The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted...The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.展开更多
Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhanc...Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhance telomerase activity.In present study,the metagenomics sequencing and quantitative real-time polymerase chain reaction analysis were employed to characterize the composition and diversity of gut microbiome in aging flies.And the alterations in the gut barrier,gut morphology,and other gut physiological indicators of aging flies were evaluated.Here,the results showed that ergothioneine induced little variations in gut microbiota composition in flies at mid-life,and significant alterations in the gut microbiota populations were only observed in flies at late-life.And ergothioneine attenuated age-related gut injuries,including decreasing reactive oxygen species levels in intestinal enterocytes,reduction of intestinal cells death,and preservation of gut integrity in aging flies.Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy.And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.展开更多
[Objectives]This study was conducted to investigate the effects of different concentrations of sodium cyclohexyl sulfamate on the growth and development of Drosophila melanogaster.[Methods]Different concentrations of ...[Objectives]This study was conducted to investigate the effects of different concentrations of sodium cyclohexyl sulfamate on the growth and development of Drosophila melanogaster.[Methods]Different concentrations of sodium cyclohexyl sulfamate were added to the culture medium,and the effects of different concentrations of sodium cyclohexyl sulfamate on the development time and weight of D.melanogaster in various life stages were statistically analyzed.[Results]High concentration of sodium cyclohexyl sulfamate delayed the time of pupation and eclosion of D.melanogaster,which made D.melanogaster lose weight.The number of male D.melanogaster in the first generation was much larger than that of female individuals,which indicated that the effect of sodium cyclohexyl sulfamate on male D.melanogaster was greater than that of female individuals.In a word,high concentration of sodium cyclohexyl sulfamate significantly inhibited the growth and development of D.melanogaster.[Conclusions]This study provides some reference data for the research perspective of food additives and the safe use of sodium cyclohexyl sulfamate.展开更多
Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the an...Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.展开更多
Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurologica...Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.展开更多
The purpose of this study was to explore the potential of the development and application of Paecilomyces hepiali,a fungus with edible and medicinal value,as a foodborne antioxidant and anti-aging agent.Its n-butanol ...The purpose of this study was to explore the potential of the development and application of Paecilomyces hepiali,a fungus with edible and medicinal value,as a foodborne antioxidant and anti-aging agent.Its n-butanol extract(PHE)from rice cultures was selected for anti-aging experiment because of significant free radical scavenging activity in vitro.In vivo,PHE could significantly prolong the mean lifespan,50%survival days,and the maximum lifespan of Drosophila on a high-fat diet.It is amazing that the mean lifespan increased from 19.1 days to 32.9 days,50%survival days increased from 15.7 days to 34.3 days,and the maximum lifespan extended from 44.7 days to 52.7 days,when the high-fat female Drosophila model was fed with 10μg/mL PHE.Further research showed that PHE reduced the accumulation of peroxide products and increased the activity of antioxidant enzymes.Then,through antioxidant activity tracking,dimerumic acid(compound 1,the IC_(50) value of 3.4μg/mL on DPPH free radicals scavenging activity),4,5-dihydroxy-3-methoxypentanoic acid(compound 2,new compound),and thymidine(compound 3)were isolated from PHE.It is worth mentioning that dimerumic acid,the major antioxidant compound of PHE(content up to 3%),was discovered in P.hepiali for the first time.It was concluded that PHE showed excellent anti-aging activity at a very low concentration on fat diet-induced high fat Drosophila melanogaster,and dimerumic acid may be its main material basis.These results indicated that PHE had the potential to be developed as antioxidant and anti-aging agent in the healthcare industry.展开更多
The conditional mutations in drosophila were obtained by γ-irradiation and selected using the test for dominant lethality. The conditional mutations survive under permissive genetic conditions and, additionally, comm...The conditional mutations in drosophila were obtained by γ-irradiation and selected using the test for dominant lethality. The conditional mutations survive under permissive genetic conditions and, additionally, commence to display novel properties. One of such properties is a recessive lethality. Ten conditional mutations that displayed recessive lethality were mapped with the help of a standard set of deletions. Half mutations contained two and more lethal defects. The fact that a large number of the lethal defects are associated with one mutation suggests that γ-irradiation is the most unlikely cause of the defects. One of the conditional mutations carried four lethal regions and had a Small barrel (Smba) visual phenotype. The Smba phenotype in the Smba/ In(2LR) Cy strain is inherited according to a parental type and disappears in the Smba/In(2LR) Pm strain. Lethality in two of the four lethal regions also disappears in this strain. A separate experiment was conducted to clarify how these regions lost a lethal manifestation after the In(2LR) Cy chromosome in the Smba/In(2LR) Cy strain was replaced with the In(2LR) Pm chromosome. The process of disappearance of the Smba phenotype was also observed in three Smba/In(2LR) Cy substocks. These data suggest that the regions of multiple recessive lethality emerge in a secondary manner under the effect of the earlier formed radiation-induced mutation in ontogene. It is assumed that the recessive lethal regions are the ontogenes with an altered DNA conformation. The conformation in ontogenes is changed in the germline cells during a regular “editing” of the individual development program.展开更多
基金Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2021-12 to L.L.)National Natural Science Foundation of China(32071009,32371063,82341248 to C.L.,31971072 and 32171154 to L.L.)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515011500 to C.L.)Shenzhen Science Technology and Innovative Commission(SZSTI JCYJ20180508152336419 to L.L.and GJHZ20200731095406021 to S.J.)。
文摘The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.
基金supported by the National Natural Science Foundation of China(32072646,31772373,and 32001832).
文摘Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhance telomerase activity.In present study,the metagenomics sequencing and quantitative real-time polymerase chain reaction analysis were employed to characterize the composition and diversity of gut microbiome in aging flies.And the alterations in the gut barrier,gut morphology,and other gut physiological indicators of aging flies were evaluated.Here,the results showed that ergothioneine induced little variations in gut microbiota composition in flies at mid-life,and significant alterations in the gut microbiota populations were only observed in flies at late-life.And ergothioneine attenuated age-related gut injuries,including decreasing reactive oxygen species levels in intestinal enterocytes,reduction of intestinal cells death,and preservation of gut integrity in aging flies.Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy.And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program(202314390006)Undergraduate Innovation and Entrepreneurship Training Program(2024DC078)Construction Project of Biological Experiment Teaching Demonstration Center in Colleges and Universities in Shaanxi Province.
文摘[Objectives]This study was conducted to investigate the effects of different concentrations of sodium cyclohexyl sulfamate on the growth and development of Drosophila melanogaster.[Methods]Different concentrations of sodium cyclohexyl sulfamate were added to the culture medium,and the effects of different concentrations of sodium cyclohexyl sulfamate on the development time and weight of D.melanogaster in various life stages were statistically analyzed.[Results]High concentration of sodium cyclohexyl sulfamate delayed the time of pupation and eclosion of D.melanogaster,which made D.melanogaster lose weight.The number of male D.melanogaster in the first generation was much larger than that of female individuals,which indicated that the effect of sodium cyclohexyl sulfamate on male D.melanogaster was greater than that of female individuals.In a word,high concentration of sodium cyclohexyl sulfamate significantly inhibited the growth and development of D.melanogaster.[Conclusions]This study provides some reference data for the research perspective of food additives and the safe use of sodium cyclohexyl sulfamate.
基金supported by the open project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China (GMU-2022-HJZ-06)。
文摘Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.
基金This work was supported by Swiss National Science Foundation,grant#31003A_175658 to VLK.
文摘Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.
基金supported by the National Natural Science Foundation of China(42006094)by Fujian Natural Science Foundation(2019J05032).
文摘The purpose of this study was to explore the potential of the development and application of Paecilomyces hepiali,a fungus with edible and medicinal value,as a foodborne antioxidant and anti-aging agent.Its n-butanol extract(PHE)from rice cultures was selected for anti-aging experiment because of significant free radical scavenging activity in vitro.In vivo,PHE could significantly prolong the mean lifespan,50%survival days,and the maximum lifespan of Drosophila on a high-fat diet.It is amazing that the mean lifespan increased from 19.1 days to 32.9 days,50%survival days increased from 15.7 days to 34.3 days,and the maximum lifespan extended from 44.7 days to 52.7 days,when the high-fat female Drosophila model was fed with 10μg/mL PHE.Further research showed that PHE reduced the accumulation of peroxide products and increased the activity of antioxidant enzymes.Then,through antioxidant activity tracking,dimerumic acid(compound 1,the IC_(50) value of 3.4μg/mL on DPPH free radicals scavenging activity),4,5-dihydroxy-3-methoxypentanoic acid(compound 2,new compound),and thymidine(compound 3)were isolated from PHE.It is worth mentioning that dimerumic acid,the major antioxidant compound of PHE(content up to 3%),was discovered in P.hepiali for the first time.It was concluded that PHE showed excellent anti-aging activity at a very low concentration on fat diet-induced high fat Drosophila melanogaster,and dimerumic acid may be its main material basis.These results indicated that PHE had the potential to be developed as antioxidant and anti-aging agent in the healthcare industry.
文摘The conditional mutations in drosophila were obtained by γ-irradiation and selected using the test for dominant lethality. The conditional mutations survive under permissive genetic conditions and, additionally, commence to display novel properties. One of such properties is a recessive lethality. Ten conditional mutations that displayed recessive lethality were mapped with the help of a standard set of deletions. Half mutations contained two and more lethal defects. The fact that a large number of the lethal defects are associated with one mutation suggests that γ-irradiation is the most unlikely cause of the defects. One of the conditional mutations carried four lethal regions and had a Small barrel (Smba) visual phenotype. The Smba phenotype in the Smba/ In(2LR) Cy strain is inherited according to a parental type and disappears in the Smba/In(2LR) Pm strain. Lethality in two of the four lethal regions also disappears in this strain. A separate experiment was conducted to clarify how these regions lost a lethal manifestation after the In(2LR) Cy chromosome in the Smba/In(2LR) Cy strain was replaced with the In(2LR) Pm chromosome. The process of disappearance of the Smba phenotype was also observed in three Smba/In(2LR) Cy substocks. These data suggest that the regions of multiple recessive lethality emerge in a secondary manner under the effect of the earlier formed radiation-induced mutation in ontogene. It is assumed that the recessive lethal regions are the ontogenes with an altered DNA conformation. The conformation in ontogenes is changed in the germline cells during a regular “editing” of the individual development program.