Search Results (770)

This article examines how the Southern lady is represented in three major Southern women’s novels set during the American Civil War: Macaria (1864) by Augusta Jane Evans Wilson, The Battle-Ground (1902) by Ellen Glasgow, and Gone with the Wind (1936) by Margaret Mitchell. Although separated by over seven decades and distinct historical perspectives—Wilson as a contemporary witness, Glasgow as a postwar observer, and Mitchell as a nostalgic inheritor—their works collectively shaped enduring images of the South in American popular culture. Through textual analysis, the study explores how each author depicts female endurance, illness, and mortality to symbolize both individual and social transformation. The heroines (Wilson’s Electra and Irene, Glasgow’s Betty Ambler, and Mitchell’s Scarlett O’Hara) embody resilience amid collapse, assuming active roles in the reconstruction of Southern identity. Their struggles reflect broader tensions between traditional femininity and emerging female agency. Ultimately, the article argues that portrayals of women’s frailty and death function as metaphors for the decline of the antebellum order and the inevitable demise of the Southern lady ideal, revealing illness and death as physical and cultural markers of the South’s transformation in war and its aftermath. Full article

Perlecan, a major heparan sulfate proteoglycan in the vascular basement membrane, plays an essential role in maintaining endothelial barrier integrity, regulating fibroblast growth factor-2 signaling, and exerting anticoagulant activity. Although alterations in perlecan expression are implicated in the initiation and progression of atherosclerosis, the upstream regulatory mechanisms remain unclear. In this study, we investigated the effects of extracellular ATP on perlecan expression in vascular endothelial cells. ATP, but not ADP or adenosine, suppressed perlecan expression at both mRNA and protein levels in a time- and concentration-dependent manner. This suppression was recovered by knockdown of P2Y2 receptor (P2Y2R), but not by P2X4 receptor, P2X7 receptor, or P2Y1 receptor knockdown, indicating the selective involvement of P2Y2R. Mechanistically, ATP reduced Akt phosphorylation mediated by P2Y2R, and inhibition of Akt by inhibitors decreased perlecan expression, whereas inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin complex 1, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, c-Jun N-terminal kinases did not exhibit this recovery effect. These results suggest that ATP downregulates perlecan synthesis via the P2Y2R-mediated inhibition of Akt signaling. Given that ATP is markedly elevated under pathological conditions, such as inflammation and platelet activation, suppression of perlecan synthesis is an important mechanism by which ATP promotes vascular disease progression. Full article

Metastasis is the leading cause of cancer-related mortality, representing a highly coordinated, multistep process in which malignant cells gain the ability to invade, survive in the circulation, and establish secondary tumors at distant sites. While genetic mutations initiate oncogenesis, accumulating evidence shows that epigenetic and epitranscriptomic regulators, encompassing DNA methylation, RNA modifications, and noncoding RNAs (ncRNAs), reshape metastatic phenotypes. This review integrates current insights into these mechanisms and their crosstalk, with a primary focus on their methylation modification. Given their plasticity and potential reversibility, these regulators are attractive targets for therapeutic intervention. Defining the dynamic interplay between DNA and RNA modifications and ncRNAs provides a coherent framework for controlling metastasis and guides the development of precision epigenetic strategies and biomarkers. Future research that integrates multi-omics approaches and spatial transcriptomics will be essential for revealing the epigenetic and epitranscriptomic layers of the metastatic landscape. Full article

Blarina paralytic peptides (BPPs), neurotoxins from shrew saliva that paralyze mealworms, share high sequence similarity with human synenkephalin [1–53] (hSYN), a peptide released from proenkephalin together with opioid peptides that mediate analgesic and antidepressant effects in the brain. Both synthetic BPP2 and hSYN induce a hyperpolarizing shift in the human T-type voltage-gated calcium channel (hCa_v3.2) at sub-micromolar concentrations, although only BPP2 causes paralysis in insects. To gain insight into the functions of these insectivorous animal-specific neurotoxins and the largely uncharacterized brain peptides, we investigated the structure prediction of BPPs and SYNs and their interactions with hCa_v3.2. AlphaFold 3 modeling complemented available cryo-EM data and accurately reproduced the overall channel architecture; however, this inactivated-state model proved unsuitable for predicting agonistic binding of BPPs and SYNs. In contrast, docking simulations using an activated-state hCa_v3.2 homology model revealed distinct ligand-dependent differences in binding energies, affinity, and conformational flexibility. Notably, the C-terminal tail of BPPs—particularly its variable length and flexibility—was identified as a key determinant for the interactions with the S4 voltage-sensing domain of the channel. These findings provide new insights into the evolutionary adaptation of venom peptides in mammals and into potential therapeutic strategies targeting neurological disorders. Full article

Background/Objectives: Although tomato consumption has been associated with positive health outcomes, it remains unclear whether it can prevent or exacerbate allergic diseases by regulating eosinophils. We explored the association between dietary tomato intake and blood eosinophil counts in Japanese individuals. Methods: This population-based, cross-sectional study included 1013 participants aged ≥ 40 years. The dietary intake of tomatoes was assessed using a validated, self-administered diet history questionnaire. The peripheral blood eosinophil count was measured, and an elevated blood eosinophil count was defined as a value that exceeded the ≥75th percentile. Results: The mean age of the participants was 62.5 ± 11.2 years, with 474 (46.8%) being male. Overall, 252 participants exhibited elevated blood eosinophil counts (≥204/μL). In the multivariable logistic regression model with adjustment for potential confounders, an increase in tomato intake of 10 g was inversely associated with an elevated blood eosinophil count (odds ratio [OR], 0.895; 95% confidence interval [CI], 0.834–0.961). Except for chronic kidney disease, the baseline participant characteristics did not influence this association. Conclusions: Low dietary tomato intake was associated with an elevated blood eosinophil count in middle-aged and older Japanese individuals. These results may provide insight into the dietary management of eosinophil-related allergic and type 2 inflammatory diseases. Full article

Background: Antimicrobial resistance (AMR) is a public health challenge, exacerbated by the inappropriate use of antibiotics (ABs) and the lack of standardized surveillance in healthcare settings. Objective: The Latin American PPS aimed to provide a standardized methodology for monitoring antibiotic use, gather data on antibiotic prescription practices, and support initiatives for antimicrobial stewardship (AMS). Methodology: Using a Spanish-adapted version of the WHO PPS methodology, a point prevalence survey (PPS) was conducted between 2022 and 2023 in 67 hospitals across five Latin American countries. Results: A total of 11,094 patients were surveyed, of which 47.9% received at least one AB; surgical and intensive care units displayed the highest prevalence. Most prescribed AB were third-generation cephalosporins (3GC) (22.0%), carbapenems (12.1%), glycopeptides (9.2%), and penicillin combinations (8.6%). A substantial use of agents classified under the WHO’s “Watch” group was found, with notable variances across countries. A multilevel logistic regression model identified that patient age, ICU admission, recent hospitalization, the presence of a catheter, and intubation were significantly associated with higher odds of AB use. In contrast, patients admitted to obstetric or pediatric wards had lower odds of receiving antibiotics. The model revealed considerable heterogeneity between countries, even after adjusting clinical and demographic factors. Conclusions: This study highlights AMS opportunities through targeted interventions, such as optimizing surgical prophylaxis, reducing the use of 3GC, carbapenems, and glycopeptides, and improving adherence to CPGs. These findings provide a comprehensive framework for policymakers and healthcare facilities to develop AMS strategies tailored to the Latin American context. Full article

JC virus (JCV) replicates within the nuclei of glial cells in the human brain and causes progressive multifocal leukoencephalopathy. JCV possesses a small, circular, double-stranded DNA genome, divided into early and late protein-coding regions. The non-coding control region (NCCR) functions bidirectionally for both early and late genes, and the agnogene is located downstream of TCR and upstream of three capsid proteins in the late region. Previously, in cell culture systems, we demonstrated that these capsid proteins accumulate in intranuclear domains known as promyelocytic leukemia nuclear bodies (PML-NBs), where they assemble into virus-like particles (VLPs). To investigate the agnogene’s function, VLPs were formed in its presence or absence, and differential gene expression was analyzed using microarray technology. The results revealed altered expression of histone-modifying enzymes, including methyltransferases (EHMT1, PRMT7) and demethylases (KDM2B, KDM5C, KDM6B), as well as various kinases and phosphatases. Notably, CTDP1, which dephosphorylates the C-terminal domain of an RNA polymerase II subunit, was also differentially expressed. The changes were predominant in the presence of the agnogene. These findings indicate that the agnogene and/or its protein product likely influence epigenetic regulation associated with PML-NBs, which may influence cell cycle control. Consistently, in human brain tissue, JCV-infected glial cells displayed maintenance of a diploid chromosomal complement, likely through G2 arrest. The precise mechanism of this, however, remains to be elucidated. Full article

High-grade gliomas (HGGs) are aggressive brain tumors with limited treatment options and poor survival outcomes. Variants including isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant, and histone 3 lysine to methionine substitution (H3K27M)-mutant subtypes demonstrate considerable tumor heterogeneity at the genetic, cellular, and microenvironmental levels. This presents a major barrier to the development of reliable models that recapitulate tumor heterogeneity, allowing for the development of effective therapies. Glioma tumor organoids (GTOs) have emerged as a promising model, offering a balance between biological relevance and practical scalability for precision medicine. In this study, we present a refined methodology for generating three-dimensional, multiregional, patient-derived GTOs across a spectrum of glioma subtypes (including primary and recurrent tumors) while preserving the transcriptomic and phenotypic heterogeneity of their source tumors. We demonstrate the feasibility of a high-throughput drug-screening platform to nominate multi-drug regimens, finding marked variability in drug response, not only between patients and tumor types, but also across regions within the tumor. These findings underscore the critical impact of spatial heterogeneity on therapeutic sensitivity and suggest that multiregional sampling is critical for adequate glioma model development and drug discovery. Finally, regional differential drug responses suggest that multi-agent drug therapy may provide better comprehensive oncologic control and highlight the potential of multiregional GTOs as a clinically actionable tool for personalized treatment strategies in HGG. Full article

Staphylococcal food poisoning (SFP) is a common foodborne illness caused by the ingestion of enterotoxins produced by Staphylococcus aureus, posing a persistent global public health concern. Although regional differences in implicated food types and predominant enterotoxins have been reported, the underlying factors remain unclear. In this study, we systematically investigated the effects of nutritional factors on the growth, biofilm formation, and production of two representative enterotoxins, SEA and SEB, by S. aureus. Specifically, we evaluated bacterial responses to different concentrations of NaCl, glucose, and tryptone. NaCl suppressed growth, biofilm formation and enterotoxin production in a dose-dependent manner. Glucose markedly inhibited both bacteria growth and enterotoxin production, with a stronger effect on SEB than SEA. In contrast, tryptone promoted bacterial growth and moderately enhanced biofilm formation but did not significantly affect enterotoxin production. Importantly, even under comparable bacterial counts, the types and amounts of SEs produced varied substantially depending on the nutrient composition. These findings provide new insights into the nutrient-dependent regulation of virulence in S. aureus and highlight the importance of considering environmental and nutritional factors when assessing risks of SFP and designing effective food safety strategies. Full article

The proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are key pathological features of vascular remodeling during pulmonary hypertension. Platelet-derived growth factor (PDGF) signaling is a major contributor to these processes. Given the importance of microRNA (miRNA) regulation in the PDGF signaling pathway in PASMCs, we hypothesized that imatinib, a tyrosine kinase inhibitor, modulates the expression levels of miRNAs responsive to PDGF signaling to ameliorate the PDGF signaling-induced PASMC phenotype. In this study, we investigated the role of miR-335-5p in PDGF signaling-induced PASMC proliferation and migration, as well as the involvement of imatinib in the regulatory network of miR-335-5p. miR-335-5p was identified as a critical negative regulator of PDGF signaling. Functional assays revealed that miR-335-5p significantly inhibits PASMC proliferation and migration. Through target prediction and validation, Rho GTPase Activating Protein 18 (ARHGAP18) was identified as a novel direct target of miR-335-5p. In addition, ARHGAP18 was found to play an essential role in regulating PASMC proliferation and migration. Although miR-335-5p was downregulated upon PDGF-BB stimulation, its expression was restored by imatinib. These findings highlight the important role of the imatinib–miR-335-5p–ARHGAP18 axis as a potential therapeutic target for pathological vascular remodeling. Full article

Two ways of anodizing 3D-printed AlSi10Mg alloy were characterized, and then their fatigue properties were evaluated. Test specimens were fabricated via a laser-powder bed fusion (L-PBF) process followed by machining. Normal and hard anodizing were both conducted in a sulfuric acid bath. The anodized layer was observed using FE-SEM/EDS. Fine Si particles dispersed in the matrix showing web-like patterns were incorporated in the anodized layer. By etching the Si particles away with Keller’s reagent, a characteristic maze-like 3D structure of anodized Al was observed. Then, rotating bending fatigue tests were carried out to evaluate the fatigue strength at 10⁷ cycles. The fatigue strength of the as-machined, normal-anodized and hard-anodized specimens was 106, 100 and 95 MPa, respectively. The fatigue limits were proportional to the surface roughness with higher linearity. By reducing the surface roughness, the fatigue strength of the hard-anodized specimen was improved. This result demonstrates the possibility of improving the fatigue properties of anodized components by reducing their surface roughness. Lastly, a CASS (copper-accelerated acetic acid salt spray) test was conducted, and superior corrosion resistance of the normal- and hard-anodized layers was verified. Full article

Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing Practice-controlled process from adipose stem cells collected during a minimally invasive liposuction procedure. The final implant is a ready-to-use moldable putty with fixed mineral content and predefined physiologic ranges of osteogenic cells and bioactive growth factors. Preclinical pharmacology studies were conducted in nude rats using a paravertebral implantation model, and subsequently, in a femoral critical-sized bone defect (CSBD) model. In a first-in-human Phase 1b/2a study, NVD003 was used for fracture osteosynthesis with classical fixation material in nine adults with recalcitrant lower limb non-union. NVD003 was also used at the discretion of treating physicians in four pediatric patients surgically treated for congenital pseudarthrosis of the tibia (CPT) with the Masquelet technique. Efficacy was evaluated as clinical healing and in terms of bone formation, bone union, and bone remodeling on radiographs and computed tomography using the extended Lane and Sandhu Scale. Results: Preclinical studies indicated that NVD003 requires cellularity for its bioactivity and moreover facilitates bone union when used as a graft material in femoral CSBD. In the clinical study, nine adult participants were successfully grafted with NVD003 and completed study follow-up to 24 months, with extended safety follow-up to 5 years ongoing. No adverse events were considered related to NVD003. Maximal bone formation occurred between 3 and 12 months post-implantation; the mean time to clinical healing was 6 months and the mean time to radiological union was 17 months. Ultimately, 89% (8/9) of patients achieved bone union without refracture. All four pediatric patients with CPT also achieved lasting bone union following grafting with NVD003. No safety signals were observed over a mean follow-up of 62.1 months. Conclusions: NVD003 represents a safe, autologous bone graft substitute product without side effects of heterotopic ossification or bone resorption. NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions. Full article

This study undertakes a thorough examination of hydrogen solubility within various metal-alloy membranes, including those based on palladium (Pd), vanadium (V), niobium (Nb), tantalum (Ta), amorphous alloys and liquid gallium (Ga). The analysis aims to outline the strengths and weaknesses of each material in terms of solubility and permeability performance. The investigation began by acknowledging the dual definitions of solubility found in literature: the “secant method”, which calculates solubility based on the hydrogen pressure corresponding to a specific sorbed hydrogen loading, and the “tangent method”, which evaluates solubility as the derivative (differential solubility) of the sorption isotherm at various square root values of hydrogen partial pressure. These distinct methodologies yield notably different outcomes. Subsequently, a compilation of experimental data for each membrane type is gathered, and these data are re-analysed to assess both solubility definitions. This enabled a clearer comparison and a deeper analysis of membrane behaviour across different conditions of temperature, pressure, and composition in terms of hydrogen solubility in the metal matrix. The re-evaluation presented in this study serves to identify the most suitable membranes for hydrogen separation or storage, as well as to pinpoint the threshold of embrittlement resulting from hydrogen accumulation within the metal lattice. Lastly, recent research has indicated that particularly promising membranes are those fashioned as “sandwich” structures using liquid gallium. These membranes demonstrate resistance to embrittlement while exhibiting superior performance characteristics. Full article

We fabricated dye-sensitized solar cells (DSSCs) co-sensitized with the organic dye YD2 and a spiropyran derivative (SPNO₂), a photochromic molecule capable of reversible isomerization under light irradiation. Upon UV exposure, SPNO₂ converts from its closed spiropyran (SP) form to the open photomerocyanine (PMC) form, which absorbs visible light and changes the optical properties of the photoelectrode. Spectroscopic analysis showed an 18% decrease in transmittance at 540 nm after UV irradiation and a 10% increase following visible light exposure. These changes were accompanied by a 0.5% increase in power conversion efficiency (η) after 5 min of UV irradiation, and a 0.83% decrease after 10 min of visible light. Although direct electron injection from PMC into TiO₂ appears inefficient, the enhanced performance is attributed to Förster resonance energy transfer (FRET) from PMC to YD2. This photoresponsive behavior highlights a co-sensitization strategy that combines dynamic optical control and efficient energy transfer. Our findings demonstrate a promising approach to designing smart DSSCs with externally tunable photovoltaic properties using photochromic sensitizers. Full article

The Sendai Framework for Disaster Risk Reduction 2015–2030 articulates the need for a clear understanding of responsibilities across public and private stakeholders, including academia. This study aimed to clarify how university faculty members in Aceh Province, Indonesia, devastated by the 2004 Aceh Tsunami, perceive the role of universities in suggesting policy recommendations for disaster risk reduction (DRR) and sustainable development, and their perspective on the relationship between those roles and the main functions of universities. A questionnaire survey was conducted with 400 respondents in Aceh Province from July 2023 to November 2023. The authors examined descriptive statistics, followed by Kruskal–Wallis tests and structural equation modeling (SEM). The authors found that most university faculty members were optimistic about the role of universities in providing policy recommendations for DRR. Furthermore, interest in DRR activities and relevant past experiences may influence their perception of these roles. The SEM analysis showed that faculty members perceive universities as key contributors to DRR policy recommendations. Based on the above, the authors posit that universities must adopt measures that empower faculty members to gain interest and experience in DRR activities. Steady progress in the main functions of universities is essential for articulating DRR policy recommendations. Full article