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
Microplastic contamination has emerged as a threat in transplantation,with evidence of its presence in human tissues and potential to compromise grafts.Transplant recipients,vulnerable due to immunosuppression and sur...Microplastic contamination has emerged as a threat in transplantation,with evidence of its presence in human tissues and potential to compromise grafts.Transplant recipients,vulnerable due to immunosuppression and surgical exposure,face risk from microplastics via airborne particles,surgical materials,and organ preservation systems.These particles trigger inflammation,oxidative stress,and immune dysregulation—pathways critical in rejection.Microplastics support biofilm formation,potentially facilitating antimicrobial resistance in clinical settings.Despite this risk,transplant-specific research is lacking.We urge action through environmental controls,material substitutions,and procedural modifications,alongside research targeting exposure pathways,biological impact,and mitigation strategies.Transplantation has historically led medical innovation and must do so in confronting this environmental challenge.Leadership from global transplant societies is essential to protect recipients and ensure safe procedures.展开更多
Despite the widespread presence and frequent detection of polycyclic aromatic hydrocarbons(PAHs)in various aspects of life,there is limited research on their exposure levels in pregnant women and cumulative exposure f...Despite the widespread presence and frequent detection of polycyclic aromatic hydrocarbons(PAHs)in various aspects of life,there is limited research on their exposure levels in pregnant women and cumulative exposure from the living environment.This study included 1311 women in late pregnancy from the Zunyi birth cohort and measured the urinary concentrations of 10 hydroxylated PAH metabolites(OH-PAHs).Risk assessment was conducted based on the estimated daily intake to calculate the hazard quotient and hazard index(HI).A linear regression model was used to analyze the relationship between creatinine-adjusted OH-PAHs concentrations and living environment and lifestyle factors,while principal component analysis was applied to trace the sources of PAHs exposure.1-OHPYR was detected in all participants’urine,with naphthalene metabolites having the highest concentrations among creatinine-adjusted PAHs.OH-PAHs concentrations were associated with housing type,room number,cooking frequency,household size,exercise frequency,fuel type,distance from main road,and drinking water source.Pregnant women using traditional fuels and living in bungalows had higher health risks than those using clean energy and living in buildings.Those living within 100 m of a main road had higher HI than those farther away.Coal combustion was identified as the primary source of PAHs exposure.The study emphasizes the importance of reducing PAHs exposure,especially for pregnant women living in polluted environments.It recommends public health interventions such as improving indoor ventilation and providing clean energy to reduce related health risks.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.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.
文摘Microplastic contamination has emerged as a threat in transplantation,with evidence of its presence in human tissues and potential to compromise grafts.Transplant recipients,vulnerable due to immunosuppression and surgical exposure,face risk from microplastics via airborne particles,surgical materials,and organ preservation systems.These particles trigger inflammation,oxidative stress,and immune dysregulation—pathways critical in rejection.Microplastics support biofilm formation,potentially facilitating antimicrobial resistance in clinical settings.Despite this risk,transplant-specific research is lacking.We urge action through environmental controls,material substitutions,and procedural modifications,alongside research targeting exposure pathways,biological impact,and mitigation strategies.Transplantation has historically led medical innovation and must do so in confronting this environmental challenge.Leadership from global transplant societies is essential to protect recipients and ensure safe procedures.
基金supported by the National Key R&D Program of China(Nos.2018YFC1004300 and 2018YFC1004302)the Science&Technology Program of Guizhou Province(Nos.QKHHBZ[2020]3002,QKHPTRC-GCC[2022]039-1 and QKHPTRCCXTD[2022]014)the Scientific Research Program of Guizhou Provincial Department of Education(No.QJJ[2023]019).
文摘Despite the widespread presence and frequent detection of polycyclic aromatic hydrocarbons(PAHs)in various aspects of life,there is limited research on their exposure levels in pregnant women and cumulative exposure from the living environment.This study included 1311 women in late pregnancy from the Zunyi birth cohort and measured the urinary concentrations of 10 hydroxylated PAH metabolites(OH-PAHs).Risk assessment was conducted based on the estimated daily intake to calculate the hazard quotient and hazard index(HI).A linear regression model was used to analyze the relationship between creatinine-adjusted OH-PAHs concentrations and living environment and lifestyle factors,while principal component analysis was applied to trace the sources of PAHs exposure.1-OHPYR was detected in all participants’urine,with naphthalene metabolites having the highest concentrations among creatinine-adjusted PAHs.OH-PAHs concentrations were associated with housing type,room number,cooking frequency,household size,exercise frequency,fuel type,distance from main road,and drinking water source.Pregnant women using traditional fuels and living in bungalows had higher health risks than those using clean energy and living in buildings.Those living within 100 m of a main road had higher HI than those farther away.Coal combustion was identified as the primary source of PAHs exposure.The study emphasizes the importance of reducing PAHs exposure,especially for pregnant women living in polluted environments.It recommends public health interventions such as improving indoor ventilation and providing clean energy to reduce related health risks.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
