Search Results (71,494)

In this work, by employing NH₄F as a structure-directing agent (SDA) and VO(acac)₂, we have manipulated the morphology of Co₃O₄, leading to the creation of a novel hexagram-like structure with exceptional evenness in distribution. To comprehend the growth mechanism and elucidate the functions of various agents involved, experiments were conducted under diverse conditions with varying reagent ratios. The results indicate that, under the influence of NH₄F as the structure-directing agent (SDA), the hexagram-shaped Co₃O₄ structure exhibits sensitivity to both reaction time and temperature, implying that its growth mechanism is regulated by the Kirkendall effect and involves partial cation exchange. Additionally, with alteration of reagent ratios, Co₃O₄ with ball-flower morphology was synthesized successfully. Through cross-section SEM examination, the observed growth mechanisms for both the hexagram and ball-flower structures were substantiated. Lastly, electrochemical performance tests of the hexagram and ball-flower structures on SC electrode were carried out, and specific capacitances were 452 C/g (1062 F/g) and 696 C/g (1339 F/g), respectively. The hexagram-shaped Co₃O₄ structure displays exceptional SC electrode material characteristics, retaining an outstanding capacitance of 93.1% even after 10,000 cycles, highlighting its superior cycle performance. This paper hopes to inspire further SC electrode materials studies based on its novel morphology modulation strategy. Full article

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer with poor clinical outcomes. There is a critical need to identify novel, druggable targets for TNBC to improve therapy response and patient outcomes. Due to their roles in critical processes driving cancer progression, kinases have been a major focus of drug discovery efforts. The role of extracellular signal-regulated kinase 5 (ERK5) in mediating TNBC extracellular matrix (ECM) has previously been described in 2D culture and in vivo. Here, we characterized the impact of ERK5 on breast cancer biology in 2D culture, 3D spheroids, and our 3D breast adipose-macrophysiological system (BA-MaPS). Methods: We assessed migration changes in MDA-MB-231 parental and ERK5-knockout (ERK5-ko) cells cultured in the three in vitro models using transwell, scratch, and spheroid pseudo-migration assays. Differential gene expression among these cell lines in the three platforms was assessed by RNA sequencing and pathway analysis. Stromal remodeling of adipocytes and matrix was evaluated by H&E and Masson’s Trichrome. Results: Across the in vitro models, ERK5 deletion impaired TNBC cell migration. ERK5-mediated transcriptomic changes included genes associated with epithelial-to-mesenchymal transition (EMT) and migration, with further analysis showing significant alterations in core and associated matrisome. Histological staining corroborated the downregulation of collagen with ERK5 depletion in the BA-MaPS. The NFκB pathway was significantly upregulated only in the ERK5-ko 2D-cultured cells, not in 3D spheroids nor the BA-MaPS model. Conclusions: These results indicate a link between ERK5 and TNBC progression through regulation of TME remodeling, EMT, and cell motility. Differences in 2D culture, 3D spheroid, and BA-MaPS underscore the importance of using physiologically relevant models in breast cancer research. Full article

More than 90% of bladder cancers are classified as urothelial carcinomas (UC), with approximately 75% of these cases presenting as non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette–Guérin (BCG) is the current standard immunotherapy for NMIBC, yet it suffers from limited efficacy, frequent tumor recurrence, and substantial toxicity. These limitations underscore the need for safer, more effective, and accessible alternatives. We investigated whether uropathogenic Escherichia coli (UPEC), a natural inducer of immune responses in the bladder, could serve as a novel intravesical immunotherapeutic agent. Using orthotopic bladder cancer models in both mice (MB49-luc) and rats (AY-27), we evaluated the efficacy, specificity, immune dependence, and safety of formaldehyde-inactivated UPEC strains, including mutants with altered type 1 fimbriae expression. Intravesical administration of inactivated UPEC significantly reduced tumor burden and prolonged survival, outperforming BCG in murine models and demonstrating equivalent efficacy with markedly reduced toxicity in rats. The antitumor effect was T cell-dependent and partially mediated by type I fimbriae, which facilitated tumor-specific adhesion. Notably, systemic (subcutaneous) administration of UPEC abrogated efficacy and increased mortality, emphasizing the necessity of localized bladder delivery. In conclusion, we identify inactivated UPEC as a potent, tumor-targeting, and T cell-dependent immunotherapeutic agent with a superior safety profile compared to BCG. This approach might represent a promising and practical alternative for bladder cancer treatment. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

Although cytoplasmic male sterility (CMS) is well established in eggplant, CMS-based interspecific hybrids with allied species have not yet been reported or studied. In this study, five previously developed CMS-based interspecific F₁ hybrids between eggplant and Solanum aethiopicum Group Aculeatum (=S. integrifolium) and Group Gilo (=S. gilo), together with their parental lines, were morphologically evaluated for 67 seedling, vegetative, floral, and fruit traits, and their heterosis for vegetative growth was studied. Male fertility was assessed based on anther morphology and pollen viability, while female fertility was evaluated through backcrosses to both parents. The hybrids exhibited predominantly intermediate phenotypes and clustered distinctly from parental lines as confirmed by principal component analysis. Remarkable heterosis was observed for most growth-related traits, indicating favorable nuclear–cytoplasmic interactions despite the use of CMS eggplant lines as maternal parents. All hybrids showed complete male sterility, characterized by non-viable pollen and pronounced anther homeotic alterations, the latter indicating CMS-related effects on male fertility. Female fertility was severely reduced, likely due to meiotic irregularities, as evidenced by the failure of most attempted backcrosses. However, successful recovery of BC₁ progeny after backcrossing one CMS-based F₁ hybrid to S. gilo demonstrates partial reproductive compatibility and provides a genetic bridge for CMS introgression into S. gilo. These results indicate that CMS systems are suitable for eggplant interspecific crosses aimed at vigorous rootstock production and CMS cytoplasm introgression into allied germplasm. Full article

Current research on glial cells has primarily focused on central nervous system glial cells (CNS glia), with relatively fewer studies on EGCs. Given the critical role of EGCs in maintaining intestinal homeostasis and neural function, this study aimed to investigate their immunomodulatory effects under inflammatory conditions. Primary EGCs were isolated and an inflammatory model was established by treatment with lipopolysaccharide (LPS). Following LPS induction, cellular samples were collected for transcriptomic analysis to identify differentially expressed genes. The analysis revealed that 88 genes were significantly altered, with 60 upregulated and 28 downregulated. Through Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping, and protein–protein interaction (PPI) network analysis, several key regulatory genes were identified: chemokine-related genes (IL8L2, IL8L1, CCL4, CCL5, and CX3CL1); negative feedback regulation-related genes (TNFAIP3 and ZC3H12A); homeostasis-maintaining genes (C1QB and LY86); and arachidonic acid metabolism-related genes (PTGS2 and GGT2). Under LPS stimulation without impairing EGC viability, EGCs may recruit immune cells by regulating the aforementioned genes. Additionally, arachidonic acid and its metabolites likely play important regulatory roles in EGC-mediated immunomodulation. These findings provide new theoretical insights and potential targets for further elucidating the pathogenesis of intestinal inflammation and developing targeted therapies. Full article

Autoimmune thyroid diseases (AITDs), including Hashimoto thyroiditis and Graves’ disease, are the most common autoimmune endocrinopathies, affecting up to 5% of the population. Pathogenetic pathways have not yet been fully elucidated, even though different immune-genetic alterations have been proposed. Specific immune defects presenting with AITDs may serve as an experimentum naturae to study the involvement of a specific pathway in the pathogenesis of the disease. In fact, since immune dysregulation with autoimmunity frequently characterize inborn errors of immunity (IEIs), understanding the mechanisms of immune tolerance breakdown leading to autoimmunity in these conditions may provide useful insight to understand the pathogenesis of AITDs. In this review, we will highlight the main immunological aspects of AITDs and their pathogenesis in IEIs. Full article

Heavy metal contamination poses critical challenges for the cultivation of medicinal plants. This study explores cadmium (Cd)-induced morpho-physiological and metabolic responses in Salvia officinalis (So) and the rare endemic Salvia ceratophylloides (Sc). Plants were exposed to cadmium contamination corresponding to 5 and 10 mg kg⁻¹ Cd (100% and 200% of the Italian regulatory limit) and assessed through gas exchange, leaf anatomy, mineral profiling, polyphenol composition, antioxidant activity, and a preliminary ecotoxicological evaluation using the Artemia salina lethality bioassay. Cd predominantly accumulated in roots, reflecting a partial exclusion strategy, and caused alterations in leaf traits, water relations, and nutrient balance. While total polyphenols generally declined, species-specific responses emerged: S. ceratophylloides increased caffeic acid derivatives, whereas S. officinalis accumulated caffeic acid, lithospermic acid A, quercetin 3-O-glucuronide, and apigenin-O-pentoside at the highest Cd exposure. Polyphenol shifts were strongly associated with antioxidant capacity. Despite higher growth sensitivity, S. ceratophylloides extracts exhibited no toxicity in the A. salina assay, indicating effective metal sequestration and low bioavailability, whereas S. officinalis extracts induced moderate to high toxicity. These findings reveal contrasting Cd tolerance and detoxification strategies, highlighting the potential of integrating plant stress physiology with ecotoxicological assessment and phytostabilization approaches to safely cultivate medicinal species on contaminated soils. Full article

Diabetic foot complications represent a major global health burden and arise from a multifactorial interaction between neuropathy, ischemia, infection, and impaired wound repair. Increasing evidence suggests that, beyond traditional vascular and metabolic risk factors, endocrine dysregulation plays a central role in shaping vascular dysfunction and tissue vulnerability in patients with diabetes. This narrative review provides an updated overview of the endocrine–vascular axis in the development, progression, and healing of diabetic foot ulcers (DFUs), integrating evidence from experimental and clinical studies identified through targeted searches of PubMed, Embase, and Scopus. We examine how alterations in insulin signaling, relative glucagon excess, adipokine imbalance, dysregulation of stress hormones, and thyroid dysfunction interact with chronic hyperglycemia, dyslipidemia, mitochondrial dysfunction, and low-grade inflammation to impair endothelial homeostasis. These disturbances promote oxidative stress, reduce nitric oxide bioavailability, and compromise microvascular perfusion, thereby creating a pro-ischemic and pro-inflammatory tissue environment that limits angiogenesis, extracellular matrix (ECM) remodeling, immune coordination, and effective wound repair. By linking pathophysiological mechanisms to clinical relevance, this review highlights potential biomarkers of endocrine–vascular dysfunction, implications for risk stratification, and emerging therapeutic perspectives targeting metabolic optimization, endothelial protection, and hormonal modulation. Finally, key knowledge gaps and priority areas for future translational and clinical research are discussed, supporting the development of integrated endocrine-based strategies aimed at improving DFU prevention, healing outcomes, and long-term limb preservation in patients with diabetes. Full article

Background/Objectives: Coupled with the already-problematic background rates of traditional cigarette consumption during pregnancy, the surging epidemic of electronic cigarette usage among pregnant women redoubles the importance of understanding the impacts of nicotine exposure during critical periods of development. To date, a burgeoning body of human epidemiological and animal model research indicates that not only the children but also the grandchildren of maternal smokers are at higher risk for neurodevelopmental disorders such as ADHD, autism, and schizophrenia and are predisposed to neurodevelopmental abnormalities which transcend these diagnoses. However, the roles of discrete cellular sub-populations in these and other intergenerational consequences of smoking during pregnancy remain indeterminate. Methods: Toward the resolution of this void in the literature, the present study characterized alterations in the gene expression profiles of dopamine receptor D1-expressing striatal cells from the first- and second-generation male progeny of female mice that were continuously exposed to nicotine beginning prior to conception, continuing throughout pregnancy, and concluding upon weaning of offspring. Results: Dopamine receptor D1-expressing striatal cells from our mouse models of the children and grandchildren of maternal smokers exhibit differential expression patterns for a multitude of genes that are (1) individually associated with neurodevelopmental disorders, (2) collectively overrepresented in gene set annotations related to brain, behavioral, neurobiological, and epigenomic phenotypes shared among neurodevelopmental disorders, and (3) orthologous to human genes that exhibit differential DNA methylation signatures in the newborns of maternal smokers. Conclusions: Together with our and others’ previous findings, the results of this study support the emerging theory that, by inducing extensive alterations in gene expression that in turn elicit cascading neurobiological changes which ultimately confer widespread neurobehavioral abnormalities, nicotine-induced epigenomic dysregulation may be a primary driver of neurodevelopmental deficits and disorders in the children and grandchildren of maternal smokers. Full article

This study was conducted to investigate the effects of dietary polyunsaturated fatty acid (PUFA) levels and FME (flavor and multiple enzymes) on the reproductive performance, nutrient digestion, and metabolism, immunity, and antioxidant capacity of sows and piglets. Forty primiparous sows [Duroc × (Landrace × York)] were randomly assigned from day 107 of gestation to day 7 post-weaning to one of four dietary treatments, low PUFA (4.6% tallow, LP), high PUFA (4.6% fish oil, HP), and LP and HP, each supplemented with 600 mg/kg FME (LP + FME, HP + FME). Results showed that dietary HP + FME supplementation significantly alleviated sow backfat loss during lactation (p < 0.05). Dietary FME supplementation significantly increased milk lactose and solids-non-fat (p < 0.05) on day 15. Meanwhile, milk protein and true protein contents were significantly lower in the LP treatment than in the LP + FME and HP treatments. The apparent total-tract digestibility (ATTD) of ash and phosphorus was improved (p < 0.05) by both HP diets and FME supplementation. The ATTD of energy and dry matter was significantly higher in LP + FME treatment than in LP and HP + FME treatments (p < 0.05). HP diets increased serum malondialdehyde (MDA, p < 0.01), total superoxide dismutase (p < 0.05) in sows, and increased serum MDA and decreased hydrogen peroxide (H₂O₂) contents in piglets (p < 0.05). Dietary FME supplementation decreased serum H₂O₂ contents and increased serum catalase activity of sows and/or piglets (p < 0.05). The serum immune markers, lipid, and protein metabolites of sows and piglets were altered (p < 0.05 or p < 0.10) by HP diets and/or FME supplementation. In conclusion, dietary fish oil (4.6% of diet replacing tallow) and FME (600 mg/kg) supplementation improved lactating performance by improving nutrient digestibility, body reserve mobilization, antioxidant capacity, and health state of sows and piglets. Full article

Field cancerization is a fundamental paradigm in tumorigenesis, emphasizing that carcinogenesis begins long before the appearance of clinically detectable lesions and often precedes recognizable premalignant changes. A direct manifestation of this process is the molecular dysregulation observed in the peritumoral mucosa—histologically normal-appearing tissue that nonetheless exhibits genetic and epigenetic alterations similar to those of the adjacent tumor. This review summarizes current evidence on the molecular alterations shared between tumor tissue and peritumoral mucosa in HNSCC and evaluates their potential as biomarkers for defining molecular margins and improving surgical precision. A literature search was conducted in PubMed using combinations of the keywords “peritumor,” “laryngeal”, “HNSCC,” and “field cancerization.” Studies were included if they directly compared tumor tissue with peritumoral mucosa and, preferably, a third set of distant normal control samples. Only nine studies met the inclusion criteria, highlighting the scarcity of focused research in this area. Reported biomarkers exhibiting comparable dysregulation in both tumor and peritumor tissues include MDM2, E2F2, CDKN2A/p16, ETS-1, MGMT, and multiple microRNAs (e.g., miR-21, miR-96-5p, miR-145-5p). These molecular signatures demonstrate the presence of a biologically altered field extending beyond histologically defined tumor margins. Peritumoral mucosal dysregulation, as a consequence of field cancerization, underscores the need to redefine surgical margins at the molecular level. The identification and validation of biomarkers reflecting this continuum could enable the establishment of molecular margins—improving risk assessment, reducing local recurrence, and advancing personalized oncologic surgery in HNSCC. Standardizing definitions and sampling protocols for “normal adjacent tissue” remains essential for future translational research. Full article

The tip-of-the-tongue (TOT) phenomenon is a transient state in which speakers momentarily fail to retrieve a known word despite preserved semantic knowledge and a strong sense of imminent recall. This review integrates cognitive and neural evidence with emerging neurochemical perspectives to develop a comprehensive biomedical framework for word-finding failures. Cognitive models of semantic–phonological transmission and interloper interference have been refined through structural, functional, and metabolic imaging to elucidate the mechanisms underlying TOT states across the lifespan. Functional neuroimaging implicates a left-lateralized fronto-temporal network, particularly the inferior frontal gyrus (IFG), anterior cingulate cortex (ACC), and temporal pole, in retrieval monitoring and conflict resolution. Structural MRI and diffusion imaging link increased TOT frequency to reduced integrity of the arcuate and uncinate fasciculi and diminished network efficiency. Proton magnetic resonance spectroscopy (¹H-MRS) introduces a neurochemical dimension, with studies of related language tasks implicating lower γ-aminobutyric acid (GABA) and altered glutamate concentrations in frontal and temporal cortices as potential contributors to slower naming and heightened retrieval interference. Together, these findings converge on a model in which transient lexical blocks arise from local disruptions in excitation–inhibition (E/I) balance that impair signal propagation within language circuits. By uniting behavioral, neuroimaging, and neurochemical perspectives, TOT research reveals how subtle perturbations in cortical homeostasis manifest as everyday cognitive lapses and highlights potential biomedical strategies to maintain communicative efficiency across the lifespan. Full article

This review synthesizes the state of the art in flapping foil technology and bridges the distinct engineering domains of bio-inspired propulsion and power generation via flow energy harvesting. This review is motivated by the observation that propulsion and power-generation studies are frequently presented separately, even though they share common unsteady vortex dynamics. Accordingly, we adopt a unified unsteady-aerodynamic perspective to relate propulsion and energy-extraction regimes within a common framework and to clarify their operational duality. Within this unified framework, the feathering parameter provides a theoretical delimiter between momentum transfer and kinetic energy extraction. A critical analysis of experimental foundations demonstrates that while passive structural flexibility enhances propulsive thrust via favorable wake interactions, synchronization mismatches between deformation and peak hydrodynamic loading constrain its benefits in power generation. This review extends the analysis to complex and non-homogeneous environments and identifies that density stratification fundamentally alters the hydrodynamic performance. Specifically, resonant interactions with the natural Brunt–Väisälä frequency of the fluid shift the optimal kinematic regimes. The present study also surveys computational methodologies and highlights a paradigm shift from traditional parametric sweeps to high-fidelity three-dimensional (3D) Large-Eddy Simulations (LESs) and Deep Reinforcement Learning (DRL) to resolve finite-span vortex interconnectivities. Finally, this review outlines the critical pathways for future research. To bridge the gap between computational idealization and physical reality, the findings suggest that future systems prioritize tunable stiffness mechanisms, multi-phase environmental modeling, and artificial intelligence (AI)-driven digital twin frameworks for real-time adaptation. Full article

Dog-assisted interventions (DAIs) are an established procedure to support military staff, but their implementation during active warfare has not yet been systematically studied. In addition, the welfare of therapy dogs participating in DAIs during war remains unexplored. Therapy dogs may develop clinically relevant emotional disorders, including trauma-related stress responses, analogous to human psychopathologies. The present study sought to monitor physiological arousal in therapy dogs performing DAI sessions with their handlers in two Ukrainian military hospitals (Vinnyzja and Kyiv). Biomarkers of hypothalamic–pituitary–adrenal (HPA) axis activity, including salivary, urinary, and hair cortisol concentrations, were assessed in Ukrainian (UA) therapy dogs to capture their acute and long-term stress responses. Additionally, cortisol levels in German (GE) therapy dogs performing similar DAIs under peaceful conditions were measured to compare cortisol levels between dogs from both regions. Results suggest that GE therapy dogs exhibited significantly higher urinary and hair cortisol levels and significantly lower salivary cortisol concentrations, reflecting alterations in longer-term glucocorticoid secretion that is possibly caused by war-related stimulation in the UA cohort. In contrast, no significant differences in salivary cortisol emerged as a consequence of performing DAIs. The present findings suggest that the environment rather than involvement in DAIs has an impact on therapy dogs’ cortisol secretion. Full article