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 The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.

This paper investigated the effects of regular aerobic exercise on protein oxidative stress and apoptosis in aging rat striatum, and further analyzed its target proteins and mechanism based on differential carbonylation proteomics. Totally 24 specific pathogen-free (SPF) 23-month-old male Sprague-Dawley (SD) rats were randomly divided into aged sedentary control group (Con-SED, n = 12) and aged regular aerobic exercise runner group (Aero-EXE, n = 12). The medium intensity of regular aerobic exercise model: The intensity of maximum oxygen consumption (VO

ObjectiveTo investigate the relationship of the characteristics of sperm donors with the results of screening and provide some reference for the screening of sperm donors.

METHODSWe statistically analyzed the screening data about 12 362 sperm donors at the Guangdong Human Sperm Bank from January 2003 to June 2017 and the relationship of the eligibility rate of screening with the donors' age, education, occupation, marriage, and fatherhood.

RESULTSOf the 12 362 sperm donors, 3 968 (32.1%) met the standards of semen quality and 3 127 (25.3%) filled all the requirements of sperm donation. The eligibility rate of screening was 27.7% in the donors aged 20－24 years, 24.3% in those aged 25－29 years, 23.8% in those aged 30－34 years, and 17.5% in those aged =≥35 years (P < 0.01); 23.5% in the senior high school students, 24% in the junior college students, 25.9% in the undergraduates, and 30.3% in the postgraduates (P < 0.01); 29.3% in the students versus 22.9% in the others (P < 0.01), 41.5% in the married versus 20.7% in the unmarried (P < 0.01), and 45.6% in the fathers versus 20.9% in the childless husbands (P < 0.01).

CONCLUSIONSA higher eligibility rate of screening was found among the sperm donors aged <35 years or with a bachelor's or higher degree, particularly among students.

Adult ; Humans ; Male ; Semen Analysis ; standards ; Spermatozoa ; Students ; statistics & numerical data ; Tissue Donors ; statistics & numerical data ; Tissue and Organ Procurement ; Young Adult

OBJECTIVETo establish osteoblast-osteoclast cell co-culture system in a Transwell chamber, and detect cell viability of osteoblasts and osteoclasts in system.

METHODSOsteoblast MC3T3-E1 and mouse monocytes RAW264.7 were cultivated in vitro. RANKL-induced mouse RAW264.7 monocytes differentiated into mature osteoclasts, osteoblast-osteoclast cell co-culture system was established in Transwell chamber. Cell activity of osteoblasts and osteoclasts were detected by CCK-8 experimenting, Alizarin Red staining, TRAP staining. The expression of OPG, ALP, RANKL, TGF-b1 gene and RANKL protein in osteoblast MC3T3-E1 were detected by PCR, Western-Blot methods. Also, the expression of RANK, NF-κB in gene and protein level in osteoclast were measured through the same method respectively.

RESULTSThe co-culture system of Mouse MC3T3-E1 cells and RAW264.7 cell were established in Transwell chamber. Co-culture system affected cell division activities of osteoblasts and osteoclasts. Differentiation of osteoblasts were increased, while differentiation of osteoclast division were slight decreased under microscope observation. OPG (0.65±0.08) and ALP (0.16±0.01) gene expression of co-culture system were less than single culture OPG(1.00±0.08) and ALP (1.01±0.16); TGF-b1(4.42±0.21) and RANKL(4.12±1.04) of osteoblasts in co-culture system were higher than TGF-b1(1.00±0.10) and RANKL(1.00±0.09) under single culture. However, gene expression of RANK(0.63±0.06) and NF-κB(0.64±0.08) in co-culture system were decreased than RANK(1.00±0.08) and NF-κB(1.00±0.09), in single culture, and had significant differences. Similarly, protein expression of OPG(0.43±0.05) and NF-κB(0.59±0.05) of co-culture system were less than OPG(0.84±0.06) and NF-κB(1.13±0.03) of single culture. While RANKL protein expression (0.54±0.03)of co-culture system was more than single culture RANKL(0.31±0.03), and had statistically differences, which was in agreement of the trend of gene expression change.

CONCLUSIONSCo-culture system of mouse MC3T3-E1 cells and RAW264.7 cell was viable in Transwell chamber, and the activity of osteoblasts is higher than osteoclasts in co-culture system.

3T3 Cells ; Animals ; Cell Differentiation ; Coculture Techniques ; Mice ; NF-kappa B ; metabolism ; Osteoblasts ; cytology ; Osteoclasts ; cytology ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism ; RAW 264.7 Cells ; Receptor Activator of Nuclear Factor-kappa B ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo summarize the clinical features of Enterococcus faecium meningitis in children.

METHODSThe clinical data of nine children with Enterococcus faecium meningitis were analyzed.

RESULTSIn all the nine children, Enterococcus faecium was isolated from blood, cerebrospinal fluid, or peripherally inserted central catheters; 6 (67%) patients were neonates, 2 (22%) patients were younger than 6 months, and 1 (11%) patient was three years and four months of age. In those patients, 56% had high-risk factors before onset, which included intestinal infection, resettlement of drainage tube after surgery for hydrocephalus, skull fracture, perinatal maternal infection history, and catheter-related infection. The main symptoms were fever and poor response. In those patients, 22% had seizures; no child had meningeal irritation sign or disturbance of consciousness. The white blood cell count and level of C-reactive protein were normal or increased; the nucleated cell count in cerebrospinal fluid was normal or mildly elevated; the protein level was substantially elevated; the glucose level was decreased. The drug sensitivity test showed that bacteria were all sensitive to vancomycin and the vancomycin treatment was effective. Only one child had the complication of hydrocephalus.

CONCLUSIONSEnterococcus faecium meningitis occurs mainly in neonates and infants. The patients have atypical clinical features. A high proportion of patients with Enterococcus faecium meningitis have high-risk factors. Enterococcus faecium is sensitive to vancomycin.

C-Reactive Protein ; analysis ; Enterococcus faecium ; drug effects ; Female ; Gram-Positive Bacterial Infections ; blood ; diagnosis ; drug therapy ; etiology ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; blood ; diagnosis ; drug therapy ; etiology ; Vancomycin ; pharmacology

OBJECTIVETo investigate the diagnostic value of clinical manifestation, laboratory examination and imaging changes for pyogenic spondylitis and to summarize the clinical characteristics of patients with pyogenic spondylitis.

METHODSThe clinical data, of 20 patients with pyogenic spondylitis were diagnosed by histopathological examination from March 2012 to March 2015, were retrospectively analyzed. There were 9 males and 11 females, aged from 43 to 72 years old with an average of 58.9 years. Included 3 cases of cervical vertebrae, 7 cases of thoracic vertebrae, 10 cases of lumbar vertebrae. Patients of blood analysis, erythrocyte sedimentation rate(ESR), C reactive protein(CRP), X rays, CT and MRI were performed before treatment. Visual analogue scale (VAS) was used to evaluate the pain of patients suffering from vertebral pain.

RESULTSAll the patients had suffered from vertebral pain before treatment. VAS was 9 points in 4 cases, 8 points in 6 cases, 7 points in 1 case, 3 points in 6 cases, and 2 points in 3 cases. Among them, 7 patients complicated with neurological symptoms, 11 with aggravating night pain, 10 with fever. WBC and Neutrophil count (NEU) of 5 cases were increased and other 15 cases were normal;CRP of 19 cases were increased and 1 case was normal;ESR of all 20 cases were increased. X rays showed the intervertebral space narrowing in all 20 cases, 13 cases complicated with destruction of vertebral body; CT showed the lesions of vertebral body in the 20 cases and complicated with destruction, sclerosis of sclerotin; MRI showed that the lesions of the vertebral body in the T1 image had uneven medium low signal, in the T2 image of the 16 cases had uneven high signal and 2 cases had uniform and high signal, 2 cases had main high signal compliated with mixed signal. Thirteen patients underwent surgical treatment and 7 patients received conservative treatment, and the patients left hospital while VAS had significantly improved after treatment.

CONCLUSIONSPyogenic spondylitis is easy to be misdiagnosed or missed in clinic. It can be combined with the clinical manifestations, laboratory examination and imaging characteristics in order to make a definite diagnosis for purulent spondylitis in early.

The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson's correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and-0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.
Brain Ischemia ; metabolism ; Humans ; Magnetic Resonance Angiography ; Retrospective Studies ; Stroke ; metabolism

Objective To investigate the quality of life and analyze its influencing factors for postoperative patients with total artificial knee joint replacement, and to provide basis for enhancing the quality of life of patients with total artificial knee joint replacement. Methods A questionnaire method was used to survey 100 postoperative patients with total artificial knee joint replacement. Data were analyzed by SPSS 12.0.Results The quality of life of total artificial knee joint replaeement patients was not good. Its main influencing factor was the rehabilitation status of artificial knee joint. Conclusions These results suggest that we should pay more attention to the quality of life of total artificial knee joint replacement patients, and strengthen the postoperative rehabilitation exercise, thereby facilitating the rehabilitation of joint function and improving patients' quality of life.

OBJECTIVETo explore the correlation between the biological characteristics of volunteer donors and sperm parameters.

METHODSSperm parameters were analyzed for 778 primary volunteer donors by CASA system with standard methods recommended by WHO including sperm concentration, motility rate, VCL, VSL, ALH, LIN, STR and BCF, and their biological characteristics were recorded.

RESULTSOf all the volunteer donors, students accounted for more than a third, 89.2 percent were under the age of 35 years, 71.6 percent between 166 and 175 cm in height, 91.7 percent of normal weight and 77.1 percent with college education. The median sperm concentration and motility rate were 107.00 x 10(6)/ml and 75 percent respectively. Age was weakly correlated with such semen indexes as concentration (r = 0.210, P = 0.000) , motility rate (r = 0.213, P = 0.000), volume (r = 0.165, P = 0.002), VAP (r = 0.259, P = 0.000), VSL (r = 0.281, P = 0.000), VCL (r = 0.190, P = 0.000), BCF (r = 0.243, P = 0.000) and LIN (r = 0.192, P = 0.000). The semen indexes of the 26-35 age group were a little better than those of the 20-25. Height showed no correlation to semen indexes. Education and occupation were somewhat related with other sperm parameters (P < 0.01) than ALH (P = 0.695/0.886).

CONCLUSIONAge, occupation and education bear some correlation with sperm parameters except ALH, while height has none with any of them.

Adult ; Age Factors ; Humans ; Image Processing, Computer-Assisted ; methods ; Male ; Occupations ; Semen ; cytology ; Sperm Count ; Sperm Motility ; physiology ; Spermatozoa ; physiology ; Students ; Tissue Donors ; statistics & numerical data