Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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.

A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells

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.

A proteomic analysis of Bcl-2 regulation of cell cycle arrest:insight into the mechanisms

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.

Research on combustion characteristics of bio-oil from sewage sludge

Combustion characteristics of bio-oil from sewage sludge were investigated using thermogravimetry(TG)andFourierTransform InfraredSpectroscopy(FT-IR)techniques.The combustion process could be divided into two weight loss stages.Light compounds volatilized and were oxidized in the first stage and the heterogeneous combustion between oxygen and heavy compounds happened in the second stage,which were confirmed by FT-IR technique.Most weight loss occurred in the first stage.The effect of heating rate was also studied and higher heatingrates were foundto facilitate the combustion process.The kinetic parameters of the two stages were calculated and the change of activation energy indicated higher heating rates benefited combustion.