Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameterdependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health. environmental health | inflammation | nanotoxicology
Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among the commercially used types of asbestos (chrysotile, crocidolite, and amosite), the carcinogenicity of chrysotile is not fully appreciated. Here, we show that all three asbestos types similarly induced MM in the rat peritoneal cavity and that chrysotile caused the earliest mesothelioma development with a high fraction of sarcomatoid histology. The pathogenesis of chrysotile-induced mesothelial carcinogenesis was closely associated with iron overload: repeated administration of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction, significantly reduced the period required for carcinogenesis; massive iron deposition was found in the peritoneal organs with high serum ferritin; and homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most frequent genomic alteration in human MM and in iron-induced rodent carcinogenesis, was observed in 92.6% of the cases studied with array-based comparative genomic hybridization. The induced rat MM cells revealed high expression of mesoderm-specific transcription factors, Dlx5 and Hand1, and showed an iron regulatory profile of active iron uptake and utilization. These data indicate that chrysotile is a strong carcinogen when exposed to mesothelia, acting through the induction of local iron overload. Therefore, an intervention to remove local excess iron might be a strategy to prevent MM after asbestos exposure.
This tutorial review introduces the current state of metallopharmaceutics development by focusing on the topics of anti-diabetic vanadium and zinc complexes. Over thousands of years, people have produced many types of inorganic compounds, and the modern concept of chemotherapy was achieved by Ehrlich, who used an arsenic-containing compound to treat syphilis. Since then, many metallopharmaceutics have been developed worldwide. This review will be helpful to researchers who are interested in the current states of not only metallopharmaceutics but also anti-diabetic metal complexes.
A 2700 h life test of a single proton exchange membrane fuel cell ͑PEMFC͒ with Nafion 112 membrane under nonsaturated humidification was conducted. In situ measurements of hydrogen crossover rate through the membrane and electrochemical active surface area ͑EAS͒ of Pt catalyst, in combination with cell polarization curves, were applied to investigate the degradation mechanism. A slow decrease of the EAS of Pt catalyst from 400 to 1900 h running was found to cause a slight voltage decay only at high current densities. However, a subsequent dramatic degradation of the membrane results in an accelerated collapse of the fuel cell.Presently, several issues ͑e.g., lifetime, cost, and reliability͒ have been delaying the commercialization of proton exchange membrane fuel cell ͑PEMFC͒ systems. 1,2 Above all, lifetime of the PEMFC is the most critical issue and may affect the other two issues. Therefore, there is a growing interest in the investigation of performance degradation of PEMFCs to develop durable PEMFCs and then put them into practical applications in the near future. 3-7 It was reported that the degradation of the membrane electrode assembly ͑MEA͒ occurred under low-humidification, 7,8 or nonhumidification conditions 9 of reactant gases, whereas no significant degradation has been observed under over-humidified condition of reactant gases. 2,10-13 However, the degradation mechanism of membrane electrode assembly ͑MEA͒ under low-humidification conditions is still ambiguous to date.In this work, life test was conducted on a single PEMFC up to 2700 h at 300 mA/cm 2 and nonsaturated humidification of H 2 and air. Note that this case of nonsaturated humidification of reactant gases is typically applied in a practical fuel cell system. The first reason is that the fuel cell easily suffers water flooding if it works under a saturated humidification. Next, the heat used for gas humidification is generally derived from fuel cell stack itself. Thus, it is difficult to make the reactant gases into a saturation or oversaturation state. In addition, the active area of the cell is 45 cm 2 (3 ϫ 15 cm) and this rectangular profile was also widely applied in a practical fuel cell system with objective of achieving efficient heat irradiation to avoid a local hot-point phenomenon in MEA. Therefore, a possible simulated environment of a practical fuel cell stack was studied in this work. To investigate the potential degradation mechanism, in situ measurements of hydrogen crossover rate through the Nafion 112 membrane and the electrochemical active surface area ͑EAS͒ of the Pt catalyst with lifetime, in combination with cell polarization curves, were carried out.
ExperimentalA 20 wt % PTFE wet-proofed carbon paper ͑Toray, TGP-H-060, 200 m in thickness͒ was employed as a backing layer. Carbon black ͑Ketjenblack EC-600JD͒ containing 40 wt % PTFE was deposited on the backing layer. The carbon-supported platinum ͑Pt 40 wt %, E-TEK͒ and PTFE ͑20 wt %͒ were ultrasonically suspended in ethanol and then applied as catalyst layer. Pt loadin...
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