Search Results (39,564)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options for patients with locally advanced or metastatic disease. Endoscopic ultrasound (EUS)-guided intra-tumoral radioactive implantation has emerged as a minimally invasive approach to enhance local tumor control while minimizing systemic toxicity. Among the available isotopes, phosphorus-32 (³²P) microparticle brachytherapy has demonstrated promising outcomes, including significant tumor regression, reductions in CA 19-9, and higher rates of tumor downstaging and surgical conversion when combined with systemic chemotherapy. Compared with stereotactic body radiotherapy (SBRT), ³²P delivers higher intratumoral radiation doses, spares adjacent healthy tissues, and can be administered during ongoing chemotherapy without treatment interruption. Additionally, preliminary evidence suggests that ³²P may modulate the tumor microenvironment, improving vascularity and enhancing chemotherapy efficacy. The procedure shows high technical success and a favorable safety profile, with minimal serious adverse events. Future directions include prospective randomized trials to validate its impact on survival, optimize dosing, and establish treatment protocols. EUS-guided intra-tumoral ³²P brachytherapy holds potential as a key component of multimodal therapy, bridging local tumor control and systemic disease management in PDAC. Full article

Growing demand for rare earth elements (REEs) necessitates the development of efficient recycling strategies from secondary sources. This work presents a complete hydrometallurgical process for recovering yttrium (Y) from spent fluorescent lamps, emphasizing the efficient coupling of a conventional acid leaching with a solid–liquid extraction system. Multi-stage sulfuric acid leaching (2 M, 65 °C, an S/L ratio of 0.25 g/L) achieved a cumulative yttrium dissolution of 71.11% over four stages, with individual stage recoveries (based on initial yttrium content) of 44.2%, 21.56%, 7.19%, and 0.68%. Kinetic and spectroscopic analyses (FTIR, SEM-EDS) revealed that the leaching rate is controlled by diffusion through an in situ formed sulfate-rich layer (CaSO₄, Na₂SO₄), as described by the Z-L-T (Zhuravlev–Leshokin–Templeman) model (Ea = 35.5 kJ mol⁻¹). The resulting leachate was subjected to solid–liquid extraction using Amberlite XAD-7 resin impregnated with D₂EHPA. Under optimal conditions, the extraction process was highly efficient, yielding over 99% yttrium recovery at an optimal pH of 0.75 with a low resin dosage of 0.1 g/L. Furthermore, the solvent-impregnated resins exhibited excellent reusability over five consecutive extraction–stripping cycles, maintaining a single-cycle stripping efficiency above 70% and a cumulative recovery exceeding 97%. This study validates the technical feasibility of an integrated leach–extract–strip process based on impregnated resins as an alternative approach for yttrium recycling from electronic waste, potentially supporting the development of a circular economy. Full article

Flexible, intelligent color-changing windows with excellent color-switching capability and fast response time rely significantly on conductive composite layers composed of electrochromic materials and flexible, transparent substrates. Herein, we developed a high-performance electrochromic film (CPC) with mechanical, humidity, and temperature insensitivity by coating sodium carboxymethyl cellulose (CMC)-dispersed PEDOT:PSS onto a CA film. In the CPC system, CMC not only effectively enhances interfacial bonding and compatibility between the hydrophobic CA film and the hydrophilic PEDOT:PSS but also enables uniform and stable deposition of PEDOT:PSS on the CA film. As a result, the designed CPC demonstrates a high optical modulation capability (the transmittance changes from 60.1% to 3%) and a response time of 2 s. In addition, the CPC features the advantages of mechanical-, humidity-, and temperature-insensitive electrochromic distinctions, where it outputs the stable coloring efficiency with 100-time bending treatment, various temperatures, and humidity in an all-day outdoor environment. The developed CPC electrochromic film offers new insights into promoting the structural simplification and sustainability of electrochromic materials. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both healthcare-associated (HA-MRSA) and community-associated (CA-MRSA) infections, posing major challenges due to its evolving antimicrobial resistance (AMR) and genetic diversity. This study investigates the prevalence, antimicrobial resistance patterns, and molecular characteristics of HA-MRSA and CA-MRSA isolates in Saudi Arabia. A retrospective analysis was conducted on 178 MRSA isolates obtained from clinical samples. MRSA identification was performed using cefoxitin disk diffusion, and antimicrobial susceptibility testing for vancomycin, linezolid, and ciprofloxacin was conducted using the BD Phoenix M50 system. Molecular characterization included SCCmec typing, spa typing, and PCR-based detection of virulence genes (pvl, tst, eta, etb, lukS, lukF). Statistical analysis was carried out using SPSS, with a significance threshold of p < 0.05. Among 1496 S. aureus isolates, 178 (11.9%) were confirmed as MRSA, with HA-MRSA (61.8%) being more prevalent than CA-MRSA (38.2%). Notably, 7.8% of HA-MRSA isolates exhibited heteroresistant vancomycin-intermediate S. aureus (hVISA). Ciprofloxacin resistance was significantly higher in HA-MRSA (85.0%) compared to CA-MRSA (38.9%). SCCmec type V was the predominant genotype (87.1%), suggesting increased infiltration of CA-MRSA strains into hospital settings. Spa typing revealed high genetic diversity, with t037 being the most common (27%). Virulence genes were detected in 6% of isolates, indicating limited dissemination of these factors. The findings highlight the increasing prevalence of MRSA, the emergence of hVISA, and shifts in clonal distribution, underscoring the need for ongoing molecular surveillance and stringent antimicrobial stewardship programs to control MRSA spread in both healthcare and community environments. Full article

Background: The prognostic value of phosphatidylinositol-3-kinase p110α, a key catalytic subunit in the PI3K/AKT pathway, in breast cancer remains controversial. This study evaluated its prognostic significance in stage I–III invasive breast cancer. Methods: p110α protein expression was detected via immunohistochemistry (IHC) in 161 patient tissue samples. Its association with overall survival (OS) and relapse-free survival (RFS) was analyzed using Kaplan–Meier and Cox proportional hazards models. Results: p110α positivity was detected in 59.0% of specimens and showed significant correlation with histological grade (p = 0.034). Survival analysis revealed that p110α positivity was associated with worse OS (log-rank p = 0.008) and RFS (log-rank p = 0.018). In multivariate analysis, p110α expression was an independent predictor of poor prognosis for both OS (HR = 2.45, 95%CI: 1.25–4.78) and RFS (HR = 2.12, 95%CI: 1.14–3.94). This association with poor prognosis was particularly pronounced in stage I–II, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative subgroups. Supporting evidence from the PROGgeneV2 database showed that high PIK3CA mRNA levels predicted inferior survival in external cohorts. Conclusions: p110α protein expression is an independent biomarker for adverse outcomes in stage I–III invasive breast cancer. Its assessment could improve prognostic evaluation and guide personalized therapy. Full article

Background: A childhood burn presents new and unfamiliar challenges to patients and their parents during recovery. These injuries can negatively impact activities such as independence in self-care, participation in physical activity, and social interaction. As such, pediatric burn patients are at risk of poorer quality of life (QoL) outcomes after their burn. In this longitudinal, observational cohort study, we examined the social, demographic, and clinical factors that were associated with a poor QoL at 12 months postburn for pediatric patients aged > 2 years with non-severe burns in Western Australia. Methods: Inpatients were recruited from the pediatric burn unit at Perth Children’s Hospital in Western Australia between February 2021 and September 2022. Demographic and family information (age, sex, postcode, parental education, languages spoken at home) and clinical data (burn cause, TBSA%, location, surgical interventions, length of stay) were collected at baseline. At 6 and 12 months, caregivers completed the Brisbane Burn Scar Impact Profile (BBSIP). Results: A total of 37 caregivers completed the Brisbane Burn Scar Impact Profile (BBSIP). For the child’s QoL, 57% of caregivers reported that some impact remained for overall QoL, 32% for sensory intensity, 46% for sensitivity, 22% for daily living (22%), and 19% for emotional reactions. Parent worry was impacted in 46% of caregivers. Being female was associated with greater long-term impacts, particularly in overall functioning and parental worry. The burn location also influenced outcomes, with injuries to the upper limbs linked to higher sensory intensity and emotional impact. Children from culturally and linguistically diverse (CaLD) backgrounds, indicated by those speaking a language other than English at home (LOTE), demonstrated significantly greater effects across several domains, including overall impact, daily living, appearance, and parent worry. Conclusions: A substantial proportion of children continued to experience impacts from non-severe burns across multiple domains, indicating that even small-area burns can have lasting effects. The factors associated with worse scores were the child being female, the families being linguistically diverse, and upper body burns. Full article

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article

Plant factories enable stable crop production, but face sustainability challenges due to intensive resource consumption. In particular, studies that quantitatively analyze nutrient use in plant cultivation and assess the environmental burdens remain scarce. To address this, this study developed and evaluated a precision nutrient management system using ion-selective electrodes (ISEs) for closed hydroponic lettuce cultivation. The system’s performance was compared with a conventional EC-based approach in terms of resource use efficiency and environmental impact using life cycle assessment (LCA). The ISE-based system effectively maintained NO₃, K, and Ca concentrations within target ranges (root mean square error (RMSE) < 52 mg·L⁻¹), producing healthy crops without the physiological disorders (tip-burn) observed in the EC-based control, while the EC-based system showed higher total fresh weight, which implies that the increase in fresh weight may not necessarily correspond to marketable yield due to the nutrient imbalances. In terms of efficiency, the ISE-based system improved water-use efficiency (WUE) by 48.4% and fertilizer-use efficiency (FUE) by 24.5%. Furthermore, LCA revealed that the ISE-based system reduced greenhouse gas emissions by 8% and freshwater ecotoxicity by 64% per kg of lettuce, primarily by extending the nutrient solution reuse period threefold. The results suggest that ion-specific precision management has the potential to enhance the sustainability and resource efficiency of plant factories. Full article

‘Candidatus Phytoplasma solani’ of the 16SrXII group is an emerging vector-borne pathogen in European crop production. The cixiid planthopper Hyalesthes obsoletus transmits 16SrXII-A stolbur phytoplasmas that are associated with diseases in grapevine, potato, and various weeds. While 16SrXII-P genomes transmitted by Pentastiridius leporinus are available, no genome of an H. obsoletus-transmissible 16SrXII-A phytoplasma has been reported from Germany. Here, we present insights into the phylogenetic position and pathogen–host interactions through the functional reconstruction of the complete 832,614 bp genome of the H. obsoletus transmissible ‘Ca. P. solani’ 16SrXII-A strain POT from a potato field. Phylogenetic analyses highlight the heterogeneity within the stolbur group using whole-genome alignment and a BUSCO-based core gene analysis approach. The POT chromosome shares highest average nucleotide identity with Italian bindweed-associated genomes and displays strong synteny with the c5 strain. Consistent with the typical phytoplasma architecture, the POT genome combines mobile-element-driven instability with a conserved core metabolism. Virulence factors include transposon-linked effectors but lack pathogenicity island organisation. POT further differs from other 16SrXII-group phytoplasmas through unique collagen-like proteins that could contribute to virulence. These findings provide a robust genomic framework that improves diagnostics, enables strain-level resolution and supports the assessment of breeding materials under stolbur phytoplasma pressure, thereby refining our understanding of stolbur phytoplasma diversity and highlighting the evolutionary divergence within the 16SrXII subgroup. Full article

As an emerging threat to global food security, wheat blast necessitates the development of a rapid and field-deployable detection system to facilitate early diagnosis, enable effective management, and prevent its further spread to new regions. In this study, we aimed to validate and improve a Recombinase Polymerase Amplification coupled with PCRD lateral flow detection (RPA-PCRD strip assay) kit for the rapid and specific identification of Magnaporthe oryzae pathotype Triticum (MoT) in field samples. The assay demonstrated exceptional sensitivity, detecting as low as 10 pg/µL of target DNA, and exhibited no cross-reactivity with M. oryzae Oryzae (MoO) isolates and other major fungal phytopathogens under the genera of Fusarium, Bipolaris, Colletotrichum, and Botrydiplodia. The method successfully detected MoT in wheat leaves as early as 4 days post-infection (DPI), and in infected spikes, seeds, and alternate hosts. Furthermore, by combining a simplified polyethylene glycol-NaOH method for extracting DNA from plant samples, the entire RPA-PCRD strip assay enabled the detection of MoT within 30 min with no specialized equipment and high technical skills at ambient temperature (37–39 °C). When applied to field samples, it successfully detected MoT in naturally infected diseased wheat plants from seven different fields in a wheat blast hotspot district, Meherpur, Bangladesh. Training 52 diverse stakeholders validated the kit’s field readiness, with 88% of trainees endorsing its user-friendly design. This method offers a practical, low-cost, and portable point-of-care diagnostic tool suitable for on-site genomic surveillance, integrated management, seed health testing, and quarantine screening of wheat blast in resource-limited settings. Furthermore, the RPA-PCRD platform serves as an early warning modular diagnostic template that can be readily adapted to detect a wide array of phytopathogens by integrating target-specific genomic primers. Full article

(1) Background: The synthetic eleven-amino acid peptide P₁₁-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P₁₁-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P₁₁-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P₁₁-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca²⁺ influx and a slight increase in ROS. Among the 84 genes examined, P₁₁-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P₁₁-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P₁₁-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells. Full article

Potassium (K) fertilization plays a key role in regulating stem morphology, particularly stem diameter, yet the influence of different K fertilizer formulations on stem structure and tensile strength remains insufficiently understood. Cereal straw is a key lignocellulosic by-product with growing importance in the circular bioeconomy. Thus, the aim of this study was to determine the links between potassium nutrition, stem structure, and mechanical behavior for four cereal species: wheat, barley, rye, and oats. There were three potassium fertilization levels (0, 60, and 120 kg K ha⁻¹) conducted in a field experiment in eastern Croatia (2021/2022). At maturity, stem morphology, macroelements (Ca, K, P, C, N), acid detergent fiber (ADF), neutral detergent fiber (NDF), and uniaxial tensile properties (maximum force, tensile strength, Young’s modulus) were determined. Cereal species was the dominant source of variation (p < 0.0001) for all traits, whereas the main effect of K was generally weak and significant only for stem diameter at the midpoint and N concentration, although K × species interactions were frequent. Oats and rye showed the most vigorous biomass production, whereas wheat exhibited by far the highest tensile strength (about 120 MPa) and stiffness (6.23 GPa), together with the highest ADF, while barley had the greatest NDF. Oat stems had the lowest ADF and NDF, indicating less lignified, more digestible tissues but mechanically weaker straw. Mechanical traits were tightly and positively correlated with ADF, NDF, and CN ratio, whereas P showed weak or negative associations with plant size and strength. Therefore, for targeted straw valorization, cereal species selection is paramount, with potassium fertilization playing a secondary, species-dependent role. Full article

Background/Objectives: Rotavirus remains a major cause of severe acute gastroenteritis
in infants worldwide. The suboptimal efficacy of current vaccines underscores the need
for alternative microbiome-based interventions, including postbiotics. Extracellular
vesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigate
diarrhea and enhance immune responses in a suckling-rat model of rotavirus infection.
Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infected
enterocytes. Methods: Polarized Caco-2 monolayers were used as a model of mature
enterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN)
or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca²⁺
concentration, ROS levels, and the expression of immune- and barrier-related genes and
proteins were assessed at multiple time points post-infection. Results: EVs from both
strains exerted broad protective effects against rotavirus-induced cellular dysregulation,
with several responses being strain-specific. EVs interfered with viral replication by
counteracting host cellular processes essential for rotavirus propagation. Specifically, EV
treatment significantly reduced rotavirus-induced intracellular Ca²⁺ mobilization, ROS
production, and COX-2 expression. In addition, both EV types reduced virus-induced
mucin secretion and preserved tight junction organization, thereby limiting viral access
to basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses via
distinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses,
whereas EcoR12 EVs preserved the expression of interferon-related signaling genes.
Conclusions: EVs from EcN and EcoR12 act through multiple complementary
mechanisms to restrict rotavirus replication, spread, and immune evasion. These findings
support their potential as effective postbiotic candidates for preventing or treating
rotavirus infection. Full article

Gold nanoparticles (Au-NP) are frequently used as model nanomaterials to study nanoparticle behavior in plants due to their analytical detectability and negligible natural background in plant tissues. However, the feasibility of visualizing the spatial distribution of foliar-applied Au-NP at low exposure levels using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) remains insufficiently explored. In this study, commercially sourced Au-NP were applied to lentil leaves (Lens culinaris var. Beluga) at a low concentration of 0.5 mg·L⁻¹ using a controlled leaf submersion approach. Leaves were sampled at 1 h, 24 h, and 96 h post-exposure and analyzed by LA-ICP-MS imaging to assess time-dependent changes in gold-associated spatial signals, and to compare elemental distribution patterns with non-exposed controls. Untreated control leaves showed no detectable gold at any sampling time point, confirming negligible native Au background. In treated leaves, LA-ICP-MS imaging revealed an initially localized Au hotspot at 1 h, followed by progressive Au redistribution toward the leaf margins and petiole region by 24 h and 96 h. Gold signals persisted over the full 96 h period, indicating stable association of Au-NP with leaf tissue. Comparative elemental mapping of Ca, Mg, K, P, Fe, Zn, and Cu showed no persistent differences in spatial distribution patterns between treated and control leaves as detectable by LA-ICP-MS. This study demonstrates the feasibility of LA-ICP-MS imaging for visualizing the deposition and temporal spatial redistribution of low-dose foliar-applied nanoparticles in intact leaves. The results provide a methodological reference for future hypothesis-driven studies that apply nanoparticles under more controlled conditions, include increased replication, and combine multiple analytical techniques. Full article

Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts. Results: Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment. Conclusions: These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis. Full article