Search Results (678)

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

This study aimed to assess skeletal and upper airway modifications induced by the Twin Block appliance in patients with Class II malocclusion due to mandibular retrusion, using two-dimensional imaging techniques. A total of 11 patients (6 males, 5 females) were included and stratified into two groups (Pre-Peak and Peak) based on skeletal maturity evaluated through the cervical vertebral maturation (CVM) method. Lateral cephalometric radiographs were obtained at the beginning (T0) and end (T1) of treatment and analyzed using DeltaDent software. The appliance was worn full-time, except during meals and oral hygiene procedures, with monthly follow-ups. Significant changes were observed between T0 and T1 across the sample. Comparison between groups revealed statistically significant differences only in the H-C3a1 and vertical height (th) parameters (p < 0.05). In conclusion, the Twin Block appliance proved effective in enhancing mandibular and dental positioning, while also exerting a favorable influence on upper airway development. Full article

In this study, a multi-objective optimization procedure with embedded topology optimization was presented. The procedure simultaneously optimizes the spatial arrangement and topology of bodies in a multi-body system. The multi-objective algorithm determines the locations of supports, joints, active loads, reactions, and load magnitudes, which serve as inputs for the topology optimization of each body. The multi-objective algorithm dynamically adjusts domain size, support locations, and load magnitudes during optimization. Due to repeated topology optimization calls within the genetic algorithm, the computational cost is significant. To address this, two reduction strategies are proposed: (I) using a coarser mesh and (II) reducing the number of iterations during the initial generations. As optimization progresses, Strategy I gradually refines the mesh, while Strategy II increases the maximum allowable iteration count. The effectiveness of both strategies is evaluated against a baseline (Reference) without reductions. By the 25th generation, all approaches achieve similar hypervolume values (Reference: 2.181; I: 2.112; II: 2.133). The computation time is substantially reduced (Reference: 42,226 s; I: 16,814 s; II: 21,674 s), demonstrating that both strategies effectively accelerate optimization without compromising solution quality. Full article

Background/Objectives: Contextual memory associated with methamphetamine (METH) use contributes to relapse and persistence of addiction. Angiotensin II type 1 receptor (AT1R) signaling has been implicated in drug reinforcement. LCZ696, a clinically used combination of sacubitril (a neprilysin inhibitor) and valsartan (an AT1R antagonist), may interfere with METH-associated memory through the modulation of dopaminergic pathways. Methods: Male C57BL/6J mice were tested in a conditioned place preference (CPP) paradigm to assess the effects of LCZ696, sacubitril (AHU377), and valsartan on METH-induced memory expression and reinstatement. Synaptic plasticity in the nucleus accumbens (NAc) was examined by assessing the levels of synaptophysin (Syp) and postsynaptic density protein 95 (Psd95), as well as dendritic spine density. Dopaminergic signaling in the ventral tegmental area (VTA) was evaluated via ELISA, Western blotting, and chromatin immunoprecipitation (ChIP), targeting cAMP response element-binding protein (Creb) binding to the tyrosine hydroxylase (Th) promoter. To further assess the role of Th, an adeno-associated virus (AAV9) carrying a CRISPR-Cas9-based sgRNA targeting Th (AAV9-Th-sgRNA) was microinjected into the VTA. Results: LCZ696 and valsartan significantly reduced METH-induced CPP and reinstatement. LCZ696 reversed METH-induced synaptic and dopaminergic alterations and suppressed Creb-mediated Th transcription. Th knockdown attenuated both CPP acquisition and relapse. Conclusions: LCZ696 disrupts METH-associated contextual memory by modulating dopaminergic signaling and Creb-dependent Th expression, supporting its potential as a treatment for METH use disorder. Full article

Buried in 1858, Cornelis Kok II’s grave lay undisturbed in Campbell, Northern Cape, until 1961 when a multiracial coalition, driven by their own sets of interests, unearthed the Griqua leader’s remains. The bones again took centre stage with the collapse of apartheid when different groups called for their return and reburial, with an assertion, variously, of ascendant Griqua, indigenous, Khoisan, and Khoikhoi identities. The 2007 reinterment again courted controversy and protest, while the contemporary neglect of the new gravesite symbolizes feelings of exclusion and marginalization among some Campbell Griqua today. By tracing the life history of Kok II’s remains, well past his natural life, we demonstrate how they serve as a flashpoint mobilized by actors with different aims and objectives at different moments. These motivations range from scientistic confirmation of genealogy and identity under apartheid rule, to post-apartheid calls for repatriation anchored to a global indigenous rights framework, to factional contestations over ownership. Marshalled towards different political projects, for all these actors, the bones nonetheless serve as a resource and link to a 19th century frontier past. Full article

Hierodula patellifera Serville is a predatory insect widely distributed in Asia. To better understand the morphology of the antennae of mantids, the antennal morphology, structure, and distribution of sensilla in nymphs and adults of H. patellifera were analyzed using scanning electron microscopy. The antennal morphology of nymphs and adults was similar and consisted of the scape, pedicel, and flagellum. Seven types and four subtypes of sensilla were identified (sensilla trichodea: StI, StII; sensilla basiconica: Sb; sensilla chaetica: Sc; sensilla coelocapitula: Sco; sensilla campaniformia: ScaI, ScaII; grooved peg sensilla: Sgp; Böhm’s bristle: Bb), and an undefined cuticular structure was observed in nymphs. Based on the external morphology and distributional features of the sensilla, we proposed to divide the adult flagellum into six parts. Furthermore, the length of the antennae gradually increased with the growth of instars, and the most obvious individual growth of antennae occurred from the 5th- to 6th-instar nymphs; sexual dimorphism in antennal length width, and sensilla distribution becomes evident from the 7th instar, and compared to adult females, the adult males presented larger flagellomeres and a large number of grooved peg sensilla. We found that mantid antennae develop through the addition of new flagellomeres at their proximal and secondary division sections, and the similarities and differences were compared with other insects. Full article

Background and Objectives: At present, intra-abdominal adhesions (IAAs) continue to be an important problem in surgery due to morbidity and mortality risks. Thymoquinone (TQ) and platelet-rich plasma (PRP) are molecules with known anti-inflammatory and antioxidant effects. However, a limited number of studies have investigated their efficacy in IAAs. In this study, we aimed to demonstrate the efficacy of TQ and PRP in reducing the development of IAAs and determine which molecule is more advantageous using an experimental animal model. Materials and Methods: Fifty-five male Wistar albino rats were included in the study. Five rats were used to obtain PRP, while fifty rats were randomly assigned to five groups (n = 10 per group): group I (sham) did not receive any treatment; group II (control) received no treatment after a cecum hemorrhage procedure; group III (saline) received 1 mL of saline treatment around the cecum after hemorrhage; group IV (PRP) received 1 mL of PRP (containing 3 × 10⁶ platelets/mL) around the cecum after hemorrhage; and group V (TQ) received 1 mL of TQ (containing 2 mg/mL TQ) around the cecum after hemorrhage. On the 10th day, IL1-β, TNF-α, E-selectin, and P-selectin levels were measured from the blood serum samples, and the cecum was histopathologically evaluated. Results: The lowest adhesion formation in terms of biochemical parameters was obtained in the TQ group (p < 0.05). Histopathological evaluations showed that saline, PRP, and TQ treatments were all effective, but none was superior. Conclusions: When histopathologically evaluated, saline, TQ, and PRP have similar effects in IAAs. However, when evaluated in terms of biochemical parameters, TQ prevented the formation of intra-abdominal adhesions more effectively than saline or PRP, owing to its strong anti-inflammatory and antioxidant properties. Full article

Introduction: Accurate staging is essential in pancreatic adenocarcinoma due to its aggressive nature and poor prognosis. The 8th edition of the AJCC TNM staging system introduced changes in tumor size criteria and nodal classification. This study compares the prognostic performance of the 7th and 8th editions in resected patients. Material and Methods: A retrospective analysis was conducted on 214 patients with pancreatic adenocarcinoma who underwent curative surgery. TNM staging was assigned according to both AJCC editions. Kaplan–Meier analysis and multivariate Cox regression, stratified by adjuvant therapy, were used to assess disease-free survival (DFS) and overall survival (OS). Results: The 8th edition TNM staging was significantly associated with lower risk of recurrence, with TNM stages I and II independently predicting better DFS (p < 0.05). In contrast, the 7th edition TNM stage I remained the only independent predictor of OS (HR = 0.376; p = 0.023). Reclassification between editions altered stage distribution, particularly within stage II. Conclusions: The 8th edition improves early recurrence stratification, while the 7th edition retains stronger prognostic value for overall survival. Both systems offer complementary insights, supporting outcome-specific staging use. Full article

Extensive cattle farming significantly contributes to Greece’s agricultural economy. In such systems, animals mainly graze on natural grasslands whose biodiversity significantly affects meat quality traits. In Greece, the sector faces several economic challenges, while the literature investigating beef quality produced by these systems is scarce. Hence, this study aimed to (i) evaluate farms’ economic performance; (ii) assess meat quality; and (iii) investigate the presence of heavy metals in liver samples of extensively reared beef cattle. The study involved three farms located in the Axios River Delta, a protected area of significant ecological importance in Northern Greece. A designated questionnaire was used to collect farm technical (herd size, meat production, grazing, feeding, reproduction, animal health) and economic data (income, variable costs). Meat samples of the Longissimus dorsi muscle (ninth rib) from 54 carcasses were collected and subjected to physicochemical (color, pH, texture, chemical composition, fatty acid profile) and microbiological analyses. Additionally, heavy metal analysis was conducted on 14 liver samples. A comparative analysis using parametric and non-parametric tests was performed to assess differences in meat quality traits between the 1st and 15th days of storage. The economic analysis showed that all studied farms operated with losses, with the average gross margin excluding subsidies being negative at EUR 130.5 ± 92.60/year per animal. Beef exhibited low fat content (1.1 ± 1.12%), with an average pH₂₄ value of 5.5 ± 0.36, respectively. The concentrations of polyunsaturated, monounsaturated, and saturated fatty acids were 2.7 ± 0.72%, 44.6 ± 4.71%, and 47.3 ± 4.91%, respectively. Over the 15-day storage period, the yellowness (b*) value (p < 0.01), hue angle (p < 0.001), cohesiveness (p < 0.01), and springiness (p < 0.01) significantly decreased, while the lightness (L*) value significantly increased (p < 0.01). The mean Total Mesophilic Viable Counts and Total Enterobacterales were 5.0 log₁₀ CFU/g and 2.34 log₁₀ CFU/g, respectively, while heavy metal concentrations in bovine livers were below the maximum limits set by the European Commission. The results suggest that, despite the financial losses observed, beef’s improved color parameters during storage, along with other favorable quality traits, highlight the potential of extensive cattle farming to meet consumer demand and support value-added marketing. Full article

This article examines the material data preserved in king’s coffins used to bury and/or rebury five different kings, which represent the surviving material evidence we have of the art produced to manufacture divinized kingship during the New Kingdom: Seqenenre Taa, Kamose, Thutmose I/Panedjem I, Thutmose III, and Ramses II. All of them were removed from their original 17th and 18th Dynasty sepulchers, stripped of valuable materials, modified, and reused in later cache burials of the 20th, 21st, and 22nd Dynasties by 20th and 21st Dynasty High Priests of Amen, who used these recrafted coffins as a means of claiming their political and ideological legitimacy. Supported with detailed evidence of the five surviving king’s coffins as objects of social and political value and sometimes relying on the coffins recovered from Tutankhamun’s tomb for comparison, this article attempts to reconstruct some of the original material state of this art as a tool of power. Full article

The high-biofidelity dummy used to evaluate occupant protection under blast conditions is often costly and vulnerable. To address the limitations of low-cost, simplified dummy head–neck structures, which exhibit significant differences in mechanical properties compared to high-biofidelity dummies, a virtual–real fusion-based test method for assessing occupant head–neck injury in under-body blast impacts is proposed. A simplified dummy head–neck physical model, designed based on human biomechanical characteristics, is constructed for physical testing. A mapping test model based on 1D convolutional neural network (1D-CNN) is developed as the virtual counterpart to process physical model test data, specifically head and chest centroid accelerations, into head centroid acceleration and upper neck axial compression force matching the Hybrid III 50th numerical model. Pendulum collision tests are conducted to simulate under-body blast impacts, generating multiple sets of head and chest acceleration data. Under identical loading conditions, the head centroid acceleration and upper neck axial compression force of the Hybrid III 50th numerical model are computed. The parameters of the mapping test model are then optimized using these simulated experimental datasets based on non-dominated sorting genetic algorithm II (NSGA-II). Validation through blast experiments demonstrates that the proposed method achieves high accuracy, with errors of 10.9% for the Head Injury Criterion (HIC₁₅) and 2.4% for upper neck maximum axial compression force compared to the Hybrid III 50th numerical model calculations. This approach effectively bridges the gap between biofidelity and cost-efficiency in dummy testing for blast impact scenarios. Full article

Background: We investigated the possibility of predicting tumor burden with salivary extracellular RNA (exRNA) biomarkers in gastric cancer patients. Methods: Saliva samples were prospectively collected from 50 gastric cancer patients who underwent gastrectomy with curative intent. Approximately 5 mL of saliva was collected before surgery and on the 5th to 7th days after surgery. The expression of three mRNAs (SPINK7, PPL, and SEMA4B) and two miRNAs (miR140-5p and miR301a) that were previously validated was determined by reverse transcription quantitative real-time PCR. Results: There were significant differences in the pre-operative expression of PPL (p = 0.025), SEMA4B (p = 0.012), and miR140-5p (p = 0.036) between pathologic stage I/II and III/IV groups. The area under the curve (AUC) of each respective multivariable model in predicting stage III/IV, which was adjusted for age and sex, was 75.4% (PPL), 82.5% (SEMA4B), and 75.5% (miR140-5p). In the multivariable model, including all three biomarkers, the AUC was 89.2%. On the other hand, none of the conventional tumor markers (CEA, CA19-9, and CA72-4) could predict tumor burden before surgery. The AUC of the multivariable model, including CEA, CA19-9, and CA72-4, was 67.2%, 66.2%, and 67.4%, respectively. When all three tumor markers were included in the multivariable model, the AUC was 70.5%. Conclusions: Noninvasively detected salivary biomarkers have been shown to have higher diagnostic accuracy than conventional tumor markers detected by invasive blood tests for estimating pre-operative tumor burden. This study demonstrates the potential utility of these biomarkers in pre-operative risk assessment and monitoring surgical treatment response to gastric cancer. Full article

The vertebral arteries supply blood to the upper spinal cord, brainstem, cerebellum, and posterior part of the brain. These arteries are susceptible to deformation from external factors such as muscular, ligamentous, or bony structures, and any interruption of blood flow may result in vertebrobasilar insufficiency. Among the osseous variants of the cervical spine with potential pathological significance, variations in the number, shape, and size of the foramen transversarium, as well as the presence of bony bridges in the first cervical vertebra, may suggest a predisposition to vertebrobasilar insufficiency. A skeletal sample from the post-Classical cemetery of Corfinio (12th–15th centuries CE; L’Aquila, Italy) was examined. Regarding the morphology of the foramen transversarium, shape variations were identified in 32 of the 108 vertebrae analysed (a prevalence of 29.6%). Particularly noteworthy are three findings in the atlas: (i) a high prevalence of foramen transversarium variants (35.7% for hypoplastic and double foramina), (ii) a coefficient of roundness consistent with a brachymorphic shape, and (iii) a high prevalence of bony bridges —especially ponticulus posticus (52.9%) and retrotransverse foramen (64.7%). All of these findings may indicate a predisposition to vertebrobasilar insufficiency in the individuals studied. It is hypothesised that external mechanical factors, such as carrying heavy loads on the head, neck, and shoulders due to work activities, along with possible genetic influences related to kinship, may have contributed to the high prevalence of these osseous variants. Full article

Background: Breast cancer stem cells (CSCs), particularly those enriched in triple-negative breast cancer (TNBC), are key contributors to tumor recurrence, metastasis, and resistance to therapy. CSCs often undergo epithelial-to-mesenchymal transformation (EMT), enhancing their invasiveness. Immune-based strategies that selectively target CSC/EMT antigens offer a promising therapeutic approach. Methods: Twelve candidate CSC/EMT-associated proteins were identified through a systematic literature review. Human serum samples were assessed for antigen-specific IgG using ELISA. Th1/Th2 cytokine profiles, in response to predicted MHC II epitopes, were measured by ELISPOT in PBMCs. Epitope immunogenicity and tumor inhibition were evaluated in murine models, using either TNBC or luminal B syngeneic breast cancer cell lines. Results: Six of the candidate proteins (SOX2, YB1, FOXQ1, MDM2, CDH3, CD105) elicited antigen-specific IgG in human serum. Th1-selective epitopes, defined by high Th1/Th2 ratios, were identified for five of these proteins. Immunization of mice with peptide pools derived from CD105, CDH3, MDM2, SOX2, and YB1 induced significant antigen-specific IFN-γ responses. Tumor growth was significantly inhibited in the vaccinated mice across both the TNBC and luminal B breast cancer models, with mean tumor volume reductions ranging from 61% to 70%. Conclusions: CSC/EMT-associated antigens are immunogenic in humans and can be targeted using Th1-selective epitope-based vaccines. Immunization with these epitopes effectively inhibits tumor growth in multiple murine models of breast cancer. These findings support further clinical evaluation of CSC/EMT-targeted vaccines, especially for high-risk or advanced-stage breast cancer patients. Full article

Lysophosphatidylinositols are degradation products of phosphatidylinositols within cell membranes and digestive metabolites of a high-fat diet in the gut. G-protein-coupled receptor 55 (GPR55) is a receptor that senses lysophosphatidylinositol and acts as an immune mediator, being primarily upregulated during immune cell activation. This study aimed to investigate the role of GPR55, using its antagonist, CID16020046, in a collagen-induced rheumatoid arthritis mouse model. It was observed that DBA-1J mice develop joint lesions characteristic of rheumatoid arthritis following immunization with bovine type II collagen. The administration of CID16020046 (1 mg/kg, intraperitoneally) alleviated rheumatoid arthritis symptoms and inflammatory responses. Histopathological analysis showed that CID16020046 reduced foot edema, proteoglycan loss, and bone erosion in the joints. CID16020046 also decreased rheumatoid-arthritis-induced serum IgG levels, as measured using enzyme-linked immunosorbent assays. The treatment reduced levels of pro-inflammatory cytokines (IL-1β and IL-6), Th1 cytokine (IFN-γ), and Th17 cytokine (IL-17A), along with matrix metalloproteinase-3 (MMP-3) and the receptor activator of nuclear factor-κB ligand (RANKL) in the feet. A significant reduction in splenomegaly was also observed, along with significant reductions in CD4⁺ T helper 1 (Th1) and Th17 cells in the spleen. Additionally, CID16020046 suppressed the differentiation of naïve T cells into CD4⁺IL-17⁺ Th17 cells. CID16020046 suppressed expression levels of inflammatory cytokine mRNAs in SW982 human synovial cells. In conclusion, blocking GPR55 alleviates collagen-induced rheumatoid arthritis symptoms by suppressing Th1 and Th17 cells in the spleen and pro-inflammatory cytokines in the joints, suggesting that GPR55 is a potential therapeutic target for autoimmune inflammatory diseases. Full article