Search Results (12,000)

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

Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these oncogenic biomarkers, Furin, IL-6, and NSD2, and their links with the inhibitor SERPINA-1 remain largely unknown. Materials and Methods: Cell proliferation is measured by colorimetric and enzymatic methods. The genetic expressions of SERPINA-1, Furin, IL-6, and NSD2 are measured by qRT-PCR, while the expression of IGF-1R on the cell surface is measured by flow cytometry. Results: The proliferation of cells overexpressing SERPINA-1 (JP7pSer+) is decreased by more than 90% compared to control cells (JP7pSer-). The kinetics of the gene expression ratios of Furin, IL-6, and NSD2 show an increase for 48 h, followed by a decrease after 72 h for the three biomarkers in JP7pSer+ cells compared to JP7pSer- cells. The expression of IGF-1R on the cell surface in both cell lines is low, with JP7pSer- cells expressing 1.33 times more IGF-1R than JP7pSer+ cells. Conclusions: These results suggest gene correlations of SERPINA-1 overexpression with decreased cell proliferation and modulation of gene expression of Furin, IL-6, and NSD2. This study should be complemented by molecular transcriptomic and proteomic experiments to better understand the interaction of SERPINA-1 with IL-6, Furin, and NSD2, and their effect on tumor progression. Full article

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

Nowadays, the circular economy is driving the construction industry towards greater sustainability for both environmental and financial purposes. One prominent area of research with significant contributions to circular economy is the reuse of steel from decommissioned structures in new construction projects. This approach is deemed far more efficient than ordinary steel recycling, due to the fact that it contributes towards reducing both the cost of the new project and the associated carbon emissions. Along these lines, the feasibility of utilizing steel wind turbine towers (WTTs) as part of a new structure is investigated herein, considering that wind turbines are decommissioned after a nominal life of approximately 25 years due to fatigue limitations. General principles of structural steel reuse are first presented in a systematic manner, followed by two case studies. Realistic data about the geometry and cross-sections of previous generation models of WTTs were obtained from the Greek Center for Renewable Energy Sources and Savings (CRES), including drawings and photographic material from their demonstrative wind farm in the area of Keratea. A specific wind turbine was selected that is about to exceed its life expectancy and will soon be decommissioned. Two alternative applications for the reuse of the tower were proposed and analyzed, with emphasis on the structural aspects. One deals with the use of parts of the tower as a small-span pedestrian bridge, while the second addresses the transformation of a tower section into a water storage tank. Several decision factors have contributed to the selection of these two reuse scenarios, including, amongst others, the geometric compatibility of the decommissioned wind turbine tower with the proposed applications, engineering intuition about the tower having adequate strength for its new role, the potential to minimize fatigue loads in the reused state, the minimization of cutting and joining processes as much as possible to restrain further CO₂ emissions, reduction in waste material, the societal contribution of the potential reuse applications, etc. The two examples are briefly presented, aiming to demonstrate the concept and feasibility at the preliminary design level, highlighting the potential of decommissioned WTTs to find proper use for their future life. Full article

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Compared to commuting, grocery shopping trips, despite their profound implications for mixed land use and transportation planning, have received limited attention in travel behavior research. Drawing upon a travel diary survey conducted in a fast-growing metropolitan region of the United States, i.e., Salt Lake County, UT, this research investigated a variety of influential factors affecting mode choices associated with grocery shopping. We analyze how built environment (BE) characteristics, measured at seven spatial scales or different ways of aggregating spatial data—including straight-line buffers, network buffers, and census units—affect travel mode decisions. Key predictors of choosing walking, biking, or transit over driving include age, household size, vehicle ownership, income, land use mix, street density, and distance to the central business district (CBD). Notably, the influence of BE factors on mode choice is sensitive to different spatial aggregation methods and locations of origins and destinations. The straight-line buffer was a good indicator for the influence of store sales amount on mode choices; the network buffer was more suitable for the household built environment factors, whereas the measurement at the census block and block group levels was more effective for store-area characteristics. These findings underscore the importance of considering both the spatial analysis method and the location (home vs. store) when modeling non-work travel. A multi-scalar approach can enhance the accuracy of travel demand models and inform more effective land use and transportation planning strategies. 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

Background/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes. Full article

Background: Cochlear implantation (CI) in pediatric patients with cochlear nerve deficiencies (CND) remains controversial due to a highly variable clinical population, lack of evidence-based guidelines, and mixed research findings. This study assessed current clinical perspectives and practices regarding CI candidacy in children with CND among hearing healthcare professionals in the USA. Methods: An anonymous 19-question online survey was distributed to CI clinicians nationwide. The survey assessed professional background, experience with aplasia and hypoplasia, and perspectives on CI versus auditory brainstem implant (ABI) candidacy, including imaging practices and outcome expectations. Both multiple-choice and open-ended responses were analyzed to identify trends and reasoning. Results: Seventy-two responses were analyzed. Most clinicians supported CI for hypoplasia (60.2%) and, to a lesser extent, for aplasia (41.7%), with audiologists more likely than neurotologists to favor CI. Respondents cited lower risk, accessibility, and the potential for benefit as reasons to attempt CI before ABI. However, many emphasized a case-by-case approach, incorporating imaging, electrophysiological testing, and family counseling. Only 22.2% considered structural factors the best predictors of CI success. Conclusions: Overall, hearing health professionals in the USA tend to favor CI as a first-line option, while acknowledging the limitations of current diagnostic tools and the importance of individualized, multidisciplinary decision-making in CI candidacy for children with CND. Findings reveal a high variability in clinical perspectives on CI implantation for pediatric aplasia and hypoplasia and a lack of clinical consensus, highlighting the need for more standardized assessment and imaging protocols to provide greater consistency across centers and enable the development of evidence-based guidelines. Full article

Background: Increasing regulatory pressure for maritime decarbonization (e.g., IMO CII, FuelEU) drives adoption of low-carbon fuels and prompts reassessment of regional ports’ competitiveness. This study aims to evaluate the economic and environmental viability of rerouting deep-sea container services to regional ports in a decarbonizing world. Methods: A scenario-based analysis is used to evaluate total costs and CO₂ emissions across the entire container shipping supply chain, incorporating deep-sea shipping, port operations, feeder services, and inland rail/road transport. The Port of Liverpool serves as the primary case study for rerouting Asia–Europe services from major ports. Results: Analysis indicates Liverpool’s competitiveness improves with shipping lines’ slow steaming, growth in hinterland shipment volume, reductions in the emission factors of alternative low-carbon fuels, and an increased modal shift to rail matching that of competitor ports (e.g., Southampton). A dual-port strategy, rerouting services to call at both Liverpool and Southampton, shows potential for both economic and environmental benefits. Conclusions: The study concludes that rerouting deep-sea services to regional ports can offer cost and emission advantages under specific operational and market conditions. Findings on factors and conditions influencing competitiveness and the dual-port strategy provide insights for shippers, ports, shipping lines, logistics agents, and policymakers navigating maritime decarbonization. Full article

A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article

This review explores sexual aggression in broiler breeder males, aiming to synthesize existing scientific evidence regarding its causes, behavioral manifestations, and consequences, while addressing the genetic, neuroendocrine, and environmental mechanisms involved. Through an extensive analysis of scientific literature, the paper highlights that intensive genetic selection aimed at enhancing growth and productivity has resulted in unintended behavioral dysfunctions. These include the reduction or absence of courtship behavior, the occurrence of forced copulations, and a notable increase in injury rates among hens. Reproductive challenges observed in meat-type breeder flocks, in contrast to those in layer lines, appear to stem from selection practices that have overlooked traits related to mating behavior. Environmental and managerial conditions, including photoperiod manipulation, stocking density, nutritional imbalances, and the use of mixed-sex rearing systems, are also identified as contributing factors to the expression of sexual aggression. Furthermore, recent genetic findings indicate a potential link between inherited neurobehavioral factors and aggressive behavior, with the SORCS2 gene emerging as a relevant candidate. Based on these insights, the review emphasizes the importance of considering behavioral parameters in breeding programs in order to reconcile productivity objectives with animal welfare standards. Future research may benefit from a more integrative approach that combines behavioral, physiological, and genomic data to better understand and address the multifactorial nature of sexual aggression in poultry systems. Full article

Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed to investigate clinical and radiological factors associated with early mortality and develop a prognostic prediction model in advanced EGFR-mutated NSCLC. Methods: A retrospective cohort was conducted in patients with EGFR-mutated NSCLC treated with first line EGFR-TKIs from January 2012 to October 2022 at Chiang Mai University Hospital. Clinical data and radiologic findings at the initiation of treatment were analyzed. A multivariable flexible parametric survival model was used to determine the predictors of death at 18 months. The predicted survival probabilities at 6, 12, and 18 months were estimated, and the model performance was evaluated. Results: Among 189 patients, 84 (44.4%) died within 18 months. Significant predictors of mortality included body mass index <18.5 or ≥23, bone metastasis, neutrophil-to-lymphocyte ratio ≥ 5, albumin-to-globulin ratio < 1, and mean pulmonary artery diameter ≥ 29 mm. The model demonstrated good performance (Harrell’s C-statistic = 0.72; 95% CI: 0.66–0.78). Based on bootstrap internal validation, the optimism-corrected Harrell’s C-statistic was 0.71 (95% CI: 0.71–0.71), derived from an apparent C-statistic of 0.75 (95% CI: 0.74–0.75) and an estimated optimism of 0.04 (95% CI: 0.03–0.04). Estimated 18-month survival ranged from 87.1% in those without risk factors to 2.1% in those with all predictors. A web-based tool was developed for clinical use. Conclusions: The prognostic model developed from fundamental clinical and radiologic parameters demonstrated promising utility in predicting 18-month mortality in patients with advanced EGFR-mutated NSCLC receiving first-line EGFR-TKI therapy. Full article

To elucidate the molecular mechanisms underlying anther abortion in celery male sterile lines, this study investigates the morphological differences of floral organs and differential gene expression patterns between two lines at the flowering stage. Using the male sterile line of celery ‘QCBU-001’ and the fertile line ‘Jinnan Shiqin’ as materials, anther structure was analyzed by paraffin sections, and related genes were detected using transcriptome sequencing and qRT-PCR. The results indicated that the anther locules were severely shrunken at maturity in the sterile lines. The callose deficiency led to abnormal development of microspores, preventing the formation of mature pollen grains and ultimately leading to complete anther abortion. The transcriptome results revealed that 3246 genes were differentially expressed in sterile and fertile lines, which were significantly enriched in pathways such as starch and sucrose metabolism and phenylpropanoid biosynthesis. Additionally, differential expression patterns of transcription factor families (MYB, bHLH, AP2, GRAS, and others) suggested their potential involvement in regulating anther abortion. Notably, the expression level of callose synthase gene AgGSL2 was significantly downregulated in sterile anthers, which might be an important cause of callose deficiency and pollen sterility. This study not only provides a theoretical basis for elucidating the molecular mechanism underlying male sterility in celery but also lays a foundation for the utilization and improvement of male sterile lines in vegetable hybrid breeding. Full article

This study aims to clarify the nonlinear pressure loss patterns of the pneumatic system in a pneumatic seeder under varying pipeline structures and airflow parameters, and to develop a rapid prediction equation for the main pipe’s pressure loss. The studied multi-branch pipeline system consists of a main pipe, a header, and ten branch pipes. The main pipe is vertically installed at the center of the header in a straight-line configuration. The ten branch pipes are symmetrically and evenly spaced along the axial direction of the header, distributed on both sides of the main pipe. The outlet directions of the branch pipes are arranged in a 180° orientation opposite to the inlet direction of the main pipe, forming a symmetric multi-branch configuration. Firstly, this study investigated the flow characteristics within the multi-branch pipeline of the pneumatic system and elaborated on the mechanism of flow division in the pipeline. The key geometric factors affecting airflow were identified. Secondly, from a microscopic perspective, CFD simulations were employed to analyze the fundamental causes of pressure loss in the multi-branch pipeline system. Finally, from a macroscopic perspective, a dimensional analysis method was used to establish an empirical equation describing the relationship between the pressure loss (P) and several influencing factors, including the air density (ρ), air’s dynamic viscosity (μ), closed-end length of the header (Δl), branch pipe 1’s flow rate (Q), main pipe’s inner diameter (D), header’s inner diameter (γ), branch pipe’s inner diameter (d), and the spacing of the branch pipe (δ). The results of the bench tests indicate that when 0.0018 m³·s⁻¹ ≤ Q ≤ 0.0045 m³·s⁻¹, 0.0272 m < d ≤ 0.036 m, 0.225 m < δ ≤ 0.26 m, 0.057 m ≤ γ ≤ 0.0814 m, and 0.0426 m ≤ D ≤ 0.0536 m, the prediction accuracy of the empirical equation can be controlled within 10%. Therefore, the equation provides a reference for the structural design and optimization of pneumatic seeders’ multi-branch pipelines. Full article