Search Results (66,927)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Antibiotic misuse accelerates resistance dissemination via plasmid conjugation, but quorum sensing (QS) regulatory mechanisms remain undefined. Using Escherichia coli (E. coli) MG1655 conjugation models (RP4-7/EC600 plasmids), we demonstrate that long-chain acyl-homoserine lactones (C10/C12-HSL) enhance transfer frequency by up to 7.7-fold (200μM C12-HSL; p < 0.001), while quorum-quenching by sub-inhibitory vanillin suppressed this effect by 95% (p < 0.0001). C12-HSL compromised membrane integrity via ompF upregulation (4-fold; p < 0.01) and conjugative pore assembly (trbBp upregulated by 1.38-fold; p < 0.05), coinciding with ROS accumulation (1.5-fold; p < 0.0001) and SOS response activation (recA upregulated by 1.68-fold; p < 0.001). Crucially, rpoS and rmf deletion mutants reduced conjugation by 65.5% and 55.8%, respectively (p < 0.001), exhibiting attenuated membrane permeability (≤65.5% reduced NPN influx; p < 0.0001), suppressed ROS (≤54% downregulated; p < 0.0001), and abolished transcriptional induction of conjugation/stress genes. Reciprocal RpoS–RMF (ribosomal hibernation factor) crosstalk was essential for AHL responsiveness, with deletions mutually suppressing expression (≤65.9% downregulated; p < 0.05). We establish a hierarchical mechanism wherein long-chain AHLs drive resistance dissemination through integrated membrane restructuring, stress adaptation, and RpoS–RMF-mediated genetic plasticity, positioning QS signaling as a viable target for curbing resistance spread. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Sloman and Rabb found support for the existence of the community of knowledge (CK) effect, which occurs when individuals are more likely to report understanding and being able to explain even fake scientific information when told that an expert understands the information. To date, no studies have been conducted that attempted to replicate original findings, let alone test the presence of the CK effect in realistic, legal scenarios. Therefore, Study One replicated original CK effect studies in a jury-eligible M-Turk sample (N = 291) using both Sloman and Rabb’s experimental stimuli as well as new stimuli. Study Two then tested the presence of the CK effect using scientific testimony in a mock court hearing from a forensic evaluator (N = 396). Not only did the CK effect improve laypeople’s perceptions of the scientific information in court, but it also improved their perceptions of the expert witness’s credibility, increased the weight assigned to the scientific information, and increased the weight assigned to the expert testimony. This effect was mediated by participants’ perceived similarity to the expert, supporting the theory behind the CK effect. These studies have important implications for the use of scientific information in court, which are discussed. Full article

Rabies remains a significant global public health concern, causing an estimated 59,000–69,000 human fatalities annually. Despite being entirely preventable through vaccination, rabies continues to impose substantial economic burdens worldwide. This study presents a scoping review of the economic research on rabies to determine overlaps and gaps in knowledge and inform future research strategies. We selected 150 studies (1973–2024) to analyze. The review categorizes the literature based on geographic distribution, species focus, and type of study. Findings indicate that economic studies are disproportionately concentrated in developed countries, such as the United States and parts of Europe, where rabies risk is low, while high-risk regions, particularly in Africa and Asia, remain underrepresented. Most studies focus on dog-mediated rabies, reflecting its dominant role in human transmission, while fewer studies assess the economic impacts of wildlife and livestock-mediated rabies. Case studies and modeling approaches dominate the literature, whereas cost–benefit and cost–effectiveness analyses—critical for informing resource allocation—are limited. The review highlights the need for more economic evaluations in rabies-endemic regions, expanded research on non-dog reservoirs, and broader use of economic methods. Addressing these gaps will be crucial for optimizing rabies control and supporting global initiatives to eliminate dog-mediated rabies by 2030. Full article

 Galectin-3 is a multifunctional protein that is associated with diseases of the chorioretinal interface, in which the retinal pigment epithelium (RPE) plays a central role in disease development and progression. Since galectin-3 can function extracellularly as well as intracellularly via different mechanisms, we developed an immortalized human RPE cell line (ARPE-19) with a knockdown for galectin-3 expression (ARPE-19/LGALS3^+/−) using a sgRNA/Cas9 all-in-one expression vector. By Western blot analysis, a reduced galectin-3 expression of approximately 48 to 60% in heterozygous ARPE-19/LGALS3^+/− cells was observed when compared to native controls. Furthermore, ARPE-19/LGALS3^+/− cells displayed a flattened, elongated phenotype with decreased E-cadherin as well as enhanced N-cadherin and α-smooth muscle actin mRNA expression, indicating an epithelial–mesenchymal transition of the cells. Compared to wildtype controls, ARPE-19/LGALS3^+/− cells had significantly reduced metabolic activity to 86% and a substantially decreased proliferation to 73%. Furthermore, an enhanced cell adhesion and a diminished migration of immortalized galectin-3 knockdown RPE cells was observed compared to native ARPE-19 cells. Finally, by Western blot analysis, reduced pAKT, pERK1/2, and β-catenin signaling were detected in ARPE-19/LGALS3^+/− cells when compared to wildtype controls. In summary, in RPE cells, endogenous galectin-3 appears to be essential for maintaining the epithelial phenotype as well as cell biological functions such as metabolism, proliferation, or migration, effects that might be mediated via a decreased activity of the AKT, ERK1/2, and β-catenin signaling pathways.  Full article

The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be a promising target for modulating these processes. Cannabinoid and cannabinoid-related receptors have been identified in the amygdala of rodents, carnivores, and humans, but not in horses. This study aimed to investigate the gene expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R), transient receptor potential vanilloid 1 (TRPV1), and peroxisome proliferator-activated receptor gamma (PPARγ) within the lateral nucleus of six equine amygdalae collected post mortem from an abattoir using quantitative real-time PCR, cellular distribution, and immunofluorescence. mRNA expression of CB1R and CB2R, but not TRPV1 or PPARγ, was detected. The percentage of immunoreactivity (IR) was calculated using ImageJ software. Cannabinoid receptor 1 immunoreactivity was absent in the somata but was strongly detected in the surrounding neuropil and varicosities and CB2R-IR was observed in the varicosities; TRPV1-IR showed moderate expression in the cytoplasm of somata and processes, while PPARγ-IR was weak-to-moderate in the neuronal nuclei. These findings demonstrate endocannabinoid system components in the equine amygdala and may support future studies on Cannabis spp. molecules acting on these receptors. Full article

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

Fertility is considered a significant demographic concern, especially in relation to climate change. This study examines how awareness of climate change, measured by five subscales—climate-friendly behavior, knowledge, personal concern, attitude, and multiplicative action—affects fertility intentions, emphasizing the mediating role of threat perception. Data were collected through an online survey administered to a sample of 817 Palestinian citizens aged 18–49 residing in the West Bank. Structural equation modeling (SEM) was utilized for the data analysis. The results revealed that climate change awareness does not directly affect fertility intentions. However, an indirect effect of climate change awareness on fertility intentions was observed, mediated by threat perception as an intervening variable. Individuals exhibiting increased awareness of climate change and perceptions of future risks demonstrated a greater likelihood of reducing their fertility intentions compared to others. Policymakers in the Palestinian territories should prioritize enhancing public awareness regarding climate change and its associated short- and long-term threats. Therefore, incorporating climate education and associated risks into fertility health programs is essential. Full article

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. 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

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS in Caenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulated pmk-1 and skn-1, modulating oxidative stress and neuronal function. pmk-1 mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS in Caenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative. Full article