环境中细颗粒物、重金属、持久性有机污染物及微纳塑料等典型环境污染物，其健康风险日益突出，开展相关毒理学机制及干预研究具有重要意义。尽管现有研究已初步揭示了部分污染物的毒性效应，但对其毒性机制的全面认知仍显不足，针对性的干预策略亦十分有限，亟需系统深入的机制探索与高效解毒方案的开发。围绕上述科学问题，本课题组聚焦环境污染物健康效应的毒理学机制及干预策略，开展了系统性研究，致力于填补多通路毒性调控与精准解毒领域的研究空白。
本课题组近年来围绕环境污染物健康效应的毒理学机制及干预取得了多项进展，主要包括：揭示了α-硫丹通过跨损伤合成聚合酶Polη介导生殖细胞致突变性的机制；阐明了光老化微塑料释放副产物、结合α-螺旋结构域抑制唾液淀粉酶活性的分子基础，并发现儿童对该效应更为敏感；虾青素通过稳定细胞膜结构、抑制颗粒物内吞及清除线粒体活性氧，高效拮抗柴油机尾气颗粒物及森林火灾PM2.5的毒性；氧化石墨烯纳米复合物通过激活自噬、上调外排转运蛋白MRP1表达及竞争性抑制重金属离子内流，实现对多氯联苯、砷、镉等典型污染物的协同解毒；趋磁细菌利用表面吸附与铁转运系统介导的内化途径，实现铅的高效富集与解毒；硒制剂则通过促进线粒体融合、抑制过度自噬及增强谷胱甘肽合成，实现甲基汞诱导的生殖与神经损伤的快速修复。上述成果从污染物毒性机制解析与解毒干预策略构建两个层面，为发展基于纳米材料、功能微生物及天然产物的高效解毒体系奠定了坚实基础，也为深入理解环境污染物毒性调控机制提供了重要启示，在环境污染治理与精准医疗领域展现出广阔的应用前景。
参考文献
1.K. Li, T. Wang, H. Li, J. He, Y. Liu, Y. Sun, Y. Zhang, Q. Zhang, A. Xu. Effects of atmospheric photochemical aging on chemical characteristics and toxicity of PM2.5 emissions from forest vegetation combustion. Environ. Sci. Technol. 60, 1952-1964 (2026).
2.H. Li, S. Wang, J. He, R. Dong, T. Wang, Y. Zhou, Y. Liu, A. Xu, Y. Liu. Photoaging amplified the inhibition of microplastics on salivary amylase function via affecting the structure of α-helix: From in vitro digestive models to human samples. Environ. Int. 210, 110221 (2026).
3.Y. Zhao, Y. Ding, R. Dong, Y. Wu, C. Zhou, Y. Nie, G. Zhao, A. Xu, Y. Liu. Antagonistic effects of selenium on methylmercury-induced toxicity through mitochondrial quality control and enhanced GSH synthesis in Caenorhabditis elegans. J. Environ. Sci. 163, 252-261 (2026).
4.H. Li, T. Wang, Y. Zhou, J. He, R. Dong, A. Xu, Y. Liu. The released micro/nano-plastics from plastic containers amplified the toxic response of disinfection by-products in human cells. Food Chem. 464, 142636 (2025).
5.R. Dong, Y. Ding, H. Li, Y. Zhao, Y. Wu, C. Zhou, A. Xu, Y. Liu. Magnetotactic bacteria antagonized lead toxicity: distinct detoxification mechanisms in magnetosome-containing/deficient bacteria. J. Environ. Sci. (2025, in press).
6.T. Wang, Y. Liu, Y. Zhou, Q. Liu, Q. Zhang, M. Sun, M. Sun, H. Li, A. Xu, Y. Liu. Astaxanthin protected against the adverse effects induced by diesel exhaust particulate matter via improving membrane stability and anti-oxidative property. J. Hazard. Mater. 456, 131684 (2023).
7.Z. Cao, M. Wang, T. Zhou, A. Xu, H. Du. Whole-genome sequencing reveals germ cell mutagenicity of α-endosulfan in Caenorhabditis elegans. Environ. Sci. Technol. 56, 16024-16032 (2022).
8.Y. Liu, X. Wang, B. Si, T. Wang, Y. Wu, Y. Liu, Y. Zhou, H. Tong, X. Zheng, A. Xu. Zinc oxide/graphene oxide nanocomposites efficiently inhibited cadmium-induced hepatotoxicity via releasing Zn ions and up-regulating MRP1 expression. Environ. Int. 165, 107327 (2022).
9.X. Wang, Y. Nie, B. Si, T. Wang, T. K. Hei, H. Du, G. Zhao, S. Chen, A. Xu, Y. Liu. Silver nanoparticles protect against arsenic induced genotoxicity via attenuating arsenic bioaccumulation and elevating antioxidation in mammalian cells. J. Hazard. Mater. 416, 125287 (2021).
10.Y. Liu, X. Wang, J. Wang, Y. Nie, H. Du, H. Dai, J. Wang, M. Wang, S. Chen, T. K. Hei, Z. Deng, L. Wu, A. Xu. Graphene oxide attenuates the cytotoxicity and mutagenicity of PCB 52 via activation of genuine autophagy. Environ. Sci. Technol. 50, 3154-3164 (2016).
本课题组致力于研究肿瘤放疗关键靶点及调控机制。通过结合核磁共振技术、基因编辑及亚细胞结构分析，系统解析放疗敏感基因调控网络，挖掘关键靶基因，明确关键靶点对辐射的响应规律，并筛选广谱、多靶点放疗增敏药物。所涉及的研究内容包括细胞死亡方式、DNA损伤修复、细胞复制应激等辐射响应过程中的核心靶分子等。从结构与功能层面解析关键靶点响应辐射治疗的分子机制，为精准放疗增敏策略的研发提供新靶点和理论依据。
1.Xu F, Xia Q, Chen B, Wang R, Zhang J, Zhao X, Zhang Z, Yao Z, Zhang J, Zhou S, LiX, Chen B, Xu A, Wu L, Zhao G*. ZNF451 collaborates withRNF8 to regulate RNF168 localization and amplify ubqutination signaling to promote DNA damage repair and regulate radiosensitivity. Cell Death and Differentiation.2025 Jul;32(7):1303-1316.
2.Zhang J, Chen B, Xu F, Wang RR, Zhao XP, Yao Z C, Zhang J, Zhou SL, Xu A, Wu L J, Zhao G*. Phospho-TRIM21 orchestrates RPA2ubiqutination switch to promote homologous recombination and tumor radio/chemo-resistance. Oncogene 2025 May;44(16):1106-1117.
3.Yang S, Wang RR, Liu L L, Xu F, Zhao X P, Yao Z C, Zhang J, Cheng X, Xu A, Wu L J, Zhao G*. RRM1 promotes homologous recombination and radio/chemo-sensitivity via enhancing USP11 and E2F1-mediated RAD51AP1 transcription. Cell Death Discovery. 2024 Dec;10(1):496.
4.Han Jing,Wang Ruru, Chen Bin, Xu Feng, Wei Liangchen, Xu An, Wu Lijun, Zhao Guoping*. Bcl-xL regulates radiation-induced ferroptosis through chaperone-mediated autophagy of GPX4 in tumor cells. Radiation Medicine and Protection. 2024. March;5(2):90-99.
5.Xiaona Li, Feng Xu, Ruru Wang, Lili Shen, Bowen Luo, Shenglan Zhou, Jie Zhang, Zhaoyang Zhang, Zhizun Cao, Kangren Zhan, Ye Zhao, Guoping Zhao*. Aspirin enhances radio/chemo-therapy sensitivity in C. elegans by inducing germ cell apoptosis and suppresses RAS overactivated tumorigenesis via mtROS-mediated DNA damage and MAPK pathway. Biochem Biophys Res Commun. 2024 Nov;735:150828.
6.Wang R, Shang Y, Chen B, Xu F, Zhang J, Zhang Z, Zhao X, Wan X, Xu A, Wu L, Zhao G*. Protein disulfide isomerase blocks the interaction of LC3-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity. Cell Death Disease. 2022 Oct;13(10):851.
7.Gao Y, Chen B. Wang R, Xu A. Wu L, Lu H*, Zhao G*. Knockdown of RRM1 in tumor cells promotes radio-chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis. Cell Death Discovery. 2022 Aug;8(1):343.
8.Chen B, Xu F, Gao Y, Hu G, Zhu K, Lu H, Xu A, Chen S, Wu L, Zhao G*. DNA damage-induced translocation of mitochondrial factor HIGDIA intothe nucleus regulates homologous recombination and radio/chemo-sensitivity. Oncogene.2022 Mar;41(13):1918-1930.
本实验室聚焦环境污染物生物治理领域，立足生态环境保护与资源循环利用，围绕微生物介导的污染修复开展系统性研究，核心涵盖三个相互关联、层层递进的研究方向，助力破解新型污染物治理难题，推动绿色修复技术创新。
第一，天然环境微生物的污染修复与高值利用研究。利用自然界中细菌、微藻等土著微生物，针对抗生素、新烟碱农药、药物及个人护理品等新型难降解有机污染物，探究其生物去除与净化机制，同时实现多糖、蛋白质等高附加值产物的同步积累，达成“治污+资源化”双重目标。
第二，环境微生物功能代谢酶的机制解析。通过体外纯化、异源表达等技术，分离鉴定微生物降解过程中的关键功能代谢酶，系统探究其催化特性、功能机制及作用靶点，为污染物降解效率提升和新型酶制剂开发提供理论支撑。
第三，工程化微生物的构建与性能优化。以环境微生物为底盘，结合合成生物学技术进行基因改造，通过基因编辑、代谢通路优化等手段，构建高性能工程化菌株，突破天然微生物降解效率低、环境适应性弱等瓶颈，显著提升其对污染物的处理效能，为实际污染场景修复提供技术方案。
参考文献
1. Y. Cheng, H. Wang, Y. Wu, Y. Ding, C. Peng, C. Qi, A. Xu, Y. Liu, Light-powered biodegradation of Imidacloprid by Scenedesmus sp. TXH202001: Assessing complete removal, metabolic pathways, and toxicity verification, J Hazard Mater, 477 (2024).
2. Y. Cheng, Z. Wang, C. Peng, S. Chen, A. Xu, X. Zheng, Y. Liu, Efficient ribavirin removal from medical wastewater by microalgae-centric: Microbial biological action and application of double-layer network hydrogel, J Hazard Mater, 494 (2025).
3. Y. Cheng, C. Zhou, K. Shan, Y. Liu, C. Peng, Y. Wu, J. Liu, A. Xu, Y. Liu, Algae-based biotransformation of COVID-19 antiviral ribavirin: Insight on metabolic effect, wastewater application and biological toxicity, Bioresource Technol, 427 (2025).
4. Y. Cheng, Y. Wu, C. Peng, Y. Yang, L. Xuan, L. Wang, Y. Wang, A. Xu, Y. Liu, Insights on aggregation-algae consortium based removal of sulfamethoxazole: Unraveling removal effect, enhanced method and toxicological evaluation, J Environ Manage, 370 (2024).
5. Y. Cheng, Z. Wang, Y. Wang, C. Peng, Y. Wu, S. Chen, A. Xu, X.W. Zheng, Y. Liu, Bacteria/alginate @ agarose-hydrogel for the removal of COVID-19 antivirals ribavirin: An integrated scheme of concentration and biotransformation, J Environ Chem Eng 13(6) (2025).
随着磁体技术在材料科学、医疗成像等领域的快速发展，强磁场环境与复杂生命体系的相互作用机制已成为前沿交叉学科的焦点。生物体在稳态强磁场（SMF）暴露下会展现出丰富的宏观表型变化，如代谢重塑、发育迟缓或行为异常。然而，许多宏观的磁生物学效应都始于微观层面生物大分子、细胞器乃至离子的空间排布与量子态改变。利用传统的宏观观测手段，研究者往往难以探寻这些表型背后的核心机制；而依托于稳态强磁场实验装置（SHMFF）与现代分子生物学成像手段，研究者已经可以在活体水平原位观察生物体对SMF的微观响应，并深入解析其分子机制。
在许安研究员课题组，我们运用多种生物学表征与强磁场下原位成像技术，系统研究了SMF对模式生物——秀丽隐杆线虫的生物学效应。在细胞发育生物学领域，我们重点聚焦SMF对生命基本过程的影响，首次揭示了超高稳态磁场（UHSMF）对线虫早期胚胎发育中纺锤体组装、取向及动力学的调控规律；同时，我们系统评估了10 T SMF对线虫精子发育的抑制作用，阐明了磁场诱导生殖细胞异常的生化基础。在代谢与环境应激领域，我们揭示了SMF在调控不同性别线虫脂质合成与分解中的差异化规律，明确了铁离子在磁场缓解环境胁迫中的核心作用，并深入阐明了SMF暴露引发铁稳态失衡及铁死亡的分子机理。此外，本课题组拟依托45.22 T SHMFF，系统研究UHSMF下秀丽隐杆线虫神经功能的力学调控机制。这些研究不仅为评估SMF的生物安全性提供了理论依据，也为未来利用磁物理手段干预生命健康与代谢疾病提供了新思路。
[1] L. Cheng, M. Wang, B. Yang, Y. Li, T. Wang, C. Xi, Y. Han, Z. Wang, Y. Fang, M. Wei, H. Du, A. Xu, Ultra-high static magnetic fields altered the embryonic division and development in Caenorhabditis elegans via multipolar spindles, Journal of Advanced Research 72 (2025) 515–526.
[2] B. Yang, L. Cheng, Y. Li, Z. Liu, C. Zhou, T. Zhou, Y. Zhao, H. Du, Z. Liao, A. Xu, Moderate static magnetic field modulated lipid metabolism abnormalities induced by continuous artificial light in Caenorhabditis elegans: Role of iron ions, Ecotoxicology and Environmental Safety 292 (2025) 117959.
[3] Z. Liu, L. Cheng, B. Yang, Z. Cao, M. Sun, Y. Feng, A. Xu, Effects of moderate static magnetic fields on the lipogenesis and lipolysis in different genders of Caenorhabditis elegans, Ecotoxicology and Environmental Safety 259 (2023) 115005.
[4] L. Cheng, B. Yang, H. Du, T. Zhou, Y. Li, J. Wu, Z. Cao, A. Xu, Moderate intensity of static magnetic fields can alter the avoidance behavior and fat storage of Caenorhabditis elegans via serotonin, Environ Sci Pollut Res 29 (2022) 43102–43113.
[5] B. Yang, Z. Yang, L. Cheng, Y. Li, T. Zhou, Y. Han, H. Du, A. Xu, Effects of 10 T static magnetic field on the function of sperms and their offspring in Caenorhabditis elegans, Ecotoxicology and Environmental Safety 240 (2022) 113671.
微生物代谢产物具有极高的化学结构多样性，构成了自然界复杂的生物活性分子体系。微生物生物合成基因簇受环境与遗传网络精准调控，胞内多条代谢流协同竞争，催生了功能各异的次级代谢产物。这种代谢多样性是微生物长期进化形成的种间化学防御策略，也是天然产物药物研发的重要资源基础。本课题组的研究重点包括以下两个方向:
1.菌种资源库的构建：过去几年，我们构建了超过20万株细菌的标准化微生物资源库。通过对环境样本的深度挖掘与定向筛选，实现了资源从规模化积累到功能化分类的转变，并针对性地开展抗菌及其他生物活性菌株的分离与精准鉴定工作。
2.活性天然产物的分离纯化：我们以生物活性为导向，针对初筛表现优异的候选菌株，利用中低压色谱、制备型HPLC以及分子排阻色谱等手段，对微生物代谢产物中的活性组分进行系统性的梯度剥离与富集，及后续纯化鉴定。