团队负责人

韩谦，博士，教授，博士生导师，永利y l65335副经理，担任海南省卫生有害生物防制协会会长、海南省生物学会副理事长、《Frontiers in Molecular Biosciences》associate editor、《热带生物学报》副主编、《中国热带医学》编委等职。在中国农业大学、丹麦哥本哈根大学、美国伊利诺伊大学、瑞典农业科学大学、美国弗吉尼亚理工大学学习和工作。从事病媒生物和寄生虫防控研究，在全健康视角下开展病媒生物、动物寄生虫和虫媒传染病的防控。共发表论文190余篇，其中SCI期刊论文110余篇。

团队介绍

永利集团病媒生物学团队以海南自贸港人民健康为己任，致力于蚊、蜱、螨、蠓等媒介生物传播疾病机制与科学防控研究。通过组学、进化生物学、CRISPR/Cas和RNAi等技术，对病媒生物的生理生化、疾病传播机制等进行了系统、深入研究，构建了蚊虫的CRISPR-Cas基因编辑和RNAi的技术平台；寻找病媒生物潜在杀虫剂及疾病传播阻断剂靶标，探究了蚊虫抗药性机制，研制了新型高效安全杀虫剂剂型；开展了人与农场动物环境媒介节肢动物和虫媒病调查，掌握了优势媒介生物的消长规律与丰度；对海南岛伴侣动物和野生动物进行疫病监测、诊断、防控技术及药效评价研究。目前，团队已申请国家、省级纵向科研项目及药企等横向科研项目38项，总经费2000万元。成立了海南省卫生有害生物防制协会，并成功组织了三届全国性的虫媒病及病媒生物防控高峰论坛，论坛宣传以全健康理念防控虫媒传染病，在国内已具有一定的影响力。通过团队近七年的共同努力，已经成为我国病媒生物学研究的主要力量之一，对我国热带地区预防医学及昆虫生物技术领域的科技进步具有积极的推动作用。

团队成员

骨干成员

教授：廖承红、郭莹莹；副教授：王金花、赵建国、许靖云；讲师：管庆丰

其他团队成员

张磊（博后）、陈平（科研助理，职业兽医师）

主要研究方向

方向1：蚊虫表皮合成、天然免疫等生理生化机制

方向2：蚊虫抗药性机制及新型杀蚊制剂研发

方向3：蜱、螨、蠓等携带病原调查及疫苗研究

方向4：虫媒传染病的流行病学与诊断技术研究

近期研究成果

1.2017-2024部分期刊论文（selected）

1) Chen, J., Wu, Y., Chen, J., Lu, H., Cheng, G., Tu, Z.J., Liao, C. and Han, Q. (2024). Roles of a newly lethal cuticular structural protein, AaCPR100A, and its upstream interaction protein, G12-like, in Aedes aegypti. Int J Biol Macromol 268, 131704.

2) Huang Y, Chen Z, Lan J, Zhang L, Chen H, Jiang L, Yu H, Liu N, Liao C*, Han Q*. (2024). MDR49 coding for both P-glycoprotein and TMOF transporter functions in ivermectin resistance, trypsin activity inhibition, and fertility in the yellow fever mosquito, Aedes aegypti. Pestic Biochem Physiol 201, 105899.

3) Intirach, J., Lv, X., Sutthanont, N., Cai, B., Champakaew, D., Chen, T., Han, Q. and Lv, Z. (2024). Molecular and next-generation sequencing analysis of tick-borne pathogens of Rhipicephalus ticks (Acari: Ixodidae) in cattle and dogs. Acta Trop 252, 107138.

4) Tang, Y., Jiang, L., Huang, Y., Chen, Z., Merkler, D.J., Zhang, L. and Han, Q. (2024). Role of arylalkylamine N-acetyltransferase 7 in reproduction and limb pigmentation of Aedes aegypti. Insect Mol Biol

5) Wang, N., Sieng, S., Liang, T., Xu, J. and Han, Q. (2024). Intestine proteomic and metabolomic alterations in dogs infected with Toxocara canis. Acta Trop 252, 107140.

6)Jiang, L. Xie, X.B., Zhang, L., Tang, Y., Zhu, X., Huang, Y., Hong, Y., Hansson, B.S., Cui, Z.J., and Han, Q. (2024). Activation of the G protein coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti. the FASEB Journal.

7) Xu, J. and Han, Q. (2024). Prevalence, Infection, and Risk to Human Beings of Toxocara canis in Domestic Food-Producing Animals. Vet Sci 11

8) Yu, H., Li, Y., Wang, H., Zhang, L., Suo, P., Su, T. and Han, Q. (2024). Preparation of a long-lasting tablet of spinosad microspheres and its residual insecticidal efficacy against the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae) larvae. Pest Manag Sci 80, 3912-3921.

9) Yu, L., Yin, Y., Wang, Q., Zhao, P., Han, Q. and Liao, C. (2024). Impact of Ae-GRD on Ivermectin Resistance and Its Regulation by miR-71-5p in Aedes aegypti. Insects 15

10) Zhao, X., Zhao, J., Wang, J., Liao, C., Guan, Q. and Han, Q. (2024). Immune protection of three serine protease inhibitors vaccine in mice against. Sci Rep. 2;14(1):7703.

11) Zhou, S., Huang, L., Lin, Y., Bhowmick, B., Zhao, J., Liao, C., Guan, Q., Wang, J., and Han, Q. (2023) Molecular surveillance and genetic diversity of Anaplasma spp. in cattle (Bos taurus) and goat (Capra aegagrus hircus) from Hainan island/province, China. BMC veterinary research 19, 213

12) Zhang, L., Tang, Y., Merkler, D. J., and Han, Q. (2023) Function, structure, evolution, regulation of a potent drug target, arylalkylamine N-acetyltransferase. Advances in protein chemistry and structural biology 134, 211-223

13) Ying, Z., Upadhyay, A., Wang, J., Han, Q., and Liu, Q. (2023) The prevalence of canine dirofilariasis in China: a systematic review and meta-analysis. Parasit Vectors 16, 207

14) Yang, C., Liao, C., Zhao, J., Guan, Q., Wang, G., and Han, Q. (2023) Dysregulation of tryptophan metabolism and distortion of cell signaling after oral exposure to ethanol and Kynurenic acid. Gene 852, 147061

15) Wang, K., Zu, H., Upadhyay, A., Zhao, J., Liao, C., Guan, Q., Wang, J., and Han, Q. (2023) Epidemiological and phylogenetic investigation of Babesia spp. in dogs of Hainan Province/Island, China. Parasitol Res 122, 2379-2383

16) Tang, Y., Chen, H., Lin, Z., Zhang, L., Upadhyay, A., Liao, C., Merkler, D. J., and Han, Q. (2023) Evolutionary genomics analysis reveals gene expansion and functional diversity of arylalkylamine N-acetyltransferases in the Culicinae subfamily of mosquitoes. Insect science 30, 569-581

17) Sieng, S., Chen, P., Wang, N., Xu, J.-Y., and Han, Q. (2023) Toxocara canis-induced changes in host intestinal microbial communities. Parasites Vectors 16, 462

18) Lin, Z., Huang, Y., Liu, S., Huang, Q., Zhang, B., Wang, T., Zhang, Z., Zhu, X., Liao, C., and Han, Q. (2023) Gene coexpression network during ontogeny in the yellow fever mosquito, Aedes aegypti. BMC genomics 24, 301

19) Lin, Y., Zhou, S., Upadhyay, A., Zhao, J., Liao, C., Guan, Q., Wang, J., and Han, Q. (2023) Molecular Detection and Phylogenetic Characterization of Anaplasma spp. in Dogs from Hainan Province/Island, China. Veterinary sciences 10

20) Liang, D., Chen, H., An, L., Li, Y., Zhao, P., Upadhyay, A., Hansson, B. S., Zhao, J., and Han, Q. (2023) Molecular identification and functional analysis of Niemann-Pick type C2 proteins，carriers for semiochemicals and other hydrophobic compounds in the brown dog tick, Rhipicephalus linnaei. Pesticide biochemistry and physiology 193, 105451

21) Li, J., Merkler, D. J., and Han, Q. (2023) Editorial: Aromatic amino acid metabolism-Volume II. Front Mol Biosci 9, 1122151

22) Guan, Q., Yang, H., Liao, C., Zhao, J., Wang, J., Liu, Y., Han, Q., and Zhang, H. (2023) In Silico Analysis and Immune Response of YaeT Protein Against Riemerella anatipestifer in Ducks. Applied biochemistry and biotechnology, 1-19

23) Chen, J., Wu, Y. C., Chen, J. K., Zhu, X. J., Merkler, D., Liao, C. H., and Han, Q. (2023) Elongases of Long-Chain Fatty Acids ELO2 and ELO9 Are Involved in Cuticle Formation and Function in Fecundity in the Yellow Fever Mosquito, Aedes aegypti. Insects 14

24) Liu, H.F., Huang, R.T., Zhao, X.Y., Yang, S.J., He, F.R., Qin, W.Q., Huang, J.H., Yu, G.B., Feng, Y.H., Li, J.C., Liao, C.H. (2023). Ca2+/pH-triggered gelation of Pickering emulsion in vitro digestion: Visualization and sustained-release performance. Food Hydrocolloid 140.

25) Bhowmick, B., Chen, H., Lozano-Fernandez, J., Vizueta, J., Ignell, R. and Han, Q. (2022) De novo transcriptome sequencing of the northern fowl mite, Ornithonyssus sylviarum, shed light on parasitiform poultry mites evolution and its chemoreceptor repertoires. Parasitol Res. 121, 521-535

26) Zhang, L., Tang, Y., Chen, H., Zhu, X., Gong, X., Wang, S., Luo, J. and Han, Q. (2022) Arylalkalamine N-acetyltransferase-1 acts on a secondary amine in the yellow fever mosquito, Aedes aegypti. FEBS Lett. doi: 10.1002/1873-3468.14316. Online ahead of print.

27) Yang, L., Wang, J.-H., Upadhyay, A., Zhao, J.-G., Huang, L.-Y., Liao, C.-H. and Han, Q. (2022) Identification of Theileria spp. and investigation of hematological profiles of their infections in goats in Hainan Island, China. Parasite. 29(3):13

28) Zhang, L., Li, M. Z., Chen, Z. H., Tang, Y., Liao, C. H. and Han, Q. (2021) Arylalkalamine N-acetyltransferase-1 functions on cuticle pigmentation in the yellow fever mosquito, Aedes aegypti. Insect science. 28, 1591-1600

29) Wang, H. C., Wang, Q. H., Bhowmick, B., Li, Y. X. and Han, Q. (2021) Functional characterization of two clip domain serine proteases in innate immune responses of Aedes aegypti. Parasit Vectors. 14, 584

30) Upadhyay, A., Waleed, R. M., Wang, J., Zhao, J., Guan, Q., Liao, C. and Han, Q. (2021) An innovative and user-friendly smartphone-assisted molecular diagnostic approach for rapid detection of canine vector-borne diseases. Parasitol Res. 120, 1799-1809

31) Lan, J., Wang, Z., Chen, Z., Zhang, L., Zhao, J., Guan, Q., Liao, C., Liu, N. and Han, Q. (2021) Identification of the Aedes aegypti nAChR gene family and molecular target of spinosad. Pest management science. 77, 1633-1641

32) Yang, C., Liao, C., Zhang, Y., Zhou, H., Diao, X., Han, Q. and Wang, G. (2020) Organ-differential responses to ethanol and kynurenic acid, a component of alcoholic beverages in gene transcription. Gene. 737, 144434

33) Upadhyay, A., Yang, H., Zaman, B., Zhang, L., Wu, Y., Wang, J., Zhao, J., Liao, C. and Han, Q. (2020) ZnO Nanolower-Based NanoPCR as an Efficient Diagnostic Tool for Quick Diagnosis of Canine Vector-Borne Pathogens. Pathogens. 9

34) Bhowmick, B., Tang, Y., Lin, F., Øines, Ø., Zhao, J., Liao, C., Ignell, R., Hansson, B. S. and Han, Q. (2020) Comparative morphological and transcriptomic analyses reveal chemosensory genes in the poultry red mite, Dermanyssus gallinae. Sci Rep. 10, 17923

35) Bhowmick, B., Lin, F., Zhao, J., Guan, Q., Liao, C. and Han, Q. (2020) An efficient high-welfare feeding device for assessing northern fowl mite interventions in vivo: an improved method for the identification of protective antigens/systemic acaricides/repellent effect. Vet Parasitol. 288, 109279

36) Han, Q., Yang, C. H., Lu, J., Zhang, Y. N. and Li, J. Y. (2019) Metabolism of Oxalate in Humans: A Potential Role Kynurenine Aminotransferase/Glutamine Transaminase/Cysteine Conjugate Beta-lyase Plays in Hyperoxaluria. Curr. Med. Chem. 26, 4944-4963

37) Bhowmick, B., Zhao, J. G., Oines, O., Bi, T. L., Liao, C. H., Zhang, L. and Han, Q. (2019) Molecular characterization and genetic diversity of Ornithonyssus sylviarum in chickens (Gallus gallus) from Hainan Island, China. Parasites Vectors. 12

38) Liao, C., Upadhyay, A., Liang, J., Han, Q. and Li, J. (2018) 3,4-Dihydroxyphenylacetaldehyde synthase and cuticle formation in insects. Dev Comp Immunol. 83, 44-50

39) Han, Q., Wong, D. M., Robinson, H., Ding, H. Z., Lam, P. C. H., Totrov, M. M., Carlier, P. R. and Li, J. Y. (2018) Crystal structure of acetylcholinesterase catalytic subunits of the malaria vector Anopheles gambiae. Insect Sci. 25, 721-724

40) Guan, H., Wang, M. Y., Liao, C. H., Liang, J., Mehere, P., Tian, M. L., Liu, H. R., Robinson, H., Li, J. Y. and Han, Q. (2018) Identification of aaNAT5b as a spermine N-acetyltransferase in the mosquito, Aedes aegypti. Plos One. 13

41) Zhao, J. G., Williams, A. R., Hansen, T. V. A., Thamsborg, S. M., Cai, J. P., Song, S. B., Chen, G., Kang, M., Zhang, Z. Z., Liu, Q. and Han, Q. (2017) An in vitro larval migration assay for assessing anthelmintic activity of different drug classes against Ascaris suum. Vet. Parasitol. 238, 43-48

42) Zhao, J. G., Han, Q., Liao, C. H., Wang, J. H., Wu, L. L., Liu, Q. and Lindsay, D. S. (2017) Effects of In Vivo and In Vitro Treatment of Ascaris suum Eggs with Anthelmintic Agents on Embryonation and Infectivity for Mice. J. Parasitol. 103, 598-601

43) Liu, Q. M., Li, C. X., Wu, Q., Shi, Q. M., Sun, A. J., Zhang, H. D., Guo, X. X., Dong, Y. D., Xing, D., Zhang, Y. M., Han, Q., Diao, X. P. and Zhao, T. Y. (2017) Identification of Differentially Expressed Genes in Deltamethrin-Resistant Culex pipiens quinquefasciatus. J. Am. Mosq. Control Assoc. 33, 324-330

2. 专利情况

1）韩谦, 赵洪伟, 兰坚强等, 2019, 一种多杀菌素半抗原及其制备方法和应用. 中国发明专利,申请号：2017101588230, 专利授权号: CN106967140B, 2019-7-21

        2）韩谦, 陈静, 廖承红, 卢浩然, 王金花, 赵建国. dsRNA及其在防治埃及伊蚊中的应用, 专利号：ZL 201911113686.4 授权公告号：CN110679606B，2020年11月10日, 中国

        3）廖承红, 陈静, 韩谦, 张磊, 卢浩然, 刁晓平. 一种用于蚊虫的RNAi纳米颗粒和制备方法及用途，专利号：ZL 201910471529.4，授权公告号：CN110396524B，2023年05月02日，中国

        4）管庆丰, 杨慧, 韩谦, 张海文, 廖承红, 赵建国, 王金花. 一种通用型鸭疫里默氏杆菌卵黄抗体及其制备方法和应用，专利号：ZL202010851975.0，授权公告号：CN111995665B，2022年03月29日，中国

3. 获奖情况

1）2024 中国发明协会发明创业奖成果奖二等奖（医药卫生类）（团队成员排名第三）

        2）2023年，海南省第二届“优秀研究生导师团队”

主持科研项目

1）国家自然科学地区基金区域创新发展联合基金重点项目，重要热带传病生物媒介扩散、传病的监测预警及生物防控技术研究，U22A20363，2023.01-2026.12， 255万， 韩谦主持。

2）国家重点研发（子课题），一站式多基因编辑供体猪创制及其安全评价—人源化异种器官(心脏、肾脏)创制与临床前功能评价研究，2024.1-2028.1， 100万，王金花主持。

3）农业农村部产业集群项目， 2023年文昌鸡优势特色产业集群项目资金-文昌鸡全健康体系构建， RZ2300005281， 2023.01-2023.12， 60万(直拨）+ 90万（配套），在研，主持。

4）农业农村部产业集群项目， 2022年文昌鸡优势特色产业集群项目资金-文昌鸡全健康体系构建， RZ2200005103， 2022.01-2022.12， 60万(直拨）+ 60万（配套），已结题，主持。

5）国家自然科学地区基金项目，伊蚊酚氧化酶生化特性以及对单酚化合物的识别机制研究，31860702，2019.1-2022.12，40万，韩谦主持。

6）国家自然科学基金国际合作重点项目，微小隐孢子虫和人隐孢子虫新发亚型家族产生的遗传机制，31820103014，2019.1- 2023.12，42.3万元， 廖承红任务负责， 赵建国参加。

7）国家自然科学基金地区项目，基于RNAi和组学技术对埃及伊蚊DOPAL合成酶在幼虫发育调控中分子机，31960703，2020.1-2023.12，40.0万元，廖承红主持。

8）海南省科技重大项目，登革热等重大疫病的病媒生物防控研究，KJZD2021035，2021.12.14--2024.12.14，500万，韩谦项目主持，廖承红课题主持，王金花、赵建国任务负责。

9）国家科技部高端外国专家引进计划，芳香族氨基酸代谢酶在蚊虫天然免疫和吸血行为中的功能研究，G2021034003L，2021.11 - 2023.10，40万元，韩谦主持，管庆丰参加。

代表性成果介绍

本团队主要研究领域为病媒生物学。2014年以来，围绕病媒生物的生理生化、天然免疫、抗病性机制和新型杀虫剂的研发，研究成果主要体现为以下几个方面：

1. 开展已知杀虫剂及靶标的深入研究可以了解抗药机制，有助于找到抗药性解决方案。本团队和国外同行合作首次解析了蚊虫的杀虫剂靶标，乙酰胆碱酯酶的晶体结构，鉴定了蚊虫多杀菌素和伊维菌素的作用靶标。

2. 蚊虫表皮合成和黑色素代谢相关酶的功能研究。本团队已成功搭建了蚊虫CRISPR/Cas9系统和RNAi技术平台，基于前期研究，主要对媒介昆虫的表皮合成和黑色素代谢相关酶类进行生理生化分析、功能研究，如芳烷基胺 N-乙酰转移酶、酚氧化酶和DOPAL合成酶等，探讨蚊虫的天然免疫机制。

3. 新型杀蚊制剂的研发。本团队成功研制出长效杀蚊虫制剂，多杀菌素微球缓释片，可用于蚊虫幼虫的防控（见下图，Pest Management Science封底）。本团队还通过RNAi干扰方法发现某些蚊虫表皮合成酶和结构蛋白或与蚊虫的发育密切相关，或对早期蚊虫具有致死性。由此，认为这些基因对蚊虫的生存极为重要，可将这些靶标基因应用到蚊虫的生物防控。关键问题是合适的环保的表达载体。目前已授权一项专利：大肠杆菌表达的蚊虫dsRNA，用甲壳素做成纳米颗粒。

4. 动物病原诊断与检测新技术的研究建立了一种由纳米材料ZnO结合PCR的检测方法，首次将纳米ZnO技术与PCR结合，以实现更高效省时的检测巴贝斯虫等原虫的感染情况，为这类疾病的快速诊断提供了技术支持。同时，还通过把一个简单、经济且易携带的LAMP 盒与智能手机连接起来，从而开发出一种针对寄生虫媒介传播疾病（例如犬埃立克氏体和犬肝簇虫）的检测系统。