Search Results (288)

Breast cancer (BC) is a primary cause of cancer-related mortality in women, making the development of novel therapeutic strategies essential. Altered lipid metabolism is a recognized hallmark of cancer, presenting a key therapeutic vulnerability. This study investigated the cytotoxic effects of the natural phenolic compound 2,3-DHBA on MCF-7 (luminal A) and MDA-MB-231 (triple-negative) human breast cancer cells and characterized the associated changes in their lipid profiles via an untargeted lipidomic approach. The in vitro cytotoxicity of 2,3-DHBA was assessed using the MTT assay at 24, 48, and 72 h against both cancer cell lines and non-cancerous L-929 fibroblasts. Following treatment with the 48-h IC₅₀ concentrations (8.61 mM for MCF-7, 5.84 mM for MDA-MB-231), total lipids were extracted and analyzed. The results showed that 2,3-DHBA exerted potent time- and dose-dependent cytotoxic effects against both BC cell lines, with significantly higher selectivity for cancer cells over healthy fibroblasts. The more aggressive MDA-MB-231 line exhibited greater sensitivity. The lipidomic analysis revealed that 2,3-DHBA induced profound cell-specific alterations across all major lipid classes, including fatty acids, glycerolipids (GLs), glycerophospholipids (GPs), and sphingolipids (SPs). These changes suggest a multi-pronged mechanism involving the disruption of membrane integrity through GP remodeling, the attenuation of survival signaling via the GL network, and a critical shift in the sphingolipid rheostat towards pro-apoptotic ceramide accumulation. This study establishes a direct link between the cytotoxic activity of 2,3-DHBA and its ability to comprehensively reprogram the cancer cell lipidome, highlighting its potential as a sophisticated metabolic modulator for breast cancer therapy. Full article

Background and Objectives: Curcumin is a turmeric-derived polyphenol, and it has shown anticancer potential in various cancers, including breast cancer (BC). Nevertheless, the molecular mechanisms underlying its effects remain incompletely defined. Hsa_circ_0001946 (CDR1as) is a circular RNA (circRNA) that promotes tumor progression by competitively inhibiting microRNA-7-5p (miR-7-5p) in BC. This study investigated whether curcumin regulates the hsa_circ_0001946/miR-7-5p/target gene axis in BC progression. Materials and Methods: BC cell lines (MCF-7 and T47D) and a non-cancerous human mammary epithelial cell line (MCF-10A) were treated with curcumin or transfected with circ_0001946 siRNA or miR-7-5p mimic. Cell proliferation, migration, apoptosis, and protein expression were analyzed by CVDK-8 analysis, a wound healing assay, and flow cytometry, respectively. Also, protein expression levels were quantified via Western blotting. In vitro and in silico findings were further validated by analyzing tumor and adjacent normal tissues from 65 luminal BC patients. Results: Curcumin inhibited the proliferation and migration of MCF-7 and T47D cells in a dose-dependent manner. Knockdown of hsa_circ_0001946 or overexpression of miR-7-5p significantly suppressed proliferation and migration and enhanced apoptosis in BC cells compared to the negative controls. Curcumin treatment led to the knockdown of hsa_circ_0001946, the overexpression of miR-7-5p, and the downregulation of hsa_circ_0001946, CKS2, TOP2A, and PARP1, while it upregulating miR-7-5p. The Western blot confirmed reduced CKS2 protein levels after curcumin treatment. The expression of both hsa_circ_0001946 and CKS2 was significantly upregulated in tumor tissues compared to that of matched adjacent normal tissues, whereas that of miR-7-5p was markedly downregulated. Conclusions: This preliminary study shows that curcumin suppresses BC tumorigenesis by modulating the hsa_circ_0001946/miR-7-5p/target gene axis. While these findings suggest a novel regulatory pathway and potential therapeutic targets, further in vivo validation and clinical trials are required to determine the translational relevance of curcumin in BC therapy. Full article

To promote the development of long-distance high-speed underwater optical wireless communication (UWOC) based on visible light, this study proposes a high-bandwidth UWOC system based on micro-light-emitting-diodes (micro-LEDs) adopting the Non-Return-to-Zero On-Off Keying (NRZ-OOK) modulation. The numerical simulations reveal that optimizing the structural parameters of gallium nitride (GaN)-based micro-LED through dimensional scaling and quantum well layer reduction may significantly enhance optoelectronic performance, including modulation bandwidth and luminous efficiency. Moreover, experimental validation demonstrated maximum real-time data rates of 420 Mbps, 290 Mbps, and 250 Mbps at underwater distances of 2.3 m, 6.9 m, and 11.5 m, respectively. Furthermore, the underwater audio communication was successfully implemented at an 11.5 m UWOC distance at an ultra-low level of incoming optical power (12.5 µW) at the photodetector (PD) site. The channel characterization yielded a micro-LED-specific attenuation coefficient of 0.56 dB/m, while parametric analysis revealed wavelength-dependent degradation patterns, exhibiting positive correlations between both attenuation coefficient and bit error rate (BER) with operational wavelength. This study provides valuable insights for optimizing underwater optical systems to enhance real-time environmental monitoring capabilities and strengthen security protocols for subaquatic military communications in the future. Full article

Ulcerative colitis (UC) is caused by an excessive immune response to gut microbiota. A recent study reported that the population of IgG-coated gut microbes increases with disease severity in patients with UC, but the role of these IgG-coated microbes in UC pathology is unclear. Serum, feces and colonoscopic lavage fluids (CLFs) were collected from pediatric UC (n = 13) and non-inflammatory bowel disease (IBD) patients (n = 15). Gut microbes were isolated from feces. Serum IgG reactivity to microbial cells and CLF-derived proteins was evaluated by Western blotting. Complement activation by the bacteria–IgG complexes was also assessed. Serum IgG reactivity to gut microbial extracts was highly variable in patients with active UC and increased with mucosal inflammation. IgG reactivity and clinical condition were inversely associated depending on disease activity. Non-IBD patients showed a similar degree of serum IgG response as that seen for patients whose UC was in remission. Lactobacillaceae bound higher amounts of IgG than other gut microbes tested and absorbed IgG to other bacteria. Lacticaseibacillus paracasei suppressed complement activation by Escherichia coli—IgG immune complexes. Appropriate IgG responses to luminal microbes might play a key role in gut microbiota stability by reducing excessive mucosal inflammation. Full article

The endoplasmic reticulum (ER) maintains protein homeostasis through chaperone-mediated folding and ER-associated degradation (ERAD). Disruption of this quality control, particularly involving the ER chaperone GRP94, contributes to diseases such as hypercholesterolemia, cancer, and immune disorders, where defective GRP94-dependent folding and the trafficking of client proteins like PCSK9, integrins, and Toll-like receptors drive pathology. Here, we characterize NSC637153 (cp153), a small molecule identified in a drGFP-based ERAD dislocation screen, as a selective probe of GRP94-dependent processes. cp153 inhibits the dislocation of ERAD substrates, preferentially affecting luminal clients, increases PCSK9 secretion, and promotes LDLR degradation. Unlike ATP-competitive HSP90 inhibitors, cp153 does not induce HSP70 or destabilize AKT, suggesting that it perturbs GRP94 function by interfering with client interaction or folding. The identification of cp153 provides a useful tool to for probing GRP94’s role in protein folding, trafficking, ER quality control, and disease-relevant signaling pathways, and supports the development of client-selective GRP94-targeted therapies. Full article

While calcium (Ca²⁺) is a universal cellular messenger, the ionic properties of magnesium (Mg²⁺) make it less suited for rapid signaling and more for structural integrity. Still, besides being a passive player, Mg²⁺ is the only active Ca²⁺ antagonist, essential for tuning the efficacy of Ca²⁺-dependent cardiac excitation–contraction coupling (ECC) and for ensuring cardiac function robustness and stability. This review aims to provide a comprehensive framework to link the structural and molecular mechanisms of Mg²⁺/Ca²⁺ antagonistic binding across key proteins of the cardiac ECC machinery to their physiopathological relevance. The pervasive “dampening” effect of Mg²⁺ on ECC activity is exerted across various players and mechanisms, and lies in the ions’ physiological competition for multiple, flexible binding protein motifs across multiple compartments. Mg²⁺ profoundly modulates the cardiac action potential waveform by inhibiting the L-type Ca²⁺ channel Cav1.2, i.e., the key trigger of cardiac ryanodine receptor (RyR2) opening. Cytosolic Mg²⁺ favors RyR2 closed or inactive conformations not only through physical binding at specific sites, but also indirectly through modulation of RyR2 phosphorylation by Camk2d and PKA. RyR2 is also potently inhibited by luminal Mg²⁺, a vital mechanism in the cardiac setting for preventing excessive Ca²⁺ release during diastole. This mechanism, able to distinguish between Ca²⁺ and Mg²⁺, is mediated by luminal partners Calsequestrin 2 (CASQ2) and Triadin (TRDN). In addition, Mg²⁺ favors a rearrangement of the RyR2 cluster configuration that is associated with lower Ca²⁺ spark frequencies. Full article

Luminous, hot, massive stars can lose mass both through quasi-steady winds driven by line-scattering of the star’s continuum luminosity, and through transient eruptions identified as Luminous Blue Variables (LBVs). This paper compares and contrasts the processes involved in steady vs. eruptive mass loss, with an emphasis on their dependence on the star’s proximity to the classical Eddington limit. For winds, I examine the role of the iron opacity bump in initiating a quasi-continuum-driven outflow, which can induce atmospheric turbulence in O-stars, an envelope inflation cycle in LBVs, or enhanced wind mass loss in WR stars. In contrast, the giant eruptions of eruptive LBVs like $\eta$ Carinae require a sudden addition of energy to the stellar envelope, like that which can occur from stellar mergers. The positive net energy imparted to a substantial fraction (>10%) of the stellar mass leads to sudden ejection that closely follows an analytic exponential similarity solution. Moreover, the rapid rotation and enhanced luminosity of the post-merger star drive a super-Eddington wind. Due to equatorial gravity darkening, this wind is stronger over the poles, sculpting a bipolar structure in the ejected mass, consistent with observations of $\eta$ Carinae’s Homunculus nebula. Full article

Background: Breast cancer, one of the most researched cancers in oncology, remains the primary cause of cancer-related mortality in women. Its biological complexity, which includes phenotypic, genetic, and microenvironmental aspects, makes modeling and treatment quite difficult. The need for more physiologically realistic models is highlighted by the comparison of two-dimensional (2D) cell cultures with 3D breast-cancer-derived spheroids, which discloses how important pathways such as epidermal growth factor receptor (EGFR) and insulin-like growth factor I receptor (IGF-IR) influence cell behavior and extracellular matrix (ECM) macromolecular expression. Methods: The purpose of this study was to utilize novel 3D cell platforms to assess the effect of inhibiting the EGFR and IGF-IR pathways, alone or in combination, on the functional properties and the expression levels of certain matrix metalloproteinases (MMPs) which are implicated in breast cancer progression (i.e., triple-negative and luminal A breast cancer subtypes) and related with the EGFR and IGF-ΙR molecular network, as also demonstrated through STRING analysis. Results: Our results demonstrated potential crosstalk between EGFR and IGF-IR signaling, which influences cell proliferation and spheroid growth, dissemination, and migration. Significant phenotypic changes proposed between 2D and 3D cell cultures, and alterations in the expression of MMPs, were also recorded. Conclusions: Both breast cancer cell lines retained acknowledged characteristics across the tested models while also exhibiting new, condition-dependent properties. Overall, our findings enhance our understanding on the interplay between the EGFR and IGF-IR pathways and underscore the value of 3D models in revealing key biological processes underlying distinct breast cancer phenotypes. Full article

Bird-dropping fouling and hotspot anomalies remain the most prevalent and detrimental defects in utility-scale photovoltaic (PV) plants; their co-occurrence on a single module markedly curbs energy yield and accelerates irreversible cell degradation. However, markedly disparate visual–thermal signatures of the two phenomena impede high-fidelity concurrent detection in existing robotic inspection systems, while stringent onboard compute budgets also preclude the adoption of bulky detectors. To resolve this accuracy–efficiency trade-off for dual-defect detection, we present YOLOv8-SG, a lightweight yet powerful framework engineered for mobile PV inspectors. First, a rigorously curated multi-modal dataset—RGB for stains and long-wave infrared for hotspots—is assembled to enforce robust cross-domain representation learning. Second, the HSV color space is leveraged to disentangle chromatic and luminance cues, thereby stabilizing appearance variations across sensors. Third, a single-head self-attention (SHSA) block is embedded in the backbone to harvest long-range dependencies at negligible parameter cost, while a global context (GC) module is grafted onto the detection head to amplify fine-grained semantic cues. Finally, an auxiliary bounding box refinement term is appended to the loss to hasten convergence and tighten localization. Extensive field experiments demonstrate that YOLOv8-SG attains 86.8% mAP@0.5, surpassing the vanilla YOLOv8 by 2.7 pp while trimming 12.6% of parameters (18.8 MB). Grad-CAM saliency maps corroborate that the model’s attention consistently coincides with defect regions, underscoring its interpretability. The proposed method, therefore, furnishes PV operators with a practical low-latency solution for concurrent bird-dropping and hotspot surveillance. Full article

Genome instability is a hallmark of cancer, often driven by mutations and altered expression of genome maintenance factors involved in DNA replication and repair. Rap1 Interacting Factor 1 (RIF1) plays a crucial role in genome stability and is implicated in cancer pathogenesis. Cells express two RIF1 splice variants, RIF1-Long and RIF1-Short, which differ in their ability to protect cells from DNA replication stress. Here, we investigate differential expression and splicing of RIF1 in cancer cell lines following replication stress and in patients using matched normal and tumour data from The Cancer Genome Atlas (TCGA). Overall RIF1 expression is altered in several cancer types, with increased transcript levels in colon and lung cancers. RIF1 also exhibits distinct splicing patterns, particularly in specific breast cancer subtypes. In Luminal A (LumA), Luminal B (LumB), and HER2-enriched breast cancers (HER2E), RIF1 Exon 31 tends to be excluded, favouring RIF1-Short expression and correlating with poorer clinical outcomes. These breast cancer subtypes also tend to exclude other short exons, suggesting length-dependent splicing dysregulation. Basal breast cancer also shows exon exclusion, but unlike other subtypes, it shows no short-exon bias. Surprisingly, however, in basal breast cancer, RIF1 Exon 31 is not consistently excluded, which may impact prognosis since RIF1-Long protects against replication stress. Full article

To address the challenges of manual inspection dependency, low efficiency, and high costs in evaluating the surface grinding quality of composite materials, this study investigated machine vision-based surface recognition algorithms. We proposed a multi-scale texture fusion analysis algorithm that innovatively integrated luminance analysis with multi-scale texture features through decision-level fusion. Specifically, a modified Rayleigh parameter was developed during luminance analysis to rapidly pre-segment unpolished areas by characterizing surface reflection properties. Furthermore, we enhanced the traditional Otsu algorithm by incorporating global grayscale mean (μ) and standard deviation (σ), overcoming its inherent limitations of exclusive reliance on grayscale histograms and lack of multimodal feature integration. This optimization enables simultaneous detection of specular reflection defects and texture uniformity variations. To improve detection window adaptability across heterogeneous surface regions, we designed a multi-scale texture analysis framework operating at multiple resolutions. Through decision-level fusion of luminance analysis and multi-scale texture evaluation, the proposed algorithm achieved 96% recognition accuracy with >95% reliability, demonstrating robust performance for automated surface grinding quality assessment of composite materials. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19′s potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs’ therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment. Full article

Coronary plaque vulnerability, more than luminal stenosis, drives acute coronary syndromes. Optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA) visualize plaque morphology in vivo, but manual interpretation is time-consuming and operator-dependent. We performed a narrative literature survey of artificial intelligence (AI) applications—focusing on machine learning (ML) architectures—for automated coronary plaque segmentation and risk characterization across OCT, IVUS, and CCTA. Recent ML models achieve expert-level lumen and plaque segmentation, reliably detecting features linked to vulnerability such as a lipid-rich necrotic core, calcification, positive remodelling, and a napkin-ring sign. Integrative radiomic and multimodal frameworks further improve prognostic stratification for major adverse cardiac events. Nonetheless, progress is constrained by small, single-centre datasets, heterogeneous validation metrics, and limited model interpretability. AI-enhanced plaque assessment offers rapid, reproducible, and comprehensive coronary imaging analysis. Future work should prioritize large multicentre repositories, explainable architectures, and prospective outcome-oriented validation to enable routine clinical adoption. Full article

Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid (EA), palmitic acid (PA), and α-linolenic acid (LNA)—on two BCA cell lines: luminal-type MCF7 and triple-negative MDA-MB-231 (MB231). All LCFAs suppressed cell viability and mitochondrial function in a dose-dependent manner, accompanied by decreased membrane potential, increased reactive oxygen species production, and a metabolic shift. Notably, OA reduced both mRNA and nuclear protein levels of estrogen receptor alpha (ERα) in MCF7 cells, leading to impaired responses to estradiol and tamoxifen. In contrast, PA induced nuclear ERα expression in MB231 cells, although ER signaling remained inactive. MicroRNA profiling revealed that OA upregulated ER-suppressive miR-22 and miR-221 in MCF7, while PA increased miR-34a in MB231, contributing to ERα induction. These findings suggest that specific LCFAs modulate ER expression through epigenetic and post-transcriptional mechanisms, altering hormonal responsiveness in BCA. Our results offer new insights into how dietary lipids may influence therapeutic efficacy and tumor behavior by regulating nuclear receptor signaling. Full article