Triggering photocatalytic performance of La2CoxMn2-xO6 via heat activation.

The La-based perovskite (LaBO3) exhibits excellent optical properties. However, its valence band (VB) potential is not sufficiently positive to reach the oxidation potential required for the cleavage of chemical bonds (such as benzylic C-H), limiting its application in photocatalysis. Herein, we report the unconventional effects of heat activation on the reduction of the dissociation energy of benzylic C-H and aqueous H-O, thereby triggering the photocatalytic activity of La2CoxMn2-xO6 perovskites. Additionally, we demonstrate that photocatalysis is the main contributor to substrate conversion in the selective oxidation of toluene and reduction of CO2. Particularly, La2Co1.5Mn0.5O6 shows excellent performance with a product yield of 550.00 mmol gcat-1 and a toluene conversion of 22,866.67 µmol gcat-1 h-1. To the best of our knowledge, this is the highest reported product yield for the selective oxidation of benzylic C-H bond of toluene. Our findings provide insight into the specific role of heat activation in photocatalysis, which is crucial for breaking and overcoming the VB barrier to realize challenging reactions.

Efficient Photoreduction of CO2 to CO with 100% Selectivity by Slowing Down Electron Transport.

It remains challenging to obtain a single product in the gas-solid photocatalytic reduction of CO2 because CO and CH4 are usually produced simultaneously. This study presents the design of the I-type nested heterojunction TiO2/BiVO4 with controllable electron transport by modulating the TiO2 component. This study demonstrates that slowing electron transport could enable TiO2/BiVO4-4 to generate CO with 100% selectivity. In addition, modifying TiO2/BiVO4-4 by loading a Cu single atom further increased the CO product yield by 3.83 times (17.33 µmol·gcat-1·h-1), while maintaining 100% selectivity for CO. Characterization and density functional theory (DFT) calculations revealed that the selectivity was mainly determined by the electron transport of the support, whereas CO2 was efficiently adsorbed and activated by the Cu single atom. Such a two-step regulation strategy of combining heterojunction with single atom enhances the possibility of simultaneously obtaining high selectivity and high yield in the photocatalytic reduction of CO2.

ATG4B as a novel biomarker for abdominal aortic aneurysm: integrated evaluation through experimental and bioinformatics analyses.

Autophagy related gene 4B (ATG4B) plays a central role in autophagy machinery, but its clinical relevance to AAA remains unknown. In this study, 205 AAA patients and 205 age- and sex-matched controls were included to detect the serum ATG4B levels. Meanwhile, abdominal aortic specimens from 24 AAA patients and 6 human organ donors were collected to evaluate the mRNA and in situ protein expression of ATG4B. We observed significantly higher ATG4B mRNA and protein expression levels in AAA group compared to those in control group, with a positive correlation between mRNA levels and serum/in situ protein levels (serum, r = 0.518, P = 0.010; in situ, r = 0.453, P = 0.026). Serum ATG4B exhibited the diagnostic potential for AAA (AUC = 0.702, sensitivity = 75.6%) and intraluminal thrombus recognition (AUC = 0.602, sensitivity = 67.9%). Logistic regression revealed a significant association between elevated serum ATG4B and an increased risk of AAA and intraluminal thrombus formation. Deceased patients displayed higher baseline serum ATG4B levels, which could predict postoperative mortality (HR = 1.028, 95%CI = 1.007-1.049, P = 0.009, AUC = 0.612, sensitivity = 84.6%). The bioinformatics analysis suggested that ATG4B may modulate cellular autophagy and influence pathways associated with inflammation, lipid metabolism, or apoptosis, thereby contributing to the occurrence and development of AAA. The drug-gene interaction network identified 13 potential therapeutic drugs targeting ATG4B. In conclusion, ATG4B may serve as a promising biomarker for the diagnosis and prognostic assessment of AAA patients and play a key role in the pathogenesis of AAA.

Efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus: A meta-analysis and systematic review.

BACKGROUND: The incidence of pruritus associated with hemodialysis (HD) patients can be as high as 70%, and ~ 40% of patients suffer from moderate to severe systemic pruritus. Difelikefalin (CR845), a peripheral restrictor κ-opioid receptor agonist, activates opioid receptors on peripheral neurons and immune cells to relieve pruritus in patients. However, the clinical effect of difelikefalin on HD-related pruritus is unclear. Therefore, the purpose of this meta-analysis and systematic review was to investigate the safety and efficacy of difelikefalin in the treatment of HD-associated pruritus. OBJECTIVE: This study explored the efficacy and safety of difelikefalin in the treatment of pruritus in HD patients by systematic review and meta-analysis. MATERIALS AND METHODS: Randomized controlled trials on difelikefalin in the treatment of pruritus in HD patients were retrieved from PubMed, Embase, Cochrane Library, and Web of Science electronic databases. The retrieval deadline was January 1, 2023. Stata 15.0 software was used for data analysis of the included studies. RESULTS: A total of 4 randomized controlled trials were included, totaling 1,268 patients (736 patients in the experimental group and 532 patients in the control group). Results of the meta-analysis showed that, compared with the control group, difelikefalin could significantly improve the Worst Itch Numeric Rating Scale score (improvement > 3; risk ratio (RR) = 1.28, 95% confidence interval (CI) (1.07, 1.53)), decrease the 5-D itch score (standardized mean difference = -0.43, 95% CI (-0.55, -0.30)), and significantly improve adverse events (RR = 1.33, 95% CI (1.13, 1.56)). CONCLUSION: Although difelikefalin can improve itching symptoms in HD patients, it can also increase adverse reactions based on the current literature. Therefore, more studies are needed to further explore the safety and efficacy of difelikefalin treatment.

BANP Participates in the Chronic Intermittent Hypoxia-Induced Senescence of Vascular Endothelial Cells by Promoting P53 Phosphorylation and Nuclear Retention.

INTRODUCTION: The objective of this study was to examine the potential induction of senescence in vascular endothelial cells (VECs) by chronic intermittent hypoxia (CIH), a defining characteristic of obstructive sleep apnea (OSA). This investigation seeks to elucidate the underlying mechanisms that contribute to the development of cardiovascular diseases in patients with OSA, with a particular focus on CIH-induced vascular aging. METHODS: The BioSpherix-OxyCycler system was used to establish models of CIH in both rats and human umbilical vein endothelial cells (HUVECs). To assess VECs' senescence, various methods were employed including EdU incorporation assay, cell cycle analysis, senescence-associated ß-galactosidase (SA-ß-gal) staining, and senescence protein testing. Vascular aging was evaluated through measurements of carotid-femoral pulse wave velocity, intima-media thickness, and Ki67 immunohistochemical staining. In order to identify the molecular mechanisms associated with CIH-induced senescence in VECs, a bioinformatics study was conducted utilizing the Gene Expression Omnibus database. RESULTS: Under conditions of CIH, HUVECs exhibited inhibited proliferation, arrested cell cycle, increased activity of SA-ß-gal, and elevated expression levels of p53 and p21 compared to HUVECs under normoxic conditions. Similarly, rats exposed to CIH displayed increased carotid-femoral pulse wave velocity, intima-media thickness, vascular permeability, and SA-ß-gal activity in VECs, along with decreased expression of arterial Ki67. BTG3-associated protein (BANP) was found to be highly expressed in CIH-induced VECs. Furthermore, the overexpression of BANP resulted in the senescence of VECs, along with elevated levels of p53 phosphorylation and nuclear localization. CONCLUSIONS: These findings demonstrate that CIH can induce VECs senescence and contribute to vascular aging. Additionally, BANP can induce VECs senescence by promoting p53 phosphorylation and nuclear retention. These discoveries offer novel insights into the increased cardiovascular risk associated with OSA, thereby presenting new possibilities for therapeutic intervention.

Effects of obstructive sleep apnea on myocardial injury and dysfunction: a review focused on the molecular mechanisms of intermittent hypoxia.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH) and is strongly associated with adverse cardiovascular outcomes. Myocardial injury and dysfunction have been commonly observed in clinical practice, particularly in patients with severe OSA. However, the underlying mechanisms remain obscure. In this review, we summarized the molecular mechanisms by which IH impact on myocardial injury and dysfunction. In brief, IH-induced cardiomyocyte death proceeds through the regulation of multiple biological processes, including differentially expressed transcription factors, alternative epigenetic programs, and altered post-translational modification. Besides cell death, various cardiomyocyte injuries, such as endoplasmic reticulum stress, occurs with IH. In addition to the direct effects on cardiomyocytes, IH has been found to deteriorate myocardial blood and energy supply by affecting the microvascular structure and disrupting glucose and lipid metabolism. For better diagnosis and treatment of OSA, further studies on the molecular mechanisms of IH-induced myocardial injury and dysfunction are essential.

Temporal and Spatial Signatures of Scylla paramamosain Transcriptome Reveal Mechanistic Insights into Endogenous Ovarian Maturation under Risk of Starvation.

Variability in food availability leads to condition-dependent investments in reproduction. This study is aimed at understanding the metabolic response and regulatory mechanism of female Scylla paramamosain in response to starvation in a temporal- and tissue-specific manner. The mud crabs were starved for 7 (control), 14, 28, and 40 days for histological and biochemical analysis in the hepatopancreas, ovary, and serum, as well as for RNA sequencing on the hepatopancreas and ovary. We further highlighted candidate gene modules highly linked to physiological traits. Collectively, our observations suggested that starvation triggered endogenous ovarian maturation at the expense of hepatopancreas mass, with both metabolic adjustments to optimize energy and fatty acid supply from hepatopancreas to ovary in the early phase, followed by the activation of autophagy-related pathways in both organs over prolonged starvation. These specific adaptive responses might be considered efficient strategies to stimulate ovarian maturation of Scylla paramamosain under fasting stress, which improves the nutritional value of female mud crabs and other economically important crustaceans.

Tailored Cl- Ligation on Supported Pt Catalysts for Selective Primary C-H Bond Oxidation.

It is challenging to achieve high selectivity over Pt-metal-oxide catalysts widely used in many selective oxidation reactions because Pt is prone to over-oxidize substrates. Herein, our sound strategy for enhancing the selectivity is to saturate the under-coordinated single Pt atoms with Cl- ligands. In this system, the weak electronic metal-support interactions between Pt atoms and reduced TiO2 cause electron extraction from Pt to Cl- ligands, resulting in strong Pt-Cl bonds. Therefore, the two-coordinate single Pt atoms adopt a four-coordinate configuration and thus inactivated, thereby inhibiting the over-oxidation of toluene over Pt sites. The selectivity for the primary C-H bond oxidation products of toluene was increased from 50.1 to 100%. Meanwhile, the abundant active Ti3+ sites were stabilized in reduced TiO2 by Pt atoms, leading to a rising yield of the primary C-H oxidation products of 249.8 mmol gcat-1. The reported strategy holds great promise for selective oxidation with enhanced selectivity.

Diagnostic and prognostic value of echocardiography in pulmonary hypertension: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: The role of echocardiography in the diagnostic and prognostic assessment of pulmonary hypertension (PH) has been widely studied recently. However, these findings have not undergone normative evaluation and may provide confusing evidence for clinicians. To evaluate and summarize existing evidence, we performed an umbrella review. METHODS: Systematic reviews and meta-analyses were searched in PubMed, Embase, Web of Science, and Cochrane Library from inception to September 4, 2022. The methodological quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the quality of evidence. RESULTS: Thirteen meta-analyses (nine diagnostic and four prognostic studies) were included after searching four databases. The methodological quality of the included studies was rated as high (62%) or moderate (38%) by AMSTAR. The thirteen included meta-analyses involved a total of 28 outcome measures. The quality of evidence for these outcomes were high (7%), moderate (29%), low (39%), and very low (25%) using GRADE methodology. In the detection of PH, the sensitivity of systolic pulmonary arterial pressure is 0.85-0.88, and the sensitivity and specificity of right ventricular outflow tract acceleration time are 0.84. Pericardial effusion, right atrial area, and tricuspid annulus systolic displacement provide prognostic value in patients with pulmonary arterial hypertension with hazard ratios between 1.45 and 1.70. Meanwhile, right ventricular longitudinal strain has independent prognostic value in patients with PH, with a hazard ratio of 2.96-3.67. CONCLUSION: The umbrella review recommends echocardiography for PH detection and prognosis. Systolic pulmonary arterial pressure and right ventricular outflow tract acceleration time can be utilized for detection, while several factors including pericardial effusion, right atrial area, tricuspid annular systolic displacement, and right ventricular longitudinal strain have demonstrated prognostic significance. TRIAL REGISTRATION: PROSPERO (CRD42022356091), https://www.crd.york.ac.uk/prospero/ .

A sustained-release microcarrier effectively prolongs and enhances the antibacterial activity of lysozyme.

Bacterial infections have become a great threat to public health in recent years. A primary lysozyme is a natural antimicrobial protein; however, its widespread application is limited by its instability. Here, we present a poly (N-isopropylacrylamide) hydrogel inverse opal particle (PHIOP) as a microcarrier of lysozyme to prolong and enhance the efficiency against bacteria. This PHIOP-based lysozyme (PHIOP-Lys) formulation is temperature-responsive and exhibits long-term sustained release of lysozyme for up to 16 days. It shows a potent antibacterial effect toward both Escherichia coli and Staphylococcus aureus, which is even higher than that of free lysozyme in solution at the same concentration. PHIOPs-Lys were demonstrated to effectively inhibit bacterial infections and enhance wound healing in a full-thickness skin wound rat model. This study provides a novel pathway for prolonging the enzymatic activity and antibacterial effects of lysozyme.

SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.

Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of gram-negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase NOX2 complex and phagolysosomal maturation after entering the phagosome, following interaction with the bacterial outer membrane proteins OmpC and OmpF. SLAM recruited a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosome, which was responsible for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing.

Silver Nanoparticles Induce Apoptosis in HepG2 Cells through Particle-Specific Effects on Mitochondria.

Silver nanoparticles (AgNPs) have been widely used in biomedical and consumer products. It remains challenging to distinguish the toxicity of AgNPs derived from the particle form or the released silver ions (Ag+). In this study, the toxic effects of two citrate-coated AgNPs (20 and 100 nm) and Ag+ were investigated in hepatoblastoma cells (HepG2 cells). The suppression tests showed that AgNPs and Ag+ induced cell apoptosis via different pathways, which led us to speculate on the AgNP-induced mitochondrial damage. Then, the mitochondrial damages induced by AgNPs and Ag+ were compared under the same intracellular Ag+ concentration, showing that the mitochondrial damage might be mainly attributed to Ag nanoparticles but not to Ag+. The interaction between AgNPs and mitochondria was analyzed using a scattered light imaging method combined with light intensity profiles and transmission electron microscopy. The colocalization of AgNPs and mitochondria was observed in both NP20- and NP100-treated HepG2 cells, indicating a potential direct interaction between AgNPs and mitochondria. These results together showed that AgNPs induced apoptosis in HepG2 cells through the particle-specific effects on mitochondria.

Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM. METHODS AND RESULTS: Three hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E', and higher E/E' (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05). CONCLUSIONS: MiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.

The Evaluation of Longitudinal Strain of Large and Small Abdominal Aortic Aneurysm by Two-Dimensional Speckle-Tracking Ultrasound.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a dangerous and lethal vascular disease. Non-invasive two-dimensional speckle-tracking imaging (2D STI) plays an important role in assessing aortic biomechanical properties. Our study aimed to evaluate the alterations of biomechanical characteristics using 2D STI in 91 AAA patients with different size. METHODS: Aneurysm strain, elastic modulus, stiffness index ß, and aortic distensibility determined by M-Mode ultrasound (US), and longitudinal strain (LS) derived from 2D STI were compared in 40 large AAA patients (diameter ≥ 55 mm) and 51 small AAA patients (diameter < 55 mm). RESULTS: Compared with small AAA group, anterior wall longitudinal strain (ALS) and posterior wall longitudinal strain (PLS) were significantly decreased in large AAA group (all P < .05) and not affected by age, symptom, hypertension, and thrombus. Meanwhile, ALS and PLS correlated negatively with maximal aneurysm diameters (r = -0.628 and -0.469, respectively, all P < .001). And only ALS was associated with M-Mode US parameters (all P < .05). Based on receiver operating characteristic (ROC) analysis, ALS and PLS had strong diagnostic values for large AAA with the area under the curve (AUC) of 0.82 and 0.72, and cut-off points of 1.71 and 1.64% with a sensitivity of 78 and 72%, and a specificity of 75 and 70%, respectively. CONCLUSIONS: LS measured by 2D STI could evaluate the biomechanical properties of aneurysm wall with different size, and add additional diagnostic value in distinguishing between small and large AAA.

Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis.

BACKGROUND: The effect of bevacizumab combined with chemotherapy on the expression of stromal cell-derived factor-1 (SDF-1) and receptor CXCR4 in epithelial ovarian cancer tumor cells and its prognosis are unknown. Our work aimed to investigate the effect of chemotherapy +/- bevacizumab on these markers and the impact of this treatment modality in clinical outcomes. METHODS: Altogether 68 patients with epithelial ovarian cancer who were treated with chemotherapy in our hospital from June 2018 to June 2019 were selected. It was an open-labeled and controlled clinical trial (ethical approval no. 20180435). The patients were grouped according to their admission order. Patients treated with paclitaxel and carboplatin were included in group A, while patients treated with bevacizumab, paclitaxel, and carboplatin were included in group B. qRT-PCR was used to detect the changes of SDF-1 and CXCR4 before and after chemotherapy. Various clinical indicators of patients in the two groups were recorded to analyze the clinical efficacy, and safety of different treatment modalities and the prognosis of the two groups was analyzed. RESULTS: The relative expression of SDF-1 and CXCR4 was positively correlated with epithelial ovarian cancer stages (P<0.00). Together, SDF-1 and CXCR4 were positively correlated in epithelial ovarian cancer staging (P<0.001). SDF-1 and CXCR4 in both groups after chemotherapy were significantly decreased (P<0.001), and the downregulation of SDF-1 and CXCR4 expression in group B was significantly higher than that in group A after chemotherapy (P<0.001). No significant difference in the metastasis rates of the two groups before chemotherapy was observed (P>0.05), but the recurrence rate after 1 year was lower in group B than in group A (P<0.05). CONCLUSION: Adding bevacizumab diminished the expression of related cancer markers SDF-1 and CXCR4 more than chemotherapy alone in patients with epithelial ovarian cancer. Furthermore, better rates of recurrence with no concerns regarding adverse drug reactions or quality of life were seen in bevacizumab plus chemotherapy group.

Identification and Evolution Analysis of the Complete Methyl Farnesoate Biosynthesis and Related Pathway Genes in the Mud Crab, Scylla paramamosain.

The sesquiterpenoid hormone methyl farnesoate (MF) plays a vital role during crustacean development, which is mainly evidenced by its varied titers during different developmental stages. However, the biosynthesis pathways of MF remain obscure to some extent. In this study, we identified the complete MF biosynthesis and related pathway genes in Scylla paramamosain, including three involved in acetyl-CoA metabolism, eight in the mevalonate pathway, five in the sesquiterpenoids synthesis pathway, and five in the methionine cycle pathway. Bioinformatics, genomic structure, and phylogenetic analysis indicated that the JH biosynthesis genes might have experienced evolution after species differentiation. The mRNA tissue distribution analysis revealed that almost all genes involving in or relating to MF syntheses were highly expressed in the mandibular organ (MO), among which juvenile hormone acid methyltransferase was exclusively expressed in the MO, suggesting that most of these genes might mainly function in MF biosynthesis and that the methionine cycle pathway genes might play a crucial regulatory role during MF synthesis. In addition, the phylogenetic and tissue distribution analysis of the cytochrome P450 CYP15-like gene suggested that the epoxidized JHs might exist in crustaceans, but are mainly synthesized in hepatopancreas rather than the MO. Finally, we also found that betaine-homocysteine S-methyltransferase genes were lost in insects while methionine synthase was probably lost in most insects except Folsomia candida, indicating a regulatory discrepancy in the methionine cycle between crustaceans and insects. This study might increase our understanding of synthetic metabolism tailored for sesquiterpenoid hormones in S. paramamosain and other closely related species.

Role of CXCL16 in BLM-induced epithelial-mesenchymal transition in human A549 cells.

Alveolar epithelial cells play an essential role in the initiation and progression of pulmonary fibrosis, and the occurrence of epithelial-mesenchymal transition (EMT) may be the early events of pulmonary fibrosis. Recent studies have shown chemokines are involved in the complex process of EMT, and CXC chemokine ligand 16 (CXCL16) is also associated with many fibrosis-related diseases. However, whether CXCL16 is dysregulated in alveolar epithelial cells and the role of CXCL16 in modulating EMT in pulmonary fibrosis has not been reported. In this study, we found that CXCL16 and its receptor C-X-C motif chemokine receptor 6 (CXCR6) were upregulated in bleomycin induced EMT in human alveolar type II-like epithelial A549 cells. Synergistic effect of CXCL16 and bleomycin in promoting EMT occurrence, extracellular matrix (ECM) excretion, as well as the pro-inflammatory and pro-fibrotic cytokines productions in A549 cells were observed, and those biological functions were impaired by CXCL16 siRNA. We further confirmed that CXCL16 regulated EMT in A549 cells via the TGF-ß1/Smad3 pathways. These results indicated that CXCL16 could promote pulmonary fibrosis by promoting the process of EMT via the TGF-ß1/Smad3 signaling pathway.

TLR4 rs1927914 polymorphism contributes to serum TLR4 levels in patients with aortic aneurysm.

Toll-like receptor 4 (TLR4) is a crucial regulator of inflammatory reactions and vascular remodeling. Elevated TLR4 expression has been proved to be correlated with an increased risk of aortic aneurysm (AA). This study aimed to explore the influence of TLR4 gene polymorphisms on TLR4 expression levels and its probable functional significance in AA disease. A total of 294 AA patients and 285 controls were enrolled in the study and serum TLR4 levels were detected by ELISA. All the participants were genotyped for two tag-SNPs in TLR4 (rs1927914 in the promoter region and rs11536889 in the 3'-untranslated region) using the KASP method. Relative luciferase activity was measured by the dual-luciferase reporter assay system. The rs1927914 TC, TC/CC genotypes and C allele showed associations with increased serum TLR4 levels in the total population and AA patients (all P<0.05). Further stratified analysis demonstrated that AA subjects with TC or TC/CC genotype of rs1927914 had significantly higher serum levels of TLR4 than those with TT genotype in male, age>60y, hypertension, diabetes, TAA type and size>5.0 cm subgroups (all P<0.05). In binary logistic analysis, rs1927914 TC genotype and dominant model presented significant associations with high TLR4 levels (OR = 1.579 and 1.431, P = 0.020 and 0.049, respectively) after adjusting age, hypertension and diabetes. However, rs11536889 polymorphism had no significant influence on serum TLR4 levels. Regarding rs1927914, luciferase activity of the C allele construct was significantly increased in comparison with the T allele construct (0.589 ± 0.004 vs. 0.340 ± 0.014, P<0.001). Our results provided evidence that rs1927914 polymorphism contributed to serum TLR4 levels, possibly by influencing promoter activity of TLR4, and could be a novel genetic factor in the formation of AA.

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication.

BACKGROUND: Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) have been investigated to play significant roles in the formation of abdominal aortic aneurysm (AAA). But the reports on the expression pattern of TLR4 and MMP9 in human AAA specimens were relatively scant. The aim of this study was to make a detailed analysis of TLR4 and MMP9 expression in situ and their association with clinical parameters involved in human AAA. METHODS: 40 AAA specimens were obtained from full-thickness aneurysmal tissues at the maximal dilation area during the open surgical repair, and 8 non-aneurysmal abdominal aortas from transplant donors served as controls. Expression of TLR4 and MMP9 protein was determined by immunohistochemistry. RESULTS: There were increased levels of TLR4 and MMP9 expression in human AAA tissues. Compared with macrophages or SMCs, lymphocytes showed a higher positive rate of TLR4 and MMP9 staining, and an elevated ratio of high MMP9 expression (all P < 0.05). There existed a significant association between TLR4 and MMP9 expression (r = 0.767, P < 0.001), and both TLR4 and MMP9 levels were statistically related to circulating CRP. Moreover, TLR4 expression in situ indicated a positive correlation with its serum level (r = 0.654, P = 0.006). Multiple analysis revealed that high TLR4 expression in situ was associated with the risk of large AAA (OR = 6.211, 95%CI = 1.226-31.480, P = 0.027), while high MMP9 expression was correlated to the presence of thrombus within AAA (OR = 5.494, 95%CI = 1.181-25.562, P = 0.030), separately compared with their low expression. CONCLUSIONS: This study confirmed the overexpression of TLR4 and MMP9 in human AAA tissues, and their close relationship implying in the pathogenesis of AAA. We further provided evidence that TLR4 had a potential effect on AAA size and MMP9 could influence the occurrence of thrombus within AAA.

Validation of evaluating left ventricular diastolic function with estimated left atrial volume from anteroposterior diameter.

BACKGROUND: Left atrial (LA) volume (LAV) is one of the recommended key variables for evaluating left ventricular (LV) diastolic function. However, only LA anteroposterior diameter (LAAP) is available in numerous large-scale existing databases. Therefore, this study aimed to validate whether LV diastolic function could be evaluated with estimated LAV from LAAP. METHODS: A total of 552 inpatients with sinus rhythm were consecutively enrolled. LAV was measured by biplane Simpson's disk summation method. LV diastolic function was evaluated according to the 2016 proposed recommendations. Best-fitting regression models of LAAP index (LAAPI)-LAV index (LAVI) were developed and equations with the highest F-value were chosen in the first 276 subjects (derivation set), and concordance for evaluating LV diastolic function between using estimated and observed LAVI was verified in the remaining 276 subjects (validation set). RESULTS: In the derivation set, the linear model has the highest F-value in all subjects and in the subjects with normal or depressed LV ejection fraction. In the validation set, using the linear equation (LAVI = 2.05 × LAAPI - 13.86), the higher area under curve and narrower range of difference were shown between estimated LAVI and observed LAVI, respectively. Further, concordance for diagnosis (overall proportion of agreement, 88.4%; κ = 0.79) and grading (overall proportion of agreement, 84.8%; κ = 0.74) of LV diastolic dysfunction was substantial between using estimated and observed LAVI. CONCLUSIONS: LV diastolic function can be evaluated with estimated LAVI from LAAPI, which might provide a surrogate method when the direct measurement of LAV is not available.