The Predictive Value of Coronary Microvascular Dysfunction For Left Ventricular Reverse Remodelling in Dilated Cardiomyopathy

AIMS: to evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR). METHODS: In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Time RESULTS: With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SI CONCLUSIONS: CMD could be found in DCM patients and was more impaired in patients with non-LVRR than LVRR patients. Tim

The predictive value of coronary microvascular dysfunction for left ventricular reverse remodelling in dilated cardiomyopathy

AimsTo evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR).MethodsIn this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Timemax), maximum signal intensity (SImax), baseline signal intensity (SIbaseline), and the difference between maximum and baseline signal intensity (SImax−baseline) were measured. Additionally, left ventricular (LV) structure, function parameters, and late gadolinium enhancement (LGE) were also recorded. The parameters were compared between healthy controls and DCM patients. Univariable and multivariable logistic regression analyses were used to determine the predictors of LVRR.ResultsWith a median follow-up period of 12 months [interquartile range (IQR), 8–13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SIbaseline, and increased Timemax (all p < 0.01). Timemax, SImax, and SImax−baseline were further decreased in LVRR than non-LVRR group (Timemax: 60.35 [IQR, 51.46–74.71] vs. 72.41 [IQR, 59.68–97.70], p = 0.017; SImax: 723.52 [IQR, 209.76–909.27] vs. 810.92 [IQR, 581.30–996.89], p = 0.049; SImax−baseline: 462.99 [IQR, 152.25–580.43] vs. 551.13 [IQR, 402.57–675.36], p = 0.038). In the analysis of multivariate logistic regression, Timemax [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.95–1.00; p = 0.032)], heart rate (OR 1.04; 95% CI 1.01–1.08; p = 0.029), LV remodelling index (OR 1.73; 95% CI 1.06–3.00; p = 0.038) and LGE extent (OR 0.85; 95% CI 0.73–0.96; p = 0.021) were independent predictors of LVRR.ConclusionsCMD could be found in DCM patients and was more impaired in patients with non-LVRR than LVRR patients. Timemax at baseline was an independent predictor of LVRR in DCM

A comprehensive approach to developing a multi-epitope vaccine against Mycobacterium tuberculosis: from in silico design to in vitro immunization evaluation

IntroductionThe Bacillus Calmette-Guérin (BCG) vaccine, currently used against tuberculosis (TB), exhibits inconsistent efficacy, highlighting the need for more potent TB vaccines.Materials and methodsIn this study, we employed reverse vaccinology techniques to develop a promising multi-epitope vaccine (MEV) candidate, called PP13138R, for TB prevention. PP13138R comprises 34 epitopes, including B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes. Using bioinformatics and immunoinformatics tools, we assessed the physicochemical properties, structural features, and immunological characteristics of PP13138R.ResultsThe vaccine candidate demonstrated excellent antigenicity, immunogenicity, and solubility without any signs of toxicity or sensitization. In silico analyses revealed that PP13138R interacts strongly with Toll-like receptor 2 and 4, stimulating innate and adaptive immune cells to produce abundant antigen-specific antibodies and cytokines. In vitro experiments further supported the efficacy of PP13138R by significantly increasing the population of IFN-γ+ T lymphocytes and the production of IFN-γ, TNF-α, IL-6, and IL-10 cytokines in active tuberculosis patients, latent tuberculosis infection individuals, and healthy controls, revealing the immunological characteristics and compare the immune responses elicited by the PP13138R vaccine across different stages of Mycobacterium tuberculosis infection.ConclusionThese findings highlight the potential of PP13138R as a promising MEV candidate, characterized by favorable antigenicity, immunogenicity, and solubility, without any toxicity or sensitization

RNA-seq Analysis of the BCG Vaccine in a Humanized Mouse Model

This study was aimed at screening differentially expressed genes (DEGs) and exploring the potential immune mechanism induced by the Bacillus Calmette-Guerin (BCG) vaccine in a humanized mouse model. Candidate DEGs between mice vaccinated with BCG or injected with PBS were identified through transcriptomics, and their biological functions, signaling pathways, and protein interaction networks were analyzed through bioinformatics. A total of 1035 DEGs were identified by transcriptomics: 398 up-regulated and 637 down-regulated. GO analysis indicated that these DEGs were significantly enriched in cell adhesion, oxygen transport, receptor complex, carbohydrate binding, serine-type endopeptidase activity, and peroxidase activity terms. KEGG analysis indicated that these DEGs were involved in the Rap1 signaling pathway, axon guidance, PI3K-Akt signaling pathway, natural killer cell mediated cytotoxicity, and cytokine-cytokine receptor interaction. Protein interaction network analysis demonstrated that the Myc, Vegfa, and Itgb3 proteins had the highest aggregation degree, aggregation coefficient, and connectivity. The BCG vaccine induced 1035 DEGs in humanized mice. Among them, the differentially expressed down-regulated genes myc and itgb3 involved in the PI3K-Akt signaling pathway may play essential roles in the immune mechanism of the BCG vaccine

Soil horizons regulate bacterial community structure and functions in Dabie Mountain of the East China

Abstract Soil bacterial communities regulate nutrient cycling and plant growth in forests. Although these bacterial communities vary with soil nutrients and plant traits, the variation and degree with soil horizons in different forest types remain unclear. Here, bacterial communities of 44 soil samples from organic horizon (O horizon) and mineral horizon (M horizon) of three forest types (Cunninghamia, broad-leaved and Pinus forests) in subtropical forests of Dabie Mountain, China were analyzed based on amplicon sequencing. We assessed the effects of soil horizons and forest types on bacterial communities. The results showed that the bacterial richness and diversity were significantly higher in the O horizon than in the M horizon. Furthermore, the bacterial community composition and functions were also remarkably different between the two soil horizons. Furthermore, forest types could affect bacterial community composition but not for diversity and functions. Moreover, soil organic matter, including the total organic carbon, available phosphorus, total organic nitrogen, available potassium, ammonium nitrogen, and pH were main drivers for bacterial community composition. The results propose robust evidence that soil horizons strongly driven bacterial community composition and diversity, and suggest that microhabitat of soil bacterial communities is important to maintain the stability of forest ecosystem

Measurement of Phthalates in Skin Wipes: Estimating Exposure from Dermal Absorption

This study has determined the levels of six phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), di­(isobutyl) phthalate (DiBP), di­(<i>n</i>-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP), and di­(2-ethylhexyl) phthalate (DEHP)) in skin wipes; examined factors that might influence the levels, including body location, time of sampling, and hand-washing; and estimated dermal absorption based on the measured levels. Skin wipes were collected from the forehead, forearm, back-of-hand, and palm of 20 participants using gauze pads moistened with isopropanol. DiBP, DnBP, and DEHP were most frequently detected; DEHP levels were substantially higher than DnBP and DiBP levels, and DnBP levels were somewhat lower than DiBP levels. The levels differed at different body locations, with palm > back-of-hand > forearm ≥ forehead. Repeated wipe sampling from six participants over a 1 month period indicated that levels at the same body location did not vary significantly. The estimated median total dermal absorption from skin surface lipids on the palm, back-of-hand, arm, and head are 0.48, 0.68, and 0.66 (μg/kg)/day for DiBP, DnBP, and DEHP, respectively. These estimates are roughly 10–20% of the total uptake reported for Chinese adults and suggest that dermal absorption contributes significantly to the uptake of these phthalates. Washing with soap and water removed more than 50% of the phthalates on the hands and may be a useful tool in decreasing aggregate phthalate exposure

Impact of Clothing on Dermal Exposure to Phthalates: Observations and Insights from Sampling Both Skin and Clothing

Clothing can either retard or accelerate dermal exposure to phthalates. To investigate the impact of clothing on dermal exposure to six phthalates (DMP/DEP/DiBP/DnBP/BBzP/DEHP) in real environments, two sets of experiments have been conducted: (1) Skin wipes were collected from 11 adults to examine the phthalate levels on both bare-skin (hand/forehead) and clothing-covered body locations (arm/back/calf); (2) Five adults were asked to wear just-washed jeans for 1 day (1^st experiment), 5 days (2^nd experiment), and 10 days (3^rd experiment). Phthalate levels on their legs were measured on selected days during the wearing period, and phthalate levels in the jeans were measured at the end of each experiment and again after washing. Measured phthalate levels on body locations covered by clothing were lower than those on uncovered locations, but still substantial. Dermal uptake would be underestimated by a factor of 2 to 5 if absorption through body locations covered by clothing were neglected. Phthalate levels in the jeans and on the legs increased with the wearing time. However, the levels in the jeans and on the legs were not strongly correlated, indicating that other pathways, e.g, contact with bedding or bedclothes, likely contribute to the levels on the legs. The efficiency with which laundering washing removed phthalates from the jeans increased with decreasing <i>K</i>_ow; median values ranged from very low (<5%) for DEHP to very high (∼75%) for DMP

Contrast-enhanced CT radiomics for preoperative prediction of stage in epithelial ovarian cancer: a multicenter study

Abstract Background Preoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset. Methods A total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test. Results Seven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P < 0.001). Conclusions The combined model integrating clinical characteristics and radiomics features shows potential as a non-invasive adjunctive diagnostic modality for preoperative evaluation of the FIGO staging status of EOC, thereby facilitating clinical decision-making and enhancing patient outcomes

Effect of Lipoxin A4 on Lipopolysaccharide-Induced Endothelial Hyperpermeability

Excessive oxidative stress, decreased antioxidant capacity, and enhanced cellular calcium levels are initial factors that cause endothelial cell (EC) hyperpermeability, which represents a crucial event in the pathogenesis of pre-eclampsia. Lipoxin A4 (LXA4) strongly attenuated lipopolysaccharide (LPS)-induced hyperpermeability through maintaining the normal expression of VE-cadherin and β-catenin. This effect was mainly mediated by a specific LXA4 receptor. LXA4 could also obviously inhibit LPS-induced elevation of the cellular calcium level and up-regulation of the transient receptor potential protein family C 1, an important calcium channel in ECs. At the same time, LXA4 strongly blocked LPS-triggered reactive oxidative species production, while it promoted the expression of the NF-E2 related factor 2 (Nrf2) protein. Our findings demonstrate that LXA4 could prevent the EC hyperpermeability induced by LPS in human umbilical vein endothelial cells (HUVECs), under which the possible mechanism is through Nrf2 as well as Ca2+-sensitive pathways