[1] [1] KHABIB M N H, SIVASANKU Y, LEE H B, et al. Alternative animal models in predictive toxicology[J]. Toxicology, 2022, 465: 153053. doi: 10.1016/j.tox.2021.153053.

[2] [2] KREWSKI D, ANDERSEN M E, TYSHENKO M G, et al. Toxicity testing in the 21st century: Progress in the past decade and future perspectives[J]. Arch Toxicol, 2020, 94(1): 1−58. doi: 10.1007/s00204-019-02613-4.

[3] [3] BRENNER S. The genetics ofCaenorhabditis elegans[J]. Genetics, 1974, 77(1): 71−94. doi: 10.1093/genetics/77.1.71.

[4] [4] ZHAO Y, CHEN J, WANG R, et al. A review of transgenerational and multigenerational toxicology in thein vivomodel animalCaenorhabditis elegans[J]. J Appl Toxicol, 2023, 43(1): 122−145. doi: 10.1002/jat.4360.

[5] [5] COOK S J, JARRELL T A, BRITTIN C A, et al. Whole-animal connectomes of bothCaenorhabditis eleganssexes[J]. Nature, 2019, 571(7763): 63−71. doi: 10.1038/s41586-019-1352-7.

[6] [6] WHITE J G, SOUTHGATE E, THOMSON J N, et al. The structure of the nervous system of the nematodeCaenorhabditis elegans[J]. Phil Trans R Soc Lond B, 1986, 314(1165): 1−340. doi: 10.1098/rstb.1986.0056.

[7] [7] SETTY H, SALZBERG Y, KARIMI S, et al. Sexually dimorphic architecture and function of a mechanosensory circuit inC. elegans[J]. Nat Commun, 2022, 13(1): 6825. doi: 10.1038/s41467-022-34661-3.

[8] [8] MOROZ L L, ROMANOVA D Y. Chemical cognition: Chemoconnectomics and convergent evolution of integrative systems in animals[J]. Anim Cogn, 2023, 26(6): 1851−1864. doi: 10.1007/s10071-023-01833-7.

[9] [9] DAG U, NWABUDIKE I, KANG D, et al. Dissecting the functional organization of theC. elegansserotonergic system at whole-brain scale[J]. Cell, 2023, 186(12): 2574−2592.e20. doi: 10.1016/j.cell.2023.04.023.

[10] [10] DOLESE D A, JUNOT M P, GHOSH B, et al. Degradative tubular lysosomes link pexophagy to starvation and early aging inC. elegans[J]. Autophagy, 2022, 18(7): 1522−1533. doi: 10.1080/15548627.2021.1990647.

[11] [11] WU J, GAO Y, XI J, et al. A high-throughput microplate toxicity screening platform based onCaenorhabditis elegans[J]. Ecotoxicol Environ Saf, 2022, 245: 114089. doi: 10.1016/j.ecoenv.2022.114089.

[12] [12] WU C W, WIMBERLY K, PIETRAS A, et al. RNA processing errors triggered by cadmium and integrator complex disruption are signals for environmental stress[J]. BMC Biol, 2019, 17(1): 56. doi: 10.1186/s12915-019-0675-z.

[13] [13] ZHENG S Q, DING A J, LI G P, et al. Drug absorption efficiency inCaenorhbditis elegansdelivered by different methods[J]. PLoS One, 2013, 8(2): e56877. doi: 10.1371/journal.pone.0056877.

[14] [14] WANG Y, ZHANG H, WU X, et al. Ecotoxicity assessment of sodium dimethyldithiocarbamate and its micro-sized metal chelates inCaenorhabditis elegans[J]. Sci Total Environ, 2020, 720: 137666. doi: 10.1016/j.scitotenv.2020.137666.

[15] [15] WANG S, CHU Z, ZHANG K, et al. Cadmium-induced serotonergic neuron and reproduction damages conferred lethality in the nematodeCaenorhabditis elegans[J]. Chemosphere, 2018, 213: 11−18. doi: 10.1016/j.chemosphere.2018.09.016.

[16] [16] NGO L T, HUANG W T, CHAN M H, et al. Comprehensive neurotoxicity of lead halide perovskite nanocrystals in nematodeCaenorhabditis elegans[J]. Small, 2024, 20(2): 2306020. doi: 10.1002/smll.202306020.

[17] [17] CURRIE S D, DOHERTY J P, XUE K S, et al. The stage-specific toxicity of per- and polyfluoroalkyl substances (PFAS) in nematodeCaenorhabditis elegans[J]. Environ Pollut, 2023, 336: 122429. doi: 10.1016/j.envpol.2023.122429.

[18] [18] ABBASS M, CHEN Y, ARLT V M, et al. Benzo[a] pyrene andCaenorhabditis elegans: Defining the genotoxic potential in an organism lacking the classical CYP1A1 pathway[J]. Arch Toxicol, 2021, 95(3): 1055−1069. doi: 10.1007/s00204-020-02968-z.

[19] [19] BARGMANN C I, HARTWIEG E, HORVITZ H R. Odorant-selective genes and neurons mediate olfaction inC. elegans[J]. Cell, 1993, 74(3): 515−527. doi: 10.1016/0092-8674(93)80053-H.

[20] [20] HIROKI S, YOSHITANE H, MITSUI H, et al. Molecular encoding and synaptic decoding of context during salt chemotaxis inC. elegans[J]. Nat Commun, 2022, 13(1): 2928. doi: 10.1038/s41467-022-30279-7.

[21] [21] YANG W, WU T, TU S, et al. Redundant neural circuits regulate olfactory integration[J]. PLoS Genet, 2022, 18(1): e1010029. doi: 10.1371/journal.pgen.1010029.

[22] [22] SUN Q, LIU C, JIANG K, et al. A preliminary study on the neurotoxic mechanism of harmine inCaenorhabditis elegans[J]. Comp Biochem Physiol Part C Toxicol Pharmacol, 2021, 245: 109038. doi: 10.1016/j.cbpc.2021.109038.

[23] [23] JEONG A, PARK S J, LEE E J, et al. Nanoplastics exacerbate Parkinson’s disease symptoms inC. elegansand human cells[J]. J Hazard Mater, 2024, 465: 133289. doi: 10.1016/j.jhazmat.2023.133289.

[24] [24] QU Z, LIU L, WU X, et al. Cadmium-induced reproductive toxicity combined with a correlation to the oogenesis process and competing endogenous RNA networks based on aCaenorhabditis elegansmodel[J]. Ecotoxicol Environ Saf, 2023, 268: 115687. doi: 10.1016/j.ecoenv.2023.115687.

[26] [26] KIM H M, LONG N P, MIN J E, et al. Comprehensive phenotyping and multi-omic profiling in the toxicity assessment of nanopolystyrene with different surface properties[J]. J Hazard Mater, 2020, 399: 123005. doi: 10.1016/j.jhazmat.2020.123005.

[27] [27] YOUSSEF K, ARCHONTA D, KUBISESKI T J, et al. Microfluidic electric parallel egg-laying assay and application toin-vivotoxicity screening of microplastics usingC. elegans[J]. Sci Total Environ, 2021, 783: 147055. doi: 10.1016/j.scitotenv.2021.147055.

[28] [28] YOON S, YOU D K, JEONG U, et al. Microfluidics in high-throughput drug screening: Organ-on-a-chip andC. elegans-based innovations[J]. Biosensors, 2024, 14(1): 55. doi: 10.3390/bios14010055.

[29] [29] WOOD A J, LO T W, ZEITLER B, et al. Targeted genome editing across species using ZFNs and TALENs[J]. Science, 2011, 333(6040): 307. doi: 10.1126/science.1207773.

[30] [30] REVATHI K, SUBRAMANIAM K. An efficient negative selection marker forMos1-mediated singlecopy integration inCaenorhabditis elegans[J]. MicroPubl Biol, 2022. doi: 10.17912/micropub.biology.000647.

[31] [31] LI J, QIN Y, SHEN C, et al. A new miniMOS tool kit capable of visualizing single copy insertion inC. elegans[J]. PeerJ, 2023, 11: e15433. doi: 10.7717/peerj.15433.

[32] [32] DU X, MCMANUS D P, FRENCH J D, et al. CRISPR/Cas9: A new tool for the study and control of helminth parasites[J]. Bioessays, 2021, 43(1): e2000185. doi: 10.1002/bies.202000185.

[33] [33] XU S. The application of CRISPR-Cas9 genome editing inCaenorhabditis elegans[J]. J Genet Genom, 2015, 42(8): 413-421. doi: 10.1016/j.jgg.2015.06.005.

[34] [34] PETER E, CANDIDO M, JONES D. TransgenicCaenorhabditis elegansstrains as biosensors[J]. Trends Biotechnol, 1996, 14(4): 125−129. doi: 10.1016/0167-7799(96)10016-0.

[35] [35] PAAVANEN-HUHTALA S, KALICHAMY K, PESSI A M, et al. Biomonitoring of indoor air fungal or chemical toxins withCaenorhabditis elegansnematodes[J]. Pathogens, 2023, 12(2): 161. doi: 10.3390/pathogens12020161.

[36] [36] WANG Z.Caenorhabditis elegansas an in vivo model organism to elucidate teratogenic effects[J]. Methods Mol Biol, 2024, 2753: 283−306. doi: 10.1007/978-1-0716-3625-1_14.

[39] [39] LIU H, FU G, LI W, et al. Oxidative stress and mitochondrial damage induced by a novel pesticide fluopimomide inCaenorhabditis elegans[J]. Environ Sci Pollut Res Int, 2023, 30(40): 91794−91802. doi: 10.1007/s11356-023-28893-z.

[40] [40] JACQUES M T, SOARES M V, FARINA M, et al. Impaired physiological responses and neurotoxicity induced by a chlorpyrifos-based formulation inCaenorhabditis elegansare not solely dependent on the active ingredient[J]. Environ Toxicol Pharmacol, 2023, 101: 104196. doi: 10.1016/j.etap.2023.104196.

[41] [41] BORA S, VARDHAN G S H, DEKA N, et al. Paraquat exposure over generation affects lifespan and reproduction through mitochondrial disruption inC. elegans[J]. Toxicology, 2021, 447: 152632. doi: 10.1016/j.tox.2020.152632.

[42] [42] GONZALEZ-HUNT C P, LUZ A L, RYDE I T, et al. Multiple metabolic changes mediate the response ofCaenorhabditis elegansto the complex I inhibitor rotenone[J]. Toxicology, 2021, 447: 152630. doi: 10.1016/j.tox.2020.152630.

[43] [43] QU M, CHEN H, LAI H, et al. Exposure to nanopolystyrene and its 4 chemically modified derivatives at predicted environmental concentrations causes differently regulatory mechanisms in nematodeCaenorhabditis elegans[J]. Chemosphere, 2022, 305: 135498. doi: 10.1016/j.chemosphere.2022.135498.

[44] [44] JIANG W, YAN W, TAN Q, et al. The toxic differentiation of micro- and nanoplastics verified by gene-edited fluorescentCaenorhabditis elegans[J]. Sci Total Environ, 2023, 856: 159058. doi: 10.1016/j.scitotenv.2022.159058.

[45] [45] WANG M, FENG Y, CAO Z, et al. Multiple generation exposure to ZnO nanoparticles induces loss of genomic integrity inCaenorhabditis elegans[J]. Ecotoxicol Environ Saf, 2023, 249: 114383. doi: 10.1016/j.ecoenv.2022.114383.

[46] [46] CHEN J, CHEN C, WANG N, et al. Cobalt nanoparticles induce mitochondrial damage and -amyloid toxicity via the generation of reactive oxygen species[J]. Neurotoxicology, 2023, 95: 155−163. doi: 10.1016/j.neuro.2023.01.010.

[47] [47] ZHANG F, YOU X, ZHU T, et al. Silica nanoparticles enhance germ cell apoptosis by inducing reactive oxygen species (ROS) formation inCaenorhabditis elegans[J]. J Toxicol Sci, 2020, 45(3): 117−129. doi: 10.2131/jts.45.117.

[48] [48] WANG Y, GAI T, ZHANG L, et al. Neurotoxicity of bisphenol A exposure onCaenorhabditis elegansinduced by disturbance of neurotransmitter and oxidative damage[J]. Ecotoxicol Environ Saf, 2023, 252: 114617. doi: 10.1016/j.ecoenv.2023.114617.

[49] [49] NICOLAI M M, WEISHAUPT A K, BAESLER J, et al. Effects of manganese on genomic integrity in the multicellular model organismCaenorhabditis elegans[J]. Int J Mol Sci, 2021, 22(20): 10905. doi: 10.3390/ijms222010905.

[50] [50] KE T, SANTAMARIA A, JUNIOR F B, et al. Methylmercury exposure-induced reproductive effects are mediated by dopamine inCaenorhabditis elegans[J]. Neurotoxicol Teratol, 2022, 93: 107120. doi: 10.1016/j.ntt.2022.107120.

[51] [51] ZHANG J, YANG W, LI Z, et al. Multigenerational exposure of cadmium trans-generationally impairs locomotive and chemotactic behaviors inCaenorhabditis elegans[J]. Chemosphere, 2023, 325: 138432. doi: 10.1016/j.chemosphere.2023.138432.

[52] [52] WANG Z, DAI S, WANG J, et al. Assessment on chronic and transgenerational toxicity of methamphetamine toCaenorhabditis elegansand associated aquatic risk through toxicity indicator sensitivity distribution (TISD) analysis[J]. Environ Pollut, 2021, 288: 117696. doi: 10.1016/j.envpol.2021.117696.

[53] [53] LU Q, BU Y, MA L, et al. Transgenerational reproductive and developmental toxicity of tebuconazole inCaenorhabditis elegans[J]. J Appl Toxicol, 2020, 40(5): 578−591. doi: 10.1002/jat.3927.

[54] [54] ZENG X S, GENG W S, JIA J J. Neurotoxin-induced animal models of parkinson disease: Pathogenic mechanism and assessment[J]. ASN Neuro, 2018, 10: 1759091418777438. doi: 10.1177/1759091418777438.

[55] [55] DA SILVA L P D, DA CRUZ GUEDES E, FERNANDES I C O, et al. ExploringCaenorhabditis elegansas Parkinson’s disease model: Neurotoxins and genetic implications[J]. Neurotox Res, 2024, 42(1): 11. doi: 10.1007/s12640-024-00686-3.

[56] [56] ENGLEMAN E A, KATNER S N, NEALBELIVEAU B S.Caenorhabditis elegansas a model to study the molecular and genetic mechanisms of drug addiction[J]. Prog Mol Biol Transl Sci, 2016, 137: 229−252. doi: 10.1016/bs.pmbts.2015.10.019.

[57] [57] SALIM C, KAN A K, BATSAIKHAN E, et al. Neuropeptidergic regulation of compulsive ethanol seeking inC. elegans[J]. Sci Rep, 2022, 12(1): 1804. doi: 10.1038/s41598-022-05256-1.

[58] [58] LEE J, JEE C, MCINTIRE S L. Ethanol preference inC. elegans[J]. Genes Brain Behav, 2009, 8(6): 578−585. doi: 10.1111/j.1601-183x.2009.00513.x.

[59] [59] KATNER S N, BREDHOLD K E, STEAGALL II K B, et al.Caenorhabditis elegansas a model system to identify therapeutics for alcohol use disorders[J]. Behav Brain Res, 2019, 365: 7−16. doi: 10.1016/j.bbr.2019.02.015.

[60] [60] MATHIES L D, BLACKWELL G G, AUSTIN M K, et al. SWI/SNF chromatin remodeling regulates alcohol response behaviors inCaenorhabditis elegansand is associated with alcohol dependence in humans[J]. Proc Natl Acad Sci USA, 2015, 112(10): 3032−3037. doi: 10.1073/pnas.1413451112.

[61] [61] YANG Y F, CHEN P J, LIAO V H. Nanoscale zerovalent iron (nZVI) at environmentally relevant concentrations induced multigenerational reproductive toxicity inCaenorhabditis elegans[J]. Chemosphere, 2016, 150: 615−623. doi: 10.1016/j.chemosphere.2016.01.068.

[62] [62] HU C, HOU J, ZHU Y, et al. Multigenerational exposure to TiO2 nanoparticles in soil stimulates stress resistance and longevity of survivedC. elegansvia activating insulin/IGF-like signaling[J]. Environ Pollut, 2020, 263(Pt A): 114376. doi: 10.1016/j.envpol.2020.114376.

[63] [63] DONG B. A comprehensive review on toxicological mechanisms and transformation products of tebuconazole: Insights on pesticide management[J]. Sci Total Environ, 2024, 908: 168264. doi: 10.1016/j.scitotenv.2023.168264.

[64] [64] YU C W, LUK T C, LIAO V H. Long-term nanoplastics exposure results in multi and trans-generational reproduction decline associated with germline toxicity and epigenetic regulation inCaenorhabditis elegans[J]. J Hazard Mater, 2021, 412: 125173. doi: 10.1016/j.jhazmat.2021.125173.

[65] [65] WAMUCHO A, HEFFLEY A, TSYUSKO O V. Epigenetic effects induced by silver nanoparticles inCaenorhabditis elegansafter multigenerational exposure[J]. Sci Total Environ, 2020, 725: 138523. doi: 10.1016/j.scitotenv.2020.138523.

[66] [66] ZHANG X, ZHONG H Q, CHU Z W, et al. Arsenic induces transgenerational behavior disorders inCaenorhabditis elegansand its underlying mechanisms[J]. Chemosphere, 2020, 252: 126510. doi: 10.1016/j.chemosphere.2020.126510.

[67] [67] MARTINI C, LIU Y F, GONG H, et al. CEBS update: Curated toxicology database with enhanced tools for data integration[J]. Nucleic Acids Res, 2022, 50(D1): D1156−D1163. doi: 10.1093/nar/gkab981.