Xia H.Production and characterization of novel monoclonal antibodies against pathological human TDP-43 proteins.J Neuropathol Exp Neurol. 2024，83(8):655-669.

4. Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development.Signal Transduct Target Ther. 2023;8(1):267.

5. Wang D, Zheng X, Chai L, Zhao J, Zhu J, Li Y, Yang P, Mao Q, Xia H.FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1.Elife.2023;12:e85659.

6. Zhu J, Yang J, Wen H, Wang M, Zheng X, Zhao J, Sun X, Yang P, Mao Q, Li Y, Xia H.Expression and functional analysis of fam76b in zebrafish.Fish Shellfish Immunol. 2023 Nov;142:109161.

7. Wu D, Wang J, Chang Y, Zhang S, Liang J, Zhao J, Yang P, Mao Q, Xia H. Rutaecarpin reduces lipids by DGKθ-dependent activation of PPARα. Obesity (Silver Spring). 2022;30(12):2424-2439.

8. Zheng X, Mi T, Wang R, Zhang Z, Li W, Zhao J, Yang P, Xia H, Mao Q. Progranulin deficiency promotes persistent neuroinflammation and causes regional pathology in the hippocampus following traumatic brain injury. Glia.2022;70(7):1317-1336.

9. Muhammad N, Wang R, Li W, Zhang Z, Chang Y, Hu Y, Zhao J, Zheng X, Mao Q, Xia H. A novel TanCAR targeting IL13Rα2 and EphA2 for enhanced glioblastoma therapy. Mol Ther Oncolytics. 2022; 24:729-741.

10. Zhu J, Xu H, Song H, Li X, Wang N, Zhao J, Zheng X, Kim KY, Zhang H, Mao Q, Xia H. CRISPR/Cas9-mediated grna gene knockout leads to neurodevelopmental defects and motor behavior changes in zebrafish. J Neurochem. 2021;157(3):520-531.

11. Zhang J, Chen H, Chen C, Liu H, He Y, Zhao J, Yang P, Mao Q, Xia H. Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy. Cancer Lett.2021,509:26-38.

12. Du C，Wu Y，Ju Y，Zhao J，Xia H. The luciferase reporter system of the MMP12 endogenous promoter for investigating transcriptional regulation of the human MMP12 gene. Electronic Journal of Biotechnology, 2020,43:55-61.

13. Mao Q, Zheng X, Gefen T, Rogalski E, Spencer CL, Rademakers R, Fought AJ, Kohler M, Weintraub S, Xia H, Mesulam MM, Bigio EH. FTLD-TDP With and Without GRN Mutations Cause Different Patterns of CA1 Pathology. J Neuropathol Exp Neurol. 2019,78(9):844-853.

14. Li Y, Wang D, Li Y, Zhu J, Zhao J, Deng Y, Rogalski EJ, Bigio EH, Rademaker AW, Xia H, Mao Q.A Highly Sensitive Sandwich ELISA to Detect CSF Progranulin: A Potential Biomarker for CNS Disorders.J Neuropathol Exp Neurol. 2019, 78(5):406-415

15. Zhang J, Zhao J, Mao Q, Xia H. A simple, efficient and economical method for isolating and culturing human umbilical cord blood‑derived mesenchymal stromal cells.Mol Med Rep. 2019,20(6):5257-5264.

16. Zhang J, Xia H. Lentiviral-Mediated Overexpression of MicroRNA-141 Promotes Cell Proliferation and Inhibits Apoptosis in Human Esophageal Squamous Cell Carcinoma. Recent Pat Anticancer Drug Discov.2019;14(2):170-176.

17. Zhu J, Wang N, Li X, Zheng X, Zhao J, Xia H, Mao Q. Suppression of Progranulin Expression Leads to Formation of Intranuclear TDP-43 Inclusions In Vitro: A Cell Model of Frontotemporal Lobar Degeneration.J Neuropathol Exp Neurol. 2019, 78(12):1124-1129.

18. Shan L, Wang D, Mao Q, Xia H. Establishment of a DGKθ Endogenous Promoter Luciferase Reporter HepG2 Cell Line for Studying the Transcriptional Regulation of DGKθ Gene. Appl Biochem Biotechnol. 2019,187(4):1344-1355.

19. Li Y, Li S, Li Y, Xia H, Mao Q. Generation of a novel HEK293 luciferase reporter cell line by CRISPR/Cas9-mediated site-specific integration in the genome to explore the transcriptional regulation of the PGRN gene. Bioengineered. 2019,10(1):98-107.

20. Chen H, Li Y, Du C, Li Y, Zhao J, Zheng X, Mao Q, Xia H. Aptazyme-mediated direct modulation of post-transcriptional sgRNA level for conditional genome editing and gene expression.J Biotechnol. 2018; 288:23-29.

21. Li Y, Zhang W, Zhao J, Li S, Shan L, Zhu J, Li Y, Zhu H, Mao Q, Xia H. Establishing a dual knock-out cell line by lentivirus based combined CRISPR/Cas9 and Loxp/Cre system. Cytotechnology. 2018,70(6):1595-1605.

22. Zhang J, Zhao J, Zheng X, Cai K, Mao Q, Xia H. (2018) Establishment of a novel hepatic steatosis cell model by Cas9/sgRNA-mediated DGKθ gene knockout. Mol Med Rep.17(2):2169-2176.

23. Li Z, Zhao J, Muhammad N, Wang D, Mao Q, Xia H. Establishment of a HEK293 cell line by CRISPR/Cas9-mediated luciferase knock-in to study transcriptional regulation of the human SREBP1 gene. Biotechnol Lett. 2018,40(11-12):1495-1506.

24. Muhammad N, Mao Q, Xia H.（2017）CART-cells for cancer therapy. Biotechnol Genet Eng Rev. 33(2):190-226.

25. Zhang W, Xiao D, Shan L, Zhao J, Mao Q, Xia H. (2017) Generation of apoptosis-resistant HEK293 cells with CRISPR/Cas mediated quadruple gene knockout for improved protein and virus production. Biotechnol Bioeng. 114(11):2539-2549.

26. Chen F, Li Y, Zhao J, Mao Q, Xia H.(2017) Domain-Specific Monoclonal Antibodies Against Human Rev-erbβ. Appl Biochem Biotechnol.182(3):978-989.

27. Mao Q, Wang D, Li Y, Kohler M, Wilson J, Parton Z, Shmaltsuyeva B, Gursel D, Rademakers R, Weintraub S, Mesulam MM, Xia H, Bigio EH（2017）. Disease and Region Specificity of Granulin Immunopositivities in Alzheimer Disease and Frontotemporal Lobar Degeneration. J Neuropathol Exp Neurol, 76(11):957-968.

28. Dai X, Li Y, Sun X, Cai K, Mao Q, Xia H.(2017) Generation of Domain-Specific Monoclonal Antibodies Against Human Glutaredoxin3. Monoclon Antib Immunodiagn Immunother. 35(6):285-292 SCI 4区

29. Li Y, Li Y, Zhao J, Zheng X, Mao Q, Xia H. (2017) Development of a Sensitive Luciferase-Based Sandwich ELISA System for the Detection of Human Extracellular Matrix 1 Protein. Monoclon Antib Immunodiagn Immunother. 35(6):273-279.SCI 4区

30. Li Y, Li Y, Ye M, Wang D, Zhao J, Sun X, Mao Q, Xia H.(2017) Biological function analysis of monoclonal antibodies against human granulins in vitro using U251 cells as a model. Protein Expr Purif. 130:55-62.

31. Zheng X, Li Y, Zhao J, Wang D, Xia H, Mao Q. (2016) Production and Characterization of Monoclonal Antibodies against Human Nuclear Protein FAM76B. PLoS One. 11(3):e0152237. SCI 3区

32. Xiao D, Zhang W, Li Y, Liu K, Zhao J, Sun X, Shan L, Mao Q, Xia H. (2016) A novel luciferase knock-in reporter system for studying transcriptional regulation of the human Sox2 gene. J Biotechnol.219:110-6. SCI 2区

33. Li Y, Li Y, Zhao J, Wang D, Mao Q, Xia H. (2016) Production and characterization of domain-specific monoclonal antibodies against human ECM1. Protein Expr Purif. 121:103-111. SCI 4区

34. Wang D, Guo Y, Li Y, Li W, Zheng X,Xia H, Mao Q.(2015)Detection of CD133 expression in U87 glioblastoma cells using a novel anti-CD133 monoclonal antibody.Oncol Lett. 9(6):2603-2608.SCI 4区

35. Chen H, Wang D, Xia R, Mao Q,Xia H.(2015) A novel adenoviral vector carrying an all-in-one Tet-On system with an autoregulatory loop for tight, inducible transgene expression.BMC Biotechnol.13;15:4. SCI 2区

36. Zhang W, Chen H, Zheng X, Wang D, Ji H, Xia H, Mao Q. (2014) Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template. J Biotechnol. 188C:1-6. SCI 2区

37. Zhang W, Wang D, Liu S, Zheng X, Ji H, Xia H*, Mao Q. (2014) Multiple copies of a linear donor fragment released in situ from a vector improve the efficiency of zinc-finger nuclease-mediated genome editing. Gene Ther. 21 (3):282-8. SCI 2区

38. Wang D, Li W, Zhang H, Mao Q, Xia H*. (2014) A targeting peptide improves the adenovirus-mediated transduction of a glioblastoma cell line. Oncol Rep 31(5):2093-8. SCI 3区

39. Chen H, Zheng X, Di B, Wang D, Zhang Y, Xia H, Mao Q. (2013) Aptamer modification improves the adenoviral transduction of malignant glioma cells. J. Biotechnol. 168(4):362-66. SCI 2区

40. Wang L, Liu Q, Li F, Qiu J, Fan H, Ma H, Zhu Y, Wu L, Han X, Yang Z, Jiang H, Wei J, Xia H. (2013) Apoptosis induced by PGC-1β in breast cancer cells is mediated by the mTOR pathway. Oncol Rep. 30(4):1631-8. SCI 3区

41. Li X, Xia R, Zhao J, Wang D, Mao Q, Xia H. (2013) A one-step ligation system for rapid generation of armed, conditionally-replicating adenoviruses. Biotechnol Lett. 35(8):1215-21. SCI 3区

42. Zhang W, Guo Y, Zhang C, Ji H, Meng W, Wang D, Li X, Mao Q, Xia H. (2012) Rescue the Failed Half-ZFN by a Sensitive Mammalian Cell-Based Luciferase Reporter System. Plos one. 7 (9):e45169.

43. Zhang W, Zheng X, Wang Y, Mao Q, Xia H. (2012) Establishment of a cell line carrying single copy of an exogenous mutant reporter gene for assaying the biological activity of ZFNs. J Biotechnol. 162(2-3):191-96.

44. Li X, Mao Q, Wang D, Xia H. (2012). A novel Ad5/11 chimeric oncolytic adenovirus for improved glioma therapy .International Journal of Oncology. 41(6):2159-65.

45. Li X, Mao Q, Wang D, Zhang W, Xia H（2012）. A fiber chimeric CRAd vector Ad5/11-D24 double-armed with TRAIL and arresten for enhanced glioblastoma therapy. Hum Gene Ther. 23(6):589-96.

46. Chai L, Liu S, Mao Q, Wang D, Li X, Zheng X, Xia H（2012）. A novel conditionally replicating adenoviral vector with dual expression of IL-24 and arresten inserted in E1 and the region between E4 and fiber for improved melanoma therapy. Cancer Gene Ther. 19(4):247-54.

47. Di B, Mao Q, Zhao J, Li X, Wang D, Xia, H（2012）. A rapid generation of adenovirus vector with a genetic modification in hexon protein.J. Biotechnol. 157(3):373-378

48. Chai, L, Mao, Q. Wang D., Li, H., Xia, H. (2011) Domain-specific monoclonal antibodies produced against human PGRN. Hybridoma. 30(3):271-8.

49. Li X, Liu S, Wang D, Chen H, Xia, H. (2011) . Adenoviral delivered eGFP-intron splicing system for multiple gene RNAi. Biotechnol Lett. 33(9):1723-8.

50. Wang, D., Liu, S., Mao, Q., Zhao, J., Xia, H. (2011). A novel vector for a rapid generation of fiber-mutant adenovirus based on one step ligation and quick screening of positive clones. J. Biotechnol. 152(3):72-6.

51. Zheng, X., Mao, Q., Wang, D., Zhao, J., Xia, H.( 2011).A novel system for rapid screening of effective siRNA target sites by one step transfection with a single vector. J. Biotechnol. 155(2):135-9.

52. Liu, S., Mao, Q., Zhang, W., Zheng, X., Bian, Y., Wang, D., Li, H., Chai, L., Zhao, J.,Xia, H. （2009）.Genetically modified adenoviral vector with the protein transduction domain of Tat improves gene transfer to CAR-deficient cells. Biosci Rep.29(2):103-9.

53. Alisky, J.M, Xia, H., Davidson, B.L. (2006). A TAT-modified fusion protein efficiently penetrates mouse hypoglossal nuclei from transduced ependyma. Neurosci Lett. 401:40-3.

54. Xia, H., Mao, Q., Eliason, S.L., Harper, S.Q., Martins, I.H. , Orr, H.T., Paulson, H.L., Yang, L., Kotin, R.M., Davidson, B.L. (2004). RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebeller ataxia. Nat.Med. 10(8): 816-20.

55. Mao, Q., Xia, H., Davidson, B.L. (2003) .Intracellular trafficking of CLN3, the protein underlying the childhood neurodegenerative disease, Batten disease. FEBS Lett. 555 (2):351-7.

56. Mao, Q., Foster, B.J., Xia, H., Davidson, B.L. (2003). Membrane topology of CLN3, the protein underlying Batten disease. FEBS Lett. 541(1-3):40-6.

57. Miller, V.M., Xia, H., Marrs,G.L.,Gouvion, C.M., Lee, G., Davidson, B.L. and Paulson, H.L. (2003). Allele-Specific Silencing of Dominant Disease Genes. Proc Natl Acad Sci U S A. 100(12):7195-200.

58. Xia, H., Mao,Q., Henry, Paulson., Davidson, B.L. (2002). siRNA-mediated gene silencing in vitro and in vivo. Nat Biotec, hnol. 20(10):1006-10.

59. Wang, G., Williams, G., Xia, H., Hickey, M., Shao, J., Davidson, B.L., McCray, P.B.(2002).Apical Barriers to Airway Epithelial Cell Gene Transfer with Amphotropic Retroviral Vector. Gene Ther. 9(14): 922-31.

60. Xia,H., Mao, Q., Davidson, B.L. (2001). The HIV tat protein transduction domain improves the biodistribution of ß-glucuronidase expressed from recombinant viral vectors. Nat. Biotechnol. 19(7): 640-4.

61. Anderson, R.D., Haskell, R.E., Xia, H., Roessler, B.J., Davidson., B,L. (2000).A simple method for the rapid generation of recombinant adenoviral vectors. Gene Ther. 7(12): 1034-8.

62. Xia, H., Anderson, B., Mao, Q., Davidson, B.L (2000). Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. J. Virol. 74(23): 11359-66.

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