Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective: To investigate the association between edentulism and the risk of social isolation in middle-aged and elderly populations, provide empirical evidence for formulating social isolation prevention and intervention policies targeting edentulous middle-aged and elderly populations. Methods: Data were derived from the baseline survey (2011) and three follow-ups (2013, 2015, 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Participants were enrolled in the follow-up from the baseline. Those identified as socially isolated in any of the follow-up surveys conducted in 2013, 2015, or 2018 were considered to have reached the endpoint; otherwise, the follow-up was continued until the end of the 2018 survey; 9 870 individuals were ultimately included. Subjects were grouped by edentulism status. Chi-square test and multivariate Cox regression analysis were performed using Stata 17.0. Results: During a median follow-up of 6.54 years, 1 800 cases of social isolation occurred, with an incidence rate of 18.23%（17.47%~18.99%）. Multivariate Cox regression showed that edentulism was associated with an increased risk of social isolation (HR=1.21, 95% CI: 1.03-1.42) after adjusting for confounders. Subgroup analysis revealed population heterogeneity. Sensitivity analyses confirmed the stability of the results. Conclusion Edentulism is associated with an increased risk of social isolation in middle-aged and elderly adults.

Objective:To investigate the molecular epidemiological characteristics of norovirus (NoV) among infectious diarrhea patients in Linyi from 2021 to 2023, and provide the scientific evidence for norovirus control and prevention.Methods:The epidemiological information and fecal samples of patients with infectious diarrhea in Linyi from 2021 to 2023 were collected and detected by real-time fluorescent quantitative PCR. The RdRp and capsid gene VP1 region of norovirus-positive specimens were amplified and sequenced used to analyze their genotype, phylogeny and homology.Results:Among the 2 311specimens, 123 (5.32%) were positive of NoV, with GI/GII group infection accounted for 17.07% (21/123) and 77.24% (95/123), respectively, GI/GII group mixed infection accounted for 5.69% (7/123). The detection rate of <1 year age group was the highest (8.86%), followed by the 1-3 years group (7.11%, 30/422) and the over 60 years group (5.29%, 23/123). The highest NoV detection rate was 7.96% (45/565) in the urban area, and the most abundant genotypes were found in the northern mountainous area. Sequence analysis showed that 61 identified NoV strains could be divided into 12 genotypes, with 4 NoV GI and 8 NoV GII. The dominant genotype differed during the 3 years, with GII.4 Sydney [P16] in 2021, GII.4 Sydney [P31] in 2022, and GII.2[P16] in 2023.Conclusions:NoV GII group was the main NoV infection in Linyi from 2021-2023 and genotypes were diverse. Children under 3 years of age and elderly people over 60 years old as susceptible groups should be given special protection. In addition, the monitoring of NoV genotype diversification should be strengthened in northern mountainous areas.

Objective:To investigate the molecular epidemiological characteristics of norovirus (NoV) among infectious diarrhea patients in Linyi from 2021 to 2023, and provide the scientific evidence for norovirus control and prevention.Methods:The epidemiological information and fecal samples of patients with infectious diarrhea in Linyi from 2021 to 2023 were collected and detected by real-time fluorescent quantitative PCR. The RdRp and capsid gene VP1 region of norovirus-positive specimens were amplified and sequenced used to analyze their genotype, phylogeny and homology.Results:Among the 2 311specimens, 123 (5.32%) were positive of NoV, with GI/GII group infection accounted for 17.07% (21/123) and 77.24% (95/123), respectively, GI/GII group mixed infection accounted for 5.69% (7/123). The detection rate of <1 year age group was the highest (8.86%), followed by the 1-3 years group (7.11%, 30/422) and the over 60 years group (5.29%, 23/123). The highest NoV detection rate was 7.96% (45/565) in the urban area, and the most abundant genotypes were found in the northern mountainous area. Sequence analysis showed that 61 identified NoV strains could be divided into 12 genotypes, with 4 NoV GI and 8 NoV GII. The dominant genotype differed during the 3 years, with GII.4 Sydney [P16] in 2021, GII.4 Sydney [P31] in 2022, and GII.2[P16] in 2023.Conclusions:NoV GII group was the main NoV infection in Linyi from 2021-2023 and genotypes were diverse. Children under 3 years of age and elderly people over 60 years old as susceptible groups should be given special protection. In addition, the monitoring of NoV genotype diversification should be strengthened in northern mountainous areas.

Objective To investigate the expression and relationship of early growth response gene-1((Egr-1)),platelet-derived growth factor-B(PDGF-B) and tranforming growth factor(TGF-?_1) in autogenous vein graft in rats,and the role in vein graft intimal hyperplasia(IH).Methods Autogenous vein graft model was(established) in 90 wistar rats.The vein graft samples were harvested at 1,2,6,24 hours,and 3,7,14,28,42 days after surgery.Normal vein was used as control group.Egr-1、PDGF-B,TGF-?_1 mRNA was measured by reverse transcription-PCR and in situ hybridization.Western blotting and immunohistochemistry were used to detect the protein expression of Egr-1,PDGF-B and TGF-?_1. Results Expression of Egr-1,PDGF-B,TGF-?_1 mRNA and protein was not detected in normal vein.In grafting vein,expression level of Egr1mRNA reached a peak at 28days,and the positive rate of Egr-1mRNA was 45%?6%;(PDGF-BmRNA) reached a peak at 14days(48%?6%);a peak of TGF-?_1mRNA was 46%?9% reached at 7days;Egr-1 protein expression reached a peak at 28days, and the positive rate of Egr-1 protein was 40%?9%.PDGF-B protein reached a peak at 28days(45%?4%),TGF-?_1 protein reached a peak at 14days(41%?7%).Conclusions Intimal hyperplasia of vein graft is closely associated withexpression of Egr-1、PDGF-B and TGF-?_1;the activation and expression of PDGF-B and TGF-?_1 may be(modulated) by Egr-1,and they may contribute to increase expression of Egr-1 by feedback.