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

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbio-sis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione(GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating in-flammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Parkinson′s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly people. In addition to motor symptoms, PD also has many non motor symptoms, such as dysosmia, constipation, cognitive impairment, etc. Among them, dysosmia is a common non motor symptom of early Parkinson′s disease. Research has confirmed that olfactory dysfunction (OD) can appear before the typical clinical symptoms of PD, which is of great significance to the diagnosis and treatment of diseases. However, at present, the pathogenesis of OD is still unclear, and the inspection methods have not been unified, and there is no complete cure. This article reviews the latest research progress of dysosmia in Parkinson′s disease.

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To explore predictive value of fragmented QRS wave (fQRS) for prognosis in patients with a‐cute no ST elevation myocardial infarction (NSTEMI).Methods : According to ECG measure result , 120 NSTEMI patients treated in our hospital from Jan 2015 to Feb 2017 were divided into fQRS group (n＝73) and no fQRS group (n＝47).Both groups received same treatment .General information and incidence of MACE during one‐year fol‐low‐up were compared between two groups .Results : There were no significant difference in heart rate ,percentage of dyslipidemia ,hypertension and diabetes mellitus between two groups ( P＞ 0. 05 all).Compared with no fQRS group ,there were significant reduction in left ventricular ejection fraction [(63. 81 ± 5.67)% vs.(52. 18 ± 5. 81)%, P＝0. 001] , and significant rise in percentage of previous myocardial infarction (21.28% vs.39. 73%, P＝0.035) and more than three coronary stenosis greater than or equal to 50%(36.17% vs.54.79%, P＝ 0.046) in fQRS group .Compared with no fQRS group ,incidence of MACE of fQRS group was higher (25. 53% vs.45.21%, P＝0.030).Conclusion :Cardiac function of NSTEMI patients with fQRS is significantly poorer than that of patients without fQRS ,so patients with fQRS predicts their state of an illness is serious and prognosis is poor .

β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis (OA) development in temporomandibular joint (TMJ), we have generated β-catenin conditional activation mice (β-cat(ex3) ) by breeding Agc1-CreER mice with β-catenin mice. Results of histologic analysis showed the progressive TMJ defects in 3- and 6-month-old β-cat(ex3) mice (tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3) mice, β-cat(ex3) mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4, and Adamts5 in TMJ of β-cat(ex3) mice. Results of proliferating cell nuclear antigen (PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3) mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.
Aggrecans ; metabolism ; Animals ; Apoptosis ; Cartilage, Articular ; metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; In Situ Nick-End Labeling ; Mice ; Osteoarthritis ; metabolism ; Phenotype ; Signal Transduction ; Surface Properties ; Temporomandibular Joint ; metabolism ; beta Catenin ; metabolism

Objective To investigate the effect of seven-step exercise regurgitation in stage I exercises on the risk of fall in patients with acute ST-elevation myocardial infarction. Methods At the time of admission, 119 patients with acute ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly divided into control group (n=58) and intervention group (n=61). All patients were given routine nursing within 7 days after operation. The patients in the intervention group were given the first three-step exercises based on the seven-step exercise regurgitation in stage I exercise apart from routine nursing within 7 days after operation. The risk of fallings was assessed on the 7th day after operation for the two groups. Result Compared with the control group, the risk of fallings on day five after operation in the intervention group was significantly lower than that in the control group (P<0.05). Conclusion The seven-step exercise of stage I cardiac rehabilitation can effectively reduce the risk of falling in patients with acute myocardial infarction after PCI.

Objective To evaluate the anti-bacteria effects of polymyxin B combined with meropenem against 30 strains pan-drug resistant pseudomonas aeruginosa that separated in clinic. Methods The minimal inhibitory concentration (MICs) of 30 strains pan-drug resistant pseudomonas aeruginosa after treated with polymyxin B and meropenem as single-use or combination use were determined by both microdilution method and checkerboard method. The FIC index was calculated, then the type of combination effect was determined according to FIC index, which was used to determine whether there was synergistic or antagonistic effects. Results The MICs of pan-drug resistant pseudomonas aeruginosa were reduced significantly after polymyxin B combined with meropenem when compared with single-use. The percentages of the FIC index that less than 0.5 and the index between 0.5 and 1 were 60%and 30%respectively. Conclusion The results indicate that the combinations of polymyxin B with meropenem have good synergistic and additive effects against pan-drug resistant pseudomonas aeruginosa, there is no antagonism.