Search Results (160)

Background: Cardiomyocyte death is a key factor in myocardial ischemia–reperfusion injury (MI/RI), and the expression patterns and molecular mechanisms of pyroptosis-related genes (PRGs) in ischemia–reperfusion injury are poorly understood. Methods: The mouse MI/RI injury-related datasets GSE61592 and GSE160516 were obtained from the Gene Expression Omnibus database, and differential expression analysis was performed on each to identify differentially expressed genes (DEGs). The DEGs were intersected with the PRGs obtained from GeneCards to identify differentially expressed PRGs in MI/RI. Enrichment analysis identified key pathways, while PPI network analysis revealed hub genes. The expression patterns and immune cell infiltration of hub genes were also investigated. The molecular docking prediction of key genes was performed using MOE software in conjunction with the ZINC small molecular compounds database. Key gene expression was validated in an external dataset (GSE4105), a mouse MI/RI model, and an HL-1 cell hypoxia/reoxygenation model via RT-qPCR. Results: A total of 29 differentially expressed PRGs were identified, which are primarily associated with pathways such as “immune system process”, “response to stress”, “identical protein binding”, and “extracellular region”. Seven key genes (Fkbp10, Apoe, Col1a2, Ppic, Tlr2, Fstl1, Serpinh1) were screened, all strongly correlated with immune infiltration. Seven FDA-approved small molecule compounds exhibiting the highest docking potential with each key gene were selected based on a comprehensive evaluation of S-scores and hydrogen bond binding energies. Apoe, Tlr2, and Serpinh1 were successfully validated across external datasets, the mouse MI/RI model, and the cardiomyocyte H/R model. Conclusions: Apoe, Tlr2, and Serpinh1 may be key genes involved in MI/RI-related pyroptosis. Targeting these genes may provide new insights into the treatment of MI/RI. Full article

Background/Objectives: A newly developed nine-protein serum signature has been utilized to enhance the accuracy of an existing three-protein signature used as a blood-based diagnostic tool. This study used the new nine-protein serum signature to evaluate the clinical sensitivity and specificity of a medical device designed to test the clinical performance of an artificial intelligence algorithm. Methods: A blood-based test using multiple reaction monitoring via mass spectrometry was performed to quantify nine proteins (APOC1, CHL1, FN1, VWF, PPBP, CLU, PRDX6, PRG4, and MMP9) in serum samples from 243 healthy controls and 222 patients with breast cancer. Results: Based on cutoff values determined by an artificial intelligence-based deep learning model, the sensitivity and specificity of the nine-protein signature in diagnosing breast cancer among all participants was 83.3% and 88.1%, respectively, whereas those of the three-protein signature were 71.6% and 85.3%, respectively. The assay yielded a positive predictive value of 86.5% for breast cancer and 13.6% for healthy controls, with corresponding negative predictive values of 14.7% and 85.3%, respectively. The accuracies of nine- and three-protein signatures were 85.8% (area under the receiver operating characteristic curve: 0.8526) and 77.0%, respectively. Conclusions: The nine-protein signature may help detect breast cancer more accurately and effectively than the three-protein signature. Full article

This study evaluated a light-cure orthodontic adhesive with the incorporation of bioactive glass particles and its effects on shear bond strength (SBS), adhesive remnant index (ARI), degree of conversion (DC), calcium release, and particle size distribution. Bioactive glass was added to the Transbond XT Adhesive (3M ESPE), resulting in five groups: TXT (0% wt of bioactive glass-incorporated—negative control); TXT20 (20% wt of bioactive glass-incorporated); TXT30 (30% wt of bioactive glass-incorporated), TXT50 (50% wt of bioactive glass-incorporated), and FLB (positive control—FL BOND II adhesive system with S-PRG particles, SHOFU Inc.). Data were analyzed with one-way ANOVA followed by Tukey’s test (α = 0.05). Quantitative SEM analysis confirmed submicron particle agglomerates (median equivalent circular diameter 0.020–0.108 µm). The TXT20 exhibited the highest values of degree of conversion (p < 0.05) (73.02 ± 3.33A). For SBS (in MPa): Control Group TXT—19.50 ± 1.40A, Group TXT20 18.22 ± 1.04AB, Group FLB 17.62 ± 1.45B, Group TXT30 14.48 ± 1.46C and Group TXT50 14.13 ± 1.02C (p < 0.05). For calcium release the group TXT50 2.23 ± 0.11D showed higher values (p < 0.05). The incorporation of distinct bioactive glass particle concentrations influenced the shear bond strength, degree of conversion, and calcium release. While the 50 wt% bioactive glass group exhibited the highest calcium release, both 20 wt% of bioactive glass group and the positive control group exhibited the highest degree of conversion without compromising the bonding strength. Full article

Osteoarthritis (OA) is the most common joint disorder worldwide. Autologous chondrocyte implantation (ACI) is an established treatment for articular cartilage defects of the knee, but its effectiveness in OA is still under investigation. In this study, we investigated the effects of a newly developed mammalian-derived collagen matrix, NC-Col, on the proliferation, migration, adhesion, and gene expression of human articular cartilage-derived chondrocytes from OA patients in vitro, using proliferation assays, wound healing assays, adhesion assays, RT-qPCR, and RNA sequencing, respectively. In addition, the effects of NC-Col were compared with three different commercially available collagen matrices, and the underlying molecular mechanisms through which NC-Col influences these cellular behaviours were explored. Our results showed that NC-Col, used as a coating matrix, enhances cell proliferation, maintains the phenotype, and upregulates Proteoglycan 4 (PRG4) in human articular cartilage-derived chondrocytes. Inhibition of the PI3K-Akt signalling pathway was found to be involved in some of these effects. In conclusion, our findings suggest that NC-Col collagen may offer new strategies for improving therapeutic outcomes in OA, particularly in the context of ACI. Full article

Kentucky bluegrass (KBG) is well-suited as a perennial groundcover in corn production due to its vigorous growth during the fall and spring and its natural dormancy during the summer, aligning with the corn growing season. However, seeds of KBG germinate slowly, potentially resulting in poor stand establishment in the Midwest, USA. This study was conducted to assess the effect of the seeding rate, the seed ratio in a perennial ryegrass/KBG mixture (PRG:KBG), and seed treatment on KBG percentage groundcover, green rating, the red/far-red ratio, soil temperature, soil moisture, and summer biomass. The split-plot design consisted of KBG seeds treated with the Hydroloc^TM hydrophilic polymer and untreated seeds with seeding rates and ratios in a randomized design. Hydroloc™ seed treatment showed a significant difference in the fall percentage of groundcover but did not affect the spring groundcover. The seed ratio had a significant effect on the fall and spring groundcover, with a ratio of 1:1 (PRG:KBG) performing best, followed by 1:3, 1:5, and 0:1. The seeding rate was also significant, with 44.8 kg ha⁻¹ having the highest groundcover, followed by 22.4 kg ha⁻¹ and 11.2 kg ha⁻¹. The red/far-red readings, which reflect plant density, gave corresponding results to the percentage of groundcover. The Hydroloc™ hydrophilic polymer increases the groundcover percentage by improving KBG establishment. These results are important for farmers and seed companies interested in using KBG as a perennial groundcover in corn production systems. We recommend a seed ratio of 1:1 (PRG:KBG) and a seeding rate of 22.4 kg ha⁻¹ to provide a dense and rapid-establishing groundcover that is also financially viable for the farmer. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

This retrospective study aimed to evaluate the prevalence, morphological types, and distribution patterns of palatoradicular grooves (PRGs) in maxillary anterior teeth using cone-beam computed tomography (CBCT) in a Turkish population. CBCT images of 1553 patients from the radiology archive of Ordu University Faculty of Dentistry (2021–2022) were reviewed. A total of 920 patients (4012 teeth) met the inclusion criteria. The presence, type, and localization of PRGs were assessed. Groove types were classified as Type 1, 2, 3A, or 3B; localization was recorded as mesial, distal, or midpalatal. Bilateral and unilateral occurrences were also analyzed. Statistical analysis involved chi-square tests, Tukey’s HSD, and Cohen’s kappa for intra-observer reliability. PRGs were detected in 23.6% of patients and 10.42% of teeth. Lateral incisors were most affected (87.56%). Type 1 grooves were most common (71.53%), with midpalatal localization being most frequent (54.07%). Bilateral grooves were significantly more prevalent than unilateral ones (p < 0.001). No significant association was found between groove type and tooth type or between gender and bilaterality. This study revealed a high prevalence of PRGs, especially in maxillary lateral incisors, with a significant tendency toward bilateral and midpalatal presentation. CBCT proved essential for detecting palatoradicular grooves, aiding diagnosis and treatment. Full article

Objectives: This study aimed to investigate the impact of platelet-rich plasma (PRP) and platelet-rich gel (PRG) on tympanic membrane closure rates, hearing improvement, and quality of life following tympanoplasty. Methods: Seventy-two patients with chronic tympanic membrane perforations were enrolled in a double-blinded, randomized controlled trial at a single tertiary referral center. All patients underwent tympanoplasty using a temporalis fascia graft and were randomly assigned to one of two groups: one group received standard tympanoplasty alone, while the other received intraoperative application of autologous PRP and PRG, in addition to the standard procedure. Results: The PRP group demonstrated a significantly higher rate of complete tympanic membrane closure compared to the control group (32/36; 88.9% vs. 24/36; 66.7%; p < 0.05). Bone conduction hearing remained unchanged in both groups, while air conduction hearing improved significantly from pre- to post-treatment in each group. However, the difference in air conduction improvement between the PRP group and the control group was not statistically significant (PRP group: Mdn = −8.25; control group: Mdn = −12.20; U = 618; z = −0.54; p = 0.30). Quality of life improved in both the PRP and control groups; however, the difference between the groups was not statistically significant (PRP group: 10.44 ± 10.46; control group: 10.47 ± 8.22; 95% CI [−4.45; 4.40]; t(66) = −0.01; p = 0.16). Conclusions: Our findings suggest that intraoperative application of autologous PRP and PRG may improve tympanoplasty outcomes, particularly in cases with lower expected success rates or when performing minimally invasive transcanal procedures under local anesthesia. However, variability in PRP preparation, application methods, and graft materials across studies limits direct comparisons. Standardized protocols and further controlled studies are necessary to clarify PRP’s clinical value in tympanoplasty. Full article

Yaks are an important livestock species on the Tibetan Plateau, but traditional grazing practices cause a sharp drop in their weight during winter, leading to grassland degradation due to overgrazing. Although off-site fattening can improve performance and protect ecology, it often leads to a negative energy balance, liver metabolism disorders, and immune impairment due to stress. However, the effects of rumen-protected glucose (RPG) and rumen-protected taurine (RPT) on yak liver health are not yet clear. The purpose of this study was to evaluate the effects of dietary RPG and RPT levels on the growth performance, serum biochemical parameters, liver antioxidant capacity, and immunity of yaks. Twenty-eight healthy yaks weighing 170 ± 10.4 kg were randomly divided into four treatments: LGLT (RPG: 1%—low RPG [LG]; RPT: 5 g/d—low RPT [LT]), LGHT (RPG: 1%—low RPG [LG]; RPT: 20 g/d—high RPT [HT]), HGLT (RPG: 3%—high RPG [HG]; RPT: 5 g/d—low RPT [LT]), and HGHT (RPG: 3%—high RPG [HG]; RPT: 20 g/d—high RPT [HT]). The results showed that compared with the LTHT treatment group, the HGHT group upregulated the serum concentrations of glucose (p = 0.004) and Interleukin-10 (p = 0.03), the relative mRNA expression of small heterodimer partners (p = 0.01), and the sterol 12-alpha-hydroxylase (p < 0.001), while reducing the serum concentration of gamma-glutamyl transferase (p = 0.048). The serum concentration of hepatic protein carbonyl (p = 0.005) and malondialdehyde (p = 0.03) was lower in the LGHT and HGHT treatment groups than in the LGLT and HGLT groups. The relative mRNA expression of Toll-like receptor 4 (p = 0.02), Interleukin-8 (p < 0.01), and Interleukin-1β (p < 0.01) was lower in the LGHT and HGHT groups than in the LGLT and HGLT groups. Tumor necrosis factor expression was lower (p = 0.04) and glucose transporter 2 expression was higher (p < 0.01) in the HGHT group compared to other treatment groups. The expression of glucokinase, glycogen synthase, pyruvate kinase, and farnesoid X receptor was higher in the HGLT treatment group than in other treatments (p < 0.01). In conclusion, dietary supplementation with 3% PRG and 5 g/d PRT can enhance liver antioxidant capacity and immune function, reduce lipid peroxidation, and promote glucose and bile acid metabolism in yaks. Full article

Breast cancer (BRCA) continues to pose a serious risk to women’s health worldwide. Neoadjuvant chemotherapy (NAC) is a critical treatment strategy. Nevertheless, the heterogeneity in treatment outcomes necessitates the identification of reliable biomarkers and prognostic models. Programmed cell death (PCD) pathways serve as a critical factor in tumor development and treatment response. However, the relationship between the diverse patterns of PCD and NAC in BRCA remains unclear. We integrated machine learning and multiple bioinformatics tools to explore the association between 19 PCD patterns and the prognosis of NAC within a cohort of 921 BRCA patients treated with NAC from seven multicenter cohorts. A prognostic risk model based on PCD-related genes (PRGs) was constructed and evaluated using a combination of 117 machine learning algorithms. Immune infiltration analysis, mutation analysis, pharmacological analysis, and single-cell RNA sequencing (scRNA-seq) were conducted to explore the genomic profile and clinical significance of these model genes in BRCA. Immunohistochemistry (IHC) was employed to validate the expression of select model genes (UGCG, BTG22, TNFRSF21, and MYB) in BRCA tissues. We constructed a PRGs prognostic risk model by using a signature comprising 20 PCD-related DEGs to forecast the clinical outcomes of NAC in BRCA patients. The prognostic model demonstrated excellent predictive accuracy, with a high concordance index (C-index) of 0.772, and was validated across multiple independent datasets. Our results demonstrated a strong association between the developed model and the survival prognosis, clinical pathological features, immune infiltration, tumor microenvironment (TME), gene mutations, and drug sensitivity of NAC for BRCA patients. Moreover, IHC studies further demonstrated that the expression of certain model genes in BRCA tissues was significantly associated with the efficacy of NAC and emerged as an autonomous predictor of outcomes influencing the outcome of patients. We are the first to integrate machine learning and bulk and scRNA-seq to decode various cell death mechanisms for the prognosis of NAC in BRCA. The developed unique prognostic model, based on PRGs, provides a novel and comprehensive strategy for predicting the NAC outcomes of BRCA patients. This model not only aids in understanding the mechanisms underlying NAC efficacy but also offers insights into personalized treatment strategies, potentially improving patient outcomes. Full article

We present three progressively refined pseudorandom function (PRF) constructions based on the learning Burnside homomorphisms with noise ($B_n$-LHN) assumption. A key challenge in this approach is error management, which we address by extracting errors from the secret key. Our first design, a direct pseudorandom generator (PRG), leverages the lower entropy of the error set (E) compared to the Burnside group ($B_r$). The second, a parameterized PRG, derives its function description from public parameters and the secret key, aligning with the relaxed PRG requirements in the Goldreich–Goldwasser–Micali (GGM) PRF construction. The final indexed PRG introduces public parameters and an index to refine efficiency. To optimize computations in Burnside groups, we enhance concatenation operations and homomorphisms from $B_n$ to $B_r$ for $n\gg r$. Additionally, we explore algorithmic improvements and parallel computation strategies to improve efficiency. Full article

Background/Objectives: This double-blinded study aimed to evaluate the clinical performance of a giomer restorative material in comparison to a nanotechnology-based restorative system for the restoration of non-carious cervical lesions over a period of 48 months. Methods: A 48-month randomized, controlled, split-mouth trial was conducted with 49 subjects at its baseline, which was reduced to 34 subjects at follow-up, yielding a statistical power of 69.55%. Cervical lesions were restored using either BEAUTIFIL II LS (BL) or 3M/ESPE Filtek Supreme Universal Restorative (FS). Clinical assessments were performed by blinded examiners, excluding the one who placed the restorations. Evaluations were based on the Hickel criteria, covering esthetic, functional, and biological properties, with comparisons made using the Wilcoxon signed-rank test. Results: Hickel scores were analyzed with the Mann–Whitney U test to compare BL and FS groups within subjects. Changes in median Hickel scores, sensitivity, and the gingival index were assessed via Friedman’s test, followed by Wilcoxon signed-rank tests with a Bonferroni correction for post-hoc comparisons. The p-values under 0.05 were considered significant, except with the Bonferroni correction. Statistical analysis showed no significant differences between materials across most Hickel parameters (p > 0.05), though BL exhibited a trend of better surface staining (76.5% excellent with BL vs. 76.5% excellent with FS) and adjacent mucosa, while FS showed slight advantages in surface luster and color match. Conclusions: The clinical evaluation of restorations for non-carious cervical lesions using giomer and nanotechnology-based restorative systems revealed no statistically significant differences according to the Hickel criteria, indicating a similar clinical performance for both restorative materials. Full article

Remediation of formerly used war zones requires knowledge of the depth of burial (DoB) of unexploded ordnances (UXOs). The DoB can vary greatly depending on soil and ballistic conditions, and their associated uncertainties. In this study, the well-known physics-based Poncelet equation is used to set a framework for stochastic prediction of the DoB of munitions in sandy, clayey sand, and clayey sediments using Monte Carlo simulations (MCSs). First, the coefficients of variation (COVs) of the empirical parameters affecting the model were computed, for the first time, from published experimental data. Second, the behavior of both normal and lognormal distributions was investigated and it was found that both distributions yielded comparable DoB predictions for COVs below 30%. However, a lognormal distribution was preferred, to avoid negative value sampling, since COVs of the studied parameters can easily exceed this threshold. Third, the performance of several MCS sampling techniques, including the Pseudorandom Generator (PRG), Latin Hypercube Sampling (LHS), and Gaussian Process Response Surface Method (GP_RSM), in predicting the DOB was explored. Different probabilistic sampling techniques produced similar DoB predictions for each soil type, but GP_RSM was the most computationally efficient method. Finally, a sensitivity analysis was conducted to determine the contribution of each random variable to the predicted DoB. Uncertainty of the density, drag coefficient, and bearing coefficient dominated the DoB in sandy soil, while uncertainty in the bearing coefficient controlled DoB in clayey sand soils. In clayey soil, all variables under various distribution conditions resulted in approximately identical predictions, with no single variable appearing to be dominant. It is recommended that Monte Carlo simulations using GP_RSM sampling from lognormally distributed effective variables be used for predicting DoB in soils with high COVs. Full article

Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cartilage degeneration. Beyond its lubricating properties, PRG4 exerts anti-inflammatory effects by interacting with Toll-like receptors, modulating inflammatory responses within the joint. The expression of Prg4 is regulated by various factors, including mechanical stimuli, inflammatory cytokines, transcription factors such as Creb5 and FoxO, and signaling pathways like TGF-β, EGFR, and Wnt/β-catenin. Therapeutic strategies targeting PRG4 in OA have shown promising results, including recombinant PRG4 protein injections, gene therapies, and small molecules that enhance endogenous Prg4 expression or mimic its function. Further research into the molecular mechanisms regulating Prg4 expression will be essential in developing more effective OA treatments. Understanding the interplay between Prg4 and other signaling pathways could reveal novel therapeutic targets. Additionally, advancements in gene therapy and biomaterials designed to deliver PRG4 in a controlled manner may hold potential for the long-term management of OA, improving patient outcomes and delaying disease progression. Full article

As an important kind of DNN (deep neural network), CNN (convolutional neural network) has made remarkable progress and been widely used in the vision and decision-making of autonomous robots. Nonetheless, in many scenarios, even a minor perturbation in input for CNNs may lead to serious errors, which means CNNs lack robustness. Formal verification is an effective method to guarantee the robustness of CNNs. Existing works predominantly concentrate on local robustness verification, which requires considerable time and space. Probabilistic robustness quantifies the robustness of CNNs, which is a practical mode of potential measurement. The state-of-the-art of probabilistic robustness verification is a test-driven approach, which is used to manually decide whether a DNN satisfies the probabilistic robustness and does not involve robustness repair. Robustness repair can improve the robustness of CNNs further. To address this issue, we propose a probabilistic model checking-driven robustness guarantee framework for CNNs, i.e., PRG4CNN. This is the first automated and complete framework for guaranteeing the probabilistic robustness of CNNs. It comprises four steps, as follows: (1) modeling a CNN as an MDP (Markov decision processes) by model learning, (2) specifying the probabilistic robustness of the CNN via the PCTL (Probabilistic Computational Tree Logic) formula, (3) verifying the probabilistic robustness with a probabilistic model checker, and (4) probabilistic robustness repair by counterexample-guided sensitivity analysis, if probabilistic robustness does not hold on the CNN. We here conduct experiments on various scales of CNNs trained on the handwriting dataset MNIST, and demonstrate the effectiveness of PRG4CNN. Full article