Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort.

Background: The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis. Methods: The single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings. Results: The IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF. Conclusion: The study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA.

The Potential of Novel Synthesized Carbon Dots Derived Resveratrol Using One-Pot Green Method in Accelerating in vivo Wound Healing.

Background: Carbon dots (CDs), a novel nanomaterial, have gained significant attention over the past decade due to their remarkable fluorescence properties, low toxicity, and biocompatibility. These characteristics make them promising in various applications, especially in biomedicine. However, most CDs are currently synthesized using chemical materials, and their biocompatibility falls short of natural compounds. Research on extracting CDs from natural sources is limited, and their potential in biomedicine remains largely unexplored. Methods: We extracted CDs from resveratrol, a natural plant compound, and enhanced their water solubility using citric acid. Characterization of resveratrol-based carbon dots (RES-CDs) was carried out using various techniques, including UV-Vis, SEM, TEM, FTIR, XRD, and fluorescence spectroscopy. Extensive biocompatibility tests, wound healing assays, cell migration studies, and angiogenesis experiments were conducted using human umbilical vein endothelial cells (HUVEC). In addition, we investigated the biocompatibility and wound healing potential of RES-CDs in an in vivo rat model of inflammation. Results: RES-CDs exhibited stable yellow-green fluorescence under 365-nanometer ultraviolet light and demonstrated excellent biocompatibility. In wound healing experiments, RES-CDs outperformed resveratrol in terms of cell scratch healing, migration, and tube formation. In a rat skin defect model, RES-CDs promoted wound healing and stimulated the formation of blood vessels and tissue regeneration near the wound site, as evidenced by increased CD31 and VEGF expression. Conclusion: Resveratrol-derived CDs with enhanced water solubility show superior performance in tissue healing compared to resveratrol. This discovery opens new possibilities for the clinical application of resveratrol-based carbon dots.

Synthesis of multicolor luminescent carbon dots based on carboxymethyl chitosan for cell imaging and wound healing application: In vitro and in vivo studies.

The construction of biomaterials that can facilitate wound healing is significantly challenging in the medical field, and bacterial infections increase this complexity. In this study, we selected the biomacromolecule carboxymethyl chitosan as a carbon source and citric acid as an auxiliary carbon source. We prepared carbon quantum dots with multicolor luminescence properties and higher quantum yields (QYs) using a facile one-pot hydrothermal method. We characterized them to select carbon dots (CDs) suitable for cell growth. Subsequently, their biocompatibility with L929 cells, antibacterial properties against Staphylococcus aureus, and efficiency in promoting wound healing in vivo were investigated. Our experimental results showed that CDs at an appropriate concentration had excellent bioimaging ability, were suitable for cell growth, and accelerated the healing of infected wounds. We believe these bioactive CDs have great potential in promoting wound healing.

Semicrystalline IrOx with Abundant Boundaries for Overall Water Splitting.

Inorganic compounds with different crystalline and amorphous states may show distinct properties in catalytic applications. In this work, we control the crystallization level by fine thermal treatment and synthesize a semicrystalline IrOx material with the formation of abundant boundaries. Theoretical calculation reveals that the interfacial iridium with a high degree of unsaturation is highly active for the hydrogen evolution reaction compared to individual counterparts based on the optimal binding energy with hydrogen (H*). At the heat treatment temperature of 500 °C, the obtained IrOx-500 catalyst has dramatically promoted hydrogen evolution kinetics, endowing the iridium catalyst with a bifunctional activity for acidic overall water splitting with a total voltage of only 1.554 V at a current density of 10 mA cm-2. In light of the remarkable boundary-enhanced catalysis effects, the semicrystalline material should be further developed for other applications.

Recent advances in carbon dots: synthesis and applications in bone tissue engineering.

Bone tissue engineering (BTE), based on the perfect combination of seed cells, scaffold materials and growth factors, has shown unparalleled potential in the treatment of bone defects and related diseases. As the site of cell attachment, proliferation and differentiation, scaffolds composed of biomaterials play a crucial role in BTE. Over the past years, carbon dots (CDs), a new type of carbon-based nanomaterial, have attracted extensive research attention due to their good biocompatibility, unique optical properties, and abundant functional groups. This paper reviews recent research progress in the use of CDs in the field of BTE. Firstly, different preparation methods of CDs are summarized. Then, the properties and categories of CDs applied in BTE are described in detail. Subsequently, the applications of CDs in BTE, including osteogenesis, fluorescence tracing, phototherapy and antibacterial activity, are presented. Finally, the challenges and future perspectives of CDs in BTE are briefly discussed to give a comprehensive picture of CDs. This review provides a theoretical basis and advanced design strategies for the application of CDs in BTE.

Strategies for Electrochemically Sustainable H2 Production in Acid.

Acidified water electrolysis with fast kinetics is widely regarded as a promising option for producing H2 . The main challenge of this technique is the difficulty in realizing sustainable H2 production (SHP) because of the poor stability of most electrode catalysts, especially on the anode side, under strongly acidic and highly polarized electrochemical environments, which leads to surface corrosion and performance degradation. Research efforts focused on tuning the atomic/nano structures of catalysts have been made to address this stability issue, with only limited effectiveness because of inevitable catalyst degradation. A systems approach considering reaction types and system configurations/operations may provide innovative viewpoints and strategies for SHP, although these aspects have been overlooked thus far. This review provides an overview of acidified water electrolysis for systematic investigations of these aspects to achieve SHP. First, the fundamental principles of SHP are discussed. Then, recent advances on design of stable electrode materials are examined, and several new strategies for SHP are proposed, including fabrication of symmetrical heterogeneous electrolysis system and fluid homogeneous electrolysis system, as well as decoupling/hybrid-governed sustainability. Finally, remaining challenges and corresponding opportunities are outlined to stimulate endeavors toward the development of advanced acidified water electrolysis techniques for SHP.

αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5.

Nav1.5, the pore-forming α subunit of the cardiac voltage-gated Na(+) channel complex, is required for the initiation and propagation of the cardiac action potential. Mutations in Nav1.5 cause cardiac arrhythmias and sudden death. The cardiac Na(+) channel functions as a protein complex; however, its complete components remain to be fully elucidated. A yeast two-hybrid screen identified a new candidate Nav1.5-interacting protein, αB-crystallin. GST pull-down, co-immunoprecipitation, and immunostaining analyses validated the interaction between Nav1.5 and αB-crystallin. Whole-cell patch clamping showed that overexpression of αB-crystallin significantly increased peak sodium current (INa) density, and the underlying molecular mechanism is the increased cell surface expression level of Nav1.5 via reduced internalization of cell surface Nav1.5 and ubiquitination of Nav1.5. Knock-out of αB-crystallin expression significantly decreased the cell surface expression level of Nav1.5. Co-immunoprecipitation analysis showed that αB-crystallin interacted with Nedd4-2; however, a catalytically inactive Nedd4-2-C801S mutant impaired the interaction and abolished the up-regulation of INa by αB-crystallin. Nav1.5 mutation V1980A at the interaction site for Nedd4-2 eliminated the effect of αB-crystallin on reduction of Nav1.5 ubiquitination and increases of INa density. Two disease-causing mutations in αB-crystallin, R109H and R151X (nonsense mutation), eliminated the effect of αB-crystallin on INa This study identifies αB-crystallin as a new binding partner for Nav1.5. αB-Crystallin interacts with Nav1.5 and increases INa by modulating the expression level and internalization of cell surface Nav1.5 and ubiquitination of Nav1.5, which requires the protein-protein interactions between αB-crystallin and Nav1.5 and between αB-crystallin and functionally active Nedd4-2.

Post-transcriptional regulation of cardiac sodium channel gene SCN5A expression and function by miR-192-5p.

The SCN5A gene encodes cardiac sodium channel Nav1.5 and causes lethal ventricular arrhythmias/sudden death and atrial fibrillation (AF) when mutated. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, and involved in the pathogenesis of many diseases. However, little is known about the regulation of SCN5A by miRNAs. Here we reveal a novel post-transcriptional regulatory mechanism for expression and function of SCN5A/Nav1.5 via miR-192-5p. Bioinformatic analysis revealed that the 3'-UTR of human and rhesus SCN5A, but not elephant, pig, rabbit, mouse, and rat SCN5A, contained a target binding site for miR-192-5p and dual luciferase reporter assays showed that the site was critical for down-regulation of human SCN5A. With Western blot assays and electrophysiological studies, we demonstrated that miR-192-5p significantly reduced expression of SCN5A and Nav1.5 as well as peak sodium current density INa generated by Nav1.5. Notably, in situ hybridization, immunohistochemistry and real-time qPCR analyses showed that miR-192-5p was up-regulated in tissue samples from AF patients, which was associated with down-regulation of SCN5A/Nav1.5. These results demonstrate an important post-transcriptional role of miR-192-5p in post-transcriptional regulation of Nav1.5, reveal a novel role of miR-192-5p in cardiac physiology and disease, and provide a new target for novel miRNA-based antiarrhythmic therapy for diseases with reduced INa.

[Therapeutic effect of endoscopic third ventriculostomy for pediatric hydrocephalus].

OBJECTIVE: To validate the proposed endoscopic third ventriculostomy success score (ETVSS) for predicting successful ETV outcomes for pediatric hydrocephalus on the basis of individual characteristics. METHODS: For 121 cases at our department from June 2007 to June 2010 at both 6 and 24 months, Actual successful rates were compared with Chi-square test and 95% confidence interval for low, moderate and high chance of success strata based on the ETVSS. Long-term successful probability was calculated with Kaplan-Meier methods. RESULTS: The 6-month ETV successful rate was higher than the mean predicted probabilities of success for both moderate and low success strata, but slightly lower for the high chance of success strata. The ETVSS accurately predicted the outcomes at 24 months; the low, medium and high chance of success strata had actual success rates of 74% (37/50), 62% (28/45) and 41% (11/26) and mean predicted successful probabilities of 81.3%, 61.4% and 34.4% respectively. CONCLUSION: ETVSS may accurately predict the overall long-term successful rates in high, moderate and low-risk groups. Thus it will aid clinical decision-making through predicting the therapeutic effect of ETV.

Effects of simvastatin on glucose metabolism in mouse MIN6 cells.

The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 µ M, 2 µ M, 5 µ M, and 10 µ M simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 (Cav1.2), and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 µ M and 10 µ M) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P < 0.05). ATP content in simvastatin-treated cells was lower than in control cells (P < 0.05). Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P < 0.05), and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P < 0.05). Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells.

Electrophysiological characteristics of a SCN5A voltage sensors mutation R1629Q associated with Brugada syndrome.

Brugada syndrome (BrS) is an inherited arrhythmogenic syndrome leading to sudden cardiac death, partially associated with autosomal dominant mutations in SCN5A, which encodes the cardiac sodium channel alpha-subunit (Nav1.5). To date some SCN5A mutations related with BrS have been identified in voltage sensor of Nav1.5. Here, we describe a dominant missense mutation (R1629Q) localized in the fourth segment of domain IV region (DIV-S4) in a Chinese Han family. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Co-expression of Wild-type (WT) or R1629Q Nav1.5 channel and hß1 subunit were achieved in human embryonic kidney cells by transient transfection. Sodium currents were recorded using whole cell patch-clamp protocols. No significant changes between WT and R1629Q currents were observed in current density or steady-state activation. However, hyperpolarized shift of steady-state inactivation curve was identified in cells expressing R1629Q channel (WT: V1/2 = -81.1 ± 1.3 mV, n = 13; R1629Q: V1/2 = -101.7 ± 1.2 mV, n = 18). Moreover, R1629Q channel showed enhanced intermediate inactivation and prolonged recovery time from inactivation. In summary, this study reveals that R1629Q mutation causes a distinct loss-of-function of the channel due to alter its electrophysiological characteristics, and facilitates our understanding of biophysical mechanisms of BrS.

Complexity-reduced scheme for feature extraction with linear discriminant analysis.

Owing to the singularity of the within-class scatter, linear discriminant analysis (LDA) becomes ill-posed for small sample size (SSS) problems. Null-space-based LDA (NLDA), which is an extension of LDA, provides good discriminant performances for SSS problems. Yet, as the original scheme for the feature extractor (FE) of NLDA suffers from a complexity burden, a few modified schemes have since been proposed for complexity reduction. In this brief, by transforming the problem of finding the FE of NLDA into a linear equation problem, a novel scheme is derived, offering a further reduction of the complexity.