Search Results (9,707)

Fan growth serves as a critical performance indicator for the sustainable development of livestreaming e-commerce (LSE). However, existing research has paid limited attention to this topic. This study investigates the unique interactive advantages of LSE over traditional e-commerce by examining how interactivity drives fan growth through the mediating role of user retention and the moderating role of anchors’ facial attractiveness. To conduct the analysis, real-time data were collected from 1472 livestreaming sessions on Douyin, China’s leading LSE platform, between January and March 2023, using Python-based (3.12.7) web scraping and third-party data sources. This study operationalizes key variables through text sentiment analysis and image recognition techniques. Empirical analyses are performed using ordinary least squares (OLS) regression with robust standard errors, propensity score matching (PSM), and sensitivity analysis to ensure robustness. The results reveal the following: (1) Interactivity has a significant positive effect on fan growth. (2) User retention partially mediates the relationship between interactivity and fan growth. (3) There is a substitution effect between anchors’ facial attractiveness and interactivity in enhancing user retention, highlighting the substitution relationship between anchors’ personal characteristics and livestreaming room attributes. This research advances the understanding of interactivity’s mechanisms in LSE and, notably, is among the first to explore the marketing implications of anchors’ facial attractiveness in this context. The findings offer valuable insights for both academic research and managerial practice in the evolving livestreaming commerce landscape. Full article

Beyond its crucial role as a tight barrier to protect the nervous system, the Blood–Brain Barrier (BBB) is increasingly being recognized for its physiological processes that affect brain function and behavior. In Drosophila melanogaster, the BBB expresses sex-specific transcripts, and a change in the sexual identity of adult BBB cells results in a significant reduction in male courtship behavior. The molecular nature of this BBB/brain interaction and the molecules that mediate it are unknown. Here we feminize BBB cells by targeted expression of the Drosophila female-specific master regulator TraF in otherwise normal males. We examined the effect on RNA expression in dissected brains by RNA sequenc-ing. We find that 283 transcripts change in comparison to normal control males. Tran-scripts representing cell signaling processes and synaptic communication are enriched, as are hormonal mediators. These transcripts provide a valuable resource for addressing questions about BBB and brain interaction. Full article

Investigating the coevolution between ecosystem services (ES) and human well-being (HWB) holds significant implications for achieving the sustainable operation of human–environment systems. However, limited research has focused on ES-HWB interactions in ecotourism-dominated counties. To address this gap, this study takes Chun’an County in Zhejiang Province, China, as a case study, with the research objective of exploring the processes, patterns, and mechanisms of the coevolution between ecosystem services (ES) and human well-being (HWB) in ecotourism-dominated counties. By integrating multi-source heterogeneous data, including land use data, the normalized difference vegetation index (NDVI), and statistical records, and employing methods such as the dynamic equivalent factor method, the PLUS model, the coupling coordination degree model, and comprehensive evaluation, we analyzed the synergistic evolution of ES-HWB in Chun’an County from 2000 to 2020. The results indicate that (1) the ecosystem service value (ESV) fluctuated between 30.15 and 36.85 billion CNY, exhibiting a spatial aggregation pattern centered on the Qiandao Lake waterbody, with distance–decay characteristics. The PLUS model confirms ecological conservation policies optimize ES patterns. (2) The HWB index surged from 0.16 to 0.8, driven by tourism-led economic growth, infrastructure investment, and institutional innovation, facilitating a paradigm shift from low to high well-being at the county level. (3) The ES-HWB interaction evolved through three phases—disordered, antagonism, and coordination—revealing tourism as a key mediator driving coupled human–environment system sustainability via a pressure–adaptation–synergy transmission mechanism. This study not only advances the understanding of ES-HWB coevolution in ecotourism-dominated counties, but also provides a transferable methodological framework for sustainable development in similar regions. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Aflatoxin contamination, primarily caused by Aspergillus flavus, poses a significant threat to peanut (Arachis hypogaea L.) production, food safety, and global trade. Despite extensive efforts, breeding for durable resistance remains difficult due to the polygenic and environmentally sensitive nature of resistance. Although germplasm such as J11 have shown partial resistance, none of the identified lines demonstrated stable or comprehensive protection across diverse environments. Resistance involves physical barriers, biochemical defenses, and suppression of toxin biosynthesis. However, these traits typically exhibit modest effects and are strongly influenced by genotype–environment interactions. A paradigm shift is underway with increasing focus on host susceptibility (S) genes, native peanut genes exploited by A. flavus to facilitate colonization or toxin production. Recent studies have identified promising S gene candidates such as AhS5H1/2, which suppress salicylic acid-mediated defense, and ABR1, a negative regulator of ABA signaling. Disrupting such genes through gene editing holds potential for broad-spectrum resistance. To advance resistance breeding, an integrated pipeline is essential. This includes phenotyping diverse germplasm under stress conditions, mapping resistance loci using QTL and GWAS, and applying multi-omics platforms to identify candidate genes. Functional validation using CRISPR/Cas9, Cas12a, base editors, and prime editing allows precise gene targeting. Validated genes can be introgressed into elite lines through breeding by marker-assisted and genomic selection, accelerating the breeding of aflatoxin-resistant peanut varieties. This review highlights recent advances in peanut aflatoxin resistance research, emphasizing susceptibility gene targeting and genome editing. Integrating conventional breeding with multi-omics and precision biotechnology offers a promising path toward developing aflatoxin-free peanut cultivars. Full article

Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery. Full article

Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article

Under the rapid development of the digital economy, the interactive relationship between exports and the digital economy has become an important issue for promoting regional economic growth. Based on the panel data of 31 provinces and municipalities in China from 2012 to 2022, this paper systematically examines the impact of exports on economic growth and the moderating role of the digital economy, and it introduces research and development (R&D) investment to test its mediating mechanism. The research finds that exports significantly promote regional economic growth. The digital economy has a negative moderating effect on the export growth effect, and it is significant in the eastern region but not significant in the central and western regions, showing obvious regional heterogeneity. R&D investment has played a partial mediating role between exports and economic growth. This paper suggests that the government should focus on regional differences, promote the deep integration of the digital economy and exports, enhance technological innovation capabilities, formulate differentiated policies based on local conditions, strengthen the construction of digital infrastructure, optimize the export structure, support the development of R&D-driven enterprises, and build a digital export system that promotes regional coordination and high-quality growth, so as to achieve high-quality coordinated sustainable regional development. This paper also has certain reference value for other developing economies, in promoting the integration of the digital economy and trade. Full article

As artificial intelligence (AI) becomes increasingly embedded in organizational development, understanding how leadership shapes employee responses to AI is critical for fostering workplace innovation. Drawing on trait activation theory, this study develops a theoretical model in which employee AI trust enhances innovative performance through AI crafting. Paternalistic leadership serves as a situational moderator, while the leader’s AI opportunity perception functions as a higher-order moderator. A three-wave survey was conducted with 523 employees from 14 AI-intensive manufacturing firms in China. Results show that the interaction between AI trust and paternalistic leadership positively predicts both AI crafting and innovative performance. In addition, AI crafting mediates the effect of the interaction term on innovative performance. Furthermore, the leader’s AI opportunity perception moderates this interactive effect: when this perception is high, the positive impact of AI trust and paternalistic leadership on AI crafting is significantly stronger; when it is low, the effect weakens. These findings contribute to the literature by clarifying the situational and cognitive conditions under which AI trust promotes innovation, thereby extending trait activation theory to AI-enabled workplaces and offering actionable insights for leadership development in the intelligent era. Full article

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Virtual influencers (VIs) on e-commerce platforms are becoming increasingly popular, enhancing the consumer experience. This study examines the consumer–brand relationship (CBR) with VIs through the perspective of social presence. Data from 1041 e-commerce platform users (e.g., Douyin, RED, Weibo) were collected and analyzed using Structural Equation Modeling (SEM). The findings reveal that both the visual and mental human-likeness of VIs significantly strengthen CBR, with social presence acting as a mediator. Additionally, the interaction between visual and mental human-likeness positively impacts social presence, which in turn enhances CBR. Moreover, consumers’ need for uniqueness moderates the relationship between social presence and CBR, providing valuable insights for virtual influencer strategies in e-commerce. This research suggests the feasibility of leveraging VI design both visually and mentally to capture new trends in developing effective virtual campaigns with digitization and metaverse technologies. This study extends the stream of research VIs use for interactive marketing, highlighting the role of parasocial relationships in interactive marketing. These findings can provide managers with a better understanding of VI design from both visual and mental aspects. Full article

Microglia, the brain’s resident innate immune cells, play a fundamental role in maintaining neural homeostasis and mediating responses to injury or infection. Upon activation, microglia undergo morphological and functional changes, including phenotypic switching between pro- and anti-inflammatory types and the release of different inflammatory mediators. These processes contribute to neuroprotection and the pathogenesis of various central nervous system (CNS) disorders. Mast cells, although sparsely located in the brain, exert a significant influence on neuroinflammation through their interactions with microglia. Through degranulation and secretion of different mediators, mast cells disrupt the blood–brain barrier and modulate microglial responses, including alteration of microglial phenotypes. Notably, mast cell-derived factors, such as histamine, interleukins, and tryptase, activate microglia through various pathways including protease-activated receptor 2 and purinergic receptors. These interactions amplify inflammatory cascades via various signaling pathways. Previous studies have revealed an exceedingly complex crosstalk between mast cells and microglia suggesting a bidirectional regulation of CNS immunity, implicating their cooperation in both neurodegenerative progression and repair mechanisms. Here, we review some of the diverse communication pathways involved in this complex interplay. Understanding this crosstalk may offer novel insights into the cellular dynamics of neuroinflammation and highlight potential therapeutic targets for a variety of CNS disorders. Full article