Trichlorfon (TCF) is an important organophosphate pesticide in agriculture. However, limited information is known about the biodegradation behaviors and kinetics of this pesticide. In this study, a newly isolated fungus (PA F-2) from pesticide-polluted soils was identified as Aspergillus sydowii on the basis of the sequencing of internal transcribed spacer rDNA. This fungus degraded TCF as sole carbon, sole phosphorus, and sole carbon-phosphorus sources in a mineral salt medium (MSM). Optimal TCF degradation conditions were determined through response surface methodology, and results also revealed that 75.31% of 100 mg/L TCF was metabolized within 7 days. The degradation of TCF was accelerated, and the mycelial dry weight of PA F-2 was remarkably increased in MSM supplemented with exogenous sucrose and yeast extract. Five TCF metabolic products were identified through gas chromatography-mass spectrometry. TCF could be initially hydrolyzed to dichlorvos and then be degraded through the cleavage of the P-C bond to produce dimethyl hydrogen phosphate and chloral hydrate. These two compounds were subsequently deoxidized to produce dimethyl phosphite and trichloroethanal. These results demonstrate the biodegradation pathways of TCF and promote the potential use of PA F-2 to bioremediate TCF-contaminated environments.
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, whose immunological mechanisms are still partially uncovered. Regulatory B cells (Bregs) and CD4+ regulatory T cells (Tregs) are subgroups of immunoregulatory cells involved in modulating autoimmunity, inflammation, and transplantation reactions. Herein, by studying the number and function of Breg and Treg cell subsets in patients with AML, we explored their potential role in the pathogenesis of AML. Newly diagnosed AML patients, AML patients in complete remission, and healthy controls were enrolled. Flow cytometry was used to detect percentages of Bregs and Tregs. ELISA was conducted to detect IL-10 and TGF-β in plasma. The mRNA levels of IL-10 and Foxp3 were measured with RT-qPCR. The relationship of Bregs and Tregs with the clinicopathological parameters was analyzed. There was a significant reduction in the frequencies of Bregs and an increase of Tregs in newly diagnosed AML patients compared with healthy controls. Meanwhile, patients in complete remission exhibited levels of Bregs and Tregs comparable to healthy controls. Furthermore, compared with healthy controls and AML patients in complete remission, newly diagnosed AML patients had increased plasma IL-10 but reduced TGF-β. IL-10 and Foxp3 mRNA levels were upregulated in the newly diagnosed AML patients. However, there were no significant differences in IL-10 and Foxp3 mRNA levels between patients in complete remission and healthy controls. Bregs and Tregs have abnormal distribution in AML patients, suggesting that they might play an important role in regulating immune responses in AML.
The mutation landscapes and clinical significance of clonal hematopoiesis (CH) in idiopathic cytopenia of undetermined significance (ICUS) is still unclear. Based on the next-generation sequencingdata of 281 ICUS patients, we sought to depict the profile of CH in ICUS and evaluate its role in disease progression. It was found that CH occurred in 27% of the patients, and was more prevalent in male patients. The incidence of CH accumulated with age. AXSL1, DNMT3A, U2AF1 and TET2 were the most frequently mutated genes. Exclusive mutations existed in DNMT3A and U2AF1, and co-occurring mutations were found between SRSF2 and TET2, SRSF2 and WT1. Fifteen of the 281 ICUS patients transformed to hematological malignancies, and CH group had a higher incidence of leukemic transformation than non-CH group. Variant allele frequencies (VAFs) of the mutated genes, such asASXL1, U2AF1 and TP53, showed an obvious elevation after disease transformation. Moreover, CH patients had a shorter overall survival and progression-free survival. These data indicated that CH was a common phenomenon in ICUS patients, and it contributed greatly to the increased risk of disease progression, suggesting the significance of gene mutation monitoring in ICUS management.
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