AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression in Toxoplasma gondii.

Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to two primary ApiAP2s (AP2XII-1 and AP2XI-2), demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of AP2XII-1 and AP2XI-2 resulted in a profound alteration in merozoite-specific genes targeted by the MORC-HDAC3 complex. Additionally, considerable overlap was observed in downstream gene profiles between AP2XII-1 and AP2XI-2, with AP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including AP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by AP2XII-1 and AP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.

Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative.

Toxoplasma gondii is a zoonotic parasite that infects one-third of the world's population and nearly all warm-blooded animals. Due to the complexity of T. gondii's life cycle, available treatment options have limited efficacy. Thus, there is an urgent need to develop new compounds or repurpose existing drugs with potent anti-Toxoplasma activity. This study demonstrates that bedaquiline (BDQ), an FDA-approved diarylquinoline antimycobacterial drug for the treatment of tuberculosis, potently inhibits the tachyzoites of T. gondii. At a safe concentration, BDQ displayed a dose-dependent inhibition on T. gondii growth with a half-maximal effective concentration (EC50) of 4.95 µM. Treatment with BDQ significantly suppressed the proliferation of T. gondii tachyzoites in the host cell, while the invasion ability of the parasite was not affected. BDQ incubation shrunk the mitochondrial structure and decreased the mitochondrial membrane potential and ATP level of T. gondii parasites. In addition, BDQ induced elevated ROS and led to autophagy in the parasite. By transcriptomic analysis, we found that oxidative phosphorylation pathway genes were significantly disturbed by BDQ-treated parasites. More importantly, BDQ significantly reduces brain cysts for the chronically infected mice. These results suggest that BDQ has potent anti-T. gondii activity and may impair its mitochondrial function by affecting proton transport. This study provides bedaquiline as a potential alternative drug for the treatment of toxoplasmosis, and our findings may facilitate the development of new effective drugs for the treatment of toxoplasmosis.

The anti-Toxoplasma activity of the plant natural phenolic compound piceatannol.

Toxoplasma gondii is an obligate intracellular protozoan that infects the nucleated cells of warm-blooded animals and causes life-threatening disease in immunocompromised patients. Due to the limited effectiveness and prominent side effects of existing drugs, there is an urgent need to develop new therapeutic options against T. gondii. Piceatannol is a natural plant compound with multiple functions such as antibacterial, antileukemic and antiparasitic activities. In the present study, the anti-T. gondii activity of piceatannol was evaluated. Piceatannol potently inhibited Toxoplasma with a half-maximal effective concentration (EC50) of 28.10 µM. Piceatannol showed a significant inhibitory effect on intracellular proliferation, inhibiting intracellular parasites at a rate of 98.9% when treatment with 100 µM piceatannol. However, the invasion ability of tachyzoites was not affected by piceatannol. By immunofluorescence assay, we noted that the parasite showed abnormalities in cell division after exposure to piceatannol. To determine the in vivo effect of piceatannol on acute infection, a model was established by infecting BALB/c mice with the virulent RH strain of T. gondii. Mice infected with 500 tachyzoites showed a significant therapeutic effect when treated with 15 mg/kg of piceatannol. These results suggest that piceatannol is a promising drug for the treatment of T. gondii.

Antimony Immobilization in Primary-Explosives-Contaminated Soils by Fe-Al-Based Amendments.

Soils at primary explosives sites have been contaminated by high concentrations of antimony (Sb) and co-occurring heavy metals (Cu and Zn), and are largely overlooked and neglected. In this study, we investigated Sb concentrations and species and studied the effect of combined Fe- and Fe-Al-based sorbent application on the mobility of Sb and co-occurring metals. The content of Sb in soil samples varied from 26.7 to 4255.0 mg/kg. In batch experiments, FeSO4 showed ideal Sb sorption (up to 97% sorption with 10% FeSO4·7H2O), whereas the sorptions of 10% Fe0 and 10% goethite were 72% and 41%, respectively. However, Fe-based sorbents enhanced the mobility of co-occurring Cu and Zn to varying levels, especially FeSO4·7H2O. Al(OH)3 was required to prevent Cu and Zn mobilization. In this study, 5% FeSO4·7H2O and 4% Al(OH)3 mixed with soil was the optimal combination to solve this problem, with Sb, Zn, and Cu stabilizations of 94.6%, 74.2%, and 82.2%, respectively. Column tests spiked with 5% FeSO4·7H2O, and 4% Al(OH)3 showed significant Sb (85.85%), Zn (83.9%), and Cu (94.8%) retention. The pH-regulated results indicated that acid conditioning improved Sb retention under alkaline conditions. However, no significant difference was found between the acidification sets and those without pH regulation. The experimental results showed that 5% FeSO4·7H2O + 4% Al(OH)3 without pH regulation was effective for the stabilization of Sb and co-occurring metals in primary explosive soils.

Evaluation of the Combined Effect of Artemisinin and Ferroptosis Inducer RSL3 against Toxoplasma gondii.

Toxoplasma gondii is a widespread intracellular pathogen that infects humans and a variety of animals. Dihydroartemisinin (DHA), an effective anti-malarial drug, has potential anti-T. gondii activity that induces ferroptosis in tumor cells, but the mechanism by which it kills T. gondii is not fully understood. In this study, the mechanism of DHA inhibiting T. gondii growth and its possible drug combinations are described. DHA potently inhibited T. gondii with a half-maximal effective concentration (EC50) of 0.22 µM. DHA significantly increased the ROS level of parasites and decreased the mitochondrial membrane potential, which could be reversed by ferroptosis inhibitors (DFO). Moreover, the ferroptosis inducer RSL3 inhibited T. gondii with an EC50 of 0.75 µM. In addition, RSL3 enhanced the DHA-induced ROS level, and the combination of DHA and RSL3 significantly increased the anti-Toxoplasma effect as compared to DHA alone. In summary, we found that DHA-induced ROS accumulation in tachyzoites may be an important cause of T. gondii growth inhibition. Furthermore, we found that the combination of DHA and RSL3 may be an alternative to toxoplasmosis. These results will provide a new strategy for anti-Toxoplasma drug screening and clinical medication guidance.

[Emission Inventory of Air pollutants for the Harmless Treatment of Municipal Solid Waste].

In order to comprehensively assess the emission status of air pollutes from domestic waste treatment plants in mainland China, the basic statistical information of 31 provinces and cities in China was systematically collected and collated. The emission factor method was adopted to establish the 2016 list of air pollutants for the harmless treatment of domestic garbage in mainland China. The results showed that in 2016, the total amount of CH4, VOCs, NH3, TSP, PM10, and PM2.5 gaseous pollutants discharged from domestic waste landfills was 3472084.50, 185117.10, 66.45, 54.94, 25.99, and 3.92 t, respectively. The total amount of CH4, SO2, NOx, NH3, VOCs, CO, TSP, PM10,PM2.5, and BC of gaseous pollutants discharged from incineration facilities was 25389.10, 6419.30, 70923.84, 221.36, 435.33, 3025.19, 221.36, 221.36, 2.21, and 2.86 t, respectively. Through the analysis of solid waste treatment sources, partial, and temporal distribution characteristics of air pollutants, and the proportion of incineration plants in the provinces and municipalities to the number of household harmless waste treatment plants, it was determined that the total amount of gaseous pollutants discharged from domestic waste incineration sources and landfill sources had an upward trend during the period 2010-2016. In 2016, domestic landfill treatment was the most important waste treatment method in China, and mainly concentrated in areas with moderate population density and large land resources, such as central and western regions. Domestic waste incineration treatment facilities are mainly concentrated in developed cities in the Yangtze River Delta, Pearl River Delta, and the Beijing-Tianjin-Hebei Region.