Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis.

Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.

Prevalence and type distribution of high-risk human papillomavirus infections among women in Wufeng County, China.

OBJECTIVE: The aim of this survey was to assess the prevalence and type distribution of oncogenic human papillomavirus (HPV) infections among women in Wufeng County of Hubei province, where the cervical cancer mortality rate is the highest in China Cervical. METHODS: DNA samples were collected from 1,100 women, then screened and quantified by a multi-fluorescent, quantitative real-time PCR assay. The cervical DNA samples were then re-typed by real-time PCR using seven-pair primers of high-risk (HR) HPVs designed to detect types 16, 31, 18/45, 33, 52, 58, and 67. RESULTS: The overall prevalence of HR HPVs was 11.14 % (95 % CI, 9.74-13.72 %) in Wufeng County, which was not statistically different between Tu (12.17 %; 95 % CI, 10.03-12.34 %) and Han nationality (8.95 %; 95 % CI, 3.55-14.35 %). Among different types of HPV, HPV 16 was the most frequently detected genotype, followed by HPV 52, 58, 18/45, and 31. The most prevalent types of HR HPV in Tu nationality were HPV 16, 52, and 58, and the most prevalent types of HR HPV in Han nationality were HPV 16, 33, and 18/45. The overall prevalence of HPV was highest in the 20-24 year age group (21.43 %; 95 % CI, 17.56-25.30 %) and the prevalence of HR HPV was associated with education. CONCLUSIONS: HPV 16, 52, and 58 are common genotypes in Wufeng County, and support the hypothesis that second-generation HPV prophylactic vaccines, including HPV 52 and 58, may offer higher protection for women in China and other areas of Asia. The findings of this study contribute to preventive and screening measures in clinical practice.

Classification and identification of polar pollutants on microplastics from freshwater using nontarget screening strategy.

Microplastics (MPs) cause an increased threat to the freshwater environment by adsorbing pollutants on their large surface area. Considering their adsorption characteristics, non-polar pollutants with high distribution coefficients have been studied extensively. However, comprehensive research on the types of polar pollutants adsorbed by MPs is lacking. In this study, a nontarget screening strategy, including classification and identification, was performed to analyze the pollutants adsorbed by MPs in Tai Lake and the Yangtze River. Compared with the pollutants adsorbed or added to raw plastics, more types of polar pollutants were found on MPs from freshwater. The nontarget classification of 4723 features on MPs from freshwater and 680 features from raw plastics were annotated based on the mass spectrometry spectra. Further identification with multiple platforms identified hundreds of pollutants absorbed by MPs in Tai Lake and Yangtze River, including industrial intermediates, medicines, and surfactants, exceeding those adsorbed by raw plastics, showing an enrichment of the pollutants on MPs in freshwater by secondary adsorption. Our study is the first to use nontarget analysis to comprehensively demonstrate MP adsorption and release of pollutants in freshwater environment, providing a significant reference for the research of MPs and the management of the water environment.

DNMT1 Methylation of LncRNA GAS5 Leads to Cardiac Fibroblast Pyroptosis via Affecting NLRP3 Axis.

Cell death and inflammation play critical roles in cardiac fibrosis. During the fibrosis process, inflammation and tissue injury were triggered; however, the mechanisms initiating cardiac fibrosis and driving fibroblast pyroptosis remained largely unknown. In this study, we identified long non-coding RNA (LncRNA)-GAS5 as the key onset of cardiac fibroblast pyroptosis and cardiac fibrosis. Here, we detected ISO-induced cardiac fibrosis models and cardiac fibroblast pyroptosis model by stimulating with LPS. We found that the expression of pyroptosis-related proteins such as caspase 1, NLRP3, and DNMT1 was increased in cardiac fibrosis tissue, while the expression of GAS5 was decreased. The overexpressing of LncRNA GAS5 was shown to increase and inhibit cardiac fibroblast pyroptosis, as well as attenuate caspase 1 and NLRP3 expression in cardiac fibroblast. However, the silencing of GAS5 was also observed; it shows the opposite situation. Furthermore, further studies revealed that treatment of DNMT inhibitor, 5-aza-2-deoxycytidine, or downregulation of DNMT1 led to increased GAS5 expression by reversion of promoter hypermethylation in cardiac fibroblast. Importantly, we have demonstrated that DNMT1 methylation of LncRNA GAS5 leads to cardiac fibroblast pyroptosis via affecting NLRP3 axis. Our findings indicate a new regulatory mechanism for cardiac fibroblast pyroptosis under LPS stress, providing a novel therapeutic target for cardiac fibrosis. Graphical Abstract.

Exploration of turn-positive RT-PCR results and factors related to treatment outcome in COVID-19: A retrospective cohort study.

The cause of some patients with negative RT-PCR results experienced turn-positive after treatment remains unclear. In addition, understanding the correlation between changes in clinical data in the course of COVID-19 and treatment outcomes is of great importance in determining the prognosis of COVID-19. To perform cause analysis of RT-PCR turn-positive and the effective screening factors related to treatment outcome in COVID-19. Clinical data, including clinical manifestations, laboratory tests, radiography results, treatment methods and outcomes, were retrospectively collected and analyzed from January to March 2020 in Renmin Hospitals of Wuhan University. 116 COVID-19 patients (40 in recurrent group, 29 in recovered group and 47 in unrecovered group) were recruited. In the recurrent group, white blood cell, Neutrophils, prothrombin time, activated partial thromboplastin time, CD3, CD4, CD8, ratio of CD4/CD8, IgG and C4 complement were of significant difference among the baseline, negative and turn-positive time points. CD19 and CT scan results were found notable difference between recurrent group and recovered group. Odds from CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT scan results validated associations with clinical outcomes of COVID-19. The so-called recurrence in some COVID-19 patients may be due to the false-negative of nucleic acid test results from nasopharyngeal swabs. Levels of CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT results were significantly correlated with the outcome of COVID-19. The cellular immunity test could be beneficial to further screen the reliability of RT-PCR test on the basis of CT images.

DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis.

Hepatic stellate cells (HSCs) activation is considered as a pivotal event in liver fibrosis. In HSCs activation and fibrosis, epigenetic events are important. Although HSCs activation alters DNA methylation, it is unknown, whether it also affects other epigenetic processes, including LncRNA and its recognition. The aim of this study was to identify the mechanism of DNA methyltransferase 1 (DNMT1) expression and its role in regulating LncRNA H19 during HSCs activation and fibrosis. Expression of DNMT1 and LncRNA H19 were determined in activated HSCs and CCl4-induced rat liver fibrosis tissue. The relationship between the LncRNA H19 and DNMT1 expression was examined in vitro. LncRNA H19 expression was reduced in activated HSCs and rat liver fibrosis tissue, whereas DNMT1 expression and methylation of the LncRNA H19 promoter were increased. Treatment of HSCs of DNMT1-siRNA blocked cell proliferation. Knockdown of DNMT1 elevated H19 expression in activated HSCs, and over-expression of DNMT1 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on ERK signal pathway. Treatment HSCs with H19-siRNA increased the expression of p-ERK1/2 in HSCs. Treatment with 5'-aza-2'-deoxycytidine in activated HSCs model reduced fibrosis gene and DNMT1 expression, enhanced H19 expression, and attenuated HSCs activation. These data connect HSCs activation with a DNMT1-LncRNA H19 epigenetic pathway that is important for liver fibrosis.

Neurological symptoms and spinal cord embolism caused by endoscopic injection sclerotherapy for esophageal varices: A case report and literature review.

RATIONALE: Spinal cord embolism is a rare complication of endoscopic injection sclerotherapy (EIS). PATIENT CONCERNS: We report a case of a 56-year-old man who presented neurological symptoms and spinal cord embolism caused by EIS on esophageal varices. Clinical signs and symptoms, laboratory tests, thoracic magnetic resonance imaging (MRI), and related treatment supported its diagnosis. DIAGNOSES:: spinal cord embolism. INTERVENTIONS: We stopped the hemostatic and anti-coagulation treatment, and switched to nerve nutrition, microcirculation, and hormone therapy, along with administering gastric mucosal protective agents. OUTCOMES: The all patient's signs and symptoms and signs of spinal cord embolism were all relieved within 3 months after the clinical treatment. LESSONS: We recommend that neurological symptoms after EIS in patients with esophageal varices should be considered a rare complication. Life-threatening conditions could be avoided by an accurate and timely diagnosis.

Assessment of ecological conditions over China's coastal areas based on land use/cover change.

Studying the changes of land use and its impacts on ecological condition in coastal areas is of great significance for understanding the evolution of the regional ecological conditions and even global change. In this study, the study area encompassed 10 provincial administrative units of China's coastal areas, covering a total of 56 cities. Based on the land use and land cover data in 1980, 1990, 1995, 2000, 2005, 2010 and 2015 and the corresponding elevation data, we assessed ecological conditions and its temporal dynamic evolution and spatial differentiation characteristics with the ecological grade index method. The effects of the elevation differentiation and land-sea gradient on the ecological condition in China's coastal areas were analyzed. The results showed that the ecological conditions of China's coastal areas were basically stable and deteriorated on the whole although partially improved from 1980 to 2015. With Hangzhou Bay as a boundary-belt, ecological conditions in southern parts were better than that in the northern parts. The ecological grade index differed significantly with the variation of elevation. The areas with elevation below 10 m were in rela-tively poor ecological condition, and the regions below 30 m had the most obvious changes of ecological conditions. Moreover, the ecological conditions increased with elevation, with a gradual turnaround trend of improvement at above 400 m. There was a gradient characteristic of the ecological grade index in China's coastal areas, showing a high-low-high pattern from land to sea. Furthermore, the maximum value of ecological condition changes appeared at a distance of 10 km to the coastline, and the values decreased with the increasing of distance to the coastline.

The prepurse-string suture technique for gastric defect after endoscopic full-thickness resection (with video).

Endoscopic full-thickness resection (EFTR) is the main treatment for gastric tumors originating from the muscularis propria or gastric extra-luminal growth tumors. Successful closure of the gastric wall defect is a critical step during EFTR.The aim of this retrospective study was to evaluate the feasibility and safety of the endoscopic prepurse-string suture (p-EPSS) technique using an endoloop and several metallic clips during EFTR to close the perforation.Twenty-five patients with gastric tumors originated from the muscularis propria or with gastric extra-luminal growth tumors who received EFTR were analyzed at the Renmin Hospital of Wuhan University from June 2016 to May 2017. Patient characteristics, tumor characteristics, operation time length, and postoperative complications were evaluated in all patients.All the 25 patients underwent a successful EFTR. Complete closure of gastric defects was also achieved. The mean operation time length was 31 ±â€Š14 minutes. The mean maximum size of tumor of was 1.7 ±â€Š1.0 cm (range 0.5-4.5 cm). No severe postoperative complications occurred, such as massive bleeding, gastric leak, peritonitis, or abdominal abscess. No patient needed surgical intervention. Wounds were well healed 1 month after EFTR. No tumor metastasis and recurrence were observed during the follow-up period (median, 7 months).The p-EPSS technique using endoloop and several sterile repositionable hemostasis clips is safe and feasible for closing gastric perforation during EFTR.

[Spatial Simulation of Black Carbon Concentrations Based on a Land Use Regression Model and Mobile Monitoring over Shanghai, China].

Black carbon (BC) is an important component of atmospheric pollution and has significant impacts on air quality and human health. Choosing Shanghai city for a case study, this paper explores the statistical characteristics and spatial patterns of BC concentrations using a mobile monitoring method, which differs from traditional fixed-site observations. Land use regression (LUR) modeling was conducted to examine the determinants for on-road BC concentrations, e.g. population, economic development, traffic, etc. These results showed that the average on-road BC concentrations were (9.86±8.68) µg·m-3, with a significant spatial variation. BC concentrations in suburban areas[(10.47±2.04) µg·m-3] were 32.03% (2.54 µg·m-3) higher than those in the city center[(7.93±2.79) µg·m-3]. Besides, meteorological factors (e.g. wind speed and relative humidity) and traffic variables (e.g. the length of roads, distance to provincial roads, distance to highway) had significant effects on on-road BC concentrations (r:0.5-0.7, P<0.01). Moreover, the LUR model, including meteorological and traffic variables performed well (adjusted R2:0.62-0.75, cross validation R2:0.54-0.69, RMSE:0.15-0.20 µg·m-3), which demonstrates that on-road BC concentrations in Shanghai are mainly affected by these factors and traffic sources to some extent. Among them, the most accurate LUR model was developed with a 100 m buffer, followed by the LUR model with a 5 km buffer. This study is of great significance for the identification of spatial distribution patterns for on-road BC concentration and exploring their influencing factors in Shanghai, which can provide a scientific basis and theoretical support for simulating and predicting the response mechanisms of BC on human health and the natural environment.

[Optimization and evaluation of key photosynthesis parameters in forest ecosystems based on FLUXNET data and VPM model.] / 基于FLUXNET观测数据与VPMæ¨¡åž‹çš„æ£®æž—ç”Ÿæ€ç³»ç»Ÿå ‰åˆä½œç”¨å ³é”®å‚æ•°ä¼˜åŒ–åŠéªŒè¯.

Gross primary productivity (GPP) plays an important role in global carbon cycle. Vegetation maximum light use efficiency (Δmax) is the key parameter for GPP simulation of terrestrial ecosystem. Based on the vegetation photosynthesis model (VPM) and the eddy covariance flux data at 40 stations from FLUXNET (179 site-years of data), we identified the key model parameters influencing the simulation of GPP with VPM through one-at-a-time (OAT) method. The cross validation method was employed to optimize the key model parameters and evaluate the model perfor-mance for global forest ecosystems. The results showed that the prediction of GPP was mostly affec-ted by Δmax, maximum temperature for photosynthesis (Tmax), and optimum temperature for photosynthesis (Topt). There were distinguishable differences for the key optimized parameters among different forest ecosystems. The optimized Δmax ranged from 0.05 to 0.08 µmol CO2·µmol-1 PAR (evergreen broad-leaved forest>evergreen coniferous forest>mixed forest>deciduous broad-leaved forest). The optimized Tmax ranged from 38 to 48 ℃,while Topt ranged from 18 to 22 ℃. With the optimized key parameters based on ecosystem types, the VPM was able to simulate the seasonal and inter-annual variations of GPP in four forest ecosystems.

Primary application of PPE68 of Mycobacterium tuberculosis.

PPE68 protein is absent from BCG and the attenuated strains of Mycobacterium tuberculosis (MTB). In this study, the shuttle plasmid pBudCE4.1/PPE68/OriM was constructed and transformed into BCG to obtain PPE68 recombination BCG (PPE68-rBCG), and BALB/c mice were immunized with PPE68-rBCG to evaluate the immunological characterization of PPE68-rBCG. The level of lgG2a, IFN-γ, IL-12 and IL-4 in serum of immunized mice were detected, the proliferation response of spleen lymphocyte were measured, the frequency of CD4(+), CD8(+) and CD4(+)/CD8(+) were determined, and the spleen and lung tissue were prepared for pathological analysis. PPE68-rBCG was constructed successfully and could induce powerful Th1 immune response in mice. Besides, we took the purified recombination PPE68 (rPPE68) protein as diagnostic antigen to detect pulmonary tuberculosis patients (n=252) and extrapulmonary tuberculosis patients (n=66). We also used anti-PPE68 polyclonal antibody as coating antibody to detect specific antigen in the same serum samples. Our data provide an experimental basis for potential application of rPPE68 in the diagnosis of tuberculosis, especially for extrapulmonary tuberculosis.