Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To investigate the correlation between serum nickel-like protein(Metrnl)level and glycolipid metabolism and inflammatory state in patients with T2DM complicated with abdominal obesity.Methods One hundred and twenty-four T2DM patients and 140 non-diabetic controls who were hospitalized in Gansu Provincial People's Hospital from May to September 2022 were selected and divided into T2DM combined abdominal obesity group(T2DM+AO,n=81),T2DM group(n=43),abdominal obesity group(AO,n=69)and normal control group(NC,n=71)according to whether they suffered from T2DM and abdominal obesity.ELISA method was used to determine the levels of serum Metrnl,IL-4 and IL-13.The correlation between serum Metrnl and the indicators of glucose and lipid metabolism,WC,BMI,VFA,FPG,HbA1c,TC,TG,LDL-C,HDL-C and the indicators of inflammatory state,IL-4 and IL-13 were analyzed.Results Compared with NC group,serum Metrnl levels in T2DM group,AO and T2DM+AO group were decreased(P＜0.05).Serum Metrnl was negatively correlated with WC,BMI,VFA,FPG,HbA1c,TG,IL-4,IL-13(P＜0.01),and positively correlated with HDL-C(P＜0.05).Age,WC,BMI and IL-4 were the influencing factors of Metrnl.WC,VFA,FPG and Metrnl were the influencing factors of T2DM combined with abdominal obesity.The ROC curve showed that serum Metrnl had a sensitivity of 82.5%and a specificity of 93.8%for the diagnosis of T2DM with abdominal obesity.Conclusions Serum Metrnl in T2DM patients with abdominal obesity is significantly reduced,and is closely related to glucose and lipid metabolism and inflammatory status.Serum Metrnl may be a novel biomarker factor for T2DM complicated with abdominal obesity.

OBJECTIVE Mitochondria plays a crucial role in cellular homeostasis by regulating various pro-cesses,including calcium signaling and mitophagy.This study aimed to explore the involvement of prohibitin 2(PHB2),an inner mitochondrial membrane protein,in the modulation of mitochondrial calcium dynamics and mitoph-agy.METHODS HEK293T cells were used as the experi-mental cells and were divided into control,PHB2 knock-down,and PHB2 overexpression groups.To evaluate mitochondrial calcium dynamics,Rhod-2 AM and Mito-Tracker Green fluorescence dyesrhod-2 staining and laser confocal microscopy were employed to visualize mito-chondrial calcium imaging.Additionally,Green-5N was utilized to measure the rate of mitochondrial calcium uptake.The mitochondrial membrane potential was assessed using JC-10 staining and laser confocal micros-copy,while cellular ATP levels were determined using ATP assay kits.Furthermore,mitochondrial autophagy was induced by treatment with CCCP,and the expression lev-els of TOM20,LC3,and PARKIN,key mitophagy-related proteins,were analyzed using Western blotting.RESULTS The results demonstrated that compared to the control group,the overexpression of PHB2 increased mitochon-drial calcium concentration,mitochondrial calcium uptake rate,ATP level and expression levels of LC3 and PAR-KIN,but decreased mitochondrial membrane potential and TOM20 expression.In contrast,PHB2 knockdown reduced mitochondrial calcium concentration,ATP level and expression levels of LC3 and PARKIN,but elevated mitochondrial membrane potential,and TOM20 expres-sion.CONCLUSION This study provides evidence that PHB2 plays a vital role in regulating mitochondrial calci-um dynamics,which in turn influences mitochondrial func-tion and modulates mitochondrial autophagy.These find-ings contribute to our understanding of the molecular mechanisms underlying the interplay between PHB2,mitochondrial calcium signaling,and mitophagy.

Objective To explore the correlations between self-management and quality of life in elderly patients with chronic heart failure (CHF) in Xinjiang Uygur Autonomous Region, so as to provide effective measures to improve quality of life of them. Methods A total of 750 elderly patients with CHF were selected as the research subjects by convenience sampling method from 5 regions of Xinjiang Uygur Autonomous Region from February to August 2015. General Data Questionnaire, Heart Failure Self-Management Scale and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were applied in the investigation to analyze the correlation between self-management and quality of life. Results A total of 750 questionnaires were distributed and 704 valid questionnaires were collected, with an effective recovery rate of 94.1%. The total score of self-management and MLHFQ in the 704 CHF patients was (47.6±11.1) and (57.1±18.5) respectively. Pearson correlation analysis showed that patients' self-management was positively correlated with quality of life (r=0.114, P＜ 0.05). Conclusions The overall level of self-management and quality of life in elderly patients with chronic heart failure in Xinjiang Region is mid-to-low. Nursing intervention can give full play to the initiative of self-management behavior in accordance with patients' cultural background, so as to improve their quality of life.

Objective To explore the effectiveness of sandplay therapy combined with family counseling in children with school phobia and its influence of child′ self-consciousness. Methods Integrative sandplay therary with family consulting were used to treat 28 patients with school phobia regularly for 2 months. Sandplay and family consulting therapy were given once a week for 45 minutes . Clinical outcomes were assessed using CGI-GI and Piers-Harris children′s self-consciousness scale before and after treatment as well as 3 months posttreatment. Results Overall response rate was 85%. In addition, the physical appearance and characteristic factor before and after treatment were no significant difference (P>0.05). The rest of the various factors and total score compared with pre-treatment significantly improved (P<0.05). After treatment for 3 months, every factor in self-consciousness of children and total score were no significant difference (P>0.05). Conclusion Integrative sandplay therapy with family counseling has better and long-lasting treatment effect to self-consciousness of children with school refusal.