Abstract
Identifying key spreaders in a network is one of the fundamental problems in the field of complex network research, and accurately identifying influential propagators in a network holds ...significant practical implications. In recent years, numerous effective methods have been proposed and widely applied. However, many of these methods still have certain limitations. For instance, some methods rely solely on the global position information of nodes to assess their propagation influence, disregarding local node information. Additionally, certain methods do not consider clustering coefficients, which are essential attributes of nodes. Inspired by the quality formula, this paper introduces a method called Structural Neighborhood Centrality (SNC) that takes into account the neighborhood information of nodes. SNC measures the propagation power of nodes based on first and second-order neighborhood degrees, local clustering coefficients, structural hole constraints, and other information, resulting in higher accuracy. A series of pertinent experiments conducted on 12 real-world datasets demonstrate that, in terms of accuracy, SNC outperforms methods like CycleRatio and KSGC. Additionally, SNC demonstrates heightened monotonicity, enabling it to distinguish subtle differences between nodes. Furthermore, when it comes to identifying the most influential Top-k nodes, SNC also displays superior capabilities compared to the aforementioned methods. Finally, we conduct a detailed analysis of SNC and discuss its advantages and limitations.
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell ...(CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of ΔNp63α, the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the β-catenin signaling pathway through direct phosphorylation of GSK-3β at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the ΔNp63α/RSK4/GSK-3β axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment.
Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced ...mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages.
To investigate the role of TNFAIP3 deletions and NF-κB activation in extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type.
In total, 138 patients with ENKTCL were included. Activation of ...NF-κB pathway and expression of TNFAIP3 (A20) were examined by immunohistochemistry. TNFAIP3 was analyzed for deletions using FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for investigating neoplasms), for mutations using Sanger sequencing, and for promoter methylation using methylation-specific sequencing.
NF-κB pathway activation was observed in 31.2% of cases (43/138), TNFAIP3 expression was negative in 15.2% of cases (21/138), and heterozygous TNFAIP3 deletion was observed in 35% of cases (35/100). TNFAIP3 exons 2 to 9 mutations and promoter methylation were not observed. Kaplan-Meier analysis showed patients with NF-κB pathway activation or TNFAIP3 heterozygous deletion to have a longer overall survival.
Our study demonstrated that NF-κB activation and TNFAIP3 heterozygous deletion confer superior survival in patients with ENKTCL.
Enantiopure alcohols are very important chemicals as highly valuable building blocks in the synthesis of pharmaceuticals, agrochemicals and materials. The direct enantioselective hydration of ...unactivated 1-alkenes is a highly straightforward and atom economy approach to access chiral alcohols, though quite challenging in organic synthesis owing to low selectivity and many environmental concerns. Herein, two novel oleate hydratases (MmOAH1 and MmOAH2) were identified from marine metagenome via a sequence-based mining approach, and the two OAHs were functionally expressed in Escherichia coli T7, purified and characterized. Both of the two OAHs exhibited surprising highly promiscuous hydratase activity toward unactivated 1-alkenes when a carboxylic acid decoy molecule was involved in the reaction. Besides its natural substrate oleate acid, a series of unactivated 1-alkenes were converted to (S)-alcohols by using the resting cell of E. coli (MmOAH1) and E. coli (MmOAH2), moderate to good conversions (6–90%) and excellent ee (>98%) were obtained. Preparative-scale experiments were also demonstrated with 1-decene and 1-tridecene, affording (S)-2-decanol and (S)-2-tridecanol in good yields and excellent ee (>99%). This study expands the biocatalytic toolbox of available enzymes for asymmetric hydration reactions and proved that the OAHs mined from marine metagenome is promising for biotechnology application in production of chiral alcohols.
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Identification of critical nodes is a prominent topic in the study of complex networks. Numerous methods have been proposed, yet most exhibit inherent limitations. Traditional approaches primarily ...analyze specific structural features of the network; however, node influence is typically the result of a combination of multiple factors. Machine learning-based methods struggle to effectively represent the complex characteristics of network structures through suitable embedding techniques and require substantial data for training, rendering them prohibitively costly for large-scale networks. To address these challenges, this paper presents an active learning model based on GraphSAGE and Transformer, named GNNTAL. This model is initially pre-trained on random or synthetic networks and subsequently fine-tuned on real-world networks by selecting a few representative nodes using K-Means clustering and uncertainty sampling. This approach offers two main advantages: (1) it significantly reduces training costs; (2) it simultaneously incorporates both local and global features. A series of comparative experiments conducted on twelve real-world networks demonstrate that GNNTAL achieves superior performance. Additionally, this paper proposes an influence maximization method based on the predictions of the GNNTAL model, which achieves optimal performance without the need for complex computations. Finally, the paper analyses certain limitations of the GNNTAL model and suggests potential solutions.
To explore the clinical efficacy of electroacupuncture intervention on severe acute pancreatitis (SAP) at early stage complicated with intestinal paralysis.
Sixty-eight cases of SAP were randomly ...divided into observation group (48 cases) and control group (20 cases). In observation group, according to the course of sickness, the early-stage subgroup (30 cases, hospitalized in 3 d) and late-stage subgroup (18 cases, hospitalized in 3-7 d) were subdivided. In control group, the conventional treatment was applied. In observation group, based on the same treatment as control group, electroacupuncture was supplemented at Zhongwan (CV 12), Zusanli (ST 36), Neiguan (PC 6), Hegu (LI 4), etc. Acute physiology and chronic health evaluation (APACHE) II scores, the recovery time of intestinal paralysis and laboratory indices, complications, operation transfer rate, death rate and the admission time were compared among groups after treatment.
The total effective rate was 83.3% (25/30) in early-stage subgroup, which was su
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