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

Lipid droplet were once simply regarded as depots for neutral lipids,but recent studies have shown that they play an important role in signal transduction,metabolism,and inflammation in glial cells,especially in microglia.Microglia are resident mononuclear phagocytes of the central nervous system and are closely associated with inflammation,phagocytosis,myelin repair,aging,and neurodegenerative diseases.However,further studies are needed to clarify the mechanism of lipid droplet formation in microglia and its influence on histopathology and related diseases.This article summarizes the recent research findings,in order to further clarify these issues.

Primary cardiac angiosarcoma is a type of soft tissue sarcoma originating in vascular endothelial cells, without obvious gender differences in the incidence rate and specific early clinical manifestations, whilstpericardial effusion often found at the first presentation of most patients. Tumors are mostly located in the right atrium and pericardium. Echocardiography is the preferred examination method for diagnosing cardiac angiosarcoma and multimodal imaging is important in the diagnosis and differential diagnosis of benign and malignant cardiac mass. This article retrospectively analyzes the 25 cases of clinical manifestations and imaging features of primary cardiac angiosarcoma.

The outbreak of novel coronavirus pneumonia(NCP) caused by 2019 novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.

Objective To investigate the effects of down-regulating Cyclin D1 expression on Mdm2 gene expression and proliferation of human hepatoma cells.Methods Cyclin D1-siRNA was transfected into the hu man hepatoma cell line Hep3B s with liposome.The experiment was divided into the blank control group,negative control siRNA (NC-siRNA) group and Cyclin D1-siRNA group.RT-PCR and Western blot were used to detect the expressions of Cyclin D1,Mdm2,Mdm4,P53 and P21.The cell cycle was measured by flow cytometer;the cellular activity was tested with MTT;the cell apoptosis was examined by TUNEL.Results Compared with the blank control group and NC-siRNA group,the expressions of P53 and P21 in the Cyclin D1-siRNA group were increased (P＜0.05),while the expressions of Cyclin D1,Mdm2 and Mdm4 were decreased (P＜0.01);there were no significant differences in the G1,S and G2 phases among 3 groups(P＞0.05);the cell vitality in the in the Cyclin D1-siRNA group was significantly weakened compared with the other two groups(P＜0.01),while the cell apoptosis was significantly enhanced(P＜0.01).Conclusion The down-regulation of Cyclin D1 gene expression could inhibit the expressions of Mdm2 and Mdm4,and up-regulates the expressions of P53 and P21.Down-regulating Cyclin D1 expression can inhibit the proliferation of liver cancer cells and promotes their apoptosis.

Objective To investigate and compare the prevalence of overweight,obesity and central obesity in 2003 and 2013 in a community in Chongqing,and to analyse their prevalence trends.Methods Surveys were conducted in 2003 and 2013 in the community population,and the investigation included questionnaires,anthropometric measurements,blood glucose and lipid determination.Results The number of participants in 2003 and 2013 were 3 073 and 5 938,respectively.The age standardized prevalence of overweight increased from 44.3％ in 2003 to 45.5％ in 2013 in males and declined from 28.3％ to 26.6％ in females,but there was no statistically significant difference(P=0.407,0.260).The age standardized prevalence of obesity was steady in males (10.0％ vs.10.3％,P＞0.05),but declined significantly in females (8.3％ vs.6.3％,P＜0.05).For central obesity,the age standardized prevalence in 2003 and 2013 was 50.9％,53.9％ in males and 39.6％,35.7％ in females,which increased significantly among males and decreased significantly among females (P=0.042,0.017).Conclusion The prevalence of overweight,general obesity and central obesity is relatively high in the community,and males have a more significant increase in the prevalence of central obesity.

Objective To study the effect of mitomycin C(MMC)‐chitosan (CS)sustained release microspheres on the scar‐ring prevention of the filtering passage during glaucoma filtering surgery .Methods Filtering surgery model was established on 96 eyes of 48 healthy adult New Zealand white rabbits which were divided into 4 groups ,24 eyes in each group .The right eyes implan‐ted MMC‐CS microspheres in 24 rabbits(group A) ,whereas that of the fellow eyes implanted empty CS microspheres(group B) , and in other 24 rabbits which right eyes only used 0 .20 mg/mL MMC cotton(group C) ,on the opposite sides with no adjunctive treatment(group D) .Intraocular pressure ,filtering bleb ,anterior chamber flare ,complications and the numbers of corneal endotheli‐al cells were observed after surgery .Rabbits were killed on the 7th ,14th and 21th day postoperatively in batch and histopathological examination was carried out .Results (1)the intraocular pressure:group A can maintain the low level of intraocular pressure for a long time ,followed by group C ,group B and group D ,and difference between groups was statistically significant (P< 0 .01) .(2) The filtering blebs :the filtering bleb survival time of group A was longer than other group(P<0 .01) .(3)Complication:there was not any complication in the 4 groups .(4)The number of corneal endothelial cells :the number of corneal endothelial cells of group A preoperative and postoperative had no statistical significance differences(P>0 .05) .(5)Histopathologic findings :group A had bet‐ter conjunctival epithelial integrity ,subconjunctival fibroblast less than other groups ,filtration had no obvious inflammation infiltra‐tion around the mouth area ,but also had fewer new collagen fibers .Conclusion MMC‐CS sustained release microspheres is a safe and effective treatment to inhibit inflammatory cells activity and fibroblast activity in surgery sites ,and can significantly improve outcome of filtration surgery .

Objective To study the effect of α-lipoic acid on the retinal expression level of VEGF and diabetic retinopathy in rats with diabetes mellitus and mechanism.Methods Totally 72 Wistar rats were divided into 4 groups:12 (control group)in group A,24 in modeling group(group B),24 in group treated withα-LA(group C)and 12 in high-glucose(group D).Group B to group D were given 60 mg/kg STZ through intraperitoneal injection,rats in group C were given 100 mg/kg α-LA and rats in group D were given 5.0% glucose-solution.The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 of 4 groups were compared by statistics.Results After 72 h,the FPG of group A was(4.57 ±0.1 5 )mmol/L,that of group B was (21.72±4.28)mmol/L,that of group C was(21.54±4.96)mmol/L and that of group D was(21.83±4.77)mmol/L,the difference had statistical significance (P <0.05).The body mass of group A was(210.5±5.2)g,that of group B was(21 1.2 ±5.7)g,that of group C was(209.8±5.8)g and that of group D was(208.7±3.4)g,the difference had no statistical significance (P >0.05).The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 among 4 groups at 4 w,8 w and 12 w had statistical difference (P <0.05).After 12 w,the difference of GR stage among group B to group D had statistical significance (P <0.05).Conclusion α-LA can inhibit the expression of VEGF in rats with diabetes mellitus,which is related to its ability to re-duce the oxidative stress and inflammation reaction,as well as to alleviate the insulin resistance.

Objective To investigate the clinical significance of ultrasound guided biopsy of peritoneum in diagnosis of unex-plained ascites .Methods A total of 95 patients with unexplained ascites after conventional examination were collected ,then under-went ultrasound inspection which showed thickened peritoneum and the relations to surrounding tissues around the planned perito-neum puncture point ,and conducted the peritoneal biopsy .Results A total of 95 were successfully biopsied with 2 -4 peritoneal tissues .Pathological examination showed that 37 cases (38 .9% ) were diagnosed as peritoneal metastatic carcinoma ,41 cases (43 . 1% ) with peritoneal tuberculosis ,5 cases (5 .2% ) with peritoneal mesothelioma ,1 case (1 .1% ) with eosinophilic granuloma ,4 ca-ses (4 .2% ) with fibrous hyperplasia ,and 7 cases (7 .4% ) with chronic inflammatory cell infiltration .The positive rate of ultra-sound guided peritoneal biopsy was 88 .4% .Conclusion The ultrasound guided biopsy of peritoneum is of clinically great signifi-cance in diagnosis of unexplained ascites .

Objective The purpose of this study was to evaluate the disinfection effectiveness and properties of acrylic resin via microwave irradiation. Methods Forty acrylic resin base dentures fabricated in a standardized procedure were chosen and divided into Group A,B,C and D randomly. Group A,B and C were immersed in 200ml distilled water and submitted to microwave irradiation at 700W for 3,4,5 minutes individually. Group D was used as positive control. Bacteria specimens from each group were got for culture and numbers were calculated. Then the four groups were tested for the flexural strength and impact strength by universal test machine before and after microwave irradiation sterilization. Results The germicidal ratio of Group B was more than 90% ,while the ratio of group C was 100%. There was no significant difference in flexural strength and impact strength between group C and group D. Conclusions Microwave irradiation for 5 minutes at 700W produced sterilization of dentures contaminated with all bacteria whereas the denture strength is not affected. Microwave irradiation at 700W solution for 5 minutes was effective to sterilize acrylic resin base dentures.