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Alpha-mangostin (α-mangostin) was discovered as a potent natural product against Gram-positive bacteria, whereas the underlying molecular mechanisms are still unclear. This study indicated that α-mangostin (at 4 × MIC) rapidly killed Staphylococcus aureus planktonic cells more effectively (at least 2-log10 CFU/ml) than daptomycin, vancomycin and linezolid at 1 and 3 h in the time-killing test. Interestingly, this study also found that a high concentration of α-mangostin (≥4×MIC) significantly reduced established biofilms of S. aureus. There were 58 single nucleotide polymorphisms (SNPs) in α-mangostin nonsensitive S. aureus isolates by whole-genome sequencing, of which 35 SNPs were located on both sides of the sarT gene and 10 SNPs in the sarT gene. A total of 147 proteins with a different abundance were determined by proteomics analysis, of which 91 proteins increased, whereas 56 proteins decreased. The abundance of regulatory proteins SarX and SarZ increased. In contrast, the abundance of SarT and IcaB was significantly reduced (they belonged to SarA family and ica system, associated with the biofilm formation of S. aureus). The abundance of cell membrane proteins VraF and DltC was augmented, but the abundance of cell membrane protein UgtP remarkably decreased. Propidium iodide and DiBaC4(3) staining assay revealed that the fluorescence intensities of DNA and the cell membrane were elevated in the α-mangostin treated S. aureus isolates. In conclusion, this study reveals that α-mangostin was effective against S. aureus planktonic cells by targeting cell membranes. The anti-biofilm effect of α-mangostin may be through inhibiting the function of SarT and IcaB.

Considering the increasing demand for gold and the scarcity of mineral resources, this study presents a promising avenue for its recovery from secondary resources. In this paper, N1,N1′-(1,4-phenylene)bis(N1-(4-aminophenyl)benzene-1,4-diamine) and 2,3,5,6-tetrafluoro-p-dibenzaldehyde were successfully prepared by the solvothermal method to synthesize a highly fluorinated covalent organic polymer with imine bonds (N-TFACOP), which can be used to recover gold ions from secondary sources. Covalent organic polymer (COP) materials have controllable structures that can be significantly improved by introducing appropriate functional groups into the structural units. The introduction of fluorine atoms with strong electron-absorbing ability into COP materials not only significantly increases the specific surface area of the materials and provides more surface active sites but also improves the chemical and thermal stability of the materials, even in strong acids and bases. The adsorption capacity for gold was further improved. At pH = 4, adsorption time of 720 min, and adsorption temperature of 45 °C, the maximum adsorption capacity of N-TFACOP for gold was as high as 2975.08 mg g−1. There was no significant decrease in the adsorption rate after six cycles, which proved that the adsorption performance for gold was significantly improved by N-TFACOP. Au(III) was reduced to monomeric gold by complexation and redox reaction between the functional atom (N) and Au(III). In summary, we verified the adsorption potential of a novel covalent organic polymer for Au(III), which provides a strong reference for the recycling of the precious gold metal from secondary resources and the protection of environmental resources. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD and IS. Numerous clinical trials have unequivocally demonstrated that reducing levels of low-density lipoprotein cholesterol (LDL-C) significantly mitigates the risk of both cardiac and cerebral vascular events, thereby enhancing patient prognosis. Consequently, LDL-C reduction remains a pivotal therapeutic strategy for CVD and IS. However, despite intensive statin therapy, a significant proportion of high-risk hypercholesterolemic patients fail to achieve sufficient reductions in LDL-C levels. In response to this challenge, an inhibitor targeting proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed as a therapeutic intervention for hyperlipidemia. Numerous randomized controlled trials (RCTs) have conclusively demonstrated that the combination of PCSK9 inhibitors and statins significantly enhances prognosis not only in patients with CVD, but also in those afflicted with symptomatic intracranial artery stenosis (sICAS). PCSK9 inhibitors significantly reduce LDL-C levels by binding to the PCSK9 molecule and preventing its interaction with LDLRs. This prevents degradation of the receptor and increases uptake of LDL-C, thereby decreasing its concentration in blood. Besides significantly reducing LDL-C levels, PCSK9 inhibitors also demonstrate anti-inflammatory and anti-atherosclerotic properties while promoting plaque stabilization and inhibiting platelet aggregation and thrombosis. This article aims to provide a comprehensive review based on the relevant literature regarding the evolving understanding of pleiotropic effects associated with PCSK9 inhibitors, particularly focusing on their impact on the cardiovascular system and central nervous system. [ABSTRACT FROM AUTHOR]

Photocatalytic water splitting for hydrogen production represents a crucial approach for obtaining green energy through artificial solar energy utilization, offering a sustainable method for energy generation that helps mitigate energy shortages and protect the environment. Among the numerous photocatalytic materials, covalent organic frameworks (COFs) have garnered significant attention and intensive study from researchers due to their distinctive benefits, such as porosity, pre‐design capability, and tunability at the atomic level. Significant advancements are made in the development of materials, enhancement of performance, and comprehension of mechanisms. In this review, recent advancements in COF‐based photocatalytic water splitting are spotlighted, both in half‐reactions and overall reactions, with a particular emphasis on the rational design of COF structures to regulate the materials' optical and electrical properties, as well as the fundamental processes of photocatalysis. Drawing from current research in this field, the existing challenges, and potential opportunities are also discussed for future development. [ABSTRACT FROM AUTHOR]

Introduction: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0–3 h and >3–4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. Methods: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0–3 h or >3–4.5 h. Results: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3–4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0–3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0–3 h: 1.06 [95% CI: 0.73–1.52], acOR in patients within >3–4.5 h: 1.19 [95% CI: 0.78–1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0–3 treated within >3–4.5 h (62.90 vs. 48.72%) but not within 0–3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. Conclusions: Our results did not support thrombectomy-alone administration within 3–4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with unclear etiology and a poor prognosis. Although the involvement of neutrophils in IPF pathogenesis has been suggested, the exact nature of this relationship remains unclear. Methods: We analyzed data from the Gene Expression Omnibus (GEO) using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and consensus cluster analysis. Neutrophil-related genes and hub genes related to neutrophils were identified and differentially expressed between IPF patients and healthy controls. We also validated the expression differences of hub genes in a bleomycin-induced mice model. Results: Immune infiltration analysis revealed a significantly decreased percentage of neutrophils in the lung tissue of IPF patients compared with healthy controls (P< 0.001) in both the train and validation sets. Neutrophil-related genes in IPF were identified by WGCNA, and functional enrichment analysis showed that these genes were mainly involved in the cytokine-cytokine receptor interaction pathway and correlated with lung disease, consistent with DEGs between IPF and healthy controls. Eight hub genes related to neutrophils were identified, including MMP16, ARG1, IL1R2, PROK2, MS4A2, PIR, and ZNF436. Consensus cluster analysis revealed a low neutrophil-infiltrating cluster that was correlated with IPF (P< 0.001), and a principal component analysis-generated score could distinguish IPF patients from healthy controls, with an area under the curve of 0.930 in the train set and 0.768 in the validation set. We also constructed a diagnostic model using hub genes related to neutrophils, which showed a reliable diagnostic value with an area under the curve of 0.955 in the train set and 0.995 in the validation set. Conclusion: Our findings provide evidence of a low neutrophil-infiltrating characteristic in the IPF microenvironment and identify hub genes related to neutrophils that may serve as diagnostic biomarkers for the disease. [ABSTRACT FROM AUTHOR]

High-resolution magnetic resonance imaging (HRMRI) is the most important and popular vessel wall imaging technique for the direct assessment of vessel wall and cerebral arterial disease. It can identify the cause of stroke in high-risk plaques and differentiate the diagnosis of head and carotid artery dissection, including inflammation, Moya Moya disease, cerebral aneurysm, vasospasm after subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, blunt cerebrovascular injury, cerebral arteriovenous malformations, and other stenosis or occlusion conditions. Through noninvasive visualization of the vessel wall in vitro, quantified assessment of luminal stenosis and pathological features of the vessel wall can provide clinicians with further disease information. In this report, technical considerations of HRMRI are discussed, and current clinical applications of HRMRI are reviewed. [ABSTRACT FROM AUTHOR]