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Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides , amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, β, and γ-amanitin at concentrations ranging from 0.3 to 100 μM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure. [Display omitted] • The cytotoxicity of amanitins differs greatly in various human cell lines. • The variable cytotoxicity is mainly due to different expression levels of OATP1B3. • Knockdown of OATP1B3 in HepG2 cells prevented α-amanitin induced cytotoxicity. • OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure. [ABSTRACT FROM AUTHOR]

Genotoxic substances widely exist in the environment and the food supply, posing serious health risks due to their potential to induce DNA damage and cancer. Traditional genotoxicity assays, while valuable, are limited by insufficient sensitivity, specificity, and efficiency, particularly when applied to complex food matrices. This study introduces a multiparametric high-content analysis (HCA) for the detection of genotoxic substances in complex food matrices. The developed assay measures three genotoxic biomarkers, including γ-H2AX, p-H3, and RAD51, which enhances the sensitivity and accuracy of genotoxicity screening. Moreover, the assay effectively distinguishes genotoxic compounds with different modes of action, which not only offers a more comprehensive assessment of DNA damage and the cellular response to genotoxic stress but also provides new insights into the exploration of genotoxicity mechanisms. Notably, the five tested food matrices, including coffee, tea, pak choi, spinach, and tomato, were found not to interfere with the detection of these biomarkers under proper dilution ratios, validating the robustness and reliability of the assay for the screening of genotoxic compounds in the food industry. The integration of multiple biomarkers with HCA provides an efficient method for detecting and assessing genotoxic substances in the food supply, with potential applications in toxicology research and food safety. [ABSTRACT FROM AUTHOR]

Ricin and abrin are highly potent plant-derived toxins, categorized as type II ribosome-inactivating proteins. High toxicity, accessibility, and the lack of effective countermeasures make them potential agents in bioterrorism and biowarfare, posing significant threats to public safety. Despite the existence of many effective analytical strategies for detecting these two lethal toxins, current methods are often hindered by limitations such as insufficient sensitivity, complex sample preparation, and most importantly, the inability to distinguish between biologically active and inactive toxin. In this study, a cytotoxicity assay was developed to detect active ricin and abrin based on their potent cell-killing capability. Among nine human cell lines derived from various organs, HeLa cells exhibited exceptional sensitivity, with limits of detection reaching 0.3 ng/mL and 0.03 ng/mL for ricin and abrin, respectively. Subsequently, toxin-specific neutralizing monoclonal antibodies MIL50 and 10D8 were used to facilitate the precise identification and differentiation of ricin and abrin. The method provides straightforward and sensitive detection in complex matrices including milk, plasma, coffee, orange juice, and tea via a simple serial-dilution procedure without any complex purification and enrichment steps. Furthermore, this assay was successfully applied in the unambiguous identification of active ricin and abrin in samples from OPCW biotoxin exercises. [ABSTRACT FROM AUTHOR]

Two kinds of ODS ferritic steels with nominal compositions (wt.%): Fe–14Cr–4.5Al–1W–0.35Y 2 O 3 and Fe–14Cr–0.5Ti–1W–0.35Y 2 O 3 have been fabricated by mechanical alloying of a pre-alloyed gas atomized powder with nano yttria powders and then consolidated by hot isostatic pressing. The effects of minor alloying elements Al and Ti on the microstructure and mechanical properties of the fabricated ODS steels have been investigated. Microstructural characterization revealed that Y–Ti–O and Y–Al–O dispersed particles were formed in the 14Cr–Ti–ODS steel and 14Cr–Al–ODS steel respectively, and the particle size of Y–Ti–O is much smaller than that of Y–Al–O. The tensile property test demonstrated that the 14Cr–Ti–ODS steel shows high strength but poor plasticity, while the 14Cr–Al–ODS steel has low strength but rather good plasticity. 14Cr–Al–ODS steel has much higher impact energy than that of 14Cr–Ti–ODS steel at the same testing temperatures. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a highly toxic blister agent which has been used many times in several wars and conflicts and caused heavy casualties. Ease of production and lack of effective therapies make SM a potential threat to public health. SM intoxication causes severe damage on various target organs, such as the skin, eyes, and lungs. In addition, SM exposure can also lead to hepatotoxicity and severe liver injuries. However, despite decades of research, the molecular mechanism underlying SM-induced liver damage remains obscure. SM can be converted into various products via complex hepatic metabolism in vivo. There are some pieces of evidence that one of the oxidation products of SM, divinyl sulfone (DVS), exhibits even more significant toxicity than SM. Nevertheless, the molecular toxicology of DVS is still hardly known. In the present study, we confirmed that DVS is even more toxic than SM in the human hepatocellular carcinoma cell line HepG2. Further mechanistic study revealed that DVS exposure (200 μM) promotes pyroptosis in HepG2 cells, while SM (400 μM) mainly induces apoptosis. DVS induces gasdermin D (GSDMD) mediated pyroptosis, which is independent of caspases activation but depends on the large amounts of reactive oxygen species (ROS) and severe oxidative stress produced during DVS exposure. Our findings may provide novel insights for understanding the mechanism of SM poisoning and may be helpful to discover promising therapeutic strategies for SM intoxication. [ABSTRACT FROM AUTHOR]

Thermal insulation materials have attracted increasing attention in recent years for energy conservation in thermal power plant. A novel ceramic composite insulation material (hereafter refer to CCIM) composed of alumina fibers and hollow silica powders with excellent pliability and thermal insulation properties has been designed and fabricated. The effects of alumina fiber and hollow silica microspheres on the performance of composite were characterized through microstructure observation using scanning electron microscopy (SEM) and thermal conductivity evaluation. In the novel CCIM, ceramic fibers and particles of different sizes were uniformly mixed to form multi-scale sizes of pores which can decrease the heat conduction and convective heat transfer at high temperature significantly. The comparison between the traditional mineral wool and the fabricated CCIMs focused on microstructure and thermal insulation property was also performed in this work. The novel CCIM shows much lower thermal conductivity than the standard value of thermal conductivity of traditional inorganic insulation materials when the mean temperature is between 126 °C and 538 °C. The novel CCIMs were applied in a supercritical Power Plant. The surface temperature and surface heat flux measured during service in the supercritical Power Plant further demonstrated that the novel ceramic composite has better insulation properties than traditional inorganic insulation materials. [ABSTRACT FROM AUTHOR]

In this study, a 9Cr oxide-dispersion strengthened (ODS) alloy with additional corrosion resistant element Al was fabricated by mechanical alloying (MA) and hot pressing (HP) to explore the impact of Al on the microstructure and mechanical property of a 9Cr ODS alloy. It is found that the Al completely dissolved into the Fe–Cr matrix after milling for 30 h. The minor phases in the Al-containing 9Cr ODS ferritic alloy were investigated by a high-energy X-ray, and were identified to be orthorhombic- YAlO 3 (YAP), bcc- Y 3 Al 5 O 12 (YAG), monoclinic- Al 2 Y 4 O 9 (YAM), and hexagonal- YAlO 3 (YAH). These phases were further confirmed by selected area diffraction pattern (SADP), energy dispersive spectroscopy (EDS), and high resolution transmission electron microscopy (HRTEM). In addition, their volume fractions were also calculated from the integrated intensities. According to the analysis of the particles and their formation sequences, the larger particles (greater than 100 nm) are identified as mainly YAG and Al 2 O 3 particles, while the particles with small size (less than 30 nm) are likely primarily YAM, YAH, and YAP particles. The yielding strength (YS) and ultimate tensile strength (UTS) at RT are 563 MPa and 744 MPa, respectively, while the YS and UTS at 700 °C are 245 MPa and 276 MPa, respectively. Although the addition Al in ODS alloys decreases the strength at RT, the values at high temperature are similar to those obtained for 9Cr ODS alloys strengthened by fine Y–Ti–O particles. [ABSTRACT FROM AUTHOR]