Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.
Humans ; Noncommunicable Diseases/prevention & control* ; Workforce ; China ; Risk Factors ; Chronic Disease

Objective To learn the immunity levels of pertussis and diphtheria among healthy people in Wenzhou City,and to provide scientific evidence for the effective control of the two diseases.Methods Stratified sampling method was applied in this investigation and 1 350 healthy people were investigated and provided serum samples.Vaccine immunization of pertussis and diphtheria and demographic characteristics were also collected.Enzyme linked immunosorbent assay (ELISA)was conducted to detect pertussis and diphtheria antibodies.Those with more than 1 00 IU/ml aged more than 3 years were also investigated the disease history.The estimated infection rate of pertussis for population aged more than 3 years was based on the test results.The attenuation trend of pertussis and diphtheria immunity levels after vaccination was analyzed contrastively.Results The antibody positive rate to pertussis was 36. 52%,and the median of antibody concentration was 1 9. 45 IU/m1 .The antibody positive rate and concentration was highest among 36 -60 years old people (64. 29%,36. 39 IU/ml ).The vaccination rate of population with more than 3 doses of DPT (Diphtheria Toxoid -Pertussis Vaccine-Tetanus Toxoid)was 95. 80%,and the corresponding positive rate was 24. 36%.The positive rate was 28. 57% in 0-3 month and 1 0. 71% in 1 0 -1 2 month after vaccination.The antibody concentration to pertussis had a negative correlation with days after vaccination(r=-0. 22,P<0. 05).The proportion of subjects with more than 1 00 IU/ml in population aged more than 3 years was 7. 91%.The estimated infection rate of pertussis for population aged more than 3 years was 49. 27%.The antibody positive rate to diphtheria was 96. 00%,and the median of antibody concentration was 0. 1 3 IU/m1 . The positive rate was highest (1 00%) among 1 -2 years old people and lowest (82. 5%) among newborns.Antibody positive rate (protective rate)and antibody concentration to diphtheria of population which had more doses of DPT or had vaccinated with DT were higher than those had not (P<0. 05 ).The sustainability of vaccine to diphtheria was higher than pertussis after vaccination of DPT.Conclusion Residents in Wenzhou are generally vulnerable to pertussis.Natural infection is considered to be an important influencing factor for the level of pertussis.The level of diphtheria antibodies in Wenzhou is high.The vaccine containing diphtheria is considered useful for children.However,it is suggested to conduct diphtheria booster immunization in older age group.