Identification of Key Ferroptosis-Related Genes in the Peripheral Blood of Patients with Relapsing-Remitting Multiple Sclerosis and Its Diagnostic Value.

Multiple sclerosis (MS) is a neurodegenerative disease with a complex pathogenesis. Re-lapsing-remitting multiple sclerosis (RRMS) is the most common subset of MS, accounting for approximately 85% of cases. Recent studies have shown that ferroptosis may contribute to the progression of RRMS, but the underlying mechanism remains to be elucidated. Herein, this study intended to explore the molecular network of ferroptosis associated with RRMS and establish a predictive model for efficacy diagnosis. Firstly, RRMS-related module genes were identified using weighted gene co-expression network analysis (WGCNA). Secondly, the optimal machine learning model was selected from four options: the generalized linear model (GLM), random forest model (RF), support vector machine model (SVM), and extreme gradient boosting model (XGB). Subsequently, the predictive efficacy of the diagnostic model was evaluated using receiver operator characteristic (ROC) analysis. Finally, a SVM diagnostic model based on five genes (JUN, TXNIP, NCOA4, EIF2AK4, PIK3CA) was established, and it demonstrated good predictive performance in the validation dataset. In summary, our study provides a systematic exploration of the complex relationship between ferroptosis and RRMS, which may contribute to a better understanding of the role of ferroptosis in the pathogenesis of RRMS and provide promising diagnostic strategies for RRMS patients.

Membrane tension sensing molecule-FNBP1 is a prognostic biomarker related to immune infiltration in BRCA, LUAD and STAD.

BACKGROUND: Formin-binding protein 1/17 (FNBP1/FBP17), as a membrane-bound protein, is wildly expressed in eukaryotic cells and performs a critical role in tumor tumorigenesis and progression. However, the relationship between FNBP1 and immune infiltrating cells, prognostic value in patients still require comprehensive understanding. We purposed to explore the correlations of FNBP1 expression, prognosis and immune infiltration levels in various cancers. METHOD: The expression and survival data of FNBP1 were collected from Oncomine, TIMER, GEPIA, Kaplan-Meier Plotter and PrognoScan databases. Correlations between FNBP1 and immune infiltrates were analyzed in TIMER and GEPIA databases. RESULTS: Compared with normal tissues, FNBP1 is significantly differentially expressed in a variety of tumor tissues. FNBP1 has significant and complex effects on the prognosis of kinds of cancers. High-expression was obviously correlated with better prognosis in breast carcinoma and lung adenocarcinoma, while worse prognosis in stomach adenocarcinoma. Besides, FNBP1 had a correlation with various immune infiltrating cells and diverse immune gene markers in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD). FNBP1 was also positively correlated with the adjustment of CD8+ cells, T cells, M2 macrophage, neutrophils, monocyte, Th1 cells, T regulatory cells (Treg) and Tumor-associated macrophages (TAMs). The expression level of FNBP1 is closely positively correlated with the expression level of multiple immune checkpoints in the three cancers. In addition, FNBP1 is significantly positively correlated with the expression levels of a variety of immunosuppressive molecules. CONCLUSION: Our findings reveal FNBP1 can serve as a significant biomarker to influence the prognosis and the immune infiltrating levels in different cancers. The differential expression of FNBP1 might not only contribute to the judgment of metastatic and non-metastatic tumors but also in the immune escape by upregulating the expression of immune checkpoints.

Interactions between the antibiotic tetracycline and humic acid: Examination of the binding sites, and effects of complexation on the oxidation of tetracycline.

The binding between dissolved organic matter (DOM) and micro-pollutants (MPs) results in significant impacts on their migration, transformation and degradation. However, the role of the DOM/MP binding on their oxidative transformation remains poorly studied. The binding of MPs by DOM, in combination with DOM's roles as a photosensitizer and/or a competitor for free radicals, needs to be considered in the context of understanding the DOM's impacts on the oxidative degradation of MPs. This study aims to explore this aspect of DOM/MP interactions based on the quantitation of humic acid (HA) and tetracycline (TET) complexation and its role in TET removal. This study also compared the degradation of free TET versus that bound in HA-TET complexes in different oxidation processes. Fourier transform infrared (FTIR) data show that the carboxyl and phenolic hydroxyl groups in HA are the main binding sites of TET, while nuclear magnetic resonance (NMR) analysis shows the binding of TET engages its -N(CH3)2 groups, and two-dimensional correlation spectroscopy (2D-COS) data show that the carboxyl groups in DOM are sensitive than phenolic groups in the binding of TET. The difference between the degradation rates (Δkobs) of the free and bound TET decreased with the increase of ionic strength using sodium nitrate, but increased with the introduction of Ca2+ and Mg2+ due to the formation of TET-Ca2+/Mg2+ complexes. Quenching experiments showed that the free radicals (•OH and •SO4-), PMS oxidant and UV light were the main contributors to the TET degradation in UV/PS, UV/PMS and UV/H2O2 processes, respectively. In-situ fluorescence time scanning and differential absorbance spectra showed that free TET was preferentially oxidized over the bound TET in all the tested treatments except UV/PS. These results provide new insights into the role of DOM/MP complexation in the degradation of MPs in natural and engineered systems.

Impact of hydrological factors on the dynamic of COVID-19 epidemic: A multi-region study in China.

Considering the live SARS-CoV-2 was detected and isolated from the excrement and urine of infected patients, the potential public health risk of its waterborne transmission should be paid broad and close attention. The purpose of the current study is to investigate the associations between COVID-19 incidences and hydrological factors such as lake area, river length, precipitation and volume of water resources in 30 regions of China. All confirmed cases for each areas were divided into two clusters including first cases cluster driven by imported cases during the period of January 20th to January 29th, 2020 and second cases cluster driven by local cases during the period of January 30th to March 1st, 2020. Based on the results of descriptive analysis and nonlinear regression analysis, positive associations with COVID-19 confirmed numbers were observed for migration scale index (MSI), river length, precipitation and volume of water resources, but negative associations for population density. The correlation coefficient in the second stage cases cluster is apparently higher than that in the first stage cases cluster. Then, the negative binomial-generalized linear model (NB-GLM) was fitted to estimate area-specific effects of hydrological variables on relative risk (RR) with the incorporation of additional variables (e.g., MSI) and the effects of exposure-lag-response. The statistically significant associations between RR and river length, the volume of water resources, precipitation were obtained by meta-analysis as 1.24 (95% CI: 1.22, 1.27), 2.56 (95% CI: 2.50, 2.61) and 1.59 (95% CI: 1.56, 1.62), respectively. The possible water transmission routes of SARS-CoV-2 and the potential capacity of long-distance transmission of SARS-CoV-2 in water environment was also discussed. Our results could provide a better guidance for local and global authorities to broaden the mind for understanding the natural-social system or intervening measures for COVID-19 control at the current or futural stage.

Staged assessment for the involving mechanism of humic acid on enhancing water decontamination using H2O2-Fe(III) process.

Humic acid (HA) as a natural coordinating agent was employed to modify the Fenton-like process by promoting the redox cycle of Fe(III)/Fe(II) and enhancing the pH tolerance. However, the roles of coordinating stages of HA-Fe(III) and the dynamic changes of iron species remain unclear. In this study, HA was introduced into the H2O2-Fe(III) process to investigate the accelerating roles of coordinating stages and systematically reveal the mechanism via the reactive oxygen species (ROS) identification, HA-Fe(III)/Fe(II) redox cycles tracking, electrochemical and kinetic analysis. Results suggested that two reaction stages were separated concerning the enhancement for HA in H2O2-Fe(III) process, including coordinating stage (slow rate) and promoting the redox stage (fast rate). HA-Fe(III) was identified as the major contributor, along with hydroxyl radical (·OH) and superoxide radical (·O2-) as the dominant ROS with formation rates calculated as 7.0 × 10-9 and 2.1 × 10-3 M s-1 via the steady-state model. Based on the density-functional theory (DFT) calculations and HPLC-MS/MS analysis, three degradation pathways of 2,4-Dichlorophenol were proposed with ten intermediate products identified, and the ecotoxicity was evaluated through Ecological Structure Activity Relationships (ECOSAR) program. This study unveiled the mechanism of HA on enhancing water decontamination via H2O2-Fe(III) process in stages.

Estimation of the potential spread risk of COVID-19: Occurrence assessment along the Yangtze, Han, and Fu River basins in Hubei, China.

Given that the novel coronavirus was detected in stool and urine from diagnosed patients, the potential risk of its transmission through the water environment might not be ignored. In the current study, to investigate the spread possibility of COVID-19 via the environmental media, three typical rivers (Yangtze, Han, and Fu River) and watershed cities in Hubei province of China were selected, and a more comprehensive risk assessment analysis method was built with a risk index proposed. Results showed that the risk index in the Yangtze River Basin is about 10-12, compared to 10-10 and 10-8 in the Han and Fu River Basins, and the risk index is gradually reduced from Wuhan city to the surrounding cities. The safety radius and safety time period for the Yangtze, Han, and Fu River are 8 km/14 h, 20 km/30 h and 36 km/36 h, respectively. The linear relationship between the risk potential calculated by the QMRA model and the multiple linear regression proved that the built index model is statistically significant. By comparing the theoretical removal rates for the novel coronavirus, our study proposed an effective method to estimate the potential spread risk of COVID-19 in the typical river basins.

Impact of leaflet thrombosis on hemodynamics and clinical outcomes after bioprosthetic aortic valve replacement: A meta-analysis.

BACKGROUND: Leaflet thrombosis (LT, also called cusp thrombosis) detected by multidetector computed tomography (MDCT) is common in bioprosthetic aortic valve replacement (bAVR). However, it remains contradictory whether MDCT-defined LT following bAVR is associated with hemodynamic deterioration and stroke. Thus, we performed the first meta-analysis to assess hemodynamic outcomes and updated the latest researches on the clinical outcomes of MDCT-defined LT after bAVR. HYPOTHESIS: MDCT-defined LT might be associated with worse hemodynamic and clinical outcomes after bAVR. METHOD: MEDLINE, EMBASE, Cochrane Library, and ClinicalTrial.gov were searched from inception to 15th April 2019. The fix-effect model was utilized to calculate odds ratio (OR) and 95% confidence interval (CI). The primary outcomes were hemodynamic stability indexes, including mean pressure gradient (MPG), left ventricular ejection fraction (LVEF), paravalvular leak (PVL), and clinical heart failure. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs), which consisted of myocardial infarction, all-cause death, stroke, and transient ischemic attack (TIA). RESULTS: Twelve studies with 4820 patients were included. The total prevalence of MDCT-defined LT was 9.7%. MDCT-defined LT was associated with a significantly increased risk of MPG (inverse variance 0.43, 95% CI: [0.30, 0.57]), MACCEs (OR 2.43, 95% CI: [1.45, 4.06]), stroke (OR 1.79, 95% CI: [1.03, 3.11]), and TIA (OR 4.09, 95% CI: [1.59, 10.54]). There were no differences for other outcomes. CONCLUSIONS: MDCT-defined LT after bAVR is associated with increased MPG and increased risk of adverse cerebrovascular events, including TIA and stroke. While LVEF, PVL, and clinical heart failure were similar between patient with and without LT.

Synthesis of nano-octahedral MgO via a solvothermal-solid-decomposition method for the removal of methyl orange from aqueous solutions.

Nano magnesium oxide has wide applications, and MgO with (111) facets has wider potential applications than MgO with (100) facets (e.g., in catalysis and adsorption). However, nano MgO with (111) polar faces has not been studied throughly, so the preparation of nano-octahedral MgO (N-O-MgO) with eight exposed (111) facets remains a great challenge. Herein, we successfully synthesised N-O-MgO via an effective solvothermal-solid-decomposition method and studied its adsorption performance. The obtained N-O-MgO showed excellent performance (229.36 mg g-1) for methyl orange (MO). The adsorption follows the pseudo-second-order kinetic equation and the Langmuir isotherm model. The dimensionless parameter R L (0.042) and Gibbs free energy ΔG (-6.538 kJ mol-1) revealed that the adsorption of MO on N-O-MgO was a spontaneous and feasible process. The adsorption of MO and methyl blue (MB) on N-O-MgO were studied to determine the adsorption sites. Based on these experiments and analysis, it was determined that the adsorption sites were magnesium ions and the adsorption mechanism was proposed to describe the adsorption process.