Search Results (907)

This study introduces xylitol, a natural compound, as a multifunctional additive to enhance the performance of alkali-activated slag/fly ash materials (AASFMs). A systematic investigation was conducted to elucidate xylitol’s mechanism in modifying AASFM properties, including fresh behavior, hydration kinetics, compressive strength, and autogenous shrinkage. The experimental findings demonstrated that xylitol significantly delayed early-age hydration while promoting more extensive hydration at later stages. Specifically, the initial and final setting times of AASFM pastes were extended by 640% and 370%, respectively, and paste flowability increased by 30%. At a 0.2% dosage, xylitol markedly reduced porosity and refined the microstructure of AASFMs, leading to improved mechanical properties. The 3-day and 28-day compressive strengths were enhanced by 39.8% and 39.7%, respectively, while autogenous shrinkage was suppressed by 61.4%. These results demonstrate the multifunctional potential of xylitol in AASFMs, serving as an effective retarder, plasticizer, strength enhancer, and shrinkage reducer. Notably, the refined pore structure induced by xylitol may also mitigate the risks of the alkali–silica reaction, though further durability validation is warranted. Full article

A one-pot synthetic methodology that combines an Ugi-Zhu three-component reaction (UZ-3CR) with a cascade sequence (intermolecular aza Diels–Alder cycloaddition/intramolecular N-acylation/decarboxylation/dehydration) using microwave-heating conditions, ytterbium (III) triflate (Yb(OTf)₃) as the catalyst, and chlorobenzene (for the first time in a multi-component reaction (MCR)) as the solvent, was developed to synthesize twelve new fluorinated-pyrrolo[3,4-b]pyridin-5-ones containing a 4-amino-7-chloroquinoline moiety, yielding 50–77% in 95 min per product, with associated atom economies around 88%, also per product. Additionally, by in vitro tests, compounds 19d and 19i were found to effectively stop early SARS-CoV-2 replication, IC₅₀ = 6.74 µM and 5.29 µM, at 0 h and 1 h respectively, while cell viability remained above 90% relative to the control vehicle at 10 µM. Additional computer-based studies revealed that the most active compounds formed strong favorable interactions with important viral proteins (M_pro, NTDα and NTDo) of coronavirus, supporting a two-pronged approach that affects both how the virus infects the cells and how it replicates its genetic material. Finally, quantum chemistry analyses of non-covalent interactions were performed from Density-Functional Theory (DFT) to better understand how the active compounds hit the virus. Full article

Honey bees are essential pollinators for the ecosystem and food crops. However, their health and survival face threats from both biotic and abiotic stresses. Fungi, microsporidia, and bacteria might significantly contribute to colony losses. Therefore, rapid and sensitive diagnostic tools are crucial for effective disease management. In this study, molecular assays were developed to quickly and efficiently detect the main honey bee pathogens: Nosema ceranae, Aspergillus flavus, Paenibacillus larvae, and Black queen cell virus. In this context, new primer pairs were designed for use in quantitative Real-time PCR (qPCR) reactions. Various protocols for extracting total nucleic acids from bee tissues were tested, indicating a CTAB-based protocol as the most efficient and cost-effective. Furthermore, excluding the head of the bee from the extraction, better results were obtained in terms of quantity and purity of extracted nucleic acids. These assays showed high specificity and sensitivity, detecting up to 250 fg of N. ceranae, 25 fg of P. larvae, and 2.5 pg of A. flavus DNA, and 5 pg of BQCV cDNA, without interference from bee DNA. These qPCR assays allowed pathogen detection within 3 h and at early stages of infection, supporting timely and efficient management interventions. Full article

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC₅₀ sensitivity (in 13%). Changes in the BAT EC₅₀ correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC₅₀ calls for further research to clarify the clinical relevance of these rapid receptor modulations. Full article

Despite intensive eradication efforts, classical swine fever (CSF) remains endemic across South America, Europe, Asia, and the Caribbean, highlighting the need for more effective surveillance and detection methods. Reverse-transcription real-time polymerase chain reaction (RRT-PCR) is the fastest, and most sensitive assay for detecting CSF virus (CSFV) genomic material. Previously, we demonstrated that spleen swabs outperformed spleen homogenates for the detection of ASFV genomic material by RRT-PCR. In this study, we compared CSFV genome detection in paired spleen homogenates and spleen swabs generated using 49 frozen and 33 fresh spleen samples collected from experimentally inoculated pigs with acute infection. The results show that the CSFV genome detection in spleen swabs is comparable to that in spleen homogenates. The study also demonstrated that the CSFV genomic material can be detected in spleen swabs during early CSFV infections, and the viruses can be successfully isolated from the swabs. The use of spleen swabs instead of spleen tissue homogenates for CSF detection will reduce labor, decrease costs associated with reporting, and increase the diagnostic throughput. Full article

The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits. AKT and JNK did not show treatment-dependent activation and lacked a correlation with functional traits, as shown by ERK1/2. These findings suggest that rrβNGFch may promote the functional activation of sperm cells, particularly during early incubation. The increase in capacitation and AR was not linked to significant changes in pathways related to cell survival or death, indicating a specific action of the treatment. In contrast, prolonged storage negatively affected all sperm parameters. ERK1/2 activation correlated with capacitation, AR, and apoptosis, supporting its role as an NGF downstream mediator. Further studies should analyze other molecular mechanisms of sperm and the potential applications of NGF in assisted reproduction. Full article

Background: Residual deficits after early treatment of developmental dysplasia of the hip (DDH) using osteotomy often led to asymmetrical gait deviations with increased repetitive rates of ground reaction force (GRF) in both hips, resulting in a higher risk of early osteoarthritis. This study investigated lower limb inter-joint coordination and swing foot control during level walking in adolescents with early-treated unilateral DDH. Methods: Eleven female adolescents treated early for DDH using Pemberton osteotomy were compared with 11 age-matched healthy controls. The joint angles and angular velocities of the hip, knee, and ankle were measured, and the corresponding phase angles and continuous relative phase (CRP) for hip–knee and knee–ankle coordination were obtained. The variability of inter-joint coordination was quantified using the deviation phase values obtained as the time-averaged standard deviations of the CRP curves over multiple trials. Results: The DDH group exhibited a flexed posture with increased variability in knee–ankle coordination of the affected limb throughout the gait cycle compared to the control group. In contrast, the unaffected limb compensated for the kinematic alterations of the affected limb with reduced peak angular velocities but increased knee–ankle CRP over double-limb support and trajectory variability over the swing phase. Conclusions: The identified changes in inter-joint coordination in adolescents with early treated DDH provide a plausible explanation for the previously reported increased GRF loading rates in the unaffected limb, a risk factor of premature OA. Full article

The combined application of fibers and lightweight aggregates (LWAs) represents an effective approach to achieving high-strength, lightweight concrete. To enhance the predictability of the mechanical properties of fiber-reinforced lightweight aggregate concrete (LWAC), this study conducts an in-depth investigation into its hydration characteristics. In this study, high-strength LWAC was developed by incorporating low water absorption LWAs, various volume fractions of basalt fiber (BF) (0.1%, 0.2%, and 0.3%), and a ternary cementitious system consisting of 70% cement, 20% fly ash, and 10% silica fume. The hydration-related properties were evaluated through isothermal calorimetry test and high-temperature calcination test. The results indicate that incorporating 0.1–0.3% fibers into the cementitious system delays the early hydration process, with a reduced peak heat release rate and a delayed peak heat release time compared to the control group. However, fitting the cumulative heat release over a 72-h period using the Knudsen equation suggests that BF has a minor impact on the final degree of hydration, with the difference in maximum heat release not exceeding 3%. Additionally, the calculation model for the final degree of hydration in the ternary binding system was also revised based on the maximum heat release at different water-to-binder ratios. The results for chemically bound water content show that compared with the pre-wetted LWA group, under identical net water content conditions, the non-pre-wetted LWA group exhibits a significant reduction at three days, with a decrease of 28.8%; while under identical total water content conditions it shows maximum reduction at ninety days with a decrease of 5%. This indicates that pre-wetted LWAs help maintain an effective water-to-binder ratio and facilitate continuous advancement in long-term hydration reactions. Based on these results, influence coefficients related to LWAs for both final degree of hydration and hydration rate were integrated into calculation models for degrees of hydration. Ultimately, this study verified reliability of strength prediction models based on degrees of hydration. Full article

This study treated the NaOH component in red mud sludge, an industrial by-product generated at 300,000 tons annually in Korea, with sulfuric and nitric acids to produce NaSO₄ and NaNO₃, respectively. The effects of acid-treated liquid red mud (LRM) on the hydration reactions and early strength development in cement mortar were investigated. Properties such as flow, setting time, hydration heat, and compressive strength were evaluated alongside hydration product analysis using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The neutralization of LRM stabilized the pH between 7 and 8. Mortars containing neutralized red mud (NRM) and sulfuric-treated red mud (SRM) exhibited shorter initial setting times and similar final setting times compared to untreated red mud (LM). After one day, XRD confirmed the presence of Ca(OH)₂ in NRM and SRM but not in LM, while SEM revealed reduced pore sizes in NRM and SRM. Depending on dosage, the compressive strength of SRM increased by 35–60% compared to Plain mortar. These results demonstrate that LRM treated with nitric or sulfuric acid has significant potential as a setting accelerator for cement mortar. Full article

Background: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte–erythroid progenitors (MEPs) signature genes and constructed a prognostic model. Methods: Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between AML-MEP and normal MEP groups. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression selected biomarkers to build a risk model and nomogram for 1-, 3-, and 5-year survival prediction. Results: Ten differentially expressed genes (DEGs) related to overall survival (OS), six (AHSP, MYB, VCL, PIM1, CDK6, as well as SNHG3) were retained post-LASSO. The model exhibited excellent efficiency (the area under the curve values: 0.788, 0.77, and 0.847). Pseudotime analysis of UMAP-defined subpopulations revealed that MYB and CDK6 exert stage-specific regulatory effects during MEP differentiation, with MYB involved in early commitment and CDK6 in terminal maturation. Finally, although VCL, PIM1, CDK6, and SNHG3 showed significant associations with AML survival and prognosis, they failed to exhibit pathological differential expression in quantitative real-time polymerase chain reaction (qRT-PCR) experimental validations. In contrast, the downregulation of AHSP and upregulation of MYB in AML samples were consistently validated by both qRT-PCR and Western blotting, showing the consistency between the transcriptional level changes and protein expression of these two genes (p < 0.05). Conclusions: In summary, the integration of single-cell/transcriptome analysis with targeted expression validation using clinical samples reveals that the combined AHSP-MYB signature effectively identifies high-risk MEP-AML patients, who may benefit from early intensive therapy or targeted interventions. Full article

Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy to treat IBD-related flares. Furthermore, antibiotics have been historically investigated for use as a bridge when initiating biologic therapy while waiting for peak biologic treatment effect to occur. This study investigated and compared the time to clinical response when treated with combination antibiotics, metronidazole monotherapy, or SOC therapy in pediatric patients with an active IBD flare. Methods: This study was a retrospective, Institution Review Board-approved, single-centered cohort study which included patients who were less than 18 years of age with a confirmed diagnosis of IBD who received conventional treatment alone or with either combination antibiotic therapy or metronidazole monotherapy to treat an active IBD flare between March 2013 and January 2024. Patients were excluded if they received antibiotic therapy to treat an active infection, had positive stool cultures or enteric pathogen polymerase chain reaction panel, or had colonic disease limited to the rectum. Results: Fifty-nine patients were included and divided into metronidazole monotherapy (n = 18), SOC therapy (n = 20), and combination antibiotics (n = 21). The primary outcome of days to clinical response was not significantly different across all groups; however, patients who received combination antibiotics achieved the fastest time to clinical response (median (IRQ))—4 days (1, 65), compared to 7.5 days (1, 119) for the SOC group and 9 days (2, 217) for the metronidazole group. Secondary outcomes of achievement of clinical response, remission, or failure were determined to be non-significant between all groups. Conclusions: There is no significant difference in time to clinical response, attaining clinical response or remission, or treatment failure rate for patients treated with combination antibiotics, metronidazole monotherapy, or SOC. However, results of this study suggest that the use of combination antibiotics plus SOC may lead to a faster time to clinical response and remission compared to SOC therapy alone. Further studies are warranted to elucidate the role of antimicrobial therapy in management of pediatric IBD. Full article

The Internet of Medical Things (IoMT) is revolutionizing healthcare by integrating smart diagnostic devices with cloud computing and real-time data analytics. The emergence of infectious diseases, including COVID-19, underscores the need for rapid and decentralized diagnostics to facilitate early intervention. Traditional centralized laboratory testing introduces delays, limiting timely medical responses. While point-of-care molecular diagnostic (POC-MD) systems offer an alternative, challenges remain in cost, accessibility, and network inefficiencies. This study proposes an IoMT-based architecture for fully automated POC-MD devices, leveraging WebSockets for optimized communication, enhancing microfluidic cartridge efficiency, and integrating a hardware-based emulator for real-time validation. The system incorporates DNA extraction and real-time polymerase chain reaction functionalities into modular, networked components, improving flexibility and scalability. Although the system itself has not yet undergone clinical validation, it builds upon the core cartridge and detection architecture of a previously validated cartridge-based platform for Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG). These pathogens were selected due to their global prevalence, high asymptomatic transmission rates, and clinical importance in reproductive health. In a previous clinical study involving 510 patient specimens, the system demonstrated high concordance with a commercial assay with limits of detection below 10 copies/μL, supporting the feasibility of this architecture for point-of-care molecular diagnostics. By addressing existing limitations, this system establishes a new standard for next-generation diagnostics, ensuring rapid, reliable, and accessible disease detection. Full article

Background/Objectives: This systematic review analyzed the epidemiologic and macro/microscopic features of manifestations of hypersensitivity reactions with oral and extra-oral involvement in orthodontic patients with fixed (FAs) or removable (RAs) appliances or clear aligners (CAs), and evaluated them based on patient and treatment characteristics to provide clinical recommendations. Methods: The study protocol followed the PRISMA guidelines and was registered on PROSPERO (CRD42024517942). Results: Thirty-one studies were qualitatively assessed and synthetized, involving 858 subjects (114 males and 714 females, 9–49 years old), of whom there were 86 with a history of allergy, and 743 wearing recorded appliances (FAs = 656, FAs and RAs = 81, intra- and extra-oral RAs = 3, CAs = 3), with a mean treatment duration of 21.5 months (6 weeks–40 months). Among 75 reports, 29 (38.67%), describing burning, gingival hyperplasia, erythema, and vesicles, had oral involvement, while 46 (61.33%) had skin, eye, and systemic involvement, with erythema, papules, conjunctival hyperemia, and vertigo. Positive allergy tests concomitant with the manifestations identified nickel 451 times, cobalt 6 times, titanium 5 times, and chromium 4 times. Management included antihistamines or corticosteroids and removing the offending materials, with treatment discontinuation/appliance substitution. Conclusions: Pre-treatment evaluations, including patient histories and allergy testing, are essential to identify potential allergens and select hypoallergenic materials like titanium or ceramic brackets; regular monitoring and early intervention during treatment are crucial to prevent severe outcomes. Full article

Excess-sulfate phosphogypsum slag cement (EPSC), offering the potential for large-scale phosphogypsum (PG) utilization, has drawn significant attention. However, its susceptibility to salt erosion in marine/saline environments remains unquantified, hindering engineering applications. This study, therefore, systematically investigates the effect of various salts (NaCl, MgCl₂, KCl, and Na₂SO₄) at different concentrations (0.5–1.5%) on the hydration mechanism and performance of EPSC using rheometry, strength tests, and microstructural characterization (XRD/SEM-EDS). The findings reveal that EPSC exhibits low initial yield stress and plastic viscosity, both of which increase over time. The addition of Na⁺, Cl⁻, and SO₄²⁻ ions promotes hydration and flocculent structure formation in the EPSC paste, thereby enhancing the yield stress and plastic viscosity. In contrast, Mg²⁺ and K⁺ ions inhibit the hydration reaction, although Mg²⁺ temporarily increases the plastic viscosity by forming Mg(OH)₂ during the initial stage of the reaction. Both Na₂SO₄ and NaCl improve mechanical properties when their concentrations are within the 0.5–1.0% range; however, excessive amounts (>1%) negatively impact these properties. Significantly, adding 0.5% NaCl significantly improves the mechanical properties of EPSC, achieving a 28-day compressive strength of 51.06 MPa—a 9.5% increase compared to the control group. XRD and SEM-EDX analyses reveal that NaCl enhances pore structure via Friedel’s salt formation, while Na₂SO₄ promotes the early nucleation of ettringite. However, excessive ettringite formation in the later stages of the hydration reaction due to Na₂SO₄ may negatively affect compressive strength due to the inherent abundance of SO₄²⁻ in the EPSC system. Therefore, attention should be paid to the effect of excessive SO₄²⁻ on the system. These results establish salt-type/dosage thresholds for EPSC design, enabling its rational use in coastal infrastructure where salt resistance is critical. Full article