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 explore the risk factors of apathy and correlations with cognitive function in patients with hypertension combined with cerebral small vessel disease(CSVD).Methods Totally 141 patients with hypertension combined with CSVD were prospectively enrolled and were divided into apathy group(n=43)and non-apathy group(n= 98)according to neuropsychiatric inventory-apathy scale(NPI-Apathy)scores.The general data,imaging marker scores and total imaging burden scores were compared between groups.In hypertension combined with CSVD patients,multivariate logistic regression analysis was performed to screen the independent risk factors of apathy,and Spearman correlation analysis was also performed to observe the correlation of apathy and cognitive function.Results The patients'age,high density lipoprotein cholesterol(HDL-C),Fazekas scores of lateral periventricular white matter hyper-intensity(WMH),cerebral microbleed of depth/infratentorial and total imaging burden scores of apathy group were all higher,while mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores were both lower than those of non-apathy group(all P＜0.05).HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy(both P＜0.05),while NPI-Apathy scores were moderately negatively correlated with cognitive function in patients with hypertension combined with CSVD(r=-0.543,-0.484,both P＜0.001).Conclusion HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy in patients with hypertension combined with CSVD.The more severe the apathy,the lower the cognitive function.

Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.
Animals ; Antibodies, Viral/blood ; *Chickens ; Chimera/genetics/immunology ; Coronavirus Infections/prevention & control/*veterinary/virology ; Female ; *Immunity, Innate ; Infectious bronchitis virus/genetics/*immunology ; Influenza A Virus, H5N1 Subtype/genetics/immunology ; Injections, Intramuscular/veterinary ; Mice ; Mice, Inbred BALB C ; Neuraminidase/genetics ; Poultry Diseases/*prevention & control/virology ; Recombinant Fusion Proteins/genetics/immunology ; Spike Glycoprotein, Coronavirus/genetics/*immunology ; Vaccines, Synthetic/administration & dosage/genetics/immunology ; Vaccines, Virus-Like Particle/administration & dosage/genetics/*immunology ; Viral Proteins/genetics

Objective To explore the therapeutic effect of Han-uvulopalatopharyngoplasty (H-UPPP) combined with coblation on treatment of type Ⅱ mild and moderate obstructive sleep apnea hypopnea syndrome (OSAHS).Methods According to the measuring parameters analyzed and clinical characteristics of velopharyngeal,68 patients were divided into 3 groups:group A (28 patients,treated by H-UPPP combined with coblation of tonsillectomy),group B (22 patients,treated by H-UPPP combined with drilling of tonsil) and group C (18 patients,treated by velopharyngeal multi-points drilling).After operation for 6 months,the pafor tients in 3 groups were detected by the polysomnography (PSG),Epworth sleepiness scale,and the parameters of velopharyngeal were compared.Results After operation for 6 months,the heal,excellence,efficiency and inefficiency patients in group A were 6,10,7,5 cases,in group B were 3,8,7,4 cases,in group C were 2,7,5,4 cases,there was no significant difference (P ＞0.05).After operation for 6 months,the apnea hyponea index (AHI) and the scores of ESS in group A,B,C were significantly lower than those before operation [(10.1 ± 2.3) times/h vs.(21.2 ± 2.5) times/h,(6.4 ± 1.0)scores vs.(16.2 ± 1.0) scores,(6.9 ± 1.3) times/h vs.(16.0 ± 1.4) times/h,(5.4 ± 1.3) scores vs.(14.5 ±1.5) scores,(7.7 ± 1.8) times/h vs.(16.0 ± 2.1) times/h,(4.1 ± 1.0) scores vs.(12.3 ± 1.9) scores],thelevel of LSaO2 was significantly higher (0.885 ±0.035 vs.0.737 ±0.030,0.871 ±0.046 vs.0.763 ±0.033,0.901 ±0.029 vs.0.820 ±0.034),there was significant difference (P ＜0.01),but there was no significant difference among 3 groups (P ＞ 0.05).After operation for 6 months,the pharyngomaxillary space,distance between uvula and posterior wall of pharynx,distance between anterior pillars in group A,B,C were significantly increased compared with those before operation [(24.6 ± 0.9) mm vs.(12.3 ± 1.2)mm,(11.6 ±1.2) mm vs.(5.4 ± 0.6) mm,(34.9 ± 1.2) mm vs.(28.3 ± 1.0) mm,(24.0 ± 0.8) mm vs.(14.3 ± 1.0) mm,(11.8 ± 0.8) mm vs.(6.3 ± 0.4) mm,(38.3 ± 0.8) mm vs.(31.9 ± 1.9) mm,(23.6 ± 1.4) mm vs.(19.9 ±1.1) mm,(7.3 ± 0.5) mm vs.(6.8 ± 0.6) mm,(38.5 ± 0.8) mm vs.(35.2 ± 1.0) mm],the length of soft palate was decreased [(31.9±0.9) mm vs.(38.3 ±0.9) mm,(25.6 ± 1.0) mm vs.(35.6 ± 1.2) mm,(29.9 ± 1.3) mm vs.(34.9 ±0.9) mtm],there was significant difference (P ＜0.01),but there was no significant difference among 3 groups (P ＞ 0.05).Conclusions H-UPPP combined with coblation on treatment of type Ⅱ mild and moderate OSAHS is effective and safe.According to the clinical characteristics of the patients to select suitable method is the key to get a satisfactory curative effect.

This study was to investigate the effects of the combination of deoxynivalenol (DON) and zearalenone (ZON) on pigs. Twenty-four weaning piglets were divided into a control group fed a diet free of mycotoxins and a toxin group fed a diet containing 1 mg/kg DON and 250 microgram/kg ZON. The results showed that supplementation of DON and ZON in diets had extensive effects on pigs. More specifically, DON and ZON caused levels of total protein, albumin, and globulin in sera to decrease (p < 0.05) by 14.5%, 6.5% and 11.3%, respectively, and at the same time increased (p < 0.05) the serum enzyme activities of gamma-glutamyltransferase, aspartate aminotransferase and alanine aminotransferase by 72.0%, 32.6% and 36.6%, respectively. In addition, DON and ZON decreased (p < 0.05) the level of anticlassical swine fever antibody titers by 14.8%. Real-time PCR showed that DON and ZON caused the mRNA expression levels of IFN-gamma, TNF-alpha, IL-2, to decrease (p < 0.05) by 36.0%, 29.0% and 35.4%, respectively. Histopathological studies demonstrated that DON and ZON caused abnormalities in the liver, spleen, lymph nodes, uterus, and kidney. The concentrations of DON and ZON used in this study are in line with the published critical values permitted by BML. Our study clearly put the standard and adequacy of safety measures for these toxins into question. The authors suggest that with the increasing availability of cellular and molecular technologies, it is time to revisit the safety standards for toxins in feeds so as to make feeds safer, providing consumers with safer products.
Animal Feed/*analysis ; Animal Nutritional Physiological Phenomena ; Animals ; Diet/veterinary ; Drug Therapy, Combination ; Female ; Swine ; Swine Diseases/blood/*chemically induced/*physiopathology ; Trichothecenes/*administration & dosage/*adverse effects/pharmacology ; Zearalenone/*administration & dosage/*adverse effects/pharmacology

OBJECTIVE To study the best surgical technique for treatment of chronic hypertrophic rhinitis(HR).METHODS Eighty six cases with HR were divided randomly into 3 groups.Thirty cases were treated by transnasal endoscopic submucous inferior turbinate resection(group A),26 cases by partial inferior turbinectomy(group B)and 30 cases by bipolar radiofrequency ablation(group C).The epithelium of the inferior turbinate of the every case in 3 groups was examined with histomorphology and ultrastructure techniques at 6 months after operation. The efficacy and the features of in the 3 groups were compared.The MTR was determined in the patients of the 3 groups.The histomorphology and ultrastructure of the inferior turbinate were observed at 6 months after operation.RESULTS All the cases with HR in 3 groups were followed up for 3 to 6 months after operation.Effective rates of group A,group B and group C were 100 %,100 % and 96.3 % respectively, while there was no significant difference among the three groups.Compared to the group B,surgical techniques applied in Group A and group C have more advantages because ultrastructure of inferior turbinate mucosal cilia and nasal mucociliary transport function were nearly normal at 3 to 6 months after operation. The advantages include operating easily,wound healing up fast.MTR between pre-and post-operation was significant difference in group B.Epithelial tissue remained intact in group A and group C,while epithelial tissue in group B was instead of fiber tissue at 6 months after operation.The ultrastructure of inferior turbinate mucosal cilia in group A and group C remained intact at 6 months after operation.CONCLUSION The transnasal endoscopic submucous inferior turbinate resection and bipolar radiofrequency ablation for treatment of chronic hypertrophy rhinitis are effective. Submucous minimally invasive surgery of the inferior turbinate deserves to be recommended.

Objective To study the feature of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer’s disease (AD) and the value of positron emission tomography (PET) scanning in diagnosis of AD. Methods 13 AD patients and 13 health controls ,Who matched in age,sex and education years,were scanned with PET. Results (1) Watching by naked eyes,there was mild decreasing of rCMRglc at parietal lobe in healthy elders. While in AD patients,there was widely decreasing of cerebral metabolism rate of glucose. The most significant region was parietal lobe, the next was temporal lobe,and the last was frontal lobe. (2) Detecting with PET and dealing with statistical parametric mapping (SPM) of 99 software,there was more significant decreasing of rCMRglc in regions 7,23,30,31 of cingulate gyrus,region 39 and 40 of pario-occipital lobe,region 20 of temporal lobe and region 6,8,9 of frontal lobe in AD group( P

OBJECTIVETo investigate the features of regional cerebral metabolic rate of glucose (rCMRglc) in patients with mild cognitive impairment (MCI) by positron emission-tomography and its relationship with neuropsychological test.

METHODSPositron emission tomography, mini-mental state examination and Wechsler memory scale were applied in 10 patients with MCI and 10 healthy volunteers as the control group.

RESULTSScores of mini-mental state examination and Wechsler memory scale in MCI patients were lower than those in the control group (P < 0.01). rCMRglc of the left orbital gyrus, right middle temporal gyrus and right putamen was lower in the MCI group than in the control group (P < 0.05). Correlation analysis in the MCI group indicated that rCMRglc of many brain regions such as the orbital gyrus, putamen, left hippocampus and parahippocampal gyrus, cingulate gyrus, left amygdaloid body, precentral gyrus, postcentral gyrus, and medial occipitotemporal gyrus in MCI patients, were correlated negatively with age; while the rCMRglc of many parts of the brain such as the left putamen, temporal lobe, anterior cingulate gyrus, left insular lobe, amygdaloid body, precentral gyrus, postcentral gyrus and medial occipitotemporal gyrus were correlated positively with mini-mental state examination; and rCMRglc of the left putamen, temporal lobe, left insular lobe, precentral gyrus and postcentral gyrus were correlated positively with Wechsler memory scale. The right putamen, the right inferior temporal gyrus, precentral gyrus, and left postcentral gyrus were correlated positively with the length of education. However, only rCMRglc of the left amygdaloid body were correlated positively with gender.

CONCLUSIONThe rCMRglc was lower in the orbital gyrus and putamen of MCI patients. Their rCMRglc were correlated with their cognitive impairment severity, age, length of education and sex.

Aged ; Brain ; metabolism ; Cognition Disorders ; metabolism ; psychology ; Female ; Glucose ; metabolism ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Tomography, Emission-Computed