The role of BTG2/PI3K/AKT pathway-mediated microglial activation in T-2 toxin-induced neurotoxicity.

T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it's involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.

The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation.

Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 µg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.

The association between intermediate-term sulfur dioxide exposure and outpatient visits for Parkinson's disease: a time-series study in southwestern China.

Parkinson's disease (PD) is the second most common human neurodegenerative disorder, and the pathogenesis of it remains poorly understood. Limited studies have shown that both long- and short-term exposure to air pollutants may be associated with increased risk of PD while lacking evidence on the effects of intermediate-term exposure. In this study, over-dispersed Poisson generalized additive models (GAMs) were applied to explore the association between intermediate-term sulfur dioxide (SO2) exposure and outpatient visits for PD in Chongqing, China, and further stratified analyses were performed by age and gender. A total of 39,984 PD cases from January 1, 2014, to December 31, 2019 (2191 days) were included. The association of intermediate-term SO2 exposure with outpatient visits for PD was statistically significant: per 1 µg/m3 increase of SO2 corresponded to 2.34% (95% CI: 0.88%, 3.80%) elevation in monthly PD outpatient visits at lag 0 (the concurrent month). Stratified analyses showed that the associations between SO2 and PD outpatient visits were stronger in younger (≤ 60 years) and female patients. In conclusion, intermediate-term SO2 exposure can be associated with an increased risk of PD outpatient visits. Our results highlight the importance of recognizing the role of intermediate-term SO2 exposure in the development of PD. In addition to focusing on the effects of long-term or short-term air pollutants, it is necessary to pay more attention to the health effects of intermediate-term exposure time windows of air pollutants, which will facilitate policy formulation and public health interventions for health risks.

Analysis of Factors Influencing Air Quality in Different Periods during COVID-19: A Case Study of Tangshan, China.

This study aimed to analyze the main factors influencing air quality in Tangshan during COVID-19, covering three different periods: the COVID-19 period, the Level I response period, and the Spring Festival period. Comparative analysis and the difference-in-differences (DID) method were used to explore differences in air quality between different stages of the epidemic and different years. During the COVID-19 period, the air quality index (AQI) and the concentrations of six conventional air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3-8h) decreased significantly compared to 2017-2019. For the Level I response period, the reduction in AQI caused by COVID-19 control measures were 29.07%, 31.43%, and 20.04% in February, March, and April of 2020, respectively. During the Spring Festival, the concentrations of the six pollutants were significantly higher than those in 2019 and 2021, which may be related to heavy pollution events caused by unfavorable meteorological conditions and regional transport. As for the further improvement in air quality, it is necessary to take strict measures to prevent and control air pollution while paying attention to meteorological factors.

The role of MAPK/NF-κB-associated microglial activation in T-2 toxin-induced mouse learning and memory impairment.

T-2 toxin is a mycotoxin with multiple toxic effects and has emerged as an important food pollutant. Microglia play a significant role in the toxicity of various neurotoxins. However, whether they participate in the neurotoxicity of T-2 toxin has not been reported. To clarify this point, an in vivo mouse model of T-2 toxin (4 mg/kg) poisoning was established. The results of Morris water maze and open-field showed that T-2 toxin induced learning and memory impairment and locomotor inhibition. Meanwhile, T-2 toxin induced microglial activation, while inhibiting microglia activation by minocycline (50 mg/kg) suppressed the toxic effect of the T-2 toxin. To further unveil the potential mechanisms involved in T-2 toxin-induced microglial activation, an in vitro model of T-2 toxin (0, 2.5, 5, 10 ng/mL) poisoning was established using BV-2 cells. Transcriptomic sequencing revealed lots of differentially expressed genes related to MAPK/NF-κB pathway. Western blotting results further confirmed that T-2 toxin (5 ng/mL) induced the activation of MAPKs and their downstream NF-κB. Moreover, the addition of inhibitors of NF-κB and MAPKs reversed the microglial activation induced by T-2 toxin. Overall, microglial activation may contribute a considerable role in T-2 toxin-induced behavioral abnormalities, which could be MAPK/NF-κB pathway dependent.

Non-negligible greenhouse gas emissions from non-sewered sanitation systems: A meta-analysis.

Current methods for estimating sanitation emissions underestimate the significance of methane emissions from non-sewered sanitation systems (NSSS), which are prevalent in many countries. NSSS play a vital role in the safe management of fecal sludge, accounting for approximately half of all existing sanitation provisions. We analyzed the distribution of global NSSS and used IPCC accounting methods to estimate the total methane emissions profiles from these systems. Then, we examined the literature to establish the level of uncertainty associated with this accounting estimate. The global methane emissions from NSSS in 2020 was estimated to as 377 (22-1003) Mt CO2e/year or 4.7% (0.3%-12.5%) of global anthropogenic methane emissions, which are comparable to the greenhouse gas (GHG) emissions from wastewater treatment plants. NSSS is the major option for open defecation and is expected to increase by 55 Mt CO2e/year after complete open defecation free. It is time to acknowledge the GHG emissions from the NSSS as a non-negligible source.

Investigation of Perfluoroalkyl Substances (PFASs) in Sediments from the Urban Lakes of Anqing City, Anhui Province, China.

Fifteen individual perfluoroalkyl substances (PFASs) were analyzed in 22 sediment samples collected from Anqing urban lakes (Anhui province, China) by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Total PFAS concentration was between 0.61 and 26 ng g- 1 dry weight. Perfluorooctane sulfonate (PFOS) was the dominant PFAS contaminant, with a concentration range of < 0.040-13 ng g- 1. Results indicated higher total PFAS concentrations in lakes located to the northwest of Anqing City than in other regions. Adjacent chemical and industrial factories were hypothesized to be responsible for these higher PFAS levels in those lakes. In comparison to other measurements obtained from other lakes, PFAS concentrations in the urban lakes of Anqing City were relatively high.