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Background: Transient Receptor Potential Melastatin 4 (TRPM4), a non-selective cation channel, plays a critical role in cardiac conduction abnormalities. Brg1, an ATP-dependent chromatin remodeler, is essential for regulating gene expression in both heart development and disease. Our previous studies demonstrated Brg1 impacted on cardiac sodium/potassium channels and electrophysiological stability, its influence on TRPM4 expression and function remained unexplored. Methods: We investigated the role of Brg1 in regulating TRPM4 expression and function through overexpression and knockdown experiments in mouse cardiomyocytes and TRPM4-overexpressing HEK293 cells by western blot, qPCR, immunofluorescence staining and patch clamp techniques. Cardiomyocytes were exposed to hypoxia for 12 h to mimic cardiac stress, and Brg1 inhibition was performed to assess its impact on TRPM4 under hypoxia. Bioinformatic analyses (STRING and JASPAR databases), Co-immunoprecipitation (Co-IP), dual luciferase reporter assays, and Chromatin Immunoprecipitation (ChIP) were employed to study the interaction between Brg1, RUNX1, and TRPM4 transcription regulation. Results: Brg1 positively regulated TRPM4 expression in mouse cardiomyocytes and modulated TRPM4 current in TRPM4-overexpressing HEK293 cells. Brg1 inhibition markedly diminishes TRPM4's hyperexpression in cardiomyocytes exposed to hypoxia. Integrative analyses utilizing STRNG databases and Protein Data Bank unveiled a putative interaction between Brg1 and the transcription factor RUNX1, and we substantiated the interaction between Brg1 and RUNX1. Several binding sites of RUNX1 with the TRPM4 promoter region were predicted by the JASPAR database, and empirical validation substantiated Brg1 modulated TRPM4 promoter activity via RUNX1 engagement. ChIP confirmed that Brg1 interacted with RUNX1 forming a transcriptional complex that located in TRPM4 promoter. Conclusion: Our study demonstrated that Brg1 and RUNX1 formed a transcriptional complex that modulated TRPM4 expression and function, especially under hypoxic conditions. These findings provided new insights into TRPM4 regulation and highlighted its potential as a therapeutic target for cardiac hypoxia-related disorders. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the relationship between the age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. Methods: This cross-sectional study enrolled 1,118 myopic patients aged 18–40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics, and high myopia. Results: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve in receiver operator characteristic analysis of 0.80. Additionally, the age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. Conclusions: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics. [ABSTRACT FROM AUTHOR]

Removal of radioactive technetium‐99 (99TcO4−) from water by effective adsorbents is highly desired but remains a challenge. The currently used resin adsorbents possess several obstacles, such as slow adsorption kinetics and low adsorption capacity. To address these issues, herein a type of fibrous adsorbent with porosity and hyper‐branched quaternary ammonium groups, namely porous cationic electrospun fibers (PCE fibers), is successfully prepared. PCE fibers can remove 97% of 99TcO4− within 1 min and the equilibrium time of 99% removal is 20 min. The predicted maximum adsorption capacity toward the surrogate ReO4− can reach 826 mg g−1, which is higher than the state of art anion‐exchange resins and most of the other reported adsorbents. Furthermore, PCE fibers have good selectivity for ReO4− in the presence of competitive anions, and can retain ReO4− uptake under extreme conditions including high acid–base and gamma irradiation. Importantly, PCE fibrous adsorptive membrane is employed for dynamic ReO4− removal from simulated Hanford LAW stream with a processing capacity of 600 kg simulated stream per kilogram PCE fibers. The excellent performance highlights the advantages of PCE fibers over traditional resins in technetium removal. [ABSTRACT FROM AUTHOR]

Background: Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported. Methods: Multiple databases were analyzed for comparing the expression of Ebp1 in normal skin and MM. Ebp1 expression was knocked down in A375 and B16 cells, and the impact of Ebp1 on the cell growth was tested by CCK-8, plate clone colony, and cell cycle assays. Scratch, transwell, and in vivo caudal vein lung metastasis tests were also used to confirm the effects of Ebp1 on melanoma cells migration, invasion, and metastasis. Furthermore, the possible molecular mechanism of Ebp1 was predicted by set enrichment analysis and verified by western blotting. Results: Ebp1 expression was substantially higher in MM than it was in normal skin, and Ebp1 was linked to the clinical stage and lymph node metastases of patients with MM. Knockdown of Ebp1 inhibited cell proliferation, migration, and invasion. In vivo experiments further verified that the knockdown of Ebp1 had an obvious inhibitory effect on lung metastasis in nude mice. Knockdown of Ebp1 reduced vimentin, N-cadherin, slug, and snail expression while increasing E-cadherin expression. Furthermore, knockdown of Ebp1 reduced the expression of β-catenin, as well as its downstream targets CyclinD1 and p-GSK3β; however, a Wnt/β-catenin agonist could reverse this effect. Conclusion: Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Calcium-dependent synaptic vesicle exocytosis is mediated by SNARE complex formation. The transition from the Munc18-1/syntaxin-1 complex to the SNARE complex is catalyzed by the Munc13-1 MUN domain and involves at least two conformational changes: opening of the syntaxin-1 linker region and extension of Munc18-1 domain 3a. However, the relationship and the action order of the two conformational changes remain not fully understood. Here, our data show that an open conformation in the syntaxin-1 linker region can bypass the requirement of the MUN NF sequence. In addition, an extended state of Munc18-1 domain 3a can compensate the role of the syntaxin-1 RI sequence. Altogether, the current data strongly support our previous notion that opening of the syntaxin-1 linker region by Munc13-1 is a key step to initiate SNARE complex assembly, and consequently, Munc18-1 domain 3a can extend its conformation to serve as a template for association of synaptobrevin-2 and syntaxin-1. [ABSTRACT FROM AUTHOR]

Highly efficient removal of bilirubin from blood by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity and slow adsorption kinetics of currently used bilirubin adsorbents (e.g., activated carbon and ion‐exchange resin). Recently, porous aromatic frameworks (PAFs) with high surface areas, tunable structures, and remarkable stability provide numerous possibilities to obtain satisfying adsorbents. Here, a cationic PAF with more mesopores, named iPAF‐6, is successfully constructed via a de novo synthetic strategy for bilirubin removal. The prepared iPAF‐6 exhibits a record‐high adsorption capacity of 1249 mg g−1 and can adsorb bilirubin from 150 mg L−1 to normal concentration in just 5 min. Moreover, iPAF‐6 shows a removal efficiency of 96% toward bilirubin in the presence of 50 g L−1 bovine serum albumin. It is demonstrated that positively charged aromatic frameworks and large pore size make a significant contribution to its excellent adsorption ability. More notably, iPAF‐6/polyethersulfone composite fibers or beads are fabricated for practical hemoperfusion adsorption, which also show better removal performance than commercial adsorbents. This work can offer a new possibility for designing PAF‐based bilirubin adsorbents with an appealing application prospect. [ABSTRACT FROM AUTHOR]

Background: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use.Methods: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR.Results: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: - 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P < 0.001) were prognostic factors for COVID-19 patients' death.Conclusions: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19. [ABSTRACT FROM AUTHOR]

Summary: To investigate the thermal characteristics and uniformity of a lithium‐ion battery (LIB) pack, a second‐order Thevenin circuit model of single LIB was modeled and validated experimentally. A battery thermal management system (BTMS) with reciprocating liquid flow was established based on the validated equivalent circuit model. The effects of the reciprocation period, battery module coolant flow rate and ambient temperature on the temperature and the temperature imbalance of batteries were studied. The results illustrate that the temperature difference can be effectively reduced by 3°C when the reciprocating period is 590 seconds. The reciprocating coolant flow rate is 11.5% and 33.3% that of the unidirectional flow BTMS for cooling and heating when same thermal effects are to be achieved. Under the same ambient temperature condition, the maximum temperature and average temperature difference can be reduced by 1.67°C and 3.77°C, respectively, at best for the battery module investigated with a reciprocating liquid‐flow cooling system. The average temperature difference and heating power consumption could be reduced by 1.2°C and 14 kJ for reciprocating liquid flow heating system with period of 295 seconds when compared with unidirectional flow. As a result, the thermal characteristics and temperature uniformity can be effectively improved, and the parasitic power consumption can be significantly reduced through adoption of a reciprocating liquid flow BTMS. [ABSTRACT FROM AUTHOR]

The present study aimed to uncover the underlying mechanisms and potential intervention targets of ischemic stroke (IS). An immune cell infiltration analysis using CIBERSORT was performed on two stroke-related datasets from the Gene Expression Omnibus database to generate a competitive endogenous RNA (ceRNA) network. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict potential biological functions of the network. Differentially expressed genes in the ceRNA network and programmed cell death-related genes were intersected to obtain common genes for a stroke ceRNA network related to programmed cell death. These genes were further verified through a middle cerebral artery occlusion rat model using reverse transcription-quantitative PCR. This built a ceRNA regulatory network based on bioinformatic analysis. In addition to the biological functions extracted from the GO and KEGG enrichment analyses, it was discovered that long non-coding (lnc)RNA-mediated ceRNA regulatory pathways were associated with programmed cell death. This included five for apoptosis (lncRNA deleted in lymphocytic leukemia 2 like (DLEU2L)/micro (miR)-4500/sulfite oxidase, lncRNA DLEU2L/miR-4500/transforming growth factor β receptor III, lncRNA DLEU2L/miR-4500/BTB and CNC homology 1 (BACH1), lncRNA DLEU2L/miR-4500/zinc finger and BTB domain containing 5 and lncRNA LINC00266-1/miR-363-3p/zinc finger protein 354B and two for ferroptosis (lncRNA DLEU2L/miR-4500/ribo-nucleotide reductase regulatory subunit M2 and lncRNA DLEU2L/miR-4500/BACH1). Based on the aforementioned results, the present study provided potential approaches for bridging programmed cell death, immune infiltration and ceRNA regulatory networks in IS. The present study may provide novel insights into the clinical diagnosis and treatment of IS, and may improve the knowledge of the regulation of pathophysiological processes for IS. [ABSTRACT FROM AUTHOR]