Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis.

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Development of selective mercury recovery technology by using iron iodide from waste sludge of non-ferrous metal smelting process.

The waste sludge from non-ferrous metal smelter contains high concentrations of mercury (Hg), arsenic (As) and sulfur (S). The Article 11 of the Minamata Convention on Mercury mandates the recovery of Hg before the disposal stage of Hg waste. However, As compounds have similar boiling points with Hg compounds, and they are considered interfering substances in the recovery of Hg. Moreover, a high concentration of S requires significant energy to volatilize Hg. This study examined the optimal conditions for selective recovery of Hg and energy reduction by introducing FeI2 as an additive during thermal treatment. Thermogravimetric analysis was utilized to evaluate the conversion of HgS to HgI2 under the influence of FeI2. The optimal conditions for thermal treatment such as temperature, treatment time, and molar ratio of [Hg]:[As]:[FeI2] were explored. The simulated waste indicated that the maximum separation efficiency of Hg was ∼95%, thereby allowing a selective separation of 81.5% of Hg from waste sludge with an Hg content of 0.33%, As content of 23.8%, and S content of 30.7%. Sequential extraction procedure was applied to evaluate the stability of Hg and As for residues. As a result, most Hg was vaporized and As was stabilized in sulfide, crystalline, and amorphous forms.

Human health risks assessment for airborne PM10-bound metals in Seoul, Korea.

Seoul, the capital city of South Korea, is the social, political, and economic center of the country. Significant levels of PM10-bound As metalloid and metals have been found in the city, which poses possible adverse health risks to the residents from inhalation exposure. Therefore, this study focuses on the health risk assessment of age-dependent cancer and non-cancer using exposure pathway and human respiratory tract (HRT) mass deposition models. In the case of non-cancer risks, the hazard quotient (HQ) of As via ingestion exposure and the hazard index (HI) was found to be significant (> 1) for the children. The cancer risks through ingestion pathway (CRing) were estimated in the order of 10-4 and 10-5 for children and adult groups, respectively. The overall CRing levels for children were estimated slightly higher than the acceptable level of cancer risk (1 × 10-4) at all locations throughout the study area. Moreover, the risks of cancer through the inhalation (CRinh) and incremental lifetime cancer risks (ILCR) due to HRT mass deposition were found to be significant (> 10-6) and with very small discrepancy in risk levels for both age groups. Furthermore, possible sources of the PM10-bound metalloid (As) and metals were predicted through correlation, principal component, and enrichment factor analysis. The results of source apportionment study indicated the local anthropogenic emission sources (vehicular, biomass/coal/oil combustion, industrial), road dust re-suspension, and trans-boundary sources were responsible for the pollution levels in Seoul, South Korea. The health risks can be minimized by reducing the pollution levels of particulate matter at source.

Cadmium adsorption characteristics of biochars derived using various pine tree residues and pyrolysis temperatures.

This study investigated the characteristics of biochars derived using various pine tree residues and pyrolysis temperatures and evaluated their Cd adsorption behaviors. The characteristics of pine tree residue biochars (PRBs) were dominantly affected by the pyrolysis temperature, and the optimum pyrolysis temperature for Cd adsorption was 600 °C. The adsorption of Cd by PRBs was divided into two stages: rapid adsorption on the initial boundary layer and slow adsorption by intraparticle diffusion. The Cd adsorption characteristics of all the PRBs were well described by pseudo-second-order and Langmuir isotherm models, and the maximum adsorption capacity was the highest in pine bark biochar (85.8 mg/g). The amounts of the cations released from the mixed pine tree residue biochars (M-PRBs) during Cd adsorption were increased, while the amount of phosphate released was decreased, indicating that exchangeable cations and phosphate on the biochar affected the Cd adsorption. In particular, the amount of Cd removed by the exchangeable cations corresponds to 23.6% of the total adsorption amount. Spectroscopic analyses using FTIR showed that the Cd adsorption on M-PRB was associated with functional groups such as CC, COH and COOH. Overall, the use of biochars derived from pine tree residue as an adsorbent is considered to be effective for both the treatment of wastewater containing heavy metals and the recycling of forest residues.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea.

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause.

Cabozantinib for the treatment of non-small cell lung cancer with KIF5B-RET fusion. An example of swift repositioning.

A new chimeric fusion transcript of KIF5B (the kinesin family 5B gene) and the RET (Rearranged during Transcription) oncogene, KIF5B-RET, was found in 1-2% of lung adenocarcinomas (LADCs) in 2012. Several related clinical trials for non-small cell lung cancer (NSCLC) with KIF5B-RET rearrangements using existing RET inhibitors, such as cabozantinib, lenvatinib, vandetanib, sunitinib, ponatinib, and AUY922, have been swiftly initiated by the discovery of the KIF5B-RET fusion gene. Anti-RET activity and the status of clinical development of cabozantinib for KIF5B-RET fusion-positive NSCLC are discussed.

Use of a stratified oxidative stress model to study the biological effects of ambient concentrated and diesel exhaust particulate matter.

Although several epidemiological studies have shown a positive relationship between exposure to ambient air particulate matter (PM) and adverse health effects in humans, there is still a fundamental lack of understanding of the most toxic particle components and the biological mechanisms through which they act. Since our studies on the biological effects of diesel exhaust particles (DEP) have highlighted the role of reactive oxygen species (ROS), catalyzed by organic chemical compounds, we set out to establish whether this constitutes an oxidative stress model that can be used to study the biological effects of ambient coarse and fine PM. We demonstrate that organic DEP extracts induce a stratified oxidative stress response, leading to heme oxygenase 1 (HO-1) expression at normal GSH/ GSSG ratios, proceed to Jun kinase activation and interleukin 8 (IL-8) production at intermediary oxidative stress levels, and culminate in cellular apoptosis in parallel with a sharp decline in GSH/GSSG ratios. We demonstrate that ambient concentrated air particulates, collected with a particle concentrator and a liquid impinger, mimic the effects of organic DEP extracts at lower oxidative stress levels. While fine PM consistently induced HO-1 expression in all most of the samples collected over a 9-mo survey period, coarse particulates were effective at inducing that effect during fall and winter. Moreover, HO-1 expression was positively correlated to the higher organic carbon (OC) and polyaromatic hydrocarbons (PAHs) content of fine versus coarse PM, as well as the rise in PAH content that occurs in coarse PM during the winter months. Although coarse and fine PM lead to a decrease in cellular glutathione (GSH)/GSSG ratios, oxidative stress did not increase to cytotoxic levels. Taken together, these data demonstrate that it is possible to use the stratified oxidative stress model developed for DEP to interpret the biological effects of coarse and fine PM. This work has important implications for the selection of relevant biological endpoints for in vivo studies.