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A single-cell landscape of the regenerating spinal cord of zebrafish 认领 引用 被引量：1
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作者 Lei Yao Xinyi Cai +5 位作者 Saishuai Yang Yixing Song Lingyan Xing Guicai Li Zhiming Cui Jiajia Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第2期780-789,共10页
Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types ... Unlike mammals,zebrafish possess a remarkable ability to regenerate their spinal cord after injury,making them an ideal vertebrate model for studying regeneration.While previous research has identified key cell types involved in this process,the underlying molecular and cellular mechanisms remain largely unexplored.In this study,we used single-cell RNA sequencing to profile distinct cell populations at different stages of spinal cord injury in zebrafish.Our analysis revealed that multiple subpopulations of neurons showed persistent activation of genes associated with axonal regeneration post injury,while molecular signals promoting growth cone collapse were inhibited.Radial glial cells exhibited significant proliferation and differentiation potential post injury,indicating their intrinsic roles in promoting neurogenesis and axonal regeneration,respectively.Additionally,we found that inflammatory factors rapidly decreased in the early stages following spinal cord injury,creating a microenvironment permissive for tissue repair and regeneration.Furthermore,oligodendrocytes lost maturity markers while exhibiting increased proliferation following injury.These findings demonstrated that the rapid and orderly regulation of inflammation,as well as the efficient proliferation and redifferentiation of new neurons and glial cells,enabled zebrafish to reconstruct the spinal cord.This research provides new insights into the cellular transitions and molecular programs that drive spinal cord regeneration,offering promising avenues for future research and therapeutic strategies. 展开更多
关键词 dividing oligodendrocyte macrophage microglia neuron proliferating oligodendrocyte radial glia single cell sequencing spinal cord regeneration transcriptome zebrafish
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Environmentally relevant concentrations of tris(2-chloroethyl) phosphate disrupt zebrafish hypothalamus-pituitary-gonad-liver axis and transgenerational reproduction 认领 引用
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作者 Yu Qiao Weiying Feng +2 位作者 Chenglian Feng Zhenfei Yan Xiaowei Jin 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第7期715-723,共9页
Tris(2-chloroethyl)phosphate(TCEP)is a widely used chlorinated organophosphorus flame retardant,that has been frequently detected in aquatic organisms and surface water.While previous studies have shown the potential ... Tris(2-chloroethyl)phosphate(TCEP)is a widely used chlorinated organophosphorus flame retardant,that has been frequently detected in aquatic organisms and surface water.While previous studies have shown the potential endocrine disrupting effects of TCEP,its long-term reproductive toxicities at environmentally relevant concentrations remain unclear.This study comprehensively analyzed the reproductive toxicity and mechanisms of TCEP in zebrafish.Zebrafish were exposed to TCEP(0.2-200μg/L)from embryo to adult stages for 120 days.Results showed significant alterations in reproductive indicators,including decreased body length and weight,reduced tissue indices and impaired gonadal development.Notably,TCEP altered sex hormone levels,with decreased 17β-estradiol(E2)and vitellogenin(VTG)in females,increased E2 and VTG in males,and reduced testosterone in both sexes.A female-biased sex ratio was observed at 22.01 and 241.84μg/L TCEP,with reduced spawning and impaired F1 offspring development.Transcriptomic analysis revealed significant alterations in hypothalamus-pituitary-gonad-liver(HPGL)axis gene expression,such as hsd17b12a.Molecular docking simulations suggested that TCEP may interfere with sex hormone receptor binding and cytochrome P450(CYP450)enzyme function.This study reveals new insights into the reproductive toxicity mechanisms of TCEP in zebrafish.The toxic effects follow an inverted U-shaped curve,with peak toxicity occurring at approximately 2.62μg/L.These findings underscore the importance of regulating this emerging contaminant in freshwater ecosystems. 展开更多
关键词 TCEP Zebrafish Reproductive toxicity Molecular docking HPGL axis
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Effects of aging on gut microbiota nearly throughout zebrafish lifespan 认领 引用
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作者 Fanshu Xiao Wengen Zhu +4 位作者 Huanping Liu Pubo Chen Yuhe Yu Zhili He Qingyun Yan 《Current Zoology》 SCIE CAS CSCD 2026年第2期303-306,共4页
Aging profoundly influences vertebrate gut microbiota,yet lifespan patterns remain poorly characterized.Utilizing the wild-type zebrafish model,this study pioneers a longitudinal investigation of gut microbiota dynami... Aging profoundly influences vertebrate gut microbiota,yet lifespan patterns remain poorly characterized.Utilizing the wild-type zebrafish model,this study pioneers a longitudinal investigation of gut microbiota dynamics from adulthood(>3 months)to old age(>3 years).We identified a significant(P<0.05)correlation between gut microbiota composition and host age.Notably,alpha-diversity was relatively stable and highest between 8–32 months,indicating this period as optimal for gut microbiota studies.The relative abundance of dominant phyla(Pseudomonadota,Actinomycetota,and Fusobacteriota)varied significantly(P<0.05)across aging stages.Crucially,these phylum-level changes were predictable using their representative genera or amplicon sequence variants.This work delineates lifelong aging effects on gut microbiota in a vertebrate model and identifies key microbial biomarkers and an optimal sampling window. 展开更多
关键词 aging effects gut microbiota lifespan patterns vertebrate model zebrafish
Morus alba leaf extract modulates melanogenesis in enzymatic,cellular,and zebrafish models 认领 引用
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作者 Mirissa Hewage Dumindu Kavinda Su-Yeon Lee +4 位作者 Yung Hyun Choi Seo Min Jeong Chang Soo Lee Hyung Won Ryu Gi-Young Kim 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2026年第6期243-255,I0004-I0021,共13页
Objective:To investigate the modulatory effects of a Morus alba leaf extract(FBCC-EP1619)on melanogenesis using enzymatic,cellular,and zebrafish models.Methods:Phytochemical profiling was conducted using UPLC-QTOF-MS/... Objective:To investigate the modulatory effects of a Morus alba leaf extract(FBCC-EP1619)on melanogenesis using enzymatic,cellular,and zebrafish models.Methods:Phytochemical profiling was conducted using UPLC-QTOF-MS/MS in negative ion mode.Mushroom tyrosinase inhibition was assessed in vitro.Cytotoxicity and melanin content were measured in B16F10 melanoma cells under basal andα-melanocyte-stimulating hormone(α-MSH)-stimulated conditions.An in vivo pigmentation model was established usingα-MSH-treated zebrafish larvae,and pigmentation was quantified.Expression of melanogenesis-related genes(mitfa and tyr)was analyzed by RT-qPCR.Results:FBCC-EP1619 contained diverse phenolic and lipid-derived metabolites.The extract significantly inhibited mushroom tyrosinase activity in a concentration-dependent manner.In B16F10 cells,it did not induce cytotoxicity but increased melanin production.In contrast,inα-MSH-stimulated zebrafish larvae,FBCC-EP1619 attenuated hyperpigmentation and significantly downregulated mitfa and tyr expression,indicating system-and stimulus-dependent regulation.Conclusions:FBCC-EP1619 differentially modulates melanogenesis depending on the biological system,enhancing basal melanin production in vitro while suppressingα-MSH-induced pigmentation in vivo.These findings provide pharmacological support for the ethnopharmacological relevance of Morus alba leaves and warrant further investigation into the underlying molecular mechanisms. 展开更多
关键词 Morus alba Melanogenesis Tyrosinase Hyperpigmentation α-MSH Zebrafish model
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Amuc_1100 alleviates HFD-induced hepatic lipid accumulation via gut microbiota in zebrafish:insights from the role of intestinal 14-3-3β/α-A 认领 引用
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作者 Qianwen Ding Ruobing Lou +13 位作者 Hui Liang Yi Wang Shangshang Tang Jian Zhang Yihui Du Chao Ran Yalin Yang Zhen Zhang Yuanyuan Yao Chen Wang Zhen Liu Oliana Carnevali Fengli Zhang Zhigang Zhou 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2026年第4期2354-2376,共23页
Background Amuc_1100,the most abundant outer membrane protein of Akkermansia muciniphila,alleviates highfat diet(HFD)-induced hepatic lipid accumulation and modulates gut microbiota in fish;however,its mechanism and m... Background Amuc_1100,the most abundant outer membrane protein of Akkermansia muciniphila,alleviates highfat diet(HFD)-induced hepatic lipid accumulation and modulates gut microbiota in fish;however,its mechanism and mediators remain unknown.Using zebrafish model,this study aims to determine the mechanism by which Amuc_1100 reduces HFD-induced hepatic lipid accumulation through modulation of gut microbiota.Methods In main study,1-month-old zebrafish were fed a low-fat diet(LFD),HFD,or HFD supplemented with 0.01%Amuc_1100(AM0.01)for 4 weeks.Body weight gain,hepatic lipid accumulation,microbial translocation,and gut microbiota composition were evaluated.In parallel,larvae at 5 d post-fertilization were fed the same diets for 7 d and analyzed by Oil Red O staining.In validation experiments,germ-free(GF)zebrafish received microbiota transplants from donor fish fed HFD or AM0.01.Antibiotics(ABS)-treated zebrafish were fed LFD,HFD,or AM0.01 for 4 weeks.Intestinal protein interacting with Amuc_1100 was identified via pull-down and co-immunoprecipitation,and its role was confirmed using protein-protein interaction(PPI)inhibitor BV02 and gene knockdown.Data were analyzed by Student's t-test or one-way ANOVA.Results Compared with HFD group,zebrafish in AM0.01 group showed lower body weight gain,reduced hepatic lipid accumulation,and decreased microbial translocation(P0.05).Using pull-down assays with intestinal proteins from LFD-fed zebrafish,we identified 14-3-3β/α-A as an interacting protein of Amuc_1100.When 14-3-3β/α-A PPI was inhibited by BV02,Amuc_1100 failed to alter the HFD-induced gut microbiota profile in 1-month-old zebrafish(P>0.05).Moreover,either BV02 treatment or 14-3-3β/α-A knockdown abolished the protective effect of Amuc_1100 against hepatic lipid accumulation in conventional and GF zebrafish(P<0.05).Conclusions Amuc_1100 reduces hepatic lipid accumulation by modulating gut microbiota through intestinal 14-3-3β/α-A,highlighting its potential as a therapeutic target. 展开更多
关键词 Amuc_1100 Gut microbiota Hepatic lipid accumulation Zebrafish 14-3-3β/α-A
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Concurrent Suppression of GABAergic and Glutamatergic Signalling Is Involved in Methcathinone-induced Addictive Behaviour in Zebrafish:Insights from Transcriptomic Profiling 认领 引用
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作者 QIAN Song ZHU Si-Si +4 位作者 QI Xin JIANG Ling-Xia XIE Song-Xu CHEN Chao-Yue WANG Bin-Jie 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2026年第4期678-687,I0067,共10页
Methcathinone,a widely abused synthetic cathinone,poses a significant public health risk because of its severe neurotoxicity and high addictive potential.In this study,we used a zebrafish model to investigate the mech... Methcathinone,a widely abused synthetic cathinone,poses a significant public health risk because of its severe neurotoxicity and high addictive potential.In this study,we used a zebrafish model to investigate the mechanisms underlying its neurobehavioural effects.Methcathinone exposure reduced larval survival and induced a range of abnormal behaviours.Most notably,conditioned place preference(CPP)tests demonstrated the potent rewarding properties of methcathinone,as shown by a significant 22.2%increase in time spent in the drug-paired light zone compared with baseline(P<0.01).Transcriptomic analysis of brain tissue revealed systemic disruption of the neuroactive ligand-receptor interaction pathway.Gene set enrichment analysis(GSEA)further revealed significant suppression ofγ-aminobutyric acid(GABA)signalling(NES=-1.64,P<0.05)and glutamate receptor signalling,including ionotropic and AMPA receptor signalling(P<0.05).Quantitative PCR validation confirmed the marked downregulation of key genes involved in these pathways:the mRNA expression of GABAergic receptors(e.g.,gabra 1 and gabra 2),glutamatergic receptors(e.g.,gria 2 and grin2B),and the dopamine transporter slc6a3 decreased by 67.0%to 97.9%(all P<0.01).These results suggest that methcathinone drives reward-seeking behaviour through a synergistic dual-target mechanism;specifically,the concurrent suppression of GABAergic inhibition and slc6a3-mediated reuptake likely facilitates dopaminergic hyperactivity,whereas the downregulation of glutamate receptors reflects a homeostatic response to overstimulation.Our findings provide novel mechanistic insight into the development of methcathinone use disorder in humans. 展开更多
关键词 methcathinone(MC) addictive behaviour transcriptomic GABAergic glutamatergic zebrafish
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Effect of amoxicillin on cartilage and bone development in zebrafish and their molecular mechanisms 认领 引用 被引量：1
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作者 Fei Long Yangfan Shangguan +2 位作者 Jiaqi Wang Hui Wang Liaobin Chen 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第4期562-572,共11页
Amoxicillin,a beta-lactam antibiotic,is the preferred treatment for numerous common infections during pregnancy.However,it has been identified as an emerging environmental pollutant.Clinical and animal studies indicat... Amoxicillin,a beta-lactam antibiotic,is the preferred treatment for numerous common infections during pregnancy.However,it has been identified as an emerging environmental pollutant.Clinical and animal studies indicate that prenatal exposure to amoxicillin may pose fetal developmental toxicity risks.In view of the environmental exposure and clinical application status of amoxicillin,this study investigated the effects of amoxicillin exposure at different concentrations and embryonic stages on the overall development of zebrafish embryos,as well as the development of cartilage and bone,and their underlying mechanisms.Our findings revealed that embryonic exposure to amoxicillin inhibited the overall,cartilage,and bone development of zebrafish in a concentration(80–400μmol/L)and stage(0–1.5 and 1.5–3.0 dpf)dependent manner.This inhibition was manifested as reduced head and body length,decreased head and eye area,shortened palatal and ceratohyal cartilage length,and diminished operculum bone area,with these effects persisting from the larval to the juvenile stage.Notably,early exposure to amoxicillin had a more pronounced impact on zebrafish embryonic cartilage development,attributed to the inhibition of the foxo3a signaling pathway.In contrast,late exposure to amoxicillin more significantly affected zebrafish embryonic bone development,associated with the inhibition of the jak2a/stat3 signaling pathway.This study has verified the toxicity of amoxicillin to cartilage and bone development and elucidated its potential mechanisms,providing a theoretical and experimental basis for evaluating the environmental exposure risk of amoxicillin and revealing its action patterns. 展开更多
关键词 Amoxicillin exposure Cartilage development Bone development Zebrafish embryo Foxo3a pathway Jak2a/stat3 pathway
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Ochratoxin C induces zebrafish embryonic neurodevelopmental defects and cerebral hemorrhaging by downregulating Notch signaling 认领 引用
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作者 Boxi Hu Dou Yang +8 位作者 Qiang Yuan Zhipeng Wang Jiejun Liu Jiali Xu Fasheng Liu Shouhua Zhang Xinjun Liao Juhua Xiao Zigang Cao 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第4期220-230,共11页
Ochratoxin C(OTC)is a commonly overlooked toxin in the ochratoxin family,found in moldy crops and poultry meat.However,its potential toxicity should not be ignored and needs further elucidation.In this study,we evalua... Ochratoxin C(OTC)is a commonly overlooked toxin in the ochratoxin family,found in moldy crops and poultry meat.However,its potential toxicity should not be ignored and needs further elucidation.In this study,we evaluated the neurotoxicity of OTC during zebrafish embryonic development.The results show that OTC affects the overall zebrafish embryonic development,resulting in reduced body length,abnormal hatching,increased yolk sac area,and decreased tail flick frequency.Additionally,OTC specifically induces cerebral hemorrhaging and abnormal motor behavior in these embryos,accompanied by changes in neurotransmitter and neurodevelopmentrelated gene expression levels.Furthermore,OTC induces upregulation of oxidative stress levels and downregulation of acetylcholinesterase(AChE)activity and adenosine triphosphatase(ATPase)activity,leading to cell apoptosis.Transcriptional assays and transgenic fluorescence photography show that OTC can inhibit Notch signaling pathway.Partial restoration of cerebral hemorrhage and neurodevelopmental defects can be achieved by administering the Notch signaling activator,sodium propionate.Molecular docking analysis indicates that the gene SLC22A6(corresponding to the human gene OAT1)as the binding target protein for OTC.In conclusion,OTC exposure may lead to zebrafish embryonic neurodevelopmental defects and cerebral hemorrhage by downregulating Notch signaling.This work provides insight into the potential threat of OTC to embryonic development. 展开更多
关键词 Ochratoxin Neurodevelopment Cerebral aemorrhage Notch Zebrafish
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Peimisine-sulfide improves inflammation caused by copper sulfate through inhibiting ferroptosis using zebrafish embryos 认领 引用
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作者 Siyu Chen Junyu Liang +5 位作者 Tingting Lin Zitong Huang Leyan Huang Liang Bu Chuanzhi Kang Chengyong He 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第4期774-783,共10页
Peimisine(PMS),a primary bioactive compound in Fritillaria,exhibits promising anti-inflammatory properties.However,its low water solubility limits bioavailability.Sulfonation of PMS yields peimisine-sulfide(PMS-S),a d... Peimisine(PMS),a primary bioactive compound in Fritillaria,exhibits promising anti-inflammatory properties.However,its low water solubility limits bioavailability.Sulfonation of PMS yields peimisine-sulfide(PMS-S),a derivative with enhanced solubility,though the biosafety profiles of both compounds remain unclear.Furthermore,the anti-inflammatory mechanism of PMS-S has yet to be elucidated.To address these gaps,we first conducted acute toxicity assays in zebrafish embryos.While 100μmol/L PMS induced significant toxicity,thioylation to PMS-S eliminated adverse effects at concentrations up to 100μmol/L(0.1–100μmol/L).Next,we established a copper sulfate(CuSO4)-induced inflammatory model in transgenic zebrafish Tg(mpeg1:EGFP).PMS-S treatment suppressed macrophage migration and aggregation at injury sites.Additionally,PMS-S reduced reactive oxygen species(ROS)levels and downregulated ferroptosis-related genes(acsl4b and fthl28),suggesting inhibition of ferroptosis as a potential anti-inflammatory mechanism.In conclusion,thioylation not only enhances the biosafety of PMS but also confers anti-inflammatory activity via ferroptosis suppression.These findings provide a mechanistic foundation for the clinical development of PMS-S as a therapeutic agent. 展开更多
关键词 Peimisine-sulfide(PMS-S) Biosafety Zebrafish Anti-inflammatory Ferroptosis
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Deficiency of pnkp in zebrafish causes microcephaly,seizures,and developmental delay through mitochondrial dysfunction 认领 引用
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作者 Gui-Hua Wang Ling-Lu Xiao +5 位作者 Wei-Min Jia Zhen-Xing Liu Hai-Bo Jia Yan-Xi Sun Zhi-Ke Zi Xian-Qin Zhang 《Zoological Research》 SCIE CSCD 2026年第2期429-443,共15页
Variants in PNKP cause a severe neurodevelopmental disorder characterized by microcephaly,seizures,and developmental delay(MCSZ).Despite clear clinical significance,the pathological mechanisms underlying this conditio... Variants in PNKP cause a severe neurodevelopmental disorder characterized by microcephaly,seizures,and developmental delay(MCSZ).Despite clear clinical significance,the pathological mechanisms underlying this condition remain incompletely understood.In this study,CRISPR/Cas9 genome editing was applied to generate a zebrafish pnkp knockout model(pnkp−/−),overcoming limitations associated with previously reported mouse models that exhibited postnatal lethality.The pnkp−/−zebrafish faithfully recapitulated key phenotypic traits observed in human PNKP deficiency,facilitating in-depth exploration of the molecular mechanisms contributing to disease.Loss of PNKP function resulted in mitochondrial DNA damage,accompanied by disruption of mitochondrial ultrastructure and bioenergetic function,increased apoptosis,and reduced autophagic activity,collectively leading to pronounced cerebral neurodevelopmental abnormalities.Transcriptomic analysis based on RNA sequencing identified marked down-regulation of gammaaminobutyric acid(GABA)receptor-related genes.Pharmacological activation of GABAA receptors with muscimol partially rescued hyperactive behavior in pnkp−/−zebrafish,suggesting a potential link between GABAergic signaling and seizure-related phenotypes.Drug screening performed using the pnkp−/−zebrafish model further identified lamotrigine as a comparatively effective compound for seizure control associated with PNKP mutations.These findings clarify mechanistic links between PNKP deficiency and MCSZ pathology,identify candidate therapeutic agents,and provide an experimental framework for investigation of disorders associated with defective DNA repair. 展开更多
关键词 PNKP Autophagy Apoptosis Zebrafish Drug screening
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Zebrafish optic nerve regeneration involves resident and retinal oligodendrocytes 认领 引用
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作者 Cristina Pérez-Montes Rosalía Hernández-García +5 位作者 Jhoana Paola Jiménez-Cubides Laura DeOliveira-Mello Almudena Velasco Rosario Arévalo Marina García-Macia Adrián Santos-Ledo 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第2期811-820,共10页
The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define... The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination. 展开更多
关键词 cell death oligodendrocytes optic nerve proliferation regeneration Sox10 Sox2 visual system zebrafish
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Deoxycorticosterone acetate–induced acceleration of embryogenesis and oxidative and metabolic stresses in zebrafish 认领 引用
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作者 Shenao Liu Kaifeng Wang +4 位作者 Wenwei Huang Jieming Zhang Chong Han Qiang Li Jian Gong 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第7期812-823,共12页
This study investigated the effects of environmentally relevant concentrations of deoxycorticosterone acetate(DOCA)on embryonic development and oxidative stress in zebrafish(Danio rerio),while also elucidating the und... This study investigated the effects of environmentally relevant concentrations of deoxycorticosterone acetate(DOCA)on embryonic development and oxidative stress in zebrafish(Danio rerio),while also elucidating the underlying molecular mechanisms.Embryos were exposed to DOCA at 5,50,and 500 ng/L,spanning both environmentally pertinent and elevated concentrations.Integrated morphological and transcriptomic analyses(RNA-seq and qRT-PCR)demonstrated dose-dependent acceleration of development,along with alterations in pigmentation,oxidative balance,and metabolic processes.At 50 ng/L,yolk extension increased by 43.3%,whereas yolk sac area decreased by 3.28%.At 500 ng/L,these effects intensified(yolk extension:44.4%;yolk sac area:−5.28%).Body pigmentation decreased by 13.7%compared to controls at 500 ng/L.At 5 ng/L,ROS levels and MDA content increased by 66.5%and 53.4%,respectively.Transcriptomic profiling at 16 h post-fertilization in embryos exposed to 500 ng/L DOCA identified significant gene expression changes concordant with phenotypic outcomes:(1)upregulation of six7,sox17,and cdx1a(associated with accelerated development);(2)downregulation of dctand slc45a2(consistent with reduced pigmentation);(3)altered redox homeostasis,indicated by nox1upregulation and hemoglobin gene downregulation;and(4)enhanced glycolytic/gluconeogenic activity,evidenced by upregulated pfkfb3,aldob,and pck2.These results demonstrate that the DOCA exposure perturbed embryonic zebrafish development,promoting accelerated morphogenesis concurrent with metabolic alterations and oxidative stress.This study provides the first evidence of DOCA’s adverse effects on fish and advances understanding of understudied corticosteroids in ecotoxicology. 展开更多
关键词 Emerging pollutant Mineralocorticoid exposure Deoxycorticosterone acetate Zebrafish Embryonic development
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Epigenetic regulation of cilia stability and kidney development by the SWI/SNF chromatin remodeling complex in zebrafish 认领 引用
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作者 Xiaoyu Cheng Qianshu Zhu +8 位作者 Shilin Ma Xiaoyu Peng Guanliang Huang Guifen Liu Wentao Zhang Yong Zhang Cizhong Jiang Andong Qiu Ying Cao 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2026年第4期630-642,共13页
Cilia are vital subcellular organelles whose assembly is regulated by master transcription factors,such as Foxj1 and Rfx.However,the mechanisms of epigenetic regulation over cilia stability remain largely unclear.Here... Cilia are vital subcellular organelles whose assembly is regulated by master transcription factors,such as Foxj1 and Rfx.However,the mechanisms of epigenetic regulation over cilia stability remain largely unclear.Here,we investigate epigenetic control by manipulating chromatin-remodeling genes in zebrafish.We demonstrate that the depletion of multiple components of the switch/sucrose non-fermentable(SWI/SNF)chromatin remodeling complex induces ciliopathy-like phenotypes in zebrafish embryos.Specifically,the loss of Actl6a,an essential component of the SWI/SNF complex,leads to cilia disassembly and cystic kidney defects,without affecting ciliary motility.Our multi-omics analyses(RNA-seq,ATAC-seq,and Fit-CUT&RUN)consistently reveal that in Actl6a-depleted pronephros or embryos,a critical set of ciliary genes,including the master regulators foxj1a and rfx2,exhibit concordant downregulation across the transcriptional level,chromatin accessibility,and SWI/SNF binding.Consistently,the depletion of foxj1a or rfx2 causes cilia assembly defects and cystic kidney formation in zebrafish.Furthermore,overexpression of either foxj1a or rfx2 mRNA substantially rescues the cystic kidney and cilia disassembly defects observed in act16a-/-mutant embryos.Collectively,these findings reveal that the SWI/SNF complex maintains cilia stability and kidney homeostasis by directly modulating the expression of the key ciliogenesis transcription factors foxj1a and rfx2. 展开更多
关键词 Cilium SWI/SNF actl6a Polycystic kidney disease Zebrafish
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Zebrafish and CRISPR—A synergistic approach to decipher and cure human diseases 认领 引用
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作者 Manikandan Sivaprakasam Aashika Raagavi Jeanpierre +2 位作者 Salma Mohammed Rajesh Srinivasan Aman Kumar Mohanty 《Animal Models and Experimental Medicine》 CAS CSCD 2026年第6期1167-1179,共13页
Rapidly emerging infectious and genetic diseases demand robust vertebrate models to investigate pathogenesis and accelerate therapeutic discovery.Zebrafish(Danio rerio)offer substantial translational value owing to th... Rapidly emerging infectious and genetic diseases demand robust vertebrate models to investigate pathogenesis and accelerate therapeutic discovery.Zebrafish(Danio rerio)offer substantial translational value owing to their conserved physiology,optical transparency,rapid reproduction,and the presence of orthologs for approximately 70%of human genes and approximately 82%of disease-associated genes.The integration of CRISPR/Cas9 technology has transformed zebrafish research,enabling efficient generation of targeted knockouts,knockins,and high-throughput mutagenesis screens.This synergy supports mechanistic dissection and modeling of cardiovascular,oncologic,viral,and other genetic disorders.Despite these advantages,rigorous allele validation,consideration of paralog redundancy,maternal contribution,and off-target analysis remain essential to ensure translational accuracy.This review summarizes current applications,methodological advances,limitations,and bestpractice recommendations for combining zebrafish models with genome editing to improve understanding and treatment of human diseases. 展开更多
关键词 animal model Cas9 CRISPR Danio rerio genome editing zebrafish
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Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish 认领 引用
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作者 Yubei Dai Qianqian Li +7 位作者 Jiaju Deng Sihang Wu Guiyi Zhang Yuebo Hu Yuqian Shen Dong Liu Han Wu Jie Gong 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2026年第1期131-142,共12页
Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis ... Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells(HCs).ldentifying the underlying genes involved in the morphogenesis and development of HCs is crucial.Our current study highlights rhpn2,a member of rho-binding proteins,as essential for vestibular HC development.The rhpn2 gene is highly expressed in the crista and macula HCs.Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number,accompanied by vestibular dysfunction.Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants.Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab.Furthermore,co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA,validating the interaction of the two proteins.rhpn2 knockout leads to a decreased expression of rock2b,a canonical RhoA signaling pathway gene.Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants.This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway,providing a target for the treatment of balance disorders. 展开更多
关键词 Stereocilia Balance disorder RhoA signaling Crista hair cell Zebrafish
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Tea polyphenols interfere with adult zebrafish lipid metabolism and gut microbiota via the gut-liver axis inducing hepatic toxicity 认领 引用
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作者 Tianci Wang Pei Wang +5 位作者 Ziru Dai Heliang Fan Likun Huang Ming Zhang Chenxiao Zhang Zhan Yin 《Food Science and Human Wellness》 SCIE CAS CSCD 2026年第3期1243-1259,共17页
This study investigated the hepatotoxic effects and mechanisms of high-dose tea polyphenols on zebrafish liver based on the gut-liver axis theory.An 8-week rearing experiment evaluated various aspects such as physiolo... This study investigated the hepatotoxic effects and mechanisms of high-dose tea polyphenols on zebrafish liver based on the gut-liver axis theory.An 8-week rearing experiment evaluated various aspects such as physiological and biochemical indicators,histology,gut microbiota,and liver transcriptomics of zebrafish.The results showed that feeding zebrafish a diet rich in high-dose tea polyphenols disrupted their hepatic lipid metabolism,ultimately causing liver damage.Tea polyphenols regulated signaling pathways related to“lipid metabolism and absorption”and“fatty acid degradation”,promoting the uptake of fatty acids and cholesterol by liver cells,inhibiting fatty acid oxidation and excretion,and causing liver fat accumulation.Additionally,high-dose tea polyphenols altered the composition of the gut microbiota,reducing microbial diversity and decreasing the production of intestinal short-chain fatty acids(SCFAs).As a result of the gut-liver axis interaction,low levels of SCFAs and harmful bacteria from the intestine were able to enter the liver through the portal vein,activating hepatic pro-inflammatory factors and causing liver inflammation.The accumulation of liver fat further promoted the expression of pro-inflammatory factors and transported them to the intestine through the bile duct,exacerbating intestinal damage in zebrafish.Therefore,caution should be exercised when using tea polyphenols as a nutritional supplement or medication,especially at high doses and with longterm use,to be aware of their potential adverse effects. 展开更多
关键词 Tea polyphenols Gut-liver axis Zebrafish Hepatic toxicity Lipid metabolism Gut microbiota
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Co-exposure to polystyrene microplastics and perfluorooctanoic acid can exacerbate lipid metabolism disorders and liver damage in adult zebrafish 认领 引用
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作者 Sijie Tian Ruixiang Li +5 位作者 Ya Zeng Lingfeng Qin Caicheng Long Taiping Qing Peng Zhang Bo Feng 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2026年第5期185-196,共12页
Microplastics(MPs)and perfluorooctanoic acid(PFOA)are common emerging environmental contaminants in aquatic environments,and their ecological risks have become a research focus.Although they coexist widely in aquatic ... Microplastics(MPs)and perfluorooctanoic acid(PFOA)are common emerging environmental contaminants in aquatic environments,and their ecological risks have become a research focus.Although they coexist widely in aquatic environments,the combined toxicity of polystyrene microplastics(PS-MPs)and PFOA to aquatic organisms remains unclear.This study investigated the individual and combined toxicity of PS-MPs and PFOA to zebrafish after 28 days of exposure.The results showed that ingestion of PS-MPs and PFOA induced intestinal and liver tissue damage,alterations in oxidative stress,and lipid index in zebrafish.The breakdown of the intestinal barrier will further lead to the increase of lipopolysaccharide in the blood.Notably,combined exposure to PS-MPs and PFOA exerted greater adverse effects than exposure to each contaminant individually.Additionally,exposure to PS-MPs and PFOA significantly disrupted the homeostasis of the intestinal microbiota,and the relative abundances of Proteobacteria and Actinobacteria significantly increased.Transcriptomic analysis further revealed that exposure to PS-MPs and PFOA would lead to the upregulation of genes related to lipid metabolism in zebrafish and alterations in pathways such as glycerolipid metabolism,fat digestion and absorption,and peroxisome proliferator-activated receptor signaling.In conclusion,this study demonstrates that combined exposure to PS-MPs and PFOA exacerbates liver and intestinal damage in zebrafish,disrupts lipid homeostasis,and may contribute to the development of nonalcoholic fatty liver disease.This study has enhanced our understanding of the environmental health risks from the coexistence of MPs and PFOA,and has reference value for formulating complex pollution control standards. 展开更多
关键词 Polystyrene microplastics(PS-MPS) Perfluorooctanoic acid(PFOA) Combined toxicity Lipid metabolism Hepatotoxicity Zebrafish
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Single and Joint Acute Toxicity Effects of Glyphosate Isopropyl Amine Salt(GIS)and Atrazine(ATZ)on Juvenile Zebrafish(Danio rerio) 认领 引用
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作者 Emmanuel Godfrey Maneno Shiqi WEI +3 位作者 Xi CHEN Mingxiao LI Shunlong MENG Meshack Chubwa Maguru 《Agricultural Biotechnology》 2026年第1期22-25,共4页
The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ ... The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC50 values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments. 展开更多
关键词 Acute toxicity Joint toxicity Glyphosate isopropyl amine salt Atrazine Zebrafish(Danio rerio)
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Fibroblast-directed melanocyte recruitment via Cxcl12–Cxcr4 axis promotes post-inflammatory hyperpigmentation and skin barrier protection in zebrafish 认领 引用
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作者 Shizheng Zhao Si Li +7 位作者 Chenyuliang Zhang Zheng Tang Ao Zhang Cong Huang Kefan Cheng Tao Yu Yan Yan Zilong Wen 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2026年第7期1305-1318,共14页
Post-inflammatory hyperpigmentation(PIH)is a common skin disorder characterized by brown or black macules.It can be categorized as transient,typically resolving within 6–12 months,or permanent,persisting for years.Wh... Post-inflammatory hyperpigmentation(PIH)is a common skin disorder characterized by brown or black macules.It can be categorized as transient,typically resolving within 6–12 months,or permanent,persisting for years.While the pathogenesis of PIH is commonly linked to localized melanocyte overactivation,the precise cellular and molecular basis for this dysregulation,as well as its physiological significance,remains poorly defined.Using an acetic acid-induced zebrafish model,we identify melanocyte migration as a critical driver of hyperpigmentation.This process is independent of immune cells but driven by fibroblasts,which secrete Cxcl12a to recruit melanocytes via the Cxcl12a–Cxcr4a axis.Fibroblast ablation irreversibly disrupts melanocyte patterning,indicating that aberrant fibroblast activity dictates the permanence of PIH.The recruited melanocytes form a dual protective barrier against both UV-induced DNA damage and microbial intrusion.The translational relevance of this mechanism is underscored by upregulated CXCL12 expression in fibroblasts from human PIH-related conditions such as keloids,acne,and atopic dermatitis.Therapeutically,the FDA-approved CXCR4 antagonist AMD3100(Plerixafor)effectively prevents and attenuates PIH in our model.Our findings elucidate a fibroblast-mediated mechanism of melanocyte recruitment in PIH,uncover previously unappreciated barrier functions of melanocytes in skin repair,and propose a promising repurposed treatment strategy. 展开更多
关键词 Zebrafish Post-inflammatory hyperpigmentation Fibroblast Melanocyte Migration
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Mechanism of Neuroprotective Effect of Tibetan Tea Theabrownin in a Zebrafish Model of Alzheimer’s Disease via Regulation of the IRE1/p-JNK/Bcl-2-Caspase-3 Signaling Pathway 认领 引用
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作者 ZHU Hui HU Hongjun +10 位作者 MA Yi JIANG Weiming SHEN Caihong AO Zonghua SONG Chuan XIONG Rong JIANG Songyue LIU Qubo ZE Rencuo XU Kewei WANG Ning 《食品科学》 EI CAS CSCD 北大核心 2026年第11期183-200,共18页
This study aimed to investigate the inhibitory activity and mechanism of theabrownin using a zebrafish model of Alzheimer’s disease(AD).Structural analysis indicated that theabrownin was a polymeric phenolic compound... This study aimed to investigate the inhibitory activity and mechanism of theabrownin using a zebrafish model of Alzheimer’s disease(AD).Structural analysis indicated that theabrownin was a polymeric phenolic compound rich in hydroxyl and carboxyl groups.The results showed that theabrownin significantly ameliorated behavioral impairments in zebrafish larvae and effectively alleviated AD-induced oxidative stress.Further molecular mechanism studies demonstrated that theabrownin delayed the progression of AD symptoms through multi-level regulatory mechanisms.At the gene expression level,RNA sequencing(RNA-Seq)and real-time polymerase chain reaction analyses indicated that theabrownin not only inhibited the upregulation of the endoplasmic reticulum stress marker genes bip and ire1 but also reversed the downregulation of atf6 and xbp1.Additionally,theabrownin significantly reduced Ca2+ATPase activity,downregulated the expression of calcium release channel-related genes,inhibited the reduction of mitochondrial respiratory chain complexes,and upregulated the expression of genes related to the tricarboxylic acid(TCA)cycle and oxidative phosphorylation(OXPHOS).At the protein level,Western blot analysis confirmed that theabrownin treatment significantly decreased the expression of the pro-apoptotic proteins Caspase-3 and phosphorylated c-Jun N-terminal kinase(p-JNK),while upregulating the expression of the anti-apoptotic protein B-cell lymphoma 2(Bcl-2).In summary,theabrownin demonstrates significant potential as a functional food component for the prevention and treatment of AD by synergistically regulating the inositolrequiring enzyme 1(IRE1)/p-JNK/Bcl-2-caspase-3 apoptotic signaling pathway through multiple targets. 展开更多
关键词 Tibetan tea theabrownin enhanced fermentation Alzheimer’s disease zebrafish
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