RESUMEN
The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
RESUMEN
Objective To investigate the effect of urinary training on urination control in infants using nappies after birth.Methods Stratified sampling method was used to investigate the daytime urination control and the using of diapers by children in kindergartens of 6 prefecture-level cities in Henan Province,China.The survey was conducted among parents of healthy children.Results In a total of 12 250 questionnaires,11 697 had response,and 10 562 valid questionnaires were collected,and the effective recovery rate was 86.22％.After the birth of infants,the age of toilet training was divided into 6 groups (0-＜ 3 months old group,3-＜ 6 months old group,6-＜ 12 months old group,12-＜ 18 months old group,18-＜ 24 months old group and no toilet training group).Results showed that toilet training within 12 months leads to higher urinary control rate compared with toilet training after 12 months and no toilet training till the age of 2 years old,70.56％ (4 831/6 847 cases) in contrast with 59.02％ (1 545/2 618 cases) and 42.48％ (466/1 097 cases),and the differences were statistically significant (x2 =114.76,335.48,all P ＜ 0.000 1).Within 12 months,there was no statistical difference in the urinary control rate between subgroups at 2 years of age(all P ＞0.05).After 12 months,the urination control rate decreased with the start time delayed till 2 years of age,and the urinary control rate at the age of 2 years old n different groups was 59.97％ (1 314/2 191 cases) and 54.10％ (231/427 cases) respectively.The results of other ages(0.5,1.0,1.5 years old) were similar to those of 2 years old.There was no difference between the groups of different genders (all P ＞ 0.05).Conclusions The use of diapers in infants before the age of 1 year to start urinary training is conducive to the development of urinary control in infants.