Increasing Exposure Dose Research Articles

Heavy metal accumulation and interaction dynamics in Brachidontes pharaonis: a bioindicator study in the Red Sea.

This work evaluates utilizing the native mussel Brachidontes pharaonis as a bioindicator and sentinel organism for monitoring heavy metals Cu, Zn, and Cd along the Red Sea coast of Egypt. Samples were collected from four coastal locations, and the concentrations of heavy metals in the mussels' tissues, shells, seawater, and sediments were analyzed. Subsequently, bioassay experiments were conducted by exposing the organisms to single, binary, and tertiary metal mixtures, and the accumulation of heavy metals was determined to elucidate the dynamics of metal-metal interactions. Field samples revealed significant variations in heavy metal concentrations in the mussels' soft tissues across different locations, with Zn ranging from 58.1 to 121.0µg/g dw (dry weight), Cu ranging between 18.3 and 36.7µg/g dw, and Cd ranging from 0.3 to 1.04µg/g dw. Conversely, the shells exhibited minimal spatial variations, with much lower contents of Cu (ranging from 1.9 to 2.8µg/g dw) and Zn (ranging from 1.8 to 1.9µg/g dw). However, the shells accumulated Cd at higher levels (ranging from 1.4 to 2.1µg/g dw) compared to the soft tissues. Following a 96-h bioassay experiment, the soft tissues displayed a linear accumulation of metals with increasing exposure dose, with Cd showing the highest accumulation rate (approximately threefold) followed by Zn (twofold) and Cu (1.7-fold). In binary and tertiary exposures, the metals exhibited a general antagonistic interaction, affecting each other's accumulation. On the other hand, the accumulation of heavy metals in the shells after the 96-h bioassay exposure did not follow a consistent linear pattern, suggesting that accumulation during this short experimental period occurs primarily through adsorption rather than the biological pathway.

Impact of vaccination on the entire population and dose-response relation of COVID-19

ObjectiveThe objective of this study is to develop a mathematical model for the COVID-19 pandemic including vaccination, the transmissibility of the virus-pathogen dose-response relationship, vaccine efficiency, and vaccination rate. MethodsThe Runge-Kutta (RK-45) method was applied to solve the proposed model with MATLAB code and the calculated results show the dynamics of the individuals in each compartment. The data of total death due to the COVID-19 pandemic in the case of the USA were collected from GitHub and the re-use of this data needs no ethical clearance. The control reproduction number was used to assess the dose-response relationship and critical vaccination coverage. ResultsWe have calculated the probability of infection and the infection risk against the different exposure doses and the virus copies, respectively. The results show that the probability of infection increases with the increasing exposure dose for certain virus copies and the risk of infection decreases with the increasing of virus copies for a certain exposure dose. The results also show that the critical vaccination coverage demands increase with an increase in transmission rate and decrease with increasing vaccine efficacy. ConclusionsIt was seen that the critical vaccination coverage corresponding to an increased transmission rate rise sharply in the beginning and then reached a threshold. Moreover, the real data of the total death cases in the USA were compared with the fitted curved of the model which validated the proposed model. Vaccination against COVID-19 is essential to control the pandemic, and achieving high vaccine uptake in the population can reduce the pandemic as fast as possible.

Impact of vaccination on the entire population and dose-response relation of COVID-19

ObjectiveThe objective of this study is to develop a mathematical model for the COVID-19 pandemic including vaccination, the transmissibility of the virus-pathogen dose-response relationship, vaccine efficiency, and vaccination rate. MethodsThe Runge-Kutta (RK-45) method was applied to solve the proposed model with MATLAB code and the calculated results show the dynamics of the individuals in each compartment. The data of total death due to the COVID-19 pandemic in the case of the USA were collected from GitHub and the re-use of this data needs no ethical clearance. The control reproduction number was used to assess the dose-response relationship and critical vaccination coverage. ResultsWe have calculated the probability of infection and the infection risk against the different exposure doses and the virus copies, respectively. The results show that the probability of infection increases with the increasing exposure dose for certain virus copies and the risk of infection decreases with the increasing of virus copies for a certain exposure dose. The results also show that the critical vaccination coverage demands increase with an increase in transmission rate and decrease with increasing vaccine efficacy. ConclusionsIt was seen that the critical vaccination coverage corresponding to an increased transmission rate rise sharply in the beginning and then reached a threshold. Moreover, the real data of the total death cases in the USA were compared with the fitted curved of the model which validated the proposed model. Vaccination against COVID-19 is essential to control the pandemic, and achieving high vaccine uptake in the population can reduce the pandemic as fast as possible.

Reproductive toxicity of polystyrene nanoplastics in Drosophila melanogaster under multi-generational exposure

Micro-nanoplastics have become a new type of pollutant worldwide and have attracted widespread attention for their potential toxicity. However, the toxicity of polystyrene nanoplastics (PS-NPs) under continuous exposure of multi-generations is still unclear. In the present study, Drosophila melanogaster was selected as an in vivo biological model to investigate the reproductive toxicity and underlying mechanism induced by PS-NPs (100 nm; 1, 10, 50, and 100 mg L−1) after continuous exposure of five generations. The results showed that PS-NPs accumulated in the crop, gut and ovaries after 5 d of exposure. It was also observed that the number of egg production and eclosion rate decreased significantly (P < 0.05) accompanied by delayed development during continuous exposure PS-NPs of multi-generations. Further analysis revealed that the degree of apoptosis and necrosis of oocytes in the F5 generation increased with the increasing exposure dose. To elucidate the underlying toxicity mechanism mediated by PS-NPs, transcriptomic analysis was performed on the ovaries of the F5 generation. The results showed that there were 102 and 208 differentially expressed genes (DEGs) in the 1 mg L−1 and 100 mg L−1 PS-NPs treatment groups, respectively, compared with the control group. The transcriptome analysis further detected the KEGG pathway with significant enrichment of DEGs, revealing obvious reproductive toxicity at the molecular level. In conclusion, this research not only highlighted the negative physiological effects of multi-generational exposure to PS-NPs on Drosophila melanogaster, but also explored potential mechanisms by transcriptomic analysis to better understand reproductive toxicity induced by multi-generational exposure.

Framework for dual-energy-like chest radiography image synthesis from single-energy computed tomography based on cycle-consistent generative adversarial network.

Dual-energy (DE) chest radiography (CXR) enables the selective imaging of two relevant materials, namely, soft tissue and bone structures, to better characterize various chest pathologies (i.e., lung nodule, bony lesions, etc.) and potentially improve CXR-based diagnosis. Recently, deep-learning-based image synthesis techniques have attracted considerable attention as alternatives to existing DE methods (i.e., dual-exposure-based and sandwich-detector-based methods) because software-based bone-only and bone-suppression images in CXR could be useful. The objective of this study was to develop a new framework for DE-like CXR image synthesis from single-energy computed tomography (CT) based on a cycle-consistent generative adversarial network. The core techniques of the proposed framework are divided into three categories: (1) data configuration from the generation of pseudo CXR from single energy CT, (2) learning of the developed network architecture using pseudo CXR and pseudo-DE imaging using a single-energy CT, and (3) inference of the trained network on real single-energy CXR. We performed a visual inspection and comparative evaluation using various metrics and introduced a figure of image quality (FIQ) to consider the effects of our framework on the spatial resolution and noise in terms of a single index through various test cases. Our results indicate that the proposed framework is effective and exhibits potential synthetic imaging ability for two relevant materials: soft tissue and bone structures. Its effectiveness was validated, and its ability to overcome the limitations associated with DE imaging techniques (e.g., increase in exposure dose owing to the requirement of two acquisitions, and emphasis on noise characteristics) via an artificial intelligence technique was presented. The developed framework addresses X-ray dose issues in the field of radiation imaging and enables pseudo-DE imaging with single exposure.

Quantitative fluoride imaging of teeth using CaF emission by laser induced breakdown spectroscopy.

In this work, we propose the use of molecular emission of calcium fluoride (CaF) by laser induced breakdown spectroscopy (LIBS) to obtain quantitative fluoride distribution images of teeth. LIBS has proved to be an efficient technique to detect low amounts of fluoride in solids, and human teeth have the advantage being a matrix rich in calcium. We used new calibration material from sintered hydroxyapatite pellets doped with fluoride to determine the optimized LIBS conditions of argon flow at 1 L min-1 and using the green emission bands of CaF in 530 nm, and obtained a calibration curve between 0 and 400 μg g-1, and LOD of 18 μg g-1. This methodology was applied within a rat model of fluoride exposure and showed increasing tooth-fluoride with increased exposure dose. To demonstrate applicability of this method in human teeth, we quantified fluoride distribution in teeth from three children from non-fluorinated and fluorinated water regions. Samples from children living in fluoridated water regions showed higher fluoride concentrations in dentine formed after birth, compared to a child from a non-fluoridated region. Teeth have been used as biomarkers for environmental exposure and this new method opens the opportunity in epidemiology research to study critical windows of early life exposure to fluoride as well.

Estimation of Shooting Part Using a Camera with Depth Sensors and Pose Estimation Method and Automatic Setting of Optimal X-ray Imaging Conditions

In this study, we propose a system that combines a depth camera with a deep learning model for estimating the human skeleton and a depth camera to estimate the shooting part to be radiographed and to acquire the thickness of the subject, thereby providing optimized X-ray imaging conditions. We propose a system that provides optimized X-ray imaging conditions by estimating the shooting part and measuring the thickness of the subject using an RGB camera and a depth camera. The system uses OpenPose, a posture estimation library, to estimate the shooting part. The recognition rate of the shooting part was 15.38% for the depth camera and 84.62% for the RGB camera at a distance of 100 cm, and 42.31% for the depth camera and 100% for the RGB camera at a distance of 120 cm. The measurement accuracy of the subject thickness was within ±10 mm except for a few cases, indicating that the X-ray imaging conditions were optimized for the subject thickness. The implementation of this system in an X-ray system is expected to enable automatic setting of X-ray imaging conditions. The system is also useful in preventing increased exposure dose due to excessive dose or decreased image quality due to insufficient dose caused by incorrect setting of X-ray imaging conditions.

Nanometrology for evaluating rare sites for molecular homogeneity

Here, we present a methodology for identifying and characterizing nanoscale sites in extreme ultraviolet (EUV) photoresists that deviate from the mean composition by 3σ. The methodology is based on nano-projectile secondary ion mass spectrometry (SIMS) operating in the event-by-event bombardment detection mode. Nanoscale analysis is achieved by probing the surface stochastically with a suite of individual nanoprojectile impacts in which each nano-projectile samples a volume that is 10 to 15 nm in diameter and up to 10 nm in depth. For each impact, the coemitted secondary ions are collected and mass-analyzed, allowing for the analysis of colocalized moieties. We applied this technique to study the fundamental processes occurring in partially developed positive-tone EUV resists, which simulate a critical problem in EUV resists, incomplete resist removal, and production of line edge features. Such features erode device yield and have been the focus of many previous studies. Using NP-SIMS, we examined the changing molecular composition in the partially developed resist and isolated measurements with a probability below 0.3%. Grouping measurements based on the number and type of detected molecular species allowed for the identification of rare sites on the surface that deviate from the mean composition. The mass spectrometry measurements showed that both the photoacid generator (PAG) cation and anion displayed decreased homogeneity on average with increasing exposure dose. The effect was more pronounced in the sites with probabilities below 0.3%, where the measured intensity of the PAG-related ions in these sites was more than twofold larger than the mean. Thus, we attribute these nanoscale sites to aggregations of PAG within the top 10 nm of the remaining film. These results suggest that identifying and characterizing the molecular composition of rare sites may be important in defect production and film stochastics.

Effect of epithelial-mesenchymal transition on cardiac fibrosis induced by oil mist particulate matter

Objective: To investigate the effects of oil-mist particulate matter (OMPM) on cardiac tissue structure fibrosis in rats and the role of epithelial-mesenchymal transition (EMT). Methods: Six-week-old Wistar rats (half male and half female) were randomly divided into 3 groups: control group (without OMPM exposure), low-dose exposure group (50 mg/m3) and high-dose exposure group (100 mg/m3), 18 rats in each group, with 6.5 hours per day of dynamic inhalation exposure. After 42 days of continuous exposure, cardiac tissues were collected for morphological observation; Western blot was used to detect fibrosis markers collagen I and collagen III levels, epithelial marker E-cadherin levels, interstitial markers N-cadherin, fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) levels, and EMT transcription factor Twist protein levels; Real-time polymerase chain reaction (RT-qPCR) was used to detect collagen I and collagen III mRNA levels. Results: After OMPM exposure, myocardial cell edema and collagen fiber deposition were increased gradually with increasing exposure dose. Western blot results showed that compared with the control group, the expression levels of collagen I, collagen III, N-Cadherin, fibronectin, vimentin, α-SMA, and Twist protein were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and protein expression levels were higher in the high-dose exposure group than those in the low-dose exposure group (P＜0.01). In contrast, E-Cadherin protein expression levels were decreased significantly, and lower in the high-dose exposure group (P＜0.01). RT-qPCR results showed that compared with the control group, collagen I and collagen III mRNA levels were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and were increased with increasing exposure dose. (P＜0.01). Conclusion: OMPM may induce cardiac fibrosis in rats by promoting EMT process.

Proton pump inhibitor-induced risk of chronic kidney disease is associated with increase of indoxyl sulfate synthesis via inhibition of CYP2E1 protein degradation

Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders in the gastrointestinal tract; however, PPI use increases the risk of chronic kidney disease (CKD) through unclear mechanisms. Considering that PPIs disturb the gut microbiome balance, which is involved in the precursor of gut-derived uremic toxin accumulation, and that gut-derived uremic toxins aggravate CKD progression, the aim of this study is to elucidate whether PPIs affect gut-derived uremic toxin metabolism, including indoxyl sulfate (IS), p-cresyl sulfate, and trimethylamine-N-oxide, as a mechanism for causing CKD. The present study showed that 3 week-treatment of PPIs (omeprazole, lansoprazole, and pantoprazole at 30 mg/kg) in mice only increased IS plasma levels among the above three gut-derived uremic toxins. Additionally, lansoprazole increased IS plasma concentrations along with increased exposure dose (7.5–30 mg/kg) and duration (1–3 weeks). However, nephrotoxicity with mild changes in glomerular structure and signs of fibrosis were observed only in groups exposed to a 3-week treatment of PPIs (30 mg/kg). As the concentrations of indole (the precursor of IS from gut metabolism) in the colon were only increased in the pantoprazole-treated group, the mechanism of increased IS exposure remains unclear. Further studies revealed that PPIs (omeprazole and lansoprazole; but not pantoprazole) increased IS production from indole in primary mouse hepatocytes in a concentration-dependent manner. Additionally, the increased protein levels of hepatic CYP2E1 (the key enzyme mediating IS formation) due to suppressed degradation resulted in an increase in IS levels. Although omeprazole and lansoprazole significantly inhibited IS uptake in hOAT1/3 in vitro, 3 weeks of PPI treatment did not reduce IS renal excretion in mice. In conclusion, PPIs induced IS synthesis via increased hepatic CYP2E1 protein level, subsequently leading to increased IS exposure. These findings present a plausible biological mechanism to explain the association of PPI use with the increased risk of CKD.

JAK2/STAT3 Signaling Pathway and Klotho Gene in Cadmium-induced Neurotoxicity In Vitro and In Vivo.

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction.

Chronic exposure to deltamethrin disrupts intestinal health and intestinal microbiota in juvenile crucian carp

The indiscriminate use of deltamethrin in agriculture and aquaculture can lead to residues increased in many regions, which poses negative impacts on intestinal health of aquatic organisms. Although the potential toxicity of deltamethrin have recently attracted attention, the comprehensive studies on intestinal injuries after chronic deltamethrin exposure remain poorly understood. Herein, in a 28-day chronic toxicity test, crucian carp expose to different concentrations of deltamethrin (0, 0.3, and 0.6 μg/L) were used as the research object. We found that the morphology changes and increased goblet cells in intestinal tissue, and the extent of tissue injury increased along with the increasing exposure dose of deltamethrin. Additionally, the genes expression of antioxidant activity (Cu/Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase 1 (GPX1), and catalase (CAT)), inflammatory response (tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin 1 beta (IL-1β)), and tight junctions (Claudin 12 (CLDN12), and tight junction protein 1 (ZO-1)) dramatically increased. Meanwhile, the apoptosis and autophagy process were triggered through caspase-9 cascade and autophagy related 5 (ATG5)- autophagy related 12 (ATG12) conjugate. Besides, chronic deltamethrin exposure increased the amount of Proteobacteria and Verrucomicrobiota, while decreased Fusobacteriota abundance, resulting in intestinal microbiota function disorders. In summary, our results highlight that chronic exposure to deltamethrin cause serious intestinal toxicity and results in physiological changes and intestinal flora disturbances.

Biomarker Responses, Gene Expression Alterations, and Histological Changes in Zebrafish (Danio rerio) After In Vivo Exposure to Polychlorinated Diphenyl Ethers.

Polychlorinated diphenyl ethers (PCDEs) have been detected in various aquatic matrices, which pose potential threats to aquatic ecosystem security. In this work, both micro and macro analysis methods were used to assess the toxicity of PCDEs to zebrafish. Results indicated that after in vivo PCDE exposure, the oxidative stress and related gene of Danio rerio were significantly changed. The higher concentration or longer exposure time could cause more severe oxidative stress in zebrafish tissues. Compared with among the five tested compounds, more obvious changes in the level of oxidative biomarkers of lower chlorinated PCDEs’ (4-mono-CDE and 4,4′-di-CDE) exposure groups were observed. The integrated biomarker response analysis and gene expression results also indicate a similar trend. Histopathological observation suggested that 4,4′-di-CDE could render liver nuclei enlargement and necrosis, hepatocyte vacuolation, and the development inhibition of ovarian cells. Transmission electron microscope photos showed that 4,4′-di-CDE caused organelle damage in the liver and ovary, including the rupture of the endoplasmic reticulum, swelling of mitochondria, and condensation of chromatin in the liver and mitochondria disappeared significantly in the ovary. The degree of damage is enhanced with the increasing exposure doses. In addition, PCDEs also significantly altered vitellogenin content and related gene (vtg1) expression, suggesting that PCDEs may be estrogen endocrine disruptors. Overall, these results provided some valuable toxicological data of PCDEs on aquatic species.

World Trade Center dust induces nasal and neurological tissue injury while propagating reduced olfaction capabilities and increased anxiety behaviors

Objective: Previous in vitro and in vivo World Trade Center particulate matter (WTCPM) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTCPM exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes. Material and Methods: WTCPM was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints. Results: WTCPM exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTCPM dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTCPM exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (p<0.05). Discussion: The potential molecular drivers of WTCPM-driven tissue injury and olfaction latency may be linked to oxidative/nitrative stress and inflammatory cascades in both upper respiratory nasal and brain tissues. Conclusion: Cumulatively, these data provide evidence of WTCPM exposure in relation to tissue damage related to oxidative stress-driven inflammation identified in the nasal cavity, propagated to olfactory bulb tissues and, potentially, over extended periods, to other CNS tissues.

Blue Light Inhibits E. coli, but Decisive Parameters Remain Hidden in the Dark: Systematic Review and Meta-Analysis.

Blue light (400–500 nm) alleviates overexposure risks associated to UV light and has therefore gained increased interest in multiple applications. This meta-analysis deals with decontamination of E. coli through the use of blue light based from nine recent publications identified via a systematic literature search. In these studies, various pathogenic and non-pathogenic E. coli strains grown in nutritional broths were exposed to wavelengths ranging from 395 to 460 nm. Five meta-analyses were performed using Cochrane’s software for meta-analyses (Review Manager): one including all studies to estimate the effect of E. coli reduction and four subgroup-analyses considering reported intensities, wavelengths, exposure dose as well as serovars/pathovars. Random effects models were used. All included studies used colony-forming units to estimate the impact of E. coli reduction. None of the included studies involved an organic matrix (e.g., skin, food related surface). Exposure to blue light had a significant and large reducing effect on viable counts of E. coli. However, substantial heterogeneity across studies was observed. Among subgroups, reported intensity and wavelength showed the clearest impact on E. coli reduction. With respect to the reported exposure dose, the picture across the spectrum was scattered, but effect sizes tend to increase with increasing exposure dose. Substantial heterogeneity was also present with respect to all serovar/pathovar subgroups among the included studies. The present body of reports does not display a strong basis for recommendation of relevant intensities, wavelengths and exposure doses for superficial blue light decontamination in medical or food safety contexts. A serious shortcoming in most studies is the absence of a clear documentation of inoculum preparation and of study parameters. We suggest improvement for study protocols for future investigations.

Prolonged Inhalation Exposure to Coal Dust on Irradiated Rats and Consequences.

The purposes of this study were to research immune system changes and liver and lung tissues in irradiated rats after prolonged exposure to coal dust. A study was carried out on 30 male Wistar rats that were divided into 3 groups: group I, intact animals; group II, exposure to coal dust and 0.2 Gy γ-irradiation; and group III, combined exposure to 6 Gy γ-irradiation and coal dust. The combination of a low and sublethal dose of γ-irradiation with coal dust leads to a significant change in immunity at the remote period. Particularly, the increase in radioactivity at the combined effect causes weakening of phagocytosis, and reduction in T lymphocytes by a factor of 2, immunoglobulin imbalance, and cytokine dysfunction develop secondary immune failure. During prolonged inhalation with coal dust of irradiated animals with the dose of 0.2 Gy, fibrosis and perivascular sclerosis of the bronchial wall of the lungs are formed, and perivascular fibrosis is formed in the liver. The increase in exposure dose up to 6 Gy in combination with coal, in the distant period, caused pulmonary hypertension amid hypertrophy of light arterial vessels and fibrous changes in arteriole, and destructive changes and collection necrosis develop in liver parenchyma. In the case of dust radiation synergy, the increase in doses leads to a significant immune deficiency, which occurs according to the “dose effect” principle; increases damage to animal tissues; and leads to liver tissue necrosis, pulmonary fibrosis, and pulmonary hypertension.

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide induces ferroptosis in neuroblastoma cells through redox imbalance.

As a widespread environmental pollutant, benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced neurotoxicity has received increasing attention. Studies have shown that BPDE-induced neurodegeneration is due partly to neuronal apoptosis. Unlike apoptosis, ferroptosis is a non-apoptotic form of programmed cell death, but its specific role in the neurotoxicity of BPDE remains unclear. In this work, we investigated the ferroptosis in BPDE-induced cell death in human neuroblastoma cell line SH-SY5Y using a specific pharmacological inhibitor. Lipid peroxides, malondialdehyde production, glutathione / glutathione peroxidase activity, superoxide dismutase activity, and iron content were evaluated. Consistent with previous studies, our data showed that 0.5 μM BPDE poisoning for 24 hr could induce cell apoptosis and that cell survival could be improved by using apoptosis inhibitors. But with prolonged exposure time (72 hr) or increased exposure dose (1.0 μM), we have elucidated and validated that BPDE triggered ferroptosis in human SH-SY5Y cells. We also revealed that suppression of ferroptosis by specific inhibitors, ferrostatin-1 and deferoxamine, significantly rescued the phenotypes of ferroptosis induced by BPDE. BPDE downregulated Nrf2 and its target genes related to redox regulation, GPX4 and SLC7A11, but upregulated HO-1. Our results first demonstrated that BPDE caused cytotoxic effects on cell death via apoptosis and ferroptosis. Most notably, long-term environmental exposure to BPDE becomes a concern due to ferroptosis. Redox imbalance is controlled by the Nrf2, SLC7A11, and HO-1, through which lipid peroxides and ferrous ion accumulation cause ferroptosis after BPDE treatment. These findings highlight that targeting ferroptosis could serve as an effective protective strategy for neurotoxicity of BPDE.

Acute exposure to paraquat affects the phenotypic differentiation of substantia nigra microglia in rats.

The toxicity of the bipyridine cationic herbicide paraquat (PQ) to the lung and kidneys has been widely documented, but the acute toxic effects of PQ on the nervous system have received little attention. This study aimed to explore the changes in the phenotypic differentiation of microglia in rats caused by acute PQ exposure. As results, acute PQ exposure induced pyknosis, edema, and apoptosis in substantia nigra neurons. Immunohistochemistry and western blotting showed that, on day 18, with the increase of exposure dose, the number of Iba-1-positive cells presented an increasing trend with no statistically significant difference among the groups (P > 0.05). Compared with the control group, the process length of Iba-1-positive cells decreased of acute 25mg/kg PQ exposure on day 18 (P < 0.05). Compared with the control group, on day 39, the number of Iba-1-positive cells in the SN decreased of acute 25mg/kg PQ exposure, while that increased of acute 45mg/kg PQ exposure (P < 0.05). The number of endpoints decreased of acute 25mg/kg PQ exposure (P < 0.05). The process length became shorter both of acute 25mg/kg and 45mg/kg PQ exposure (P < 0.05). On day 69, compared with the control group, the number of Iba-1-positive cells in the SN significantly increased of acute 45mg/kg PQ exposure (P < 0.05). The number of endpoints increased and the process length became longer of acute 25mg/kg PQ exposure (P < 0.05). Then, the mean fluorescence intensity of inducible nitric oxide synthase (iNOS) and arginine 1 (ARG1) was compared. The number of the M1 phenotype of microglia increased during the early stage of acute 25mg/kg PQ exposure, whereas the number of the M2 phenotype of microglia increased during the early stage of acute 45mg/kg PQ exposure (P < 0.05). On day 39, compared with the control group, the expression of iNOS in the SN of acute 45mg/kg PQ exposure increased than of acute 25mg/kg exposure. The expression of Arg-1 of 25mg/kg PQ exposure was significantly increased (P < 0.05). On day 69, the expression of iNOS and ARG1 increased in the 25 and 45mg/kg PQ exposure groups. In summary, changes in microglia phenotypic differentiation were related to exposure dose and exposure time (P < 0.05).

Effects of low-concentration glyphosate and aminomethyl phosphonic acid on zebrafish embryo development

Glyphosate (GLY) is the most widely used broad-spectrum, non-selective herbicide in the world, whose main degradation product is aminomethyl phosphonic acid (AMPA). Because of long-term and large-scale use, residual GLY and AMPA in the environment pose great environmental and human health threats. The purpose of this study is to evaluate the effects and mechanism of residual low-concentrations of GLY and AMPA in the environment on the development of zebrafish embryos. Zebrafish embryos were exposed to 0, 1, 10, 100, and 700 ng·mL−1 GLY and AMPA for 72 h (from 2 to 74 h post-fertilization). With increasing exposure dose, heart rates of both embryos and larvae showed a rising trend and obvious arrhythmia appeared. Defects in cardiac development and function of zebrafish juveniles may be related to altered transcription levels of cardiac development genes (TBX5, NKX2.5, BMP4) and apoptosis genes (Bcl-2, Bax). In addition, pericardial edema and bone deformation of zebrafish embryos may be caused by inhibition of Na+/K+-ATPase and Ca2+-ATPase after exposure to GLY and AMPA. The present results demonstrated that at typical environmental residual concentrations of GLY and AMPA had similar developmental toxicity in zebrafish embryos.

Utilization of As50Se50 thin films in electron beam lithography

Chalcogenide glass of As50Se50 composition have been intensively studied for its interesting physical and chemical properties. Presented manuscript explores the applicability of As50Se50 thermally evaporated thin films in electron beam lithography exploiting wet etching in amine based solution. As50Se50 films proved to be highly sensitive negative resist. Decrease of the etching selectivity with increasing accelerating voltage and its increase with increasing exposure dose were observed. Height irregularities of prepared structures connected with the electron beam scattering and preferential etching of upper edges were observed and thoroughly studied. Comparison of photoinduced chemical resistance changes showed same trends as in case of electron beam induced changes – chemical resistance significantly increased with increasing exposure dosages.