Search Results (37,449)

Chicken coccidiosis, caused by obligate intracellular protozoa of the genus Eimeria, inflicts substantial economic losses on the global poultry industry. The extensive use of anticoccidial drugs has led to widespread resistance, underscoring the need for molecular markers associated with this resistance. Our previous RNA-seq analysis revealed differential expressions of glucose-6-phosphate isomerase (EtG6PI) between drug-sensitive (DS) and maduramycin-resistant (MRR) strains of Eimeria tenella. In this study, we examined EtG6PI expression across developmental stages using qPCR and Western blotting, finding that both transcription and translation peaked in second-generation merozoites. Furthermore, EtG6PI expression was significantly upregulated in MRR strains in a dose-dependent manner and was also elevated in field isolates exhibiting maduramycin resistance. Indirect immunofluorescence localized EtG6PI to the parasite surface, cytoplasm, and parasitophorous vacuole membrane (PVM), with signal intensity increasing during intracellular development. In addition, anti-rEtG6PI polyclonal antibodies significantly inhibited sporozoite invasion of host cells in vitro. These results indicate that EtG6PI plays a role in host cell invasion, a process essential for parasite proliferation, and is associated with maduramycin resistance in E. tenella, supporting its potential as a biomarker for resistance detection in field settings. Full article

Mesenchymal stromal cells derived from adipose tissue (ASCs) are widely used in regenerative medicine, requiring scalable expansion strategies that preserve both cellular function and biological quality. However, current bioprocess optimization approaches are primarily guided by proliferation and phenotypic stability, often overlooking genomic integrity as a critical attribute. In this study, we developed a stirred-tank bioreactor system for ASC expansion on microcarriers and applied a genotoxicity-informed optimization strategy by integrating growth kinetics, metabolic profiling, and DNA damage assessment across multiple operational conditions (B₁–B₅), including variations in dissolved oxygen, agitation, inoculum density, and medium renewal. Optimized culture conditions (B5) enabled high cell productivity within a reduced cultivation period (9 days), while maintaining high viability (>90%), mesenchymal immunophenotype, and differentiation capacity. Distinct metabolic profiles were associated with enhanced proliferation, with increased glycolytic activity observed under optimized conditions. Despite these favorable outcomes, genotoxic analyses revealed a progressive, time-dependent accumulation of DNA damage and increased micronucleus frequency during expansion. Notably, these alterations did not impair cell proliferation, phenotype, or differentiation potential, indicating that conventional optimization metrics may not fully capture underlying genomic changes. Collectively, our findings demonstrate that bioprocess optimization based solely on classical performance parameters may overlook relevant biological alterations. By incorporating genotoxic endpoints into the evaluation framework, this study provides a refined approach for assessing large-scale stem cell expansion and contributes to improving the robustness and reliability of biomanufacturing strategies for therapeutic applications. Full article

The IGF-1Eb isoform has been proposed as a stress-responsive variant of IGF-1, yet its significance in cancer remains unclear. This investigation aims to clarify its role across breast, prostate and liver cancer cell lines and determine whether its loss or supplementation is associated with alterations in cellular behavior and stress adaptation. Eb expression was modulated through targeted silencing and exogenous peptide addition. Cellular responses were evaluated under normal conditions and UV stress using proliferation, viability and rescue experiments, wound healing, immunofluorescence for Eb-knockdown confirmation, qRT-PCR, Annexin V/PI apoptosis, and PI cell-cycle evaluation. Across six cancer cell lines, Eb peptide given before UV stress was associated with partial protective effects, whereas post-UV treatment was associated with improved recovery and partial restoration of proliferative capacity. The rescue effect differed by cell type, with prostate and breast cells showing the strongest responses and liver-derived lines displaying more modest improvements. Eb knockdown revealed clear cell-type-specific dependencies. PC3 cells showed markedly reduced proliferation (p < 0.01) and sharply decreased post-UV viability (p < 0.0001). HepG2 cells maintained higher growth without UV but displayed reduced recovery following UV exposure, whereas MDA-MB-231 exhibited elevated apoptosis (p < 0.05) with limited additional UV sensitivity. Eb peptide may exert a dual, timing-dependent role, supporting protection before UV damage and facilitating recovery-associated responses afterward, with its impact differing across cell lines. Full article

This study evaluates volatile extracts (HE1 and HE2) from the lichen Pseudevernia furfuracea as eco-friendly agents to control algal proliferation, specifically targeting the cyanobacterium Microcystis aeruginosa and the green microalga Chlorella sorokiniana. Both extracts exhibited potent anti-microalgal activity against the two species with a minimum inhibitory concentration (MIC) ranging from 375 to 750 µg/mL. Furthermore, both extracts reduced cell density by more than 98% after eight days of treatment. Chlorophyll a and protein levels decreased significantly (>80%) in both species, indicating suppression of pigment synthesis. However, their physiological responses were distinct: M. aeruginosa underwent early acute oxidative stress and severe membrane damage, while C. sorokiniana exhibited delayed oxidative activation and a negative growth rate, suggesting non-lytic metabolic inhibition. An in silico study by molecular docking of the most abundant compounds identified in these volatile extracts, such as terpenoids (abietatriene, δ-cadinene) and a phenolic compound (atraric acid), showed that these compounds interact with vital cellular targets in M. aeruginosa and C. sorokiniana and likely contribute to the effects observed in these two species. Predictive toxicity by applying the ADMET framework confirmed the favorable bioavailability and low acute toxicity of these volatile compounds. Therefore, P. furfuracea volatiles are promising, species-specific, and environmentally safe candidates for mitigating aquatic algal proliferation through targeted oxidative and metabolic interference. Full article

Neonicotinoids are among the most widely used classes of insecticides worldwide. However, growing evidence links their exposure to metabolic disturbances, including DNA damage, endocrine disruption, and hepatic dysfunction. In this study, transcriptomic analyses were applied to investigate the gene expression changes induced by two neonicotinoids, clothianidin and thiacloprid. Our results revealed distinct treatment-driven transcriptional signatures, characterized by the upregulation of gene sets enriched in pathways associated with mitochondrial regulation, neuronal signaling, and neurodegeneration-related molecular processes, alongside the downregulation of genes involved in core metabolic processes. In addition, neonicotinoid exposure modulated gene sets associated with xenobiotic detoxification, immune response, cell proliferation, and cell adhesion. Notably, clothianidin and thiacloprid induced compound-specific transcriptional profiles, despite sharing a common mechanism of action. Furthermore, combined exposure resulted in gene expression patterns that differed from those observed with individual treatments. Together, these findings demonstrate that neonicotinoids can elicit divergent molecular responses, highlighting the importance of compound-specific toxicological assessment in non-target species. Full article

Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, often incorporating additional materials like collagen or conductive polymers to enhance their performance. This review examines how material composition, scaffold architecture, and fabrication strategy influence biological response and functional recovery. This comprehensive review follows PRISMA guidelines and uses comprehensive searches of PubMed, MEDLINE, Embase, Web of Science, Cochrane Central, and ClinicalTrials.gov for studies published through 2025. Studies were screened for eligibility based on substance type, mechanical properties, production methods, and outcomes. Findings were synthesized qualitatively. Twelve studies were included, comprising rat (50%), canine (8.3%), and in vitro (41.7%) models. Analysis reveals that silk fibroin acts as a highly adaptable mechanical backbone. It can consistently integrate with bioactive additives (collagen, dECM) or conductive polymers (Polypyrrole, MXene) to meet specific therapeutic demands. For spinal cord injuries, composites reached a compressive modulus capable of resisting physiological pressures and preventing scaffold collapse. In soft tissue applications, silk–hydrogel blends provided localized release of exosomes and small molecules during the acute injury phase, reducing neuroinflammatory markers. Additionally, adding conductive materials allowed the scaffolds to bridge electrical gaps and promote Schwann cell proliferation and neuronal differentiation. Furthermore, 3D bioprinting enabled the creation of defined microchannels that replicate native fascicular architecture. In vivo outcomes consistently showed superior axonal regeneration, myelination, and synaptic reconnection compared to controls, correlating with significant improvements in electrophysiological and motor function. This review highlights the clinical potential of silk fibroin-based 3D-printed biomaterials for nerve regeneration, including neural repair and neural tissue engineering. More recent studies place greater emphasis on integrating mechanical, architectural, and biological considerations into scaffold design, resulting in increasingly multifunctional scaffold systems. Despite promising efficacy, the heterogeneity of fabrication methods and the predominance of rodent models highlight the need for standardized protocols and evaluations in relevant models to facilitate clinical translation. Full article

Vitrification is a vital tool for the long-term preservation of animal genetic resources, yet cryoinjury—manifesting as oxidative stress, structural damage, and metabolic disorders—severely compromises its efficacy. Here, we investigated the protective effects of melatonin (MT) supplementation on the cryotolerance of mouse morulae. First, mouse morulae were assigned to four groups treated with vitrification and thawing media containing MT (0, 10⁻³, 10⁻⁵, and 10⁻⁷ M) to determine optimal MT concentration. Subsequently, embryos treated with the optimal MT concentration were evaluated for developmental competence, oxidative stress, apoptosis, and mitochondrial function. Furthermore, transcriptome sequencing was performed to elucidate MT-regulated molecular pathways. The results demonstrated that MT supplementation at 10⁻⁵ M significantly enhanced developmental competence, as evidenced by increased blastocyst rate, hatched blastocyst rate, total cell number and the inner cell mass (ICM)-to-total cell ratio compared to the MT-free group (p < 0.05). Consequently, embryo transfer outcomes showed higher live births and weaned pups in the 10⁻⁵ M MT group versus those in controls (p < 0.05), achieving levels comparable to fresh embryos (p > 0.05). Mechanistically, MT reversed cryoinjury-induced mitochondrial dysfunction by elevating membrane potential(MMP) and Adenosine Triphosphate(ATP) production while reducing Reactive Oxygen Species (ROS) accumulation (p < 0.05). Transcriptomic analysis further revealed that vitrification perturbed metabolic pathways, including amino acid/fatty acid degradation and glucose/pyruvate metabolism. MT downregulated cryoinjury-induced overexpression of Rela and Nfkb1, inhibiting excessive NF-κB activation and alleviating metabolic dysfunction. Additionally, MT restored expression of nucleotide synthesis genes (Ctps2, Nme4, Gmps, Nudt2, Ppat, Impdh2) critical for cell proliferation, and reversed downregulation of mitochondrial genes Sucla2 and Timm17a, confirming restoration of mitochondrial homeostasis. In conclusion, melatonin alleviates vitrification-induced cryoinjury by restoring mitochondrial function, which rescues nucleotide synthesis and partially reverses associated metabolic dysfunction. These findings advance MT-mediated cryoprotection and underscore its translational value for embryo cryopreservation in animal genetic resource conservation. Full article

Background/Objectives: Ki-67 is widely used as an immunohistochemical marker of tumor proliferation in hormone receptor-positive (HR-positive), HER2-negative breast cancer, but its interpretation is limited by variability and uncertain concordance with genomic assays. The Oncotype DX^® Recurrence Score (RS) is a validated multigene assay with established prognostic and predictive utility. This study evaluated the relationship between Ki-67 and RS in clinical practice. Methods: We retrospectively analyzed women in Greece with early-stage estrogen receptor-positive, HER2-negative breast cancer without distant metastasis (pM0) who underwent Oncotype DX testing between 2020 and 2023. Eligible patients were node-negative or postmenopausal with node-positive disease. RS was categorized as low (0–25) or high (>25). Ki-67 was assessed using binary (<20% vs. ≥20%) and three-tier (≤5%, >5–<30%, ≥30%) classifications. Associations were analyzed using correlation, concordance, and non-parametric methods. Results: Among 2967 patients, the median RS was 16, with similar distributions across nodal subgroups. Ki-67 and RS demonstrated a modest positive correlation as continuous variables (R = 0.30, p < 0.001). After stratification, associations with RS were observed only in tumors with high Ki-67 expression, whereas no correlation was detected in low or intermediate groups. RS distributions differed significantly across Ki-67 strata. Overall concordance between Ki-67-based proliferation categories and RS-based genomic risk was 56.2%, with discordant cases in both directions. Conclusions: Ki-67 shows a modest association with Oncotype DX RS, but substantial discordance indicates Ki-67 should not substitute genomic testing in HR-positive/HER2-negative early breast cancer. Full article

The rapid proliferation of Large Language Models (LLMs) is increasing electricity demand from data centers, creating new challenges for power-demand forecasting and grid planning. A key difficulty is that architecture- and deployment-related information that affects inference load is often private to LLM providers. This paper proposes a two-stage, mechanism-assisted forecasting framework under information asymmetry. In the first stage, a stylized incentive mechanism elicits verifiable reduced-form demand parameters from LLM providers at a chosen reporting precision. In the second stage, the elicited parameters are incorporated into forecasting models as architecture- and deployment-informed features. Using calibrated synthetic scenarios constructed from public data-center energy reports, open LLM-inference energy benchmarks, and secondary public estimates, we find that incorporating elicited parameters reduces the mean squared error (MSE) of the ResNet forecasting backbone by 65.1% relative to an architecture-agnostic ResNet baseline. Similar improvements are observed for a gradient-boosting model, indicating that the main empirical value comes from procuring informative provider-side demand features rather than from a specific neural architecture. The results should be interpreted as a proof-of-concept demonstration rather than a full operational model of LLM serving or power-system dispatch. Full article

Background: As the most lethal neuroendocrine tumor, small cell lung cancer (SCLC) can drive its progression by hijacking neuronal mechanisms. At the core of this neural integration is the N-methyl-D-aspartate receptor (NMDAR) complex. However, its pan-cancer expression and clinical significance in SCLC remain poorly understood. Methods: We characterized NMDAR transcriptomic profiles across human cancers to develop the NMDAscore, and analyzed three independent European and Asian SCLC cohorts to identify prognostic biomarkers. Furthermore, we investigated the molecular mechanisms of GRIN2A and evaluated the efficacy of GluN2 inhibitors. Results: The developed NMDAscore exhibited significant prognostic correlations in ACC, COAD, KIRC, UVM, KIRP, OV, PCPG, UCS, THCA, THYM, HNSC, KICH, LGG, and PAAD. Focusing on the SCLC cohorts, we identified GRIN2A (encoding the GluN2A subunit) as a statistically relevant prognostic biomarker associated with poor survival. Mechanistically, GRIN2A upregulation correlates with the activation of neuro-synaptic signaling, metabolic reprogramming, genomic instability, and an immune-cold microenvironment characterized by CD8⁺ T cell exclusion. Pharmacological inhibition of GluN2 using dizocilpine and the FDA-approved antagonist memantine suppressed SCLC proliferation and tumorigenicity in vitro, in 3D tumor spheroids and in vivo xenograft models. Conclusions: Collectively, these findings establish GRIN2A as a prognostic biomarker, linking synaptic hijacking, metabolic plasticity, immune evasion, and drug resistance, and identify the therapeutic potentials of the GluN2 inhibitors dizocilpine and memantine for SCLC. Full article

Hepatocellular carcinoma (HCC) represents one of the most lethal malignancies worldwide and is characterized by profound metabolic reprogramming during its development. Paraoxonase 1 (PON1), a liver-synthesized secretory protein involved in lipid metabolism, has an incompletely defined role in cancer biology. This study aimed to systematically investigate the expression pattern, clinical features, and biological function of PON1 in HCC through an integrated approach combining data mining, RNA-seq and experimental verification. Our results demonstrated that PON1 expression is significantly downregulated in HCC tissues compared with adjacent tissues. Clinically, significant disparities were observed in gender (χ² = 19.305, p < 0.0001), tumor stage (χ² = 18.030, p = 0.0004), and tumor grade (χ² = 13.391, p = 0.0039) between patients with high and low PON1 expression in HCC. Low PON1 expression was associated with poor prognosis (TCGA_LIHC, log-rank: χ² = 9.290, p = 0.0023; ICGC_LIRI, log-rank: χ² = 8.469, p = 0.0036; GSE14520, log-rank: χ² = 9.746, p = 0.0018). Univariate and multivariate Cox regression analyses revealed PON1 as an independent prognostic biomarker. Pathway analysis showed that PON1-positively correlated genes enriched in pathways such as peroxisome and fatty acid degradation, whereas PON1-negatively correlated genes mainly in the cell cycle pathway. Functional experiments confirmed that knockdown of PON1 promoted HCC cell proliferation, migration, invasion and inhibited apoptosis, whereas overexpression of PON1 reversed these malignant phenotypes. Mechanistically, we uncovered that PON1 exerts its tumor-suppressive effects by negatively regulating TANK and CXCL3, key molecules of the NOD-like receptor signaling pathway. In summary, our findings identify PON1 as an independent prognostic biomarker in HCC and demonstrate the tumor-suppressive role of PON1, indicating its potential as a therapeutic target for HCC. Full article

Breast cancer is a type of cancer with the highest incidence and mortality rates among women. PD-L1 suppresses the proliferation and activation of T cells, thereby enabling cancer cells to evade immune surveillance and facilitating tumor progression. Micheliolide (MCL) is a guaianolide-type sesquiterpene lactone with broad biological activities. Our results revealed that radiation upregulates PD-L1 expression in breast cancer cells, while MCL pretreatment can inhibit this effect. Bioinformatics analysis combined with shRNA interference experiments confirmed that radiation upregulates PD-L1 by activating the IRF1-STAT1 signaling pathway, while MCL represses PD-L1 transcription by suppressing this pathway. In addition, MCL also downregulates PD-L1 protein level through accelerating proteasomal degradation of PD-L1. In vivo experiments demonstrated that MCL combined with radiotherapy significantly inhibits the growth of syngeneic tumors and increases intratumoral CD8⁺ T cell infiltration and the frequencies of granzyme B-positive cells. Taken together, our results indicate that MCL enhances T-cell-mediated antitumor immunity and improves radiotherapy efficacy through inhibiting IRF1-STAT1 signaling pathway-driven PD-L1 transcription and promoting PD-L1 protein degradation. This study provides a theoretical basis for the clinical application of MCL as an immunomodulator and radiosensitizer. Full article

Background/Objectives: Melanoma is a highly aggressive cancer with a strong metastatic potential, and therapeutic resistance remains a major clinical challenge despite advances in targeted therapies and immunotherapies. Secreted frizzled-related protein 1 (sFRP1) exhibits context-dependent roles in cancer; however, its function in metastatic melanoma remains poorly defined. This study investigated the role of sFRP1 in melanoma progression and evaluated the anti-tumor effects of the pharmacological compound WAY-316606. Methods: sFRP1 expression was quantified in metastatic melanoma cell lines, xenograft models, and TCGA datasets. The anti-tumor effects of WAY-316606 on cell viability, cell cycle progression, cell migration and invasion, and expression of extracellular matrix (ECM)-related genes were assessed using WST assays, flow cytometry, wound healing and transwell invasion assays, and quantitative real-time PCR, respectively. Results: sFRP1 expression was consistently elevated in metastatic melanoma cell lines, xenograft models, and TCGA datasets, and high sFRP1 expression was associated with poor overall survival. WAY-316606 selectively suppressed melanoma cell viability with minimal cytotoxic effects on non-tumorigenic cells, and induced G1 phase cell cycle arrest. Furthermore, WAY-316606 markedly impaired the migratory and invasive capacities of metastatic melanoma cells, accompanied by downregulation of key ECM remodeling and fibrosis-related genes, including VIM, CCN2, FN1, and TGFBI. sFRP1 knockdown partially phenocopied the anti-migratory and gene expression effects of WAY-316606. Conclusions: Collectively, our findings identify sFRP1-asscoaited signaling contribute to aggressive melanoma phenotypes and highlight the therapeutic potential of its pharmacological inhibition using WAY-316606. Full article

Thrombosis remains a critical challenge for blood-contacting implants, with early-stage protein adsorption and platelet activation playing decisive roles. In this study, we constructed a TiO₂/CuO semiconductor heterojunction on titanium surfaces to generate a stable built-in electric field, creating a self-activated bioelectric microenvironment without external stimulation. We evaluated its cytocompatibility and hemocompatibility through static in vitro assays. To distinguish the contributions of surface chemistry, topography, and bioelectric cues, we include control groups of Ti (untreated), TNW (TiO₂ network, topography control), and Ti/CuO (CuO nanoparticles without heterojunction, Cu²⁺ release control). The heterojunction significantly enhances human umbilical vein endothelial cell (HUVEC) adhesion and proliferation while simultaneously suppressing fibrinogen adsorption, platelet adhesion/activation (as assessed by morphological changes), and whole-blood cell adhesion. Compared with Ti/CuO, the heterojunction (TCH) induces substantially stronger endothelialization and anticoagulant effects despite similar Cu²⁺ release levels (~0.047 μM, far below the reported pro-angiogenic threshold of ~5.0 μM), indicating a predominant role of the built-in electric field. This study preliminarily demonstrates a previously unrecognized role of bioelectric cues in modulating early blood–material interactions. Following rigorous validation under physiologically relevant dynamic flow conditions and in vivo models, interfacial bioelectric engineering emerges as a promising new strategy for designing anticoagulant biomaterials. Full article

Several lipid-management guidelines now favor non-fasting lipid measurements for cardiovascular risk assessment. In parallel, this review evaluated the potential clinical utility of non-fasting glucose measures, which may better reflect real-world glycemic responses, capture postprandial dysregulation not detected by fasting glucose, and offer greater practicality in routine clinical settings. Postprandial plasma glucose measured 4–7.9 h after a meal (PPG_4–7.9h) shows relative stability within this window and appears to be a promising marker for diagnosing diabetes and predicting mortality from cardiovascular disease (CVD) and cancer. Similarly, 2 h plasma glucose during an oral glucose tolerance test performed 4–7.9 h after a meal (2 h PG_OGTT4–7.9h) demonstrates diagnostic and prognostic value, particularly for diabetes and cardiovascular mortality. Notably, the diagnostic and predictive performance of these non-fasting measures is not inferior to that of traditional fasting glucose assessments. Mechanistically, postprandial hyperglycemia may contribute to CVD through increased oxidative stress and inflammation, endothelial dysfunction, and promotion of atherogenesis and thrombogenesis. It may also increase cancer risk via oxidative stress, inflammation, and insulin-mediated cellular proliferation. In addition, it may enhance lipogenesis to form membrane lipids supporting tumor growth. Further research is required to establish the clinical applicability, optimal thresholds, and generalizability of these non-fasting glucose measures. Full article