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 assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Background The subway environment, characterized by dense crowds, relatively enclosed architectural structures, and insufficient ventilation, poses various health hazards. Population health risk attributable to subway hygiene have become an important public health issue. Objective To evaluate the current environmental hygiene of metro line X in Nanjing, and to provide a scientific basis for the prevention and control of harmful factors and the establishment of relevant standards. Methods Station halls, platforms, and carriages of Nanjing metro line X were monitored in March 2023. Six stations were selected by stratified sampling, and monitored once during the morning peak hours (9:00—11:00). Carriage monitoring was conducted after a full day of operation (21:00—22:00). The monitoring indicators included physical factors such as temperature, relative humidity, wind speed, illuminance, and noise (A-weighted); air quality factors such as carbon dioxide (CO₂), carbon monoxide (CO), respirable particulate matter (PM₁₀), fine particulate matter (PM_2.5), ammonia (NH₃), formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), ozone (O₃), total bacterial count, and total fungi count; hygiene status of the inner surface of the central air conditioning ventilation system, such as dust accumulation, total bacterial count, and total fungi count; supply air, such as PM_10, PM_2.5, total bacterial count, and total fungi count; and surface microorganisms on objects, such as total bacterial count, total fungi count, coliform bacteria, and Staphylococcus aureus. Results were evaluated and discussed according to Hygienic indicators and limits for public places (GB 37488-2019) and Hygienic specification of central air conditioning ventilation systems in public buildings (WS 394-2012). Results The environmental temperature medians (P₂₅, P₂₅) in the platforms and carriages of Nanjing metro line X were 20.7 (19.95, 21.65) ℃ and 21.8 (19.80, 35.80) °C, respectively, which exceeded the standard limits. The relative humidity and noise level in the carriages were 38.80% (24.6%, 46.3%) and 79.50 (76.25, 82.00) dB, respectively, failing to meet the national health standards. The total fungi count in supply air in 22.2% of the monitoring points exceeded the standard value. Coliform bacteria and Staphylococcus aureus were detected on the surfaces of some high-touch objects, with the bathroom faucet being the most severely contaminated. The medians (P₂₅, P₂₅) of temperature [21.8 (19.8, 35.8) ℃], wind speed [0.48 (0.39, 1.02) m·s⁻¹], noise [79.5 (76.25, 82.00) dB, and CO₂ content [0.079% (0.070%, 0.091%)] in the carriages were higher than those in the station halls and platforms (P<0.05). There were significant differences in microclimate, air particulate matter, and air microbial levels between urban and suburban stations (P<0.05); the concentrations of PM₁₀ [0.076 (0.046, 0.079) mg·m⁻³)] and PM_2.5 [0.063 (0.044, 0.068) mg·m⁻³)] in suburban stations were 2 times higher than those of urban stations. The temperature [21.60 (20.45, 21.80) ℃], humidity [45.20% (40.95%, 50.10%)], CO₂ [0.100% (0.100%, 0.825%)], and PM₁₀ concentration [0.070 (0.041, 0.080) mg·m⁻³] in transfer stations were all significantly higher than those in non-transfer stations (P<0.05). The temperature at stations was significantly correlated with the CO₂ content (r_s=0.6107, P<0.001), the concentration of air particulate matter and the content of air microorganisms were positively correlated with the relative humidity (P<0.05), and the air PM₁₀ and PM_2.5 concentrations were positively correlated with the total bacterial count and the total fungi count (P<0.05). There was a significant positive correlation between the total bacterial count and the total fungi count on the inner surface of the air duct (r_s=0.5877, P<0.05). The concentrations of PM₁₀ and PM_2.5 in supply air were positively correlated (r_s=0.9635, P<0.001), and both were also positively correlated with the total bacterial count in supply air (r_s=0.6848 and 0.6511, P=0.002 and 0.003). Conclusion All chemical factors of metro line X in Nanjing meet the national standards, while physical factors (temperature, relative humidity, wind speed, and noise) exceed the standards, and coliform bacteria and Staphylococcus aureus are detected on the surfaces of bathroom faucets and carriage poles. It is advisable to reinforce microclimate management and noise reduction measures in carriages, while ensuring regular cleaning and disinfection of public facilities and equipment.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4⁺ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4⁺ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4⁺ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/10⁶ CD4⁺ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

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.

Background: Hepatocyte growth factor (HGF)/cMet pathway is necessary for repair and regeneration following acute kidney injury (AKI). We evaluated the clinical potential of plasma HGF and soluble cMet as prognostic biomarkers for severe AKI requiring continuous renal replacement therapy (CRRT). Methods: One hundred thirty-six patients with severe AKI who participated in the VENUS (volume management under body composition monitoring in critically ill patients on CRRT) trial between 2017 and 2019 were enrolled in this study. We investigated associations between plasma HGF and cMet concentrations and all-cause mortality. Results: Plasma HGF and soluble cMet levels were positively correlated. Patients were divided into three groups based on their HGF and soluble cMet concentrations. The day D 0, D2, and D7 highest concentration HGF groups had significantly higher in-hospital mortality after adjusting for sex, body mass index, Acute Physiology and Chronic Health Evaluation II, and age-adjusted Charlson comorbidity index score, especially on D7 (hazard ratio, 4.26; 95% confidence interval, 1.71–10.62; p = 0.002). D7 soluble cMet level was also associated with mortality. Receiver operating characteristic curve analysis indicated that D7 HGF and soluble cMet levels were best at predicting mortality. Addition of plasma HGF and soluble cMet to conventional prognostic indices significantly improved the predictive value for mortality on D7. However, plasma HGF and soluble cMet were not associated with fluid status. Conclusion Plasma HGF and soluble cMet levels were significant predictors of the outcomes of severe AKI patients undergoing CRRT. There was no correlation between plasma HGF and soluble cMet levels and fluid balance.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

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.