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Fullerenols, a water-soluble polyhydroxy derivative of fullerene, hold promise in medical and materials science due to their unique properties. However, concerns about their potential embryotoxicity remain. Using a pregnancy mouse model and metabolomics analysis, our findings reveal that fullerenols exposure during pregnancy not only significantly reduced mice placental weight and villi thickness, but also altered the classes and concentrations of metabolites in the mouse placenta. Furthermore, we found that fullerenols exposure reduced the levels of CYP3A4, ERα and estriol (E3), while increasing the levels of estradiol (E2) and oxidative stress both in mouse placenta and placental trophoblast cells, and exogenous supplementation with E3 and ER agonists was effective in restoring these changes in vitro. Moreover, CYP3A4 inhibition was effective in decreasing intracellular E3 levels, whereas overexpression of CYP3A4 resisted the fullerenols-induced decrease in E3 expression Additionally, we synthesized glutathione-modified fullerenols (C60-(OH)n-GSH), which demonstrated improved biocompatibility and reduced embryotoxicity by enhancing intracellular glutathione levels and mitigating oxidative stress. In summary, our results demonstrated that fullerenols exposure decreased E3 synthesis by inhibiting CYP3A4 and exacerbated oxidative stress through downregulation of estrogen receptor activation and decreased glutathione levels. These findings highlight the risks of fullerenols exposure during pregnancy and offer strategies for safer nanomaterial development. [ABSTRACT FROM AUTHOR]

Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area. [ABSTRACT FROM AUTHOR]

The photovoltaic performances of n-i-p or inverted p-i-n BaSi2 homojunction solar cells are limited by the parasitic high light absorption of n-BaSi2 or p-BaSi2 window layer. In this work, diverse electron transport materials (ETMs) and hole transport materials (HTMs) are employed instead of BaSi2 as window layers to promote the performances of BaSi2 solar cells, and the effects of different ETMs and HTMs were simulated and comprehensively studied. For n-ETM/i-BaSi2/p-BaSi2 solar cells, the solar cell with ZnO exhibits the highest efficiency of 28.21%. As increasing the thicknesses of ETM layer from 5 nm to 100 nm, the efficiency for n-BaSi2/i-BaSi2/p-BaSi2 solar cell decreases seriously from 24.52% to 15.99%, while the solar cells with wide band gap ETMs including SnO2, TiO2 and ZnO show neglectable change in performances. The performances n-ETM/i-BaSi2/p-BaSi2 solar cells are affected by donor like defects more than acceptor like defects in i-BaSi2. For p-HTM/i-BaSi2/n-BaSi2 solar cells, employing Cu2O, CuI, CuSCN or NiO as HTM layer produces evident valence band discrepancies at HTM/i-BaSi2 interfaces. Heavy doping in HTM layer is necessary desired to overcome the energy band barriers. As increasing the thicknesses of HTM layer from 5 nm to 100 nm, the efficiency for p-BaSi2/i-BaSi2/n-BaSi2 solar cell also decreases from 24.52% to 15.99%, while the solar cells with wide band gap HTMs including CuI, CuSCN and NiO show neglectable change, and the efficiency for p-Cu2O/i-BaSi2/n-BaSi2 solar cells decreases slightly from 25.86% to 24.88%. The performances of p-HTM/i-BaSi2/n-BaSi2 solar cells are affected by acceptor like defects more than donor like defects in i-BaSi2. [ABSTRACT FROM AUTHOR]

Glial cell line-derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self-renewal genes, including B-cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self-renewal of SSCs. [ABSTRACT FROM AUTHOR]

Iron oxides nanoparticles (FeOX NPs), including α-Fe2O3, γ-Fe2O3, and Fe3O4, are employed in many technological applications. However, very few studies have investigated the embryonic developmental toxicity of FeOX NPs. In this study, metabolomics analysis were used to uncover the potential mechanisms of FeOX NPs developmental toxicity on embryo–larval zebrafish and mice. Our results indicated that γ-Fe2O3 NP treatment could cause increased mortality, dropped hatching rate, etc., while α-Fe2O3 and Fe3O4 NPs showed no obvious effect. Through metabolomics analysis, a total of 42 metabolites were found to be significantly changed between the γ-Fe2O3 NP-treated group and the control group (p < 0.05). Pathway enrichment analysis indicated the impairment of mitochondria function. γ-Fe2O3 NP treatment caused abnormal mitochondrion structure and a decrease in mitochondrial membrane potential in zebrafish embryos. Meanwhile, ATP synthesis was decreased while oxidative stress levels were affected. It is noteworthy that acetyl-l-carnitine (ALCAR) (p = 6.79E − 04) and l-carnitine (p = 1.43E − 03) were identified with minimal p values, the relationship between the two counter-balance was regulated by acetyltransferase (crata). Subsequently, we performed rescue experiments with ALCAR on zebrafish embryos, and found that the mortality rates reduced and hatching rates raised significantly in the γ-Fe2O3 NP-treated group. Additionally, γ-Fe2O3 exposure could lead to increased absorbed fetus rate, decreased placental weight, lower expression of acetyltransferase (Crat), reduced ATP synthesis as well as increased oxidative stress (p < 0.05). Our findings demonstrated that γ-Fe2O3 NP might affect the mitochondrial membrane potential and ATP synthesis by affecting the metabolism of ALCAR, thereby stimulating oxidative stress, cell apoptosis, and causing embryonic development toxicity. [ABSTRACT FROM AUTHOR]

Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is crucial in placenta development. However, the mechanism of PPARγ in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPARγ worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPARγ and its downstream viability, migration, angiogenesis-related genes HMOX1, ANGPTL4, VEGFA, MMP-2, MMP-9, and upregulated inflammatory genes p65, IL-6, IL-1β, and TNF-α in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPARγ had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPARγ agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPARγ pathway. Our findings reveal that activation of PPARγ might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus. [ABSTRACT FROM AUTHOR]