Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

Genetic and immunologic characteristics of colorectal cancer patients with KRAS mutations and predictive significance of tumor immune microenvironment in adjuvant chemotherapy

Colorectal cancer(CRC)is one of the most common cancers around the world,and it is one of the leading causes of cancer-related death.1 Although anti-EGFR therapy and immune checkpoint inhibitor(ICl)therapy are becoming more and more important for colorectal therapy,however,clinical outcomes of current treatments for metastatic CRC,especially with ICls,have been shown to be affected by the status of KRAS.Therefore,KRAS mutation status detection has become a very important diagnostic factor for managing metastatic CRC patients.

Preliminary study on blood coagulation and hemostatic effect and acute toxicity of Oxalis corniculata L.ethanol extract

In the present study,we aimed to observe the effects of ethanol extract of Oxalis corniculata L.on bleeding time(BT)and coagulation time(CT)and determine its acute toxicity in mice.Firstly,the ethanol extract of O.corniculata was administered to 40 mice,which were randomly divided into the normal control group,Yunnan Baiyao control group,low-dose group,and high-dose group.The low-dose(0.6 g/kg)and high-dose(1.2 g/kg)groups received ethanol extract of O.corniculata by gavage,and the BT and CT of the mice were measured by the slide method and tail clipping method,respectively.Secondly,the median lethal dose method was used with 50 mice to observe the physiological state,poisoning reaction,and death of the mice after intragastric administration.Finally,on the 14th day of the experiment,a necropsy was performed to observe any abnormality of the organs.In conclusion,in the coagulation and hemostasis tests,there were no statistical differences between the groups(P>0.05),while there was a significant dose-response relationship,and the BT and CT were significantly shorter than those of the negative control group,which were comparable to the Yunnan Baiyao control group.Moreover,in the acute toxicity test,the median lethal dose of ethanol extract of O.corniculata was 6.0291 g/kg,with a 95%confidence interval of 5.3065–6.7829 mg/kg.