Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the da...Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the damage caused to the CNS is different.To investigate whether different doses of AA have different effects on brain cells,we performed single-nucleus RNA sequencing of the brain.The findings indicated that short-term high-dose(acute)AA directly disrupted protein synthesis and protein structure stability on the endoplasmic reticulum.Additionally,acute AA was observed to downregulate genes that inhibit apoptosis and autophagy,promote apoptosis,accelerate cell aging,and affect cell function in glial cells(Glia).Longterm low-dose(chronic)AA exposure elevated Ca^(2+)concentration,increased protein autophosphorylation,and induced mitochondrial dysfunction,resulting in impaired axonal transport and disrupted metabolism of Kenyon cells(KCs).These findings highlight the cell type-specific effects of AA,where acute exposure disrupts Glia protein homeostasis,and chronic exposure impairs calcium signaling and axonal transport in KCs.Such results deepen our understanding of AA-induced neurotoxicity and lay the groundwork for developing targeted therapeutic strategies to mitigate its effects on the CNS.展开更多
Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on th...Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on the toxicity of single PFAS such as perfluorooctanoic acid(PFOA)and perfluorobutanoic acid(PFBA),the knowledge of their combined effects is relatively limited.In this study,we explored the immune response of the gut in large yellow croaker(Larimichthys crocea)under the combined stress of PFOA and PFBA.Histologicalanalyses revealed that the combined effect induced intestinal vacuolization and decreased the length of intestinal villi.And it significantly activated pro-inflammatory pathways with marked upregulation of tnfα,il1β,il6 and myd88 expressions,particularly after 14 days of exposure.Gut microbiota analysis revealed substantial dysbiosis,including 1)reduced alpha diversity,2)increased abundance of potential pathogenic taxa(Proteobacteria and Spirochaetota),and 3)depletion of beneficial Firmicutes.PICRUSt-based functional prediction indicated temporal metabolic shifts,with upregulation of DNA repair pathways at day 3 and enhanced bacterial motility protein activity at days 7 and 14 of post-exposure.The Pearson correlation analysis further indicated that these immune genes had significant positive correlations with Vibrio and Brevinema,and negative correlations with Streptococcus.Our present study will provide novel insights into the microbiome-mediated immunomodulation in the larger yellow croaker exposed to combined PFAS,which will be helpful for healthy farming of economically important marine species.展开更多
基金supported by the National Natural Science Foundation of China Project(32230081).
文摘Acrylamide(AA)is a common carcinogen that affects the development and function of the central nervous system(CNS).At present,the toxic injuries of common AA are mainly divided into acute and chronic attacks,and the damage caused to the CNS is different.To investigate whether different doses of AA have different effects on brain cells,we performed single-nucleus RNA sequencing of the brain.The findings indicated that short-term high-dose(acute)AA directly disrupted protein synthesis and protein structure stability on the endoplasmic reticulum.Additionally,acute AA was observed to downregulate genes that inhibit apoptosis and autophagy,promote apoptosis,accelerate cell aging,and affect cell function in glial cells(Glia).Longterm low-dose(chronic)AA exposure elevated Ca^(2+)concentration,increased protein autophosphorylation,and induced mitochondrial dysfunction,resulting in impaired axonal transport and disrupted metabolism of Kenyon cells(KCs).These findings highlight the cell type-specific effects of AA,where acute exposure disrupts Glia protein homeostasis,and chronic exposure impairs calcium signaling and axonal transport in KCs.Such results deepen our understanding of AA-induced neurotoxicity and lay the groundwork for developing targeted therapeutic strategies to mitigate its effects on the CNS.
基金supported by the Ningbo Natural Science Foundation(Youth Foundation,No.2024J449)the Scientific Research Foundation for Introduced Talents of Ningbo University(Nos.ZX2022000602 and ZX2024000043)。
文摘Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on the toxicity of single PFAS such as perfluorooctanoic acid(PFOA)and perfluorobutanoic acid(PFBA),the knowledge of their combined effects is relatively limited.In this study,we explored the immune response of the gut in large yellow croaker(Larimichthys crocea)under the combined stress of PFOA and PFBA.Histologicalanalyses revealed that the combined effect induced intestinal vacuolization and decreased the length of intestinal villi.And it significantly activated pro-inflammatory pathways with marked upregulation of tnfα,il1β,il6 and myd88 expressions,particularly after 14 days of exposure.Gut microbiota analysis revealed substantial dysbiosis,including 1)reduced alpha diversity,2)increased abundance of potential pathogenic taxa(Proteobacteria and Spirochaetota),and 3)depletion of beneficial Firmicutes.PICRUSt-based functional prediction indicated temporal metabolic shifts,with upregulation of DNA repair pathways at day 3 and enhanced bacterial motility protein activity at days 7 and 14 of post-exposure.The Pearson correlation analysis further indicated that these immune genes had significant positive correlations with Vibrio and Brevinema,and negative correlations with Streptococcus.Our present study will provide novel insights into the microbiome-mediated immunomodulation in the larger yellow croaker exposed to combined PFAS,which will be helpful for healthy farming of economically important marine species.
