Impact of Beijing’s“Coal to Electricity”program on ambient PM_(2.5) and the associated reactive oxygen species(ROS)

The Beijing“Coal to Electricity”program provides a unique opportunity to explore air quality impacts by replacing residential coal burning with electrical appliances.In this study,the atmospheric ROS(Gas-phase ROS and Particle-phase ROS,abbreviated to G-ROS and P-ROS)were measured by an online instrument in parallel with concurrent PM_(2.5) sample collections analyzed for chemical composition and cellular ROS in a baseline year(Coal Use Year-CUY)and the first year following implementation of the“Coal to Electricity”program(Coal Ban Year-CBY).The results showed PM_(2.5) concentrations had no significant difference between the two sampling periods,but the activities of G-ROS,P-ROS,and cellular ROS in CBY were 8.72 nmol H_(2)O_(2)/m^(3),9.82 nmol H 2 O 2/m 3,and 2045.75μg UD/mg PM higher than in CUY.Six sources were identified by factor-analysis from the chemical components of PM_(2.5).Secondary sources(SECs)were the dominant source of PM_(2.5) in the two periods,with 15.90%higher contribution in CBY than in CUY.Industrial Emission&Coal Combustion sources(Ind.&CCs),mainly from regional transport,also increased significantly in CBY.The contributions of Aged Sea Salt&Residential Burning sources to PM_(2.5) decreased 5.31% from CUY to CBY.The correlation results illustrated that Ind.&CCs had significant positive correlations with atmospheric ROS,and SECs significantly associated with cellular ROS,especially nitrates(r=0.626,p=0.000).Therefore,the implementation of the“Coal to Electricity”program reduced PM_(2.5) contributions from coal and biomass combustion,but had little effect on the improvement of atmospheric and cellular ROS.

Metabolic reprogramming and redox adaptation in sorafenib-resistant leukemia cells:detected by untargeted metabolomics and stable isotope tracing analysis

Background:Internal tandem duplications(ITD)within the juxtamembrane domain of FMS-like tyrosine kinase 3(FLT3)represent a poor prognostic indicator in acute myeloid leukemia(AML).Therapeutic benefits of tyrosine kinase inhibitors,such as sorafenib,are limited due to the emergence of drug resistance.While investigations have been con-ducted to improve the understanding of the molecular mechanisms underlying the resistance to this FLT3 inhibitor,a profile of cell functioning at the metabolite level and crosstalk between metabolic pathways has yet to be created.This study aimed to elucidate the alteration of metabolomic profile of leukemia cells resistant to the FLT3 inhibitor.Methods:We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations,namely the murine BaF3/ITD-R and the human MV4-11-R cell lines.We performed a global untargeted metabolomics and stable isotope-labe-ling mass spectrometry analysis to identify the metabolic alterations relevant to the therapeutic resistance.Results:The resistant cells displayed fundamentally rewired metabolic profiles,characterized by a higher demand for glucose,accompanied by a reduction in glucose flux into the pentose phosphate pathway(PPP);and by an increase in oxidative stress,accompanied by an enhanced glutathione synthesis.We demonstrated that the highest scoring network of altered metabolites in resistant cells was related to nucleotide degradation.A stable isotope tracing experiment was performed and the results indicated a decrease in the quantity of glucose entering the PPP in resistant cells.Further experiment suggested that the inhibition of major enzymes in the PPP consist of glucose-6-phosphate dehydrogenase deficiency(G6PD)in the oxidative arm and transketolase(TKT)in the non-oxidative arm.In addition,we observed that chronic treatment with sorafenib resulted in an increased oxidative stress in FLT3/ITD-positive leu-kemia cells,which was accompanied by decreased cell proliferation and an enhanced antioxidant response.Conclusions:Our data regarding comparative metabolomics characterized a distinct metabolic and redox adaptation that may contribute to sorafenib resistance in FLT3/ITD-mutated leukemia cells.