AIM:To elucidate the effects of melatonin on cisplatininduced hepatocellular carcinoma(HepG2) cell death and to identify potential cross-talk pathways.METHODS:Hepatocellular carcinoma HepG2 cells were treated with mel...AIM:To elucidate the effects of melatonin on cisplatininduced hepatocellular carcinoma(HepG2) cell death and to identify potential cross-talk pathways.METHODS:Hepatocellular carcinoma HepG2 cells were treated with melatonin and/or cisplatin for 24 to 48 h.Cell viability and the 50% cytotoxic concentration(CC50) were calculated by MTT assays.The effects and intracellular events induced by the selected concentrations of melatonin(1 mmol/L) and cisplatin(20 μmol/L) were investigated.Cell death and survival detection were primarily evaluated using a fluorescence microscope to assess 4',6 diamideno-2-phenylindol DNA staining and acridine orange lysosome staining and then further analyzed with immunocytochemistry using an anti-LC3 antibody.The potential molecularresponses mediated by melatonin against cisplatin after the combined treatment were investigated by reverse transcription-polymerase chains reaction and Western blot analyses of the genes and proteins associated with cell survival and death.A cell cycle analysis was performed using a flow cytometry assay.RESULTS:Melatonin had a concentration-dependent effect on HepG2 cell viability.At 1 mmol/L,melatonin significantly increased the cell viability percentage and decreased reactive oxygen species production due to cisplatin.Melatonin reduced cisplatin-induced cell death,decreasing phosphorylated p53 apoptotic protein,cleaved caspase 3 and Bax levels but increasing anti-apoptotic Bcl-2 gene and protein expression.When combined with cisplatin,melatonin induced S phase(DNA synthesis) cell cycle arrest and promoted autophagic events in HepG2 cells.Melatonin also had a concentration-dependent effect on Beclin-1 and its autophagic regulator mammalian target of rapamycin(mTOR) as well as the DNA excision repair cross complementary 1(ERCC1) protein.The expression levels of these proteins were altered in HepG2 cells during cisplatin or melatonin treatment alone.In the combination treatment,melatonin reversed the effects of cisplatin by suppressing the over-expression of mTOR and ERCC 1 and enhancing the expression levels of Beclin-1 and microtubule-associated protein-light chain3-Ⅱ,leading to intracellular autophagosome progression.CONCLUSION:Melatonin attenuated cisplatin-induced cell death in HepG2 cells via a counter-balance between the roles of apoptotic- and autophagy-related proteins.展开更多
Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL ...Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.展开更多
Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in posthar...Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in postharvest vegetables.This study demonstrates that MT increases cGMP concentration and the expression of the cGMP synthesis gene BcGC1 in pak choi.The c GMP inhibitor LY83583 destroys effect of MT delaying the leaf senescence.LY83583 also prevents MT treatment from reducing the expression of chlorophyll metabolism-related genes(BcNYC1,BcNOL,BcPPH1/2,BcSGR1/2,and BcPAO)and senescence genes(BcSAG12 and BcSAG21).It also inhibits MT from reducing the activity of the key chlorophyll catabolism enzymes Mg-dechelatase,pheophytinase,and pheide a oxygenase.Thus,the ability of MT to maintain high levels of chlorophyll metabolites is also destroyed.The Arabidopsis c GMP synthetic gene mutant atgc1 was used to confirm that delayed leaf senescence caused by MT is mediated,at least in part,by the second messenger c GMP.展开更多
The exogenous application of melatonin by the root drenching method is an effective way to improve crop drought resistance.However,the optimal concentration of melatonin by root drenching and the physiological mechani...The exogenous application of melatonin by the root drenching method is an effective way to improve crop drought resistance.However,the optimal concentration of melatonin by root drenching and the physiological mechanisms underlying melatonin-induced drought tolerance in cotton(Gossypium hirsutum L.)roots remain elusive.This study determined the optimal concentration of melatonin by root drenching and explored the protective effects of melatonin on cotton roots.The results showed that 50μmol L-1 melatonin was optimal and significantly mitigated the inhibitory effect of drought on cotton seedling growth.Exogenous melatonin promoted root development in drought-stressed cotton plants by remarkably increasing the root length,projected area,surface area,volume,diameter,and biomass.Melatonin also mitigated the drought-weakened photosynthetic capacity of cotton and regulated the endogenous hormone contents by regulating the relative expression levels of hormone-synthesis genes under drought stress.Melatonin-treated cotton seedlings maintained optimal enzymatic and non-enzymatic antioxidant capacities,and produced relatively lower levels of reactive oxygen species and malondialdehyde,thus reducing the drought stress damage to cotton roots(such as mitochondrial damage).Moreover,melatonin alleviated the yield and fiber length declines caused by drought stress.Taken together,these findings show that root drenching with exogenous melatonin increases the cotton yield by enhancing root development and reducing the root damage induced by drought stress.In summary,these results provide a foundation for the application of melatonin in the field by the root drenching method.展开更多
Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrate...Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.展开更多
Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model ...Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes.We treated the rats with exercise and melatonin therapy for 7 consecutive days.Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power rhythm.Additionally,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory abilities.At the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone.These findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.展开更多
Objective:To investigate whether melatonin(MT)secretion in different parts of the gastrointestinal tract(GIT)exhibits seasonal variations and its correlation with immune regulation.Methods: Sixty Sprague-Dawley rats w...Objective:To investigate whether melatonin(MT)secretion in different parts of the gastrointestinal tract(GIT)exhibits seasonal variations and its correlation with immune regulation.Methods: Sixty Sprague-Dawley rats were divided into control and model groups,and the pineal gland was removed in the model group.Stomach,jejunum,ileum,and colon tissues were obtained during the spring equinox,summer solstice,beginning of autumn,autumn equinox,and winter solstice.The levels of MT,MT receptors(MR),arylalkylamine N-acetyltransferase(AANAT),hydroxyindole-O-methyltransferase(HIOMT),interleukin-2(IL-2),and interleukin-10(IL-10)in the GIT were measured using enzyme-linked immunosorbent assay.Results: Except for the stomach,the jejunum,ileum,and the colon showed seasonal tendencies in MT secretion.In the control group,MT secretion in the jejunum and ileum was the highest in the long summer,and colonic MT secretion was the highest in winter.In the model group,MT levels in the colon were highest in the summer.The seasonal rhythms of the MR,AANAT,HIOMT,IL-2,and IL-10 in the colon were roughly similar to those of MT,and changed accordingly after pinealectomy.Conclusions: Gastrointestinal MT secretion is related to seasonal changes,and MT secretion in each intestinal segment is influenced by different seasons.The biological effects of MT in the gut are inextricably linked to the mediation of MR,and a hormone-receptor linkage exists between MT and MR.The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.展开更多
Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated tha...Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.展开更多
基金Supported by Center of Excellence on Environmental Health and Toxicology,Science and Technology Postgraduate Education and Research Development Office,Thailand Ministry of Education
文摘AIM:To elucidate the effects of melatonin on cisplatininduced hepatocellular carcinoma(HepG2) cell death and to identify potential cross-talk pathways.METHODS:Hepatocellular carcinoma HepG2 cells were treated with melatonin and/or cisplatin for 24 to 48 h.Cell viability and the 50% cytotoxic concentration(CC50) were calculated by MTT assays.The effects and intracellular events induced by the selected concentrations of melatonin(1 mmol/L) and cisplatin(20 μmol/L) were investigated.Cell death and survival detection were primarily evaluated using a fluorescence microscope to assess 4',6 diamideno-2-phenylindol DNA staining and acridine orange lysosome staining and then further analyzed with immunocytochemistry using an anti-LC3 antibody.The potential molecularresponses mediated by melatonin against cisplatin after the combined treatment were investigated by reverse transcription-polymerase chains reaction and Western blot analyses of the genes and proteins associated with cell survival and death.A cell cycle analysis was performed using a flow cytometry assay.RESULTS:Melatonin had a concentration-dependent effect on HepG2 cell viability.At 1 mmol/L,melatonin significantly increased the cell viability percentage and decreased reactive oxygen species production due to cisplatin.Melatonin reduced cisplatin-induced cell death,decreasing phosphorylated p53 apoptotic protein,cleaved caspase 3 and Bax levels but increasing anti-apoptotic Bcl-2 gene and protein expression.When combined with cisplatin,melatonin induced S phase(DNA synthesis) cell cycle arrest and promoted autophagic events in HepG2 cells.Melatonin also had a concentration-dependent effect on Beclin-1 and its autophagic regulator mammalian target of rapamycin(mTOR) as well as the DNA excision repair cross complementary 1(ERCC1) protein.The expression levels of these proteins were altered in HepG2 cells during cisplatin or melatonin treatment alone.In the combination treatment,melatonin reversed the effects of cisplatin by suppressing the over-expression of mTOR and ERCC 1 and enhancing the expression levels of Beclin-1 and microtubule-associated protein-light chain3-Ⅱ,leading to intracellular autophagosome progression.CONCLUSION:Melatonin attenuated cisplatin-induced cell death in HepG2 cells via a counter-balance between the roles of apoptotic- and autophagy-related proteins.
文摘Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.
基金supported by the National Natural Science Foundation of China(Grant No.32001451)Jiangsu Agriculture Science and Technology Innovation Fund[Grant No.CX(20)1008]。
文摘Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in postharvest vegetables.This study demonstrates that MT increases cGMP concentration and the expression of the cGMP synthesis gene BcGC1 in pak choi.The c GMP inhibitor LY83583 destroys effect of MT delaying the leaf senescence.LY83583 also prevents MT treatment from reducing the expression of chlorophyll metabolism-related genes(BcNYC1,BcNOL,BcPPH1/2,BcSGR1/2,and BcPAO)and senescence genes(BcSAG12 and BcSAG21).It also inhibits MT from reducing the activity of the key chlorophyll catabolism enzymes Mg-dechelatase,pheophytinase,and pheide a oxygenase.Thus,the ability of MT to maintain high levels of chlorophyll metabolites is also destroyed.The Arabidopsis c GMP synthetic gene mutant atgc1 was used to confirm that delayed leaf senescence caused by MT is mediated,at least in part,by the second messenger c GMP.
基金supported by grants from the National Natural Science Foundation of China(32301947,32272220 and 32172120)the China Postdoctoral Science Foundation(2023M730909)the Natural Science Foundation of Hebei Province,China(C2020204066 and C2021204140)。
文摘The exogenous application of melatonin by the root drenching method is an effective way to improve crop drought resistance.However,the optimal concentration of melatonin by root drenching and the physiological mechanisms underlying melatonin-induced drought tolerance in cotton(Gossypium hirsutum L.)roots remain elusive.This study determined the optimal concentration of melatonin by root drenching and explored the protective effects of melatonin on cotton roots.The results showed that 50μmol L-1 melatonin was optimal and significantly mitigated the inhibitory effect of drought on cotton seedling growth.Exogenous melatonin promoted root development in drought-stressed cotton plants by remarkably increasing the root length,projected area,surface area,volume,diameter,and biomass.Melatonin also mitigated the drought-weakened photosynthetic capacity of cotton and regulated the endogenous hormone contents by regulating the relative expression levels of hormone-synthesis genes under drought stress.Melatonin-treated cotton seedlings maintained optimal enzymatic and non-enzymatic antioxidant capacities,and produced relatively lower levels of reactive oxygen species and malondialdehyde,thus reducing the drought stress damage to cotton roots(such as mitochondrial damage).Moreover,melatonin alleviated the yield and fiber length declines caused by drought stress.Taken together,these findings show that root drenching with exogenous melatonin increases the cotton yield by enhancing root development and reducing the root damage induced by drought stress.In summary,these results provide a foundation for the application of melatonin in the field by the root drenching method.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.
基金supported by China Rehabilitation Research Center,No.2021zx-03the Special Fund for Joint Training of Doctoral Students between the University of Health and Rehabilitation Sciences and China Rehabilitation Research Center,No.2020 kfdx-008(both to TZ)。
文摘Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes.We treated the rats with exercise and melatonin therapy for 7 consecutive days.Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power rhythm.Additionally,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory abilities.At the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone.These findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.
基金supported by the National Natural Science Foundation of China(81001482 and 81973716).
文摘Objective:To investigate whether melatonin(MT)secretion in different parts of the gastrointestinal tract(GIT)exhibits seasonal variations and its correlation with immune regulation.Methods: Sixty Sprague-Dawley rats were divided into control and model groups,and the pineal gland was removed in the model group.Stomach,jejunum,ileum,and colon tissues were obtained during the spring equinox,summer solstice,beginning of autumn,autumn equinox,and winter solstice.The levels of MT,MT receptors(MR),arylalkylamine N-acetyltransferase(AANAT),hydroxyindole-O-methyltransferase(HIOMT),interleukin-2(IL-2),and interleukin-10(IL-10)in the GIT were measured using enzyme-linked immunosorbent assay.Results: Except for the stomach,the jejunum,ileum,and the colon showed seasonal tendencies in MT secretion.In the control group,MT secretion in the jejunum and ileum was the highest in the long summer,and colonic MT secretion was the highest in winter.In the model group,MT levels in the colon were highest in the summer.The seasonal rhythms of the MR,AANAT,HIOMT,IL-2,and IL-10 in the colon were roughly similar to those of MT,and changed accordingly after pinealectomy.Conclusions: Gastrointestinal MT secretion is related to seasonal changes,and MT secretion in each intestinal segment is influenced by different seasons.The biological effects of MT in the gut are inextricably linked to the mediation of MR,and a hormone-receptor linkage exists between MT and MR.The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.
基金supported by the National Natural Science Foundation of China(31901964)the Natural Science Foundation of Hebei,China(C2021204158)+3 种基金the Science and Technology Project of Hebei Education Department,China(BJK2022012)the Introduced Talents Project of Hebei Agricultural University,China(YJ201904)the earmarked fund for Hebei Apple Innovation Team of Modern Agroindustry Technology Research System,China(HBCT2024150205)the earmarked fund for the China Agricultural Research System,China(CARS-27).
文摘Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.