Search Results (7,260)

To address the central cracking problem in continuous casting slabs of 38CrMoAl steel, high-temperature tensile tests were performed using a Gleeble-3800 thermal simulator to characterize the hot ductility of the steel within the temperature range of 600–1200 °C. The phase transformation behavior was computationally analyzed via the Thermo-Calc software, while the microstructure, fracture morphology, and precipitate characteristics were systematically investigated using a metallographic microscope (MM), a field-emission scanning electron microscope (FE-SEM), and transmission electron microscopy (TEM). Additionally, the effects of different holding times and cooling rates on the microstructure and precipitates of 38CrMoAl steel were also studied. The results show that the third brittle temperature region of 38CrMoAl steel is 645–1009 °C, and the fracture mechanisms can be classified into three types: (I) in the α single-phase region, the thickness of intergranular proeutectoid ferrite increases with rising temperature, leading to reduced hot ductility; (II) in the γ single-phase region, the average size of precipitates increases while the number density decreases with increasing temperature, thereby improving hot ductility; and (III) in the α + γ two-phase region, the precipitation of proeutectoid ferrite promotes crack propagation and the dense distribution of precipitates at grain boundaries causes stress concentration, further deteriorating hot ductility. Heat treatment experiments indicate that the microstructures of the specimen transformed under water cooling, air cooling, and furnace cooling conditions as follows: martensite + proeutectoid ferrite → bainite + ferrite → ferrite. The average size of precipitates first decreased, then increased, and finally decreased again with increasing holding time, while the number density exhibited the opposite trend. Therefore, when the holding time was the same, reducing the cooling rate could increase the average size of the precipitates and decrease their number density, thereby improving the hot ductility of 38CrMoAl steel. Full article

This study investigated the effects of color shade and curing time on the degree of conversion (DC) and microhardness of colored compomers. A total of 162 samples (81 for DC, 81 for microhardness) were prepared, with nine samples per color group (gold, blackberry, green, pink, orange, lemon, blue, silver) and for the control. Samples were subdivided into three polymerization subgroups (3 s/3200 mW/cm², 10 s/1000 mW/cm², 20 s/1000 mW/cm²). The DC was analyzed via fourier transform infrared spectroscopy (FTIR) and microhardness was measured using Vickers testing. Statistical analysis included two-way ANOVA and Spearman correlation (α = 0.05). The colored compomers demonstrated a significantly lower DC compared to the control group (p ≤ 0.001). Among the tested colors, green exhibited the lowest DC (33.3%), while orange showed the highest (51.0%). A significant difference in DC was observed across curing times (p = 0.005), with the 3 s and 20 s groups exhibiting significantly higher conversion rates than the 10 s group. Microhardness values exhibited significant variation depending on the color (p < 0.001). Gold compomers demonstrated the lowest microhardness, whereas silver compomers showed comparable performance with the control group (p = 0.154). A moderate correlation between DC and microhardness was observed overall (ρ = 0.42, p = 0.003). However, the observed relationships were color-dependent: orange displayed a strong positive correlation (ρ = 0.78), whereas pink revealed no meaningful association (ρ = −0.15). Color and curing time critically influence compomer performance. High-intensity short curing is viable for lighter colors, while darker colors require extended curing. Customized protocols are essential to optimize clinical outcomes in pediatric dentistry. Full article

Background/Objectives: In-office bleaching commonly employs high concentrations of hydrogen peroxide (HP) or carbamide peroxide (CP), which may compromise enamel integrity. This in vitro paired-design study aimed to compare the chemical and mechanical effects of three commercial bleaching agents—Opalescence Boost (40% HP), Opalescence Quick (45% CP), and BlancOne Ultra+ (35% HP)—on human enamel. The null hypothesis assumed no significant differences between the control and treated samples. Given the ongoing debate over pH, active ingredients, and enamel impact, comparing whitening systems remains clinically important. Methods: Forty-two extracted teeth were assigned to three experimental groups (n = 14) with matched controls. Each underwent a single bleaching session per manufacturer protocol: Opalescence Boost (≤60 min), Opalescence Quick (15–30 min), and BlancOne Ultra+ (three light-activated cycles of 8–10 min). Enamel chemical changes were analyzed by Fourier transform infrared (FTIR) spectroscopy (phosphate and carbonate bands), and surface hardness by Vickers microhardness testing. Paired t-tests (α = 0.05) assessed statistical significance. Results: FTIR analysis revealed alterations in phosphate and carbonate bands for all agents, most notably for Opalescence Boost and BlancOne Ultra+. Microhardness testing showed significant reductions in enamel hardness for Opalescence Boost (control: 37.21 ± 1.74 Hv; treated: 34.63 ± 1.70 Hv; p = 0.00) and Opalescence Quick (control: 45.82 ± 1.71 Hv; treated: 39.34 ± 1.94 Hv; p < 0.0001), whereas BlancOne Ultra+ showed no significant difference (control: 51.64 ± 1.59 HV; treated: 51.60 ± 2.34 Hv; p = 0.95). Conclusions: HP-based agents, particularly at higher concentrations, caused greater enamel alterations than CP-based products. While clinically relevant, the results should be interpreted cautiously due to in vitro limitations and natural enamel variability. Full article

Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article

The growing demand for food and the environmental impact of conventional agriculture have prompted the search for sustainable alternatives. Phycocyanin (PC) and total phenolic compounds (TPC) extracted from Spirulina platensis have shown potential for the biological control of phytopathogens. The extraction method directly influences the yield and stability of these compounds. This study aimed to establish an efficient extraction protocol for PC and TPC and to evaluate their antimicrobial efficacy in vitro against Colletotrichum orchidearum, Fusarium nirenbergiae, and Alternaria sp. isolated from hydroponically grown lettuce. The phytopathogens were identified based on phylogenetic analyses using sequences from the ITS, EF1-α, GAPDH, and RPB2 gene regions. This is the first report of C. orchidearum in hydroponic lettuce culture in Brazil, expanding its known host range. Extracts were obtained using hydroalcoholic solvents and phosphate buffer (PB), combined with ultrasound-assisted extraction (bath and probe). The extracts were tested for in vitro antifungal activity. Data were analyzed by ANOVA (p < 0.05), followed by Tukey’s test. The combination of the PB and ultrasound probe resulted in the highest PC (95.6 mg·g⁻¹ biomass) and TPC (21.9 mg GAE·g⁻¹) yields, using 10% (w/v) biomass. After UV sterilization, the extract retained its PC and TPC content. The extract inhibited C. orchidearum by up to 53.52% after three days and F. nirenbergiae by 54.17% on the first day. However, it promoted the growth of Alternaria sp. These findings indicate that S. platensis extracts are a promising alternative for the biological control of C. orchidearum and F. nirenbergiae in hydroponic systems. Full article

Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS^•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article

Background/Objectives: The quality of clinical studies is largely determined by the bioanalytical methods used for testing study samples. Rigorous assay validation following defined criteria, for example, the European Medicines Agency guideline for bioanalytical method validation, is a prerequisite for such assays. Alpha1-antitrypsin (AAT) measurement, i.e., the specific measurement of AAT protein and its associated elastase-inhibitory activity, is an integral part of assay panels for clinical studies addressing AAT deficiency. Specifically, AAT must be measured in the matrix of citrated human plasma as well as in diluted solutions with high salt concentrations obtained through bronchoalveolar lavage (BAL). Sensitive and selective measurement methods are required, as BAL has a low level of AAT. Methods: We present the validation data obtained for three AAT measurement methods. Two of them, nephelometry and the enzyme-linked immunosorbent assay, which clearly differ in their sensitivity, provide AAT protein concentrations. The third is the highly sensitive, newly developed elastase complex formation immunosorbent assay that specifically measures the inhibitory activity of AAT against its pivotal target, protease neutrophil elastase. Using samples with relevant AAT concentrations, we addressed the assays’ characteristics: accuracy, precision, linearity, selectivity, specificity, limit of quantification and short-term analyte stability Results: Overall, the three methods demonstrated low total errors, a combined measure reflecting accuracy and precision, even at low analyte concentrations of less than 0.5 µg/mL; adequate linearity over the required assay range; and acceptable selectivity and specificity. Furthermore, the short-time stability of the analyte was also demonstrated. Conclusions: All three AAT measurement methods met the acceptance criteria defined by the guidelines on bioanalytical assay validation, qualifying these methods for clinical sample analysis. Full article

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

Despite cognitive workload (CW) being a critical metric in several applications, no technology exists to seamlessly and reliably quantify CW. Previously, we demonstrated the feasibility of a wearable MagnetoCardioGraphy (MCG) sensor to classify high vs. low CW based on MCG-derived heart rate variability (mHRV). However, our sensor was unable to address certain critical operational requirements, resulting in noisy signals, often to the point of being unusable. In addition, test conditions for the participants were not decoupled from motion (i.e., physical activity (PA)), raising questions as to whether the noted changes in mHRV were attributed to CW, PA, or both. This study reports software and hardware advancements to optimize the MCG data quality, and investigates whether changes in CW (in the absence of PA) can be reliably detected. Performance is validated for healthy adults (n = 10) performing three types of CW tasks (one for low CW and two for high CW to eliminate the memory effect). Results demonstrate the ability to retrieve MCG R-peaks throughout the recordings, as well as the ability to differentiate high vs. low CW in all cases, confirming that CW does modulate the mHRV. A paired Bonferroni t-test with significance $\alpha =0.01$ confirms the hypothesis that an increase in CW decreases mHRV. Our findings lay the groundwork toward a seamless, practical, and low-cost sensor for monitoring CW. Full article

Background/Objectives: Maxillofacial silicone prostheses’ long-term color stability remains a challenge. This study aimed to evaluate and compare the color stability of conventional and digital maxillofacial silicone elastomers mixed with nano-sized antimicrobial additives (ZnO nanoparticles and chlorhexidine salt-CHX) at various concentrations over a 10-week period. Methods: A total of nine groups (n = 10) of maxillofacial silicone elastomers were prepared. These included a control group (no additives), conventionally pigmented silicone, digitally pigmented silicone (Spectromatch system), and silicone mixed with ZnO or CHX at 1%, 3%, and 5% by weight. Specimens were fabricated in steel molds and cured at 100 °C for 1 h. Color measurements were performed at baseline and after 1, 4, 6, and 10 weeks using a Minolta Chroma Meter (CIELAB system, ΔE₀₀ formula). Data were analyzed using two-way ANOVA and Tukey HSD post hoc tests (α = 0.05). Results: Color changes (ΔE₀₀) ranged from 0.74 to 2.83 across all groups. The conventional pigmented silicone group showed the highest color difference (ΔE₀₀ = 2.83), while the lowest was observed in the ZnO 1% group (ΔE₀₀ = 0.74). Digital silicone and all antimicrobial-modified groups exhibited acceptable color stability (ΔE₀₀ < 3.1). Time significantly affected color difference, with the largest change occurring during the first four weeks (p < 0.05), followed by stabilization. Regression analysis confirmed high color stability over time for all groups except the conventional pigmented group. Conclusions: This is one of the first studies to directly compare digital and conventional pigmentation methods combined with nano-antimicrobials in maxillofacial silicones. Maxillofacial silicone elastomers mixed with up to 5% ZnO or CHX maintained acceptable color stability over 10 weeks. Digital pigmentation is similar to conventional methods. The incorporation of nano-antimicrobials offers significant microbial resistance and improved color retention. Full article

Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article

We report an investigation on the cobalt(II) chelation mechanism by a modified α-maltoside ligand 9 decorated with two iminodiacetate (IDA) residues on C6,C6′ positions. Herein we uncovered the capacity of this biodegradable ligand to chelate cobalt(II), an ionic metal contaminant in the environment that is used, in particular, in lithium-ion batteries. The interactions between cobalt(II) and synthesized ligand 9 were systematically studied using different analytical methods such as ¹H and ¹³C NMR, potentiometry, spectrophotometry, ITC, and ICP-AES. We observed a high affinity for the 1:1 complex, one cobalt(II) associated with two iminodiacetate groups, which is 10-fold higher than the 2:1 complex, where each of the two IDA groups interacts alone with a cobalt(II). Taking into account the log β_CoL value obtained (≈12.3) with the stoichiometry 1:1, the strength of this complexation with cobalt(II) can be ranked as follows for the most common ligands: IDA < MIDA < NTA < 9 < EDTA < TTHA < DTPA. We further completed a preliminary remediation test with water contaminated with cobalt(II) and recovered cobalt(II) metal using Chelex^® resin, which allowed a recycling of the synthetic ligand for future recovering experiments. The results shed light on the great potential of using this synthetic ligand as an effective and green remediation tool. Full article

Background/Objectives: Phase II oncology trials often rely on single-arm designs to test $H_0:\pi ={\pi }_0$ versus $H_a:\pi >{\pi }_0$, especially when randomized trials are infeasible due to cost or disease rarity. Traditional approaches, such as the exact binomial test and Simon’s two-stage design, tend to be conservative, with actual Type I error rates falling below the nominal $\alpha$ due to the discreteness of the underlying binomial distribution. This study aims to develop a more efficient and flexible method that maintains accurate Type I error control in such settings. Methods: We propose a convolution-based method that combines the binomial distribution with a simulated normal variable to construct an unbiased estimator of $\pi$. This method is designed to precisely control the Type I error rate while enabling more efficient trial designs. We derive its theoretical properties and assess its performance against traditional exact tests in both one-stage and two-stage trial designs. Results: The proposed method results in more efficient designs with reduced sample sizes compared to standard approaches, without compromising the control of Type I error rates. We introduce a new two-stage design incorporating interim futility analysis and compare it with Simon’s design. Simulations and real-world examples demonstrate that the proposed approach can significantly lower trial cost and duration. Conclusions: This convolution-based approach offers a flexible and efficient alternative to traditional methods for early-phase oncology trial design. It addresses the conservativeness of existing designs and provides practical benefits in terms of resource use and study timelines. Full article

Many vertebrates have evolved resistance to snake venom as a result of coevolutionary chemical arms races. In Australian skinks (family Scincidae), who often encounter venomous elapid snakes, the frequency, diversity, and molecular basis of venom resistance have been unexplored. This study investigated the evolution of neurotoxin resistance in Australian skinks, focusing on mutations in the muscle nicotinic acetylcholine receptor (nAChR) α1 subunit’s orthosteric site that prevent pathophysiological binding by α-neurotoxins. We sampled a broad taxonomic range of Australian skinks and sequenced the nAChR α1 subunit gene. Key resistance-conferring mutations at the toxin-binding site (N-glycosylation motifs, proline substitutions, arginine insertions, changes in the electrochemical state of the receptor, and novel cysteines) were identified and mapped onto the skink organismal phylogeny. Comparisons with other venom-resistant taxa (amphibians, mammals, and reptiles) were performed, and structural modelling and binding assays were used to evaluate the impact of these mutations. Multiple independent origins of α-neurotoxin resistance were found across diverse skink lineages. Thirteen lineages evolved at least one resistance motif and twelve additional motifs evolved within these lineages, for a total of twenty-five times of α-neurotoxic venoms resistance. These changes sterically or electrostatically inhibit neurotoxin binding. Convergent mutations at the orthosteric site include the introduction of N-linked glycosylation sites previously known from animals as diverse as cobras and mongooses. However, an arginine (R) substitution at position 187 was also shown to have evolved on multiple occasions in Australian skinks, a modification previously shown to be responsible for the Honey Badger’s iconic resistance to cobra venom. Functional testing confirmed this mode of resistance in skinks. Our findings reveal that venom resistance has evolved extensively and convergently in Australian skinks through repeated molecular adaptations of the nAChR in response to the enormous selection pressure exerted by elapid snakes subsequent to their arrival and continent-wide dispersal in Australia. These toxicological findings highlight a remarkable example of convergent evolution across vertebrates and provide insight into the adaptive significance of toxin resistance in snake–lizard ecological interactions. Full article

Objective: To evaluate the concordance of automated 3D superimposition methods applied to digital models, with a focus on methods that consider stable palatal regions as geometric reference landmarks versus those that do not. Design and setting: This was a prospective, cross-sectional study using digital model files of patients undergoing orthodontic treatment in a university clinical setting. Participants: Sixty-one patients were prospectively enrolled and divided into three groups based on the type of orthodontic treatment they received: (20) non-extractive orthodontic treatment without intermaxillary elastics, (21) intermaxillary elastics, and (20) control subjects with no orthodontic movement. The inclusion criteria included the availability of complete pre- and post-treatment digital casts and the absence of significant craniofacial anomalies. Methods: Three superimposition methods were tested: (1) superimposition according to palate and palatal ridges, (2) best-fit superimposition of arches in occlusion, and (3) best-fit superimposition of individual arches. Discrepancies were identified by comparing the spatial positions derived from each method. Within three spatial axes, deviations of ±0.5 mm and ±1.15° were not considered significant. Bland–Altman plots were used to quantify palatal rugae based and non-based spatial differences between methods. Differences in the superimposition results between the three patient groups were evaluated using ANOVA tests. Results: Differences in spatial position between the superimposition methods often exceeded the acceptable range. The results were compared between the three patient groups with a statistical significance of α = 0.05. In the present study, the high reliability of the superimposition method based on the palate and palatal ridges was observed. Conclusion: Superimposition methods based on the palate and palatal rugae provide superior accuracy in determining treatment-related changes in upper arch digital models. These findings illustrate the need for appropriate selection of superimposition techniques based on the study objective of using clinically relevant techniques. Full article