Search Results (1,074)

Reliable prediction of tunnel thruster performance under reverse, or off-design, reverse operating direction (ROD) conditions, is crucial for modern vessels that require bidirectional thrust from a single unit—such as yachts and offshore support vessels. Despite the increasing demand for such a capability, there remains limited understanding of the unsteady hydrodynamic behavior and performance implications of ROD operation. This study addresses this gap through a scale-resolving computational fluid dynamics (CFD) investigation of a full-scale, fixed-pitch propeller with a diameter of 0.62, installed in a tunnel geometry representative of yacht-class side thrusters. Using advanced turbulence modeling, we compare the thruster’s performance under both the normal operating direction (NOD) and ROD. The results reveal notable differences: in ROD, the upstream separation zone was more compact and elongated, average thrust increases by approximately 3–4%, and torque and pressure fluctuations rise by 15–30%. These findings demonstrate that a single tunnel thruster can meet bidirectional manoeuvring requirements. However, the significantly elevated unsteady loads during ROD operation offer a plausible explanation for the increased noise and vibration frequently observed in practice. Full article

Sacred choral music continues to hold a significant place in contemporary concert settings, with historical and newly composed works featuring in today’s choral programmes. Contemporary choral composers have continued to engage with the longstanding tradition of setting sacred texts to music, bringing fresh interpretations through their innovative compositional techniques and fusion of styles. Irish composer Rhona Clarke’s (b. 1958) expansive choral oeuvre includes a wealth of both sacred and secular compositions but reveals a notable propensity for the setting of sacred texts in Latin. Her synthesis of archaic and contemporary techniques within her work demonstrates both the solemn and visceral aspects of these texts, as well as a clear nod to tradition. This article focuses on Clarke’s choral work O Vis Aeternitatis (2020), a setting of a text by the medieval musician and saint Hildegard of Bingen (c. 1150). Through critical score analysis, we investigate the piece’s melodic, harmonic, and textural frameworks; the influence of Hildegard’s original chant; and the use of extended vocal techniques and contrasting vocal timbres as we articulate core characteristics of Clarke’s compositional style and underline her foregrounding of the more visceral aspects of Hildegard’s words. Clarke’s fusion of creative practices from past and present spotlights moments of dramatic escalation and spiritual importance, and exhibits the composer’s distinctive compositional voice as she reimagines Hildegard’s text for the twenty-first century. Full article

Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1β (IL-1β) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1β proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1β proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Chronic inflammation plays a central role in the progression and complications of chronic kidney disease (CKD). The nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway has emerged as a crucial mediator of the inflammatory response in CKD. This cross-sectional study evaluated the expression of NLRP3 in patients with CKD undergoing different treatments. Blood samples were collected from 32 non-dialysis (ND) patients [63 (11.2) years, estimated glomerular filtration rate, 43.5 (22.0) mL/min, BMI, 29.5 (10.0) kg/m²)], 50 hemodialysis (HD) patients [48.5 (16.5) years, 60.5 (50) months on HD, BMI, 24.2 (4.9) kg/m²)], and 8 peritoneal dialysis (PD) patients [56.5 (8.5) years, 40.5 (41.2) months on PD, BMI, 28.8 (2.6) kg/m²)]. The mRNA expression level of NLRP3 was measured using real-time PCR. The cytokines and the malondialdehyde (MDA) levels were also assessed. The results indicated that the mRNA level of NLRP3 was significantly elevated in patients undergoing HD (1.23, IQR = 0.95) compared with that in non-dialysis patients (0.79, IQR = 0.35) and in patients undergoing PD (0.77, IQR = 0.38) after adjusting for confounding variables, including age, sex, BMI, and dialysis duration. Furthermore, the MDA levels were significantly higher in HD patients. NLRP3 is upregulated in HD patients, and the results suggested that the inflammasome may be associated with oxidative stress in patients with CKD. Full article

The main challenge after engraftment of human tissues to mice is the development of graft-versus-host disease. It often occurs in an acute form, which reduces the time frame for observations. This is especially important to take into account when planning long-term studies of chronic diseases such as HIV infection. In addition, in mice, even with a similar genotype but different origin, the interaction between the graft and the recipient’s organism can manifest itself differently. We engrafted human immune cells in three different concentrations into immunodeficient NOD/Shi-Prkdc^scid Il2rg^em1/Cyagen mice. Then, the initial points of development of a severe graft-versus-host reaction and the maximum possible time window for humane observation were determined. The study included regular complete blood count and the monitoring of the dynamics of the concentration of human cells in the blood of mice. In addition, the effect of grafts on the activation of the recipient’s immune system was assessed. Finally, necropsy and histological and immunohistochemical examinations of the organs were performed to determine the localization of human cells. In this way, critical factors determining the success of human immune system reconstitution in mice were identified. Full article

Soybean (Glycine max) is a protein-rich legume crop that plays an important role in achieving food security. The aim of this study was to isolate soybean-nodulating rhizobia from Côte d’Ivoire soils and evaluate their potential as efficient strains in order to develop local bioinoculants. For this objective, 38 composite soil samples were collected from Côte d’Ivoire’s five major climatic zones. These soils were used as substrate to trap the nodulating rhizobia using the promiscuous soybean variety R2-231. A total of 110 bacterial strains were isolated and subsequently identified. The analysis of ITS (rDNA16S-23S), glnII and recA sequences revealed a relatively low genetic diversity of these native rhizobia. Moreover, the ITS phylogeny showed that these were scattered into two Bradyrhizobium clades dominated by the B. elkanii supergroup, with ca. 75% of all isolates. Concatenated glnII-recA sequence phylogeny confirmed that the isolates belong in the majority to ‘B. brasilense’, together with B. vignae and some putative genospecies of Bradyrhizobium that needs further elucidation. The core gene phylogeny was found to be incongruent with nodC and nifH phylogenies, probably due to lateral gene transfer influence on the symbiotic genes. The diversity and composition of the Bradyrhizobium species varied significantly among different sampling sites, and the key explanatory variables identified were carbon (C), magnesium (Mg), nitrogen (N), pH, and annual precipitation. Based on both shoot biomass and leaf relative chlorophyll content, three isolates consistently showed a higher symbiotic effectiveness than the exotic inoculant strain Bradyrhizobium IRAT-FA3, demonstrating their potential to serve as indigenous elite strains as bioinoculants. Full article

Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D₃ treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune response, had been investigated. Eight multiparous cows were treated with 10 mL vitamin D₃ (1 million IU cholecalciferol/mL) intramuscularly on day 273 of pregnancy, while eight others remained untreated and served as controls. Placental tissues were collected post-calving, and gene expression was analyzed using quantitative real-time PCR. Among 23 genes, 5 showed significant downregulation in the treated group: CaBP-9k (reduced by 88.1% from 32.80 ± 91.50 to 3.90 ± 8.54), ESR1 (reduced by 95.7% from 7.89 ± 17.87 to 0.34 ± 0.34), LHR (reduced by 96.5% from 3.75 ± 5.45 to 0.13 ± 0.17), NOD1 (reduced by 94.1% from 4.21 ± 7.00 to 0.25 ± 0.30), and TLR1 (reduced by 99.7% from 24.80 ± 61.45 to 0.07 ± 0.08). These results suggest that vitamin D₃ supplementation affects key pathways related to calcium transport, reproductive function, and immune response in the bovine placenta. These molecular changes may help to explain improved calcium homeostasis and reduced postpartum complications, offering insights into how targeted nutritional interventions can enhance reproductive efficiency in high-producing dairy cows. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

The Bacillus Calmette-Guérin (BCG) vaccine confers broad, non-specific immunity that may bolster defenses against respiratory viruses. While NOD2 (nucleotide-binding oligomerization domain-containing protein 2)-driven pathways are central to innate immune responses, the contribution of surface receptor modulation on monocytes to shaping these responses remains underexplored. We analyzed whole-blood cultures from BCG-vaccinated Polish children, stratified by serostatus to SARS-CoV-2 and RSV, and stimulated for 48 h with live BCG, purified viral antigens, or both. RT-qPCR quantified mRNA levels of NOD2 and key cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF), while flow cytometry assessed CD14, HLA-DR, CD11b, and CD206 expression. Co-stimulation with BCG + RSV elicited the strongest transcriptional response, notably a 2–4-fold upregulation of NOD2, IL-1β, and IL-6 versus RSV alone. In SARS-CoV-2(+) donors, RSV alone induced higher NOD2 expression than BCG or BCG + RSV, while IL-2 peaked following BCG + SARS-CoV-2. Across conditions, NOD2 positively correlated with IL-4 and IL-6 but negatively correlated with IL-1β in SARS-CoV-2 cultures. Viral antigens increased CD14 and HLA-DR on monocytes, suggesting activation; CD206 rose only in dual-seropositive children. Our findings indicate that BCG stimulation affects pediatric antiviral immunity through NOD2-related cytokine production and induction of a CD14⁺HLA-DR⁺ phenotype, supporting its potential role in boosting innate defenses against respiratory pathogens. Full article

Cutibacterium acnes (C. acnes) is a commensal bacterium of the skin microbiota that can transform itself into a pathogen depending on the peculiar susceptibility of the host: it is the sole microorganism so far to be found in the specific organ lesions of sarcoidosis, and C. acnes-induced activation of T-helper-type-1 cell responses is generally higher in patients with sarcoidosis than in healthy subjects. This bacterium acts as an opportunistic agent in several inflammatory conditions other than sarcoidosis, such as prostate cancer and prosthetic joint infections. Both innate and adaptive immunity systems are involved in the pathogenesis of C. acnes-mediated sarcoid lesions, and a seminal role is played by host toll-like receptor (TLR)-2, TLR-4, TLR-6, NOD-like receptors, and mononuclear cell cytoplasmic receptors. This review summarizes current knowledge on the potential cause–effect relationship existing between C. acnes and sarcoidosis, addressing issues of future research directions and novel therapeutic strategies in the management of a complex disease such as sarcoidosis. Full article

Background: Symbiotic gut microbiota can enhance cancer therapy efficacy, while treatment-induced dysbiosis may reduce effectiveness or increase toxicity. Our preclinical study compared the anticancer effects and impact on fecal microbiota and metabolites of two water-soluble SN-38 derivatives (BN-MePPR and BN-MOA), with those observed after treatment with Irinotecan, and the FOLFOX regimen in NOD scid gamma mice bearing patient-derived colon adenocarcinoma xenografts (CRC PDX). Methods: Five individual experiments with Irinotecan and its derivatives and eight individual experiments with FOLFOX were conducted using eight CRC PDX models. Chemotherapeutics were administered intraperitoneally 4–5 times at 5-day intervals. Fecal samples were collected before and after treatment. Microbiota composition was analyzed by 16S rRNA gene (V3–V4 regions) sequencing. Mass spectrometry was used to quantify short-chain fatty acids (SCFAs) and amino acids (AAs). Results: All treatments significantly inhibited tumor growth versus controls. However, no significant changes were observed in gut microbiota α- and β-diversity between treated and untreated groups. Tumor progression in controls was associated with increased abundance of Marvinbryantia, Lactobacillus, Ruminococcus, and [Eubacterium] nodatum group. FOLFOX-treated mice showed increased Marvinbryantia, Bacteroides, and Candidatus Arthromitus, and decreased Akkermansia. No distinct taxa changes were found in the Irinotecan or derivative groups. SCFA levels remained unchanged across groups, while BN-MePPR, BN-MOA, and Irinotecan all increased AA concentrations. Conclusions: Contrary to earlier toxicological data, these findings indicate a relatively limited impact of the tested chemotherapeutics on the gut microbiome and metabolome, emphasizing the importance of research method selection in preclinical studies. Full article

Schwann cells (SCs) play a crucial role in peripheral nerve repair by supporting axonal regeneration and remyelination. While extensive research has been conducted using rodent SCs, increasing attention is being directed toward human SCs due to species-specific differences in phenotypical and functional properties, and accessibility of human SCs derived from diverse sources. A major challenge in translating SC-based therapies for nerve repair lies in the inability to replicate human SC myelination in vitro, posing a significant obstacle to drug discovery and preclinical research. In this study, we compared the myelination capacity of human, rodent, and porcine SCs in various co-culture conditions, including species-matched and cross-species neuronal environments in a serum-free medium. Our results confirmed that rodent and porcine SCs readily myelinate neurites under standard culture conditions after treatment with ascorbic acid for two weeks, whereas human SCs, at least within the four-week observation period, failed to show myelin staining in all co-cultures. Furthermore, we investigated whether cell culture manipulation impairs human SC myelination by transplanting freshly harvested and predegenerated human nerve segments into NOD-SCID mice for four weeks. Despite supporting host axonal regeneration into the grafts, human SCs exhibited very limited myelination, suggesting an intrinsic species-specific restriction rather than a cell culture-induced defect. These observations suggest fundamental differences between human and rodent SCs and highlight the need for human-specific models and protocols to advance our understanding of SC myelination. Full article

This study evaluated the acaricidal effects of biosurfactants produced by Serratia ureilytica against the two-spotted spider mite Tetranychus urticae and their compatibility with the predatory mite Ambliseus swirski. The biosurfactants were obtained via liquid cultures of the bacterial strains. In the laboratory, T. urticae was exposed via acaricide-immersed leaves and A. swirskii via acaricide-coated glass vials. In the greenhouse, mite-infested plants were sprayed with the biosurfactants. In the laboratory, biosurfactants produced by S. ureilytica NOD-3 and UTS exhibited strong acaricidal activity, causing 95% mortality in adults and reducing egg viability by more than 60%. In the greenhouse trial, all biosurfactants significantly suppressed T. urticae populations at all evaluated periods (7, 14, and 21 days post-application). Gas chromatography–mass spectrometry (GC-MS) analysis of the biosurfactants identified several fatty acids, including hexadecanoic acid, pentanoic acid, octadecanoic acid, decanoic acid, and tetradecanoic acid, as well as the amino acids L-proline, L-lysine, L-valine, and glutamic acid. These fatty acids and amino acids are known structural components of lipopeptides. Furthermore, the bioinformatic analysis of the genomes of the three S. ureilytica strains revealed nonribosomal peptide synthetase (NRPS) gene clusters homologous to those involved in the biosynthesis of lipopeptides. These findings demonstrate that S. ureilytica biosurfactants are promising eco-friendly acaricides, reducing T. urticae populations by >95% while partially sparing A. swirskii. Full article

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article