Explore the vast range of titles available.

Noble metal electrocatalysts (e.g., Pt, Ru, etc.) suffer from sluggish kinetics of water dissociation for the electrochemical reduction of water to molecular hydrogen in alkaline and neutral pH environments. Herein, we found that an integration of Ru nanoparticles (NPs) on oxygen-deficient WO 3-x manifested a 24.0-fold increase in hydrogen evolution reaction (HER) activity compared with commercial Ru/C electrocatalyst in neutral electrolyte. Oxygen-deficient WO 3-x is shown to possess large capacity for storing protons, which could be transferred to the Ru NPs under cathodic potential. This significantly increases the hydrogen coverage on the surface of Ru NPs in HER and thus changes the rate-determining step of HER on Ru from water dissociation to hydrogen recombination. While water splitting electrolysis offers an appealing means to produce H 2 fuel, catalysts show sluggish reaction rate in neutral media. Here, authors utilize hydrogen spillover from oxygen-deficient tungsten oxides to Ru nanoparticles to boost the neutral-pH H 2 evolution performances.

Background: Refractory apical periodontitis (RAP) is an oral infectious disease characterised by persistent inflammation, progressive alveolar bone destruction, and delayed bone healing. RAP has received increasing attention, because it cannot be cured after repeated root canal therapies. The aetiology of RAP is related to the complex interplay between the pathogen and its host. However, the exact pathogenesis of RAP remains unclarified and includes several factors, such as microorganism immunogenicity, host immunity and inflammation, and tissue destruction and repair. Enterococcus faecalis is the dominant pathogen involved in RAP, and has evolved multiple strategies to ensure survival, which cause persistent intraradicular and extraradicular infections. Objective: To review the crucial role of E. faecalis in the pathogenesis of RAP, and open new avenues for prevention and treatment of RAP. Methods: The PubMed and Web of Science databases were searched for pertinent publications, employing the search terms \"Enterococcus faecalis\", \"refractory apical periodontitis\", \"persistent periapical periodontitis\", \"pathogenicity\", \"virulence\", \"biofilm formation\", \"dentine tubule\", \"immune cell\", \"macrophage\", and \"osteoblast\". Results and Conclusion: Besides its high pathogenicity due to various virulence mechanisms, E. faecalis modulates the macrophage and osteoblast responses, including regulated cell death, cell polarisation, cell differentiation, and inflammatory response. An in-depth understanding of the multifaceted host cell responses modulated by E. faecalis will help to design potential future therapeutic strategies and overcome the challenges of sustained infection and delayed tissue healing in RAP.

Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.

Chlorogenic acid (CA) is an effective ingredient that can strengthen immunity during following the COVID-19 era. The current cost of CA is high owing to its complex purification process and low yield (approximately 2%). In this study, a one-step path orthogonal experiment was designed based on the results from Gauss calculation, which consisted of acidity, coordination, and hydrolysis in molecules. The optimized extraction conditions were 60 ℃, 60 min, 1:20 liquid ratio, and 40% ethanol in a nitrogen atmosphere controlled using a device of our own design, which led to CA yields of up to 6.35% from potato leaves. The purified CA was analyzed using high-performance liquid chromatography, thin-layer chromatography, ultraviolet–visible spectroscopy, and molecular fluorescence. This accurate and reproducible method can not only be used to obtain high yields of CA but can also be used for the quality control of active plant products and their isomers.

Background Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis. Results Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift. Conclusion This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium–mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.

Intercellular communication is essential for almost all physiological and pathological processes. Endothelial cell (EC)-derived exosomes, working as mediators for intercellular information exchange, are involved in the pathophysiological mechanisms of atherosclerosis. However, the effect of inflamed endothelial exosomes on the function of macrophages (Mϕ) is poorly defined. This study aims to unravel how exosomes derived from tumor necrosis factor-α (TNF-α)-stimulated ECs (exo-T) affect Mϕ . Exosomes derived from untreated ECs (exo) and exo-T were identified by using TEM, NTA, and western blot, and we observed that PKH67-labeled exo/exo-T were taken up by Mϕ. Exposure to exo-T for 24 h not only skewed Mϕ to the M1 subtype and exacerbated lipid deposition, but also promoted Mϕ apoptosis, while it did not significantly affect Mϕ migration, as detected by RT-qPCR, Dil-ox-LDL uptake assay, flow cytometry, wound healing assay, and transwell assay, respectively. In addition, exo/exo-T-related microRNA-Seq revealed 104 significantly differentially expressed microRNAs (DE-miRNAs). The target genes of DE-miRNAs were mainly enriched functionally in metabolic pathways, MAPK signaling pathway, etc., as determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We further demonstrated by immunoblotting that exo-T intervention improves the phosphorylation of MAPK/NF-κB-related proteins. Collectively, this study reveals that inflamed endothelial exosomes (TNF-α-stimulated EC-derived exosomes) work as a functional mediator to affect Mϕ function and may activate Mϕ through MAPK/NF-κB signaling pathways.

Objective Develop a nomogram to predict postoperative venous thromboembolism (VTE) risk in gynecologic malignancy patients. Methods This study retrospectively examined 2020 patients with gynaecological malignancies of Fujian Provincial Hospital and Fujian Provincial Hospital South Branch (Jinshan Hospital). Independent VTE predictors were identified via least absolute shrinkage and selection operator(LASSO) regression analysis and multivariate regression.A nomogram was constructed and validated. Performance was assessed using AUC, calibration curves, and decision curve analysis (DCA). Results The predictive nomogram model consists of the following six factors: Triglyceride, Arrhythmia, Varicose vein, Hypoproteinemia, History of VTE, Tumor types.The resulting model showed good predictive performance in the derivation group (AUC 0.804, 95% CI 0.760–0.848) and in the validation group(AUC 0.824, 95% CI 0.760–0.887).The calibration curve showed that predictive nomogram had good consistency.The decision curve analysis revealed that within the probability threshold range of 5–80% (training group) and 10–70%(validation group), the predictive model yielded higher net benefits. Conclusion The nomogram for predicting the risk of VTE after surgery for gynecological gynecologic malignancies demonstrated good identification accuracy and consistency. These predictors are easily accessible to clinicians, enabling them to individualize their assessment of patients.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) in high-risk populations and cardiovascular events in secondary prevention. We now review the limitations of the current approach to lipid management in CKD and information on CKD patients from clinical trials of anti-PCSK9 monoclonal antibodies alirocumab and evolocumab. In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated significant superiority of alirocumab on LDL-cholesterol lowering in comparison to placebo and ezetimibe, respectively, when added to statins, and case reports have shown efficacy in nephrotic syndrome. A detailed analysis of CKD subgroups in general population trials of anti-PCSK9 strategies addressing events is needed, given the limited efficacy of statins in CKD both in terms of lipid lowering and events, the high rate of statin non-compliance in these patients, and the high lipoprotein(a) levels. This information should guide the design of trials addressing the safety profile and efficacy on cardiovascular outcomes of PCSK9-targeted therapies in CKD patients.

Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg −1 ) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg −1 [95% CI, 0.06–0.11 mg kg −1 ]) when compared with group control (0.14 mg kg −1 [95% CI, 0.13–0.16 mg kg −1 ]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg −1 [95% CI, 0.05–0.12 mg kg −1 ] in group granisetron and 0.14 mg kg −1 [95% CI, 0.12–0.16 mg kg −1 ] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed. Advances in the formulation and delivery of 7 + 3 with liposomal cytarabine and daunorubicin (Vyxeos) have improved overall survival in secondary AML. Increased understanding of the genetic underpinnings of AML has led to targeting actionable mutations such as FLT3, IDH1/2 and TP53, and BCL2 or hedgehog pathways in more frail populations. Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement