Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labe...Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.展开更多
B cell lymphoma 2(Bcl-2)is an important antiapoptotic gene that plays a dual role in the maintenance of the dynamic balance between the survival and death of cancer cells.In our previous study,Bcl-2 was shown to delay...B cell lymphoma 2(Bcl-2)is an important antiapoptotic gene that plays a dual role in the maintenance of the dynamic balance between the survival and death of cancer cells.In our previous study,Bcl-2 was shown to delay the G0/G1 to S phase entry by regulating the mitochondrial metabolic pathways to produce lower levels of adenosine triphosphate(ATP)and reactive oxygen species(ROS).However,the detailed molecular mechanisms or pathways by which Bcl-2 regulates the cell cycle remain unknown.Here,we compared the effects of Bcl-2 overexpression with an empty vector control in the NIH3T3 cell line synchronized by serum starvation,and evaluated the effects using proteomic analysis.The effect of Bcl-2 on cell cycle regulation was detected by monitoring Bcl-2 and p27 expression.The result of subsequent proteomic analysis of Bcl-2 overexpressing cells identified 169 upregulated and 120 downregulated proteins with a 1.5-fold change.These differentially expressed proteins were enriched in a number of signaling pathways predominantly involving the ribosome and oxidative phosphorylation,according to the data of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.These results indicated that Bcl-2 potentially acts at the translation level to influence proteins or enzymes of the respiratory chain or in the ribosome,and thereby regulates the cell cycle.Additionally,differentially expressed proteins involved in oxidative phosphorylation were determined to account for most of the effects of Bcl-2 on the cell cycle mediated by the mitochondrial pathway investigated in our previous study.These results can provide assistance for additional in-depth studies on the regulation of the cell cycle by Bcl-2.The results of the proteomic analysis determined the mechanism of Bcl-2-dependent delay of the cell cycle progression.In summary,the results of this study provide a novel mechanistic basis for identifying the key proteins or pathways for designing and developing precisely targeted cancer drugs.展开更多
Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP...Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.展开更多
Amorphous materials are attractive candidates for fabricating the superconducting nanowire single-photon detectors(SNSPDs) due to their superior tolerance and scalability over crystalline niobium nitride. However, the...Amorphous materials are attractive candidates for fabricating the superconducting nanowire single-photon detectors(SNSPDs) due to their superior tolerance and scalability over crystalline niobium nitride. However, the reduced superconducting transition temperature degenerates both operating temperature and saturation efficiency. Herein, the SNSPD(6.5 nm thickness and 50 nm width) based on the amorphous Mo0.8Si0.2 film with a high optical absorption coefficient demonstrates close-to-unity intrinsic detection efficiency for 1550 nm photons from 75 m K to 2.2 K. Further, a high-performance array SNSPD with optimized 90 nm-width wires is also demonstrated. As-fabricated uniform 4-pixel SNSPD exhibits a saturation plateau for the photon counts at 2.2 K,which overcomes the limitation of operation at low temperature(< 1 K) for traditional amorphous SNSPDs.Coupled with superior intrinsic quantum efficiency, highly efficient photon counts, and low dark count ratio, this detector paves a way for achieving high efficiency and superior yield for large array systems.展开更多
基金supported by the National Natural Science Foundation of China(No.82204094)the Key Research and Development Program of Ningxia(No.2022BEG03084)the National Key Research and Development Program of China(No.2018YFC1004202)。
文摘Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.
基金This work was supported by the Ningxia Higher Education Scientific Research Project(No.NGY2018-69)the National Natural Science Foundation of China(No.81960480),the Key Research and Development Program of Ningxia(No.2018BEB04008)the Ningxia Medical University Scientific Research Project(No.XT2017015),China.
文摘B cell lymphoma 2(Bcl-2)is an important antiapoptotic gene that plays a dual role in the maintenance of the dynamic balance between the survival and death of cancer cells.In our previous study,Bcl-2 was shown to delay the G0/G1 to S phase entry by regulating the mitochondrial metabolic pathways to produce lower levels of adenosine triphosphate(ATP)and reactive oxygen species(ROS).However,the detailed molecular mechanisms or pathways by which Bcl-2 regulates the cell cycle remain unknown.Here,we compared the effects of Bcl-2 overexpression with an empty vector control in the NIH3T3 cell line synchronized by serum starvation,and evaluated the effects using proteomic analysis.The effect of Bcl-2 on cell cycle regulation was detected by monitoring Bcl-2 and p27 expression.The result of subsequent proteomic analysis of Bcl-2 overexpressing cells identified 169 upregulated and 120 downregulated proteins with a 1.5-fold change.These differentially expressed proteins were enriched in a number of signaling pathways predominantly involving the ribosome and oxidative phosphorylation,according to the data of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.These results indicated that Bcl-2 potentially acts at the translation level to influence proteins or enzymes of the respiratory chain or in the ribosome,and thereby regulates the cell cycle.Additionally,differentially expressed proteins involved in oxidative phosphorylation were determined to account for most of the effects of Bcl-2 on the cell cycle mediated by the mitochondrial pathway investigated in our previous study.These results can provide assistance for additional in-depth studies on the regulation of the cell cycle by Bcl-2.The results of the proteomic analysis determined the mechanism of Bcl-2-dependent delay of the cell cycle progression.In summary,the results of this study provide a novel mechanistic basis for identifying the key proteins or pathways for designing and developing precisely targeted cancer drugs.
基金supported by the National Natural Science Foundation of China(No.81960480)the Key Research and Development Program of Ningxia,China(No.2018BEB04008)。
文摘Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.
基金supported by the National Key R&D Program of China (2017YFA0304002)the National Natural Science Foundation of China (12033002, 61571217, 61521001, 61801206 and 11227904)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the Jiangsu Provincial Key Laboratory of Advanced Manipulating Technique of Electromagnetic Waves
基金National Key Research and Development Program of China (2017YFA0304002)National Natural Science Foundation of China (12033002, 62071218, 61521001, 62071214, 61801206, 11227904)+5 种基金Key-Area Research and Development Program of Guangdong Province(2020B0303020001)Fundamental Research Funds for the Central UniversitiesPriority Academic Program Development of Jiangsu Higher Education InstitutionsRecruitment Program for Young ProfessionalsQing Lan ProjectJiangsu Provincial Key Laboratory of Advanced Manipulating Technique of Electromagnetic Waves。
文摘Amorphous materials are attractive candidates for fabricating the superconducting nanowire single-photon detectors(SNSPDs) due to their superior tolerance and scalability over crystalline niobium nitride. However, the reduced superconducting transition temperature degenerates both operating temperature and saturation efficiency. Herein, the SNSPD(6.5 nm thickness and 50 nm width) based on the amorphous Mo0.8Si0.2 film with a high optical absorption coefficient demonstrates close-to-unity intrinsic detection efficiency for 1550 nm photons from 75 m K to 2.2 K. Further, a high-performance array SNSPD with optimized 90 nm-width wires is also demonstrated. As-fabricated uniform 4-pixel SNSPD exhibits a saturation plateau for the photon counts at 2.2 K,which overcomes the limitation of operation at low temperature(< 1 K) for traditional amorphous SNSPDs.Coupled with superior intrinsic quantum efficiency, highly efficient photon counts, and low dark count ratio, this detector paves a way for achieving high efficiency and superior yield for large array systems.