Black carbon (BC) correlates with the occurrence and progression of atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that BC could impair vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that IL-33 exerts a significant biological role in cardiovascular disease, but little is known about the molecular regulation of IL-33 expression at present. We first found that BC significantly increased IL-33 mRNA in EA.hy926 cells in a concentration and time-dependent manner, and we conducted this study to explore its underlying mechanism. We identified that BC induced mitochondrial damage and suppressed autophagy function in EA.hy926 cells, as evidenced by elevation of the aspartate aminotransferase (GOT2), reactive oxygen species (ROS) and p62, and the reduction of mitochondrial membrane potential (ΔΨm). However, ROS cannot induce IL-33 mRNA-production in BC-exposed EA.hy926 cells. Further, experiments revealed that BC could promote IL-33 mRNA production through the PI3K/Akt/AP-1 and p38/AP-1 signaling pathways. It is concluded that BC could induce oxidative stress and suppress autophagy function in endothelial cells. This study also provided evidence that the pro-cardiovascular-diseases properties of BC may be due to its ability to stimulate the PI3K/AKT/AP-1 and p38/AP-1 pathway, further activate IL-33 and ultimately result in a local vascular inflammation.
BackgroundAs air pollution has been paid more attention to by public in recent years, effects and mechanism in particulate matter-triggered health problems become a focus of research. Lysosomes and mitochondria play an important role in regulation of inflammation. Interleukin-33 (IL-33) has been proved to promote inflammation in our previous studies. In this study, macrophage cell line RAW264.7 was used to explore the mechanism of IL-33 up-gradation, effects on lysosomes and mitochondria induced by 1,4-naphthoquinone black carbon (1,4-NQ-BC).Results50μg/mL 1,4-NQ-BC exposure for 24 h dramatically increased expression of IL-33 in RAW264.7 cells. Lysosomal membrane permeability was damaged by 1,4-NQ-BC treatment, and higher mitochondrial membrane potential and ROS level were induced by 1,4-NQ-BC. The results of proteomics suggested that expression of ferritin light chain was increased after cells were challenged with 1,4-NQ-BC, and it was verified by Western blot. Meanwhile, expressions of p62 and LC3B-II were increased by 50μg/mL 1,4-NQ-BC in RAW264.7 cells. Ultimately, expression of IL-33 could return to same level as control in cells treated with 50μg/mL 1,4-NQ-BC and 50μM deferoxamine combined.Conclusions1,4-NQ-BC induces IL-33 upregulation in RAW264.7 cells, and it is responsible for higher lysosomal membrane permeability and ROS level, lower mitochondrial membrane potential, and inhibition of autophagy. Ferritin light chain possibly plays an important role in the upregulation of IL-33 evoked by 1,4-NQ-BC.
Designing dependable solar PV systems that last a long time and function in a wide variety of temperatures in low earth orbit requires precise forecast of solder interconnect lifespans, yet useful prediction methodology has rarely been studied. Here, a strategy for measuring the solder interconnects' fatigue life was established using experimental, computational, and analytical methodologies. Thermal aging, material characterization, and thermal cycling were used to explore the physics of failure. Equilibrium liquid surface simulation and finite element modeling were used to establish the geometry of the solder interconnects, and to obtain the strain distribution. To accurately predict the lifespan of solder interconnects, microstructure evolution modeling, constitutive equation fitting, and fatigue model calibration were performed. We have demonstrated that increasing the stand-off height of solder interconnects can delay the onset of fatigue cracks and prolong total fatigue life in photovoltaic systems using this integrated approach to busbar-to-wire solder interconnects. Interconnects with large solder quantity have a long life due to slow crack propagation with low averaged plastic work, but they have about the same number of cycles to fatigue crack initiation due to relatively stable plastic strain range during heat cycling. The proposed approach could be used to motivate the design of strong interconnects in photovoltaic systems that can withstand rigorous thermal cycling.
Black carbon (BC) is an important component of atmospheric PM 2.5 and the second largest contributor to global warming. 1,4-naphthoquinone-coated BC (1,4 NQ-BC) is a secondary particle with great research value, so we chose 1,4 NQ-BC as the research object. In our study, mitochondria and lysosomes were selected as targets to confirm whether they were impaired by 1,4 NQ-BC, label free proteomics technology, fluorescent probes, qRT-PCR and western blots were used to investigate the mechanism of 1,4 NQ-BC toxicity. We found 494 differentially expressed proteins (DEPs) in mitochondria and 86 DEPs in lysosomes using a proteomics analysis of THP1 cells after 1,4 NQ-BC exposure for 24 h. Through proteomics analysis and related experiments, we found that 1,4 NQ-BC can damage THP-1-M cells by obstructing autophagy, increasing lysosomal membrane permeability, disturbing the balance of ROS, and reducing the mitochondrial membrane potential. It is worth noting that 1,4 NQ-BC prevented the removal of FTL by inhibiting autophagy, and increased IL-33 level by POR/FTL/IL-33 axis. We first applied proteomics to study the damage mechanism of 1,4 NQ-BC on THP1 cells. Our research will enrich knowledge of the mechanism by which 1,4 NQ-BC damages human macrophages and identify important therapeutic targets and adverse outcome pathways for 1,4 NQ-BC-induced damage.
As an alternative to octabromodiphenyl ether (octa-BDE), 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) has been widely used in a variety of combustible materials, such as plastics, textiles and furniture. Previous studies have demonstrated the thyroid toxicity of traditional brominated flame retardants for example octa-BDE clearly. Nevertheless, little is known about the thyroid toxicity of alternative novel brominated flame retardants BTBPE. In this study, it was demonstrated that BTBPE in vivo exposure induced FT4 reduction in 2.5, 25 and 250 mg/kg bw treated group and TT4 reduction in 25 mg/kg bw treated group. TG, TPO and NIS are key proteins of thyroid hormone synthesis. The results of western blot and RT-PCR from thyroid tissue showed decreased protein levels and gene expression levels of TG, TPO and NIS as well as regulatory proteins PAX8 and TTF2. To investigate whether the effect also occurred in humans, anthropogenic Nthy-ori 3-1 cells were selected. Similar results were seen in in vitro condition. 2.5 mg/L BTBPE reduced the protein levels of PAX8, TTF1 and TTF2, which in turn inhibited the protein levels of TG and NIS. The results in in vitro experiment were consistent with that in in vivo , suggesting possible thyrotoxic effects of BTBPE on humans. It was indicated that BTBPE had the potential interference of T4 generation and the study provided more evidence of the effects on endocrine disorders.
Abstract Yttrium is a typical heavy rare earth element with widespread use in numerous sectors. Only one previous study has indicated that yttrium has the potential to cause developmental immunotoxicity (DIT). Therefore, there remains a paucity of evidence on the DIT of yttrium. This study aimed to explore the DIT of yttrium nitrate (YN) and the self‐recovery of YN‐induced DIT. Dams were treated with 0, 0.2, 2, and 20 mg/kg bw/day YN by gavage during gestation and lactation. No significant changes were found in innate immunity between the control and YN‐treated groups in offspring. In female offspring at postnatal day 21 (PND21), YN markedly inhibited humoral and cellular immune responses, the proliferative capacity of splenic T lymphocytes, and the expression of costimulatory molecules in splenic lymphocytes. Moreover, the inhibitory effect on cellular immunity in female offspring persisted to PND42. Unlike females, YN exposure did not change the adaptive immune responses in male offspring. Overall, maternal exposure to YN showed a strong DIT to offspring, with the lowest effective dose of 0.2 mg/kg in the current study. The toxicity of cellular immunity could persist throughout development into adulthood. There were sex‐specific differences in YN‐induced DIT, with females being more vulnerable.
Black carbon (BC) was the strongest light-absorbing component in particulate matter (PM), and formed by incomplete combustion of diesel, coal, biofuels and outdoor biomass. BC is an important component of atmospheric PM and the second largest contributor to global warming. Secondary particles are particles formed by re-reaction in the atmosphere. 1,4-naphthoquinone coated BC (1,4 NQ-BC) can be used as a secondary particle with great research value, so we chose 1,4 NQ-BC as the research object. In our study, mitochondria and lysosomes were selected as the target to confirm whether they were impaired by 1,4 NQ-BC, meanwhile proteomics technology, fluorescent probe technology, qRT-PCR and Western blot were used to further extrapolate the mechanism of 1,4 NQ-BC toxicity. We found that 494 differentially expressed proteins (DEPs) in mitochondria and 86 DEPs in lysosomes using proteomics analysis in THP1 cells after 1,4 NQ-BC exposure for 24 h. Through proteomics analysis and related experiments, we found that 1,4 NQ-BC can damage THP-1-M cells by obstructing autophagy, increasing lysosomal membrane permeability, disturbing the balance of ROS, and reducing mitochondrial membrane potential. It is worth noting that FTL could regulate the expression of IL-33 as an upstream regulator of IL-33. In addition, cell death patterns, mineral absorption, abnormal level of ROS and FTL/POR/IL-33 axis can be used as the research direction to further study the damage mechanism of 1,4 NQ-BC on THP-1-M cells. Our research will enrich the damage mechanism of 1,4 NQ-BC on human macrophages and provide important therapeutic targets and adverse outcome pathway for 1,4 NQ-BC induced damage.Funding Information: The study was supported by the Earmarked Fund for (No. 82173470).Declaration of Interests: The authors declare that there are no conflicts of interest.
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