High-performance seawater oxidation by a homogeneous multimetallic layered double hydroxide electrocatalyst.

SignificanceSeawater is one of the most abundant resources on Earth. Direct electrolysis of seawater is a transformative technology for sustainable hydrogen production without causing freshwater scarcity. However, this technology is severely impeded by a lack of robust and active oxygen evolution reaction (OER) electrocatalysts. Here, we report a highly efficient OER electrocatalyst composed of multimetallic layered double hydroxides, which affords superior catalytic performance and long-term durability for high-performance seawater electrolysis. To the best of our knowledge, this catalyst is among the most active for OER and it advances the development of seawater electrolysis technology.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

Objective: To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods: From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results: A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions: The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

Electronic Structure Regulation of Nickel Phosphide for Efficient Overall Water Splitting.

Rational design and fabrication of efficient and low-cost catalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are crucial for hydrogen production from water electrolysis. Herein, we report heteroatom Fe-incorporated Ni5P4 (Fe-NiP) as an excellent bifunctional catalyst for overall water splitting. Density functional theory (DFT) calculations reveal that heteroatom Fe effectively steers the electronic structure of Ni5P4, which optimizes the hydrogen adsorption behavior. Additionally, the hierarchical conductive framework of Fe-NiP contributes to abundant active sites. Thus, the Fe-NiP catalyst shows robust performance with enhanced intrinsic catalytic activity. As a good bifunctional catalyst, it demands low overpotentials of 144 and 223 mV to deliver a current density of 10 mA cm-2 for HER and OER, respectively. Considering the good bifunctional activity, an outstanding electrolyzer has been successfully assembled, which is superior to the benchmark of a RuO2(+)//Pt/C(-) electrolyzer. This study sheds light on steering the electronic structure of electrocatalysts through a heteroatom modulation strategy.

Effects of Spironolactone on Hypoxia-Inducible Factor-1α in the Patients Receiving Coronary Artery Bypass Grafting.

ABSTRACT: We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

Preliminary study of the relationship between promoter methylation of the ANGPTL2 gene and coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is primarily caused by atherosclerosis of coronary arteries. It is largely an inflammatory disease of the vascular wall. The inflammation is related to DNA methylation. Angiopoietin-like protein 2 (ANGPTL2) has various functions in several chronic inflammatory diseases. Macrophage-derived ANGPTL2 was reported to accelerate CHD development. It is reported that DNA hypomethylation in the promoter region of ANGPTL2 gene was associated with acute coronary syndrome (ACS), a type of CHD. Our objective was to explore the correlation between promoter methylation of the ANGPTL2 gene and CHD, and to investigate the association between methylation status and clinical characteristics of CHD patients. METHODS: Firstly, we collected 122 CHD patients and 58 non-CHD participants from Han Chinese population and purified the peripheral blood DNA. The purified DNA was subjected to bisulfite modification. After bisulfite conversion, the target DNA locus was amplified using polymerase chain reaction (PCR), and the PCR products were measured by pyrosequencing. Finally, the methylation level was calculated according to the sequencing result, and the data were analyzed using xx software. RESULTS: CHD patients had a relatively lower methylation levels (P50: 7.67% [P25: 6.22%, P75: 10.43%]) in the ANGPTL2 promoter region than did controls (P50: 8.25% [P25: 5.46%, P75: 17.98%], P = 0.001), indicating an association between ANGPTL2 promoter methylation and CHD (OR: 0.890; 95% CI, 0.832-0.953; adjusted P = 0.001). A breakdown analysis by gender showed that ANGPTL2 promoter methylation was associated with CHD in females (adjusted P = 0.002) but not in males (adjusted P = 0.404). We found no correlation between gene methylation and other clinical characteristics. CONCLUSIONS: The present work provides evidence to support an association between ANGPTL2 promoter DNA methylation status and the risk profile of CHD in females. Our data indicated that in females, promoter DNA hypomethylation of the ANGPTL2 gene is associated with an increased risk of CHD.

The Complete Chloroplast Genomes of Punica granatum and a Comparison with Other Species in Lythraceae.

Pomegranates (Punica granatum L.) are one of the most popular fruit trees cultivated in arid and semi-arid tropics and subtropics. In this study, we determined and characterized three complete chloroplast (cp) genomes of P. granatum cultivars with different phenotypes using the genome skimming approach. The complete cp genomes of three pomegranate cultivars displayed the typical quadripartite structure of angiosperms, and their length ranged from 156,638 to 156,639 bp. They encoded 113 unique genes and 17 are duplicated in the inverted regions. We analyzed the sequence diversity of pomegranate cp genomes coupled with two previous reports. The results showed that the sequence diversity is extremely low and no informative sites were detected, which suggests that cp genome sequences may be not be suitable for investigating the genetic diversity of pomegranate genotypes. Further, we analyzed the codon usage pattern and identified the potential RNA editing sites. A comparative cp genome analysis with other species within Lythraceae revealed that the gene content and organization are highly conserved. Based on a site-specific model, 11 genes with positively selected sites were detected, and most of them were photosynthesis-related genes and genetic system-related genes. Together with previously released cp genomes of the order Myrtales, we determined the taxonomic position of P. granatum based on the complete chloroplast genomes. Phylogenetic analysis suggested that P. granatum form a single clade with other species from Lythraceae with a high support value. The complete cp genomes provides valuable information for understanding the phylogenetic position of P. gramatum in the order Myrtales.

The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology.

Pomegranate (Punica granatum L.) has an ancient cultivation history and has become an emerging profitable fruit crop due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the limited genomic resources have restricted further elucidation of genetics and evolution of these interesting traits. Here, we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336-Mb genome, consists of 2177 scaffolds with an N50 size of 1.7 Mb and contains 30 903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis share the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the colour formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence provides an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding.

miRNAs Regulate hERG.

BACKGROUND: The human ether-a-go-go-related gene (hERG) is the major molecular component of the rapidly activating delayed rectifier K+ current (Ikr ). Impairment of hERG function is believed to be a mechanism causing long-QT syndromes (LQTS). Growing evidences have shown that microRNAs (miRNAs) are involved in functional modulation of the hERG pathway. The purpose of this study was to screen and validate miRNAs that regulate the hERG pathway. The miRNAs identified in this study will provide new tools to assess the mechanism of LQTS. METHODS: Six miRNAs were selected by algorithm predictions based on potential interaction with hERG. The effects of each miRNA on hERG were assessed by use of the Dual-Luciferase Reporter assay system, qRT-PCR, Western blotting, and confocal fluorescence microscopy. Furthermore, whole-cell patch clamp technique was used to validate the effect of miR-103a-1 on the electrophysiological characteristic of the Ikr of the hERG protein channel. RESULTS: miR-134, miR-103a-1, miR-143, and miR-3619 significantly downregulated luciferase activity (P < 0.05) in a reporter test system. These 4 miRNAs significantly suppressed expression of hERG mRNA and protein in U2OS cells (P < 0.05).Corresponding AMOs rescued expression of hERG mRNA and protein. Confocal microscopy showed that all 4 miRNAs reduced the expression of both immature and mature hERG protein. miR-103a-1 decreased the maximum current and tail current amplitudes of hERG channel. CONCLUSIONS: Expression and functions of hERG are regulated by specific miRNAs.

Effects of Ca2+-activated potassium and inward rectifier potassium channel on the differentiation of endothelial progenitor cells from human peripheral blood.

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that have the propensity to differentiate into mature endothelial cells (ECs). The transplantation of EPCs has been shown to enhance in vivo postnatal neo-vasculogenesis, as well as repair infarcted myocardium. Via the whole-cell patch clamp technique, numerous types of ion channels have been detected in EPCs, including the inward rectifier potassium channel (IKir), Ca2+-activated potassium channel (IKCa), and volume-sensitive chloride channel, but their influence on the differentiation of EPCs has yet to be characterized. The present study was designed to investigate: (1) which ion channels have the most significant impact on the differentiation of EPCs; (2) what role ion channels play in the functional development of EPCs; (3) the mRNA and protein expression levels of related ion channel subunits in EPCs. In our study, EPCs were obtained from the peripheral blood of healthy adults and cultured with endothelial growth factors. When EPCs differentiate into mature ECs, they lose expression of the stem cell/progenitor marker CD133, as analyzed by flow cytometry (0.44±0.20 %). However, treatment with the potassium channel inhibitor, tetraethylammonium (TEA) results in an increase in CD133+ cells (25.50±7.55 %). In a functional experiment, we observed a reduction in the capacity of TEA treated ECs (differentiated from EPCs) to form capillary tubes when seeded in Matrigel. At the mRNA and protein levels, we revealed several K+ subtypes, including KCNN4 for IKCa, KCNNMA1 for BKCa and Kir3.4 for IKir. These results demonstrate for the first time that potassium channels play a significant role in the differentiation of EPCs. Moreover, inhibition of potassium channels may depress the differentiation of EPCs and the significant potassium channel subunits in EPCs appear to be IKCa, BKCa and Kir3.4.

Investigating molecular markers linked to acute myocardial infarction and cuproptosis: bioinformatics analysis and validation in the AMI mice model.

Cuproptosis-related key genes play a significant role in the pathological processes of acute myocardial infarction (AMI). However, a complete understanding of the molecular mechanisms behind this participation remains elusive. This study was designed to identify genes and immune cells critical to AMI pathogenesis. Based on the GSE48060 dataset (31 AMI patients and 21 healthy persons, GPL570-55999), we identified genes associated with dysregulated cuproptosis and the activation of immune responses between normal subjects and patients with a first myocardial attack. Two molecular clusters associated with cuproptosis were defined in patients with AMI. Immune infiltration analysis showed that there was significant immunity heterogeneity among different clusters. Multiple immune responses were closely associated with Cluster2-specific differentially expressed genes (DEGs). The generalized linear model machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.870). A final two-gene-based generalized linear model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.719, GSE66360 and AUC = 0.856, GSE123342). Column graph, calibration curve, and decision curve analyses also proved the accuracy of AMI prediction. We also constructed a mouse C57BL/6 model of AMI (3 h, 48 h, and 1 week) and used qRT-PCR and immunofluorescence to detect the expression changes of CBLB and ZNF302. In this study, we present a systematic analysis of the complex relationship between cuproptosis and a first AMI attack, and provide new insights into the diagnosis and treatment of AMI.

Safety assessment of clomiphene: a real-world pharmacovigilance analysis from the Food and Drug Administration adverse event reporting system.

BACKGROUND: Clomiphene is widely used for the treatment of anovulatory infertility, yet there remain many unrecognized adverse events (AEs). The objective of this study is to provide a comprehensive overview of the safety profile of clomiphene. METHODS: The data were derived from the first quarter of 2004 to the third quarter of 2023 from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The detection of new AE signals involved the use of four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). RESULTS: A total of 16,677,289 AE reports were acquired from the FAERS database, and there were 2,620 AEs specifically reported in 720 patients following clomiphene use. The AEs encompassed 102 preferred terms (PTs) across 24 system organ classes (SOCs). Some new AEs were identified, including conjoined twins (0.5%), Potter's syndrome (0.3%), genitalia external ambiguous (0.3%), esophageal atresia (0.6%), and anal atresia (0.3%). CONCLUSIONS: Although the majority of AEs aligned with the drug instruction, some new AE signals such as conjoined twins and genitalia external ambiguous were not captured. Well-designed studies are required to demonstrate the safety of clomiphene.

Screening of Secretory Proteins Linking Major Depressive Disorder with Heart Failure Based on Comprehensive Bioinformatics Analysis and Machine Learning.

BACKGROUND: Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD's involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF. METHODS: GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF. Differential expression analysis (DEA) and WGCNA were used to detect HF key genes and MDD-associated secretory proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis were used to reveal potential mechanisms and drugs for MDD-related HF. Then, four machine learning (ML) algorithms (including GLM, RF, SVM, and XGB) were used to screen candidate biomarkers, construct diagnostic nomograms, and predict MDD-related HF. Furthermore, the MCPcounter algorithm was used to explore immune cell infiltration in HF, and MR analysis was performed to explore the causal effect of immunophenotypes on HF. Finally, the validation of the association of MDD with reduced left ventricular ejection fraction (LVEF) and the performance assessment of diagnostic biomarkers was accomplished based on animal models mimicking MDD. RESULTS: The MR analysis showed that the MDD was linked to an increased risk of HF (OR = 1.129, p < 0.001). DEA combined with WGCNA and secretory protein gene set identified 315 HF key genes and 332 MDD-associated secretory proteins, respectively. Through PPI and MCODE analysis, 78 genes were pinpointed as MDD-related pathogenic genes for HF. The enrichment analysis revealed that these genes were predominantly enriched in immune and inflammatory regulation. Through four ML algorithms, two hub genes (ISLR/SFRP4) were identified as candidate HF biomarkers, and a nomogram was developed. ROC analysis showed that the AUC of the nomogram was higher than 0.90 in both the HF combined dataset and two external cohorts. In addition, an immune cell infiltration analysis revealed the immune dysregulation in HF, with ISLR/SFRP4 displaying notable associations with the infiltration of B cells, CD8 T cells, and fibroblasts. More importantly, animal experiments showed that the expression levels of ISLR (r = -0.653, p < 0.001) and SFRP4 (r = -0.476, p = 0.008) were significantly negatively correlated with LVEF. CONCLUSIONS: The MR analysis indicated that MDD is a risk factor for HF at the genetic level. Bioinformatics analysis and the ML results suggest that ISLR and SFRP4 have the potential to serve as diagnostic biomarkers for HF. Animal experiments showed a negative correlation between the serum levels of ISLR/SFRP4 and LVEF, emphasizing the need for additional clinical studies to elucidate their diagnostic value.

Impact of dietary antioxidants on female infertility risk: evidence from NHANES.

The composite dietary antioxidant index (CDAI) serves as a valuable instrument for evaluating the intake of dietary antioxidants. This research aims to clarify the connection between CDAI and the risk of female infertility by analyzing data from the National Health and Nutrition Examination Survey from 2013 to 2018. Participants underwent two 24-h dietary recall interviews to calculate CDAI. Female infertility was determined through two questionnaires. Logistic regression model, restricted cubic spline and subgroup analysis were employed to examine the association between CDAI and female infertility. The study encompassed 2162 participants. Participants with female infertility had lower CDAI levels compared to those without. Following adjustment for confounding variables, a negative association between CDAI levels and female infertility was observed (Q4 vs. Q1, OR [95% CI] 0.392 [0.193, 0.795], P = 0.016). RCS demonstrated a statistically significant linear negative relationship between CDAI and female infertility. Subgroup analysis showed no significant interaction. This study illustrates a negative link between the CDAI and female infertility, indicating that higher consumption of dietary antioxidants may be associated with a reduced risk of female infertility. Additional rigorously designed prospective studies are necessary to validate these results.

Polyunsaturated fatty acids and diabetic microvascular complications: a Mendelian randomization study.

Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis.

To evaluate the clinical efficacy of etonogestrel subcutaneous implant (ENG-SCI) with that of the levonorgestrel-releasing intrauterine system (LNG-IUD) for adenomyosis treatment. A prospective randomized cohort study was conducted including 108 patients (50 patients in ENG-SCI group and 58 in the LNG-IUD group) with adenomyosis from January 2019 to July 2021. After 3 months of treatment, both ENG-SCI group and LNG-IUD group showed significant improvement in patients' visual analog scale, pictorial blood loss assessment chart (PBAC), and uterine volume (P ＜ 0.05). The uterine volume of patients in LNG-IUD group decreased more significantly than that in the ENG-SCI group since 3 months of treatment. The PBAC score in the LNG-IUD group improved better than that in the ENG-SCI group since 6 months of treatment (P ＜ 0.05). No significant difference in the occurrence rate of ideal vaginal bleeding patterns and the hemoglobin levels between the two groups was observed. The ENG-SCI group had a higher probability of weight gain and progesterone-related side effects (P ＜ 0.05). Both ENG-SCI and LNG-IUD were effective in treatment of adenomyosis. However, LNG-IUD had a more significant effect in treating adenomyosis-related dysmenorrhea, excessive menstrual flow, anemia, and uterine enlargement, with relatively fewer side effects.

Exploring diagnostic biomarkers of type 2 cardio-renal syndrome based on secreted proteins and bioinformatics analysis.

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.

Meta-analyses of four eosinophil related gene variants in coronary heart disease.

The goal of our study is to assess the contribution of four eosinophil related gene variants (rs12619285, rs1420101, rs3184504 and rs4143832) to the risk of coronary heart disease (CHD). We conducted four meta-analyses of studies examining the association between four eosinophil related gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. A case-control study was conducted between 162 CHD cases and 119 non-CHD controls to explore their contribution to CHD. For rs3184504 of SH2B3 gene, the meta-analysis was performed among 19 study stages among 94,555 participants. Significant association between rs3184504 and CHD risk was observed in European and South Asian populations (OR = 1.13, 95% CI = 1.10-1.16, p < 0.0001, fixed-effect method). For the other SNPs (rs12619285, rs1420101, and rs4143832), we combined our case-control data with the previous studies and found no association of them with the risk of CHD. No significant contribution of the four genetic variants to CHD was observed in Han Chinese (p > 0.05). In conclusion, our results supported a significant association between rs3184504 of SH2B3 gene and the risk of CHD in Europeans and South Asians, although we were unable to observe association between the four variants and the risk of CHD in Han Chinese.

Simultaneous determination of dopamine, sertonin and ascorbic acid at a glassy carbon electrode modified with carbon-spheres.

A novel glassy carbon electrode (GCE) modified with carbon-spheres has been fabricated through a simple casting procedure. The modified GCE displays high selectivity and excellent electrochemical catalytic activities towards dopamine (DA), serotonin (5-HT), and ascorbic acid (AA). In the co-existence system, the peak separations between AA and DA, DA and 5-HT, and AA and 5-HT are large up to 230, 180, and 410 mV, respectively. Differential pulse voltammetry (DPV) has been employed to simultaneously detect DA, 5-HT, and AA, and the linear calibration curves for DA, 5-HT, and AA are obtained in the range of 20.0-150.0 µM, 40.0-750.0 µM and 300.0-2,000.0 µM with detection limits (S/N = 3) of 2.0 µM, 0.7 µM and 0.6 µM, respectively. The proposed electrode has been applied to detect DA, 5-HT, and AA in real samples using standard addition method with satisfactory results.

MiR-125b-5p Targets MTFP1 to Inhibit Cell Proliferation, Migration, and Invasion and Facilitate Cell Apoptosis in Endometrial Carcinoma.

MicroRNAs (miRNAs) are recognized as latent diagnostic, prognostic, and therapeutic biomarkers for endometrial carcinoma (EC). We attempted to discuss function and mechanism of miR-125b-5p in EC cell progression. This study manifested a decreased miR-125b-5p level and an increased mitochondrial fission process 1 (MTFP1) level in EC, and there was an inverse correlation between them. Moreover, in vitro assays were performed. The results denoted that miR-125b-5p could target a putative binding site on MTFP1 3'UTR to reduce MTFP1 expression, thereby repressing cell malignant behaviors. Besides, the promoting impact of MTFP1 overexpression on malignant phenotypes of EC cells could be restored by miR-125b-5p up-regulation. Considering, our investigation exhibited that miR-125b-5p curbed EC cell malignant phenotypes through targeting MTFP1. This study generates a fresh functional mechanism for EC occurrence and progression, which also lays the groundwork for clinical therapies.

Overexpression of circRNA circFAT1 in Endometrial Cancer Cells Increases Their Stemness by Upregulating miR-21 Through Methylation.

Background: Circular (Circ)RNA circFAT1 play tumor-suppressive or oncogenic roles in different cancers. Microarray analysis observed altered expression of circFAT1 in endometrial cancer (EC) and its inverse correlation with miR-21. Materials and Methods: Expression of circFAT1 and miR-21 in EC and paired nontumor tissues collected from 62 EC patients was analyzed by quantitative reverse transcription PCR (RT-qPCR). An experiment was conducted to evaluate the expression and interaction between circFAT1 and miR-21, followed by RT-qPCR and methylation-specific PCR. The role of circFAT1 and miR-21 in regulating the stemness was assessed by cell stemness assay. Heml 1.0 software was used to show differential gene expression. ANOVA Tukey's test and Pearson's correlation coefficient was used. Results: CircFAT1 was upregulated in EC and positively correlated with miR-21 across EC tissues. In RL95-2 and HEC-1-A cells, overexpression of circFAT1 increased the expression levels of miR-21 and decreased the methylation of miR-21 gene, whereas overexpression of miR-21 did not alter the expression of circFAT1. Cell stemness analysis showed that overexpression of circFAT1 and miR-21 increased cell stemness, and miR-21 inhibition decreased cell stemness. Moreover, inhibitor of miR-21 suppressed the role of circFAT1. Conclusions: In conclusion, circFAT1 is upregulated in EC and it may increase cancer cell stemness by upregulating miR-21.