Search Results (10,001)

This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article

Camelina sativa (CS) is an emerging sustainable oilseed crop with interesting feed application potentialities. The research assessed the potentiality of Camelina sativa (CS) in the diet for free-range laying hens, aiming at reaching a nutritional claim. To this purpose, two feeding groups of hens (n = 100 Livorno hens, n = 25 hens/pen) were farmed outdoor and received either a Control diet, which was a commercial diet for laying hens, or a CS diet. The latter was formulated to include the 5% CS cake and 1% CS oil, replacing conventional feedstuffs. Diets were isoprotein and isoenergy and were available ad libitum throughout the laying period (February–September). At day 1, n = 12 eggs/diet were sampled to assess the initial proximate composition and FA profile. Every 7 days the sampling was repeated to analyze the eggs’ FA profile, up to day 35. At the end of the laying season, n = 6 hens/dietary treatment were slaughtered and subjected to meat quality evaluations. Results highlighted that a 28-day feeding was the period required to obtain 227 mg of C18:3 n-3 and 81 mg of C20:5 n-3 + C22:6 n-3/100 g egg, whereas a further 7 days of feeding trial were ineffective in further enhancing the omega-3 FA content of eggs. CS eggs were comparable to Control ones for overall physical traits, proximate composition, and shelf-life. In addition, at the end of the laying period, the meat of CS hens was also found to be healthier than that of Control ones, thanks to a higher omega-3 FA proportion (p < 0.01), which was, however, not sufficient to reach any nutritional claim. Instead, the proximate composition of CS meat was overall comparable to Control hens. In conclusion, the present research demonstrated that feeding Camelina sativa meal and oil to laying hens is feasible and allows to reach the nutritional claim in eggs “rich in omega-3 FA” after a feeding period of 28 days, without any negative effects on other eggs’ quality trials. Camelina sativa can thus be defined as a promising sustainable feedstuff for the poultry sector for diversification purposes and to enhance the nutritional quality of eggs. Full article

Bovine endometritis is a common postpartum disease that significantly impairs reproductive performance and reduces economic sustainability in dairy and beef cattle. It is primarily caused by gram-negative and -positive bacteria, triggering strong inflammatory responses in the endometrium. Serum amyloid A (SAA) is an acute-phase protein and precursor of amyloid A (AA) in AA amyloidosis. In cattle, multiple SAA isoforms have been identified; however, the biological functions of SAA3 remain unclear. Hence, this study investigated the role of SAA3 in bovine endometrial epithelial cells (BEnEpCs) following stimulation with gram-negative or -positive bacterial antigens. BEnEpCs were treated with lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and, subsequently, the expression levels of SAA3 and SAA1 mRNA were compared by real-time PCR. To further investigate protein-level changes, immunocytochemistry (ICC) was performed to assess the expressions of SAA3 and SAA1. These analyses revealed that SAA3 mRNA expression was significantly enhanced by LPS and LTA, whereas SAA1 mRNA remained undetectable or showed only minimal responsiveness. Notably, only SAA3 protein expression increased in response to stimulation. These results indicate that SAA3 plays a crucial role in the innate immune response of BEnEpCs against gram-negative bacteria. Our in vitro findings may facilitate understanding of the innate immune activity in bovine uterus. Full article

In order to achieve the efficient utilization of agricultural by-products and overcome the bottleneck of animal feed shortages in dry seasons, this study utilized corn stover (CS; Zea mays L.) as a material to systematically investigate the dynamic changes in the fermentation quality, bacterial community structure, and pathogenic risk of silage under different fermentation times (0, 3, 7, 15, and 30 days). CS has high nutritive value, including crude protein and sugar, and can serve as a carbon source and a nitrogen source for silage fermentation. After ensiling, CS silage (CSTS) exhibited excellent fermentation quality, characterized by relatively high lactic acid content, low pH, and ammonia nitrogen content within an acceptable range. In addition, neither propionic acid nor butyric acid was detected in any of the silages. CS exhibited high α-diversity, with Serratia marcescens being the dominant bacterial species. After ensiling, the α-diversity significantly (p < 0.05) decreased, and Lactiplantibacillus plantarum was the dominant species during the fermentation process. With the extension of fermentation days, the relative abundance of Lactiplantibacillus plantarum significantly (p < 0.05) increased, reaching a peak and stabilizing between 15 and 30 days. Ultimately, lactic acid bacteria dominated and constructed a microbial symbiotic network system. In the bacterial community of CSTS, the abundance of “potential pathogens” was significantly (p < 0.01) lower than that of CS. These results provide data support for establishing a microbial regulation theory for silage fermentation, thereby improving the basic research system for the biological conversion of agricultural by-products and alleviating feed shortages in dry seasons. Full article

Purpose: To assess the performance of 2D T2-weighted (w) Turbo Spin Echo (TSE) MRI reconstructed with a deep learning (DL)-powered super resolution reconstruction (SRR) algorithm combining compressed sensing (CS) denoising and resolution upscaling for high-resolution hippocampal imaging in patients with (epileptic) seizures and suspected hippocampal pathology. Methods: A 2D T2w TSE coronal hippocampal sequence with compressed sense (CS) factor 1 (scan time 270 s) and a CS-accelerated sequence with a CS factor of 3 (scan time 103 s) were acquired in 28 patients. Reconstructions using the SRR algorithm (CS 1-SSR-s and CS 3-SSR-s) were additionally obtained in real time. Two readers graded the images twice, based on several metrics (image quality; artifacts; visualization of anatomical details of the internal hippocampal architecture (HIA); visibility of dentate gyrus/pes hippocampi/fornix/mammillary bodies; delineation of gray and white matter). Results: Inter-readout agreement was almost perfect (Krippendorff’s alpha coefficient = 0.933). Compared to the CS 1 sequence, the CS 3 sequence significantly underperformed in all 11 metrics (p < 0.001-p = 0.04), while the CS 1-SRR-s sequence outperformed in terms of overall image quality and visualization of the left HIA and right pes hippocampi (p < 0.001-p < 0.04) but underperformed in terms of presence of artifacts (p < 0.01). Lastly, relative to the CS 1 sequence, the CS 3-SRR-s sequence was graded worse in terms of presence of artifacts (p < 0.003) but with improved visualization of the right pes hippocampi (p = 0.02). Conclusion: DL-powered SSR demonstrates its capacity to enhance imaging performance by introducing flexibility in T2w hippocampal imaging; it either improves image quality for non-accelerated imaging or preserves acceptable quality in accelerated imaging, with the additional benefit of a reduced scan time. Full article

Chloroplasts, as the organelles primarily responsible for photosynthesis, require a substantial supply of iron ions. Conversely, due to Fe toxicity, the homeostasis of these ions is subject to tight regulation. Permease in chloroplast 1 (PIC1) has been identified as the primary iron importer into chloroplasts. However, previous studies suggested the existence of a distinct pathway for Fe transfer to chloroplasts, likely involving mitoferrin-like 1 (MFL1) protein. In this work, Arabidopsis MFL1 (AtMFL1) and its cucumber homolog (CsMFL1) were characterized using, among others, Arabidopsis protoplasts as well as both yeast and Arabidopsis mutants. Localization of both proteins in chloroplasts has been shown to be mediated via an N-terminal transit peptide. At the gene level, MFL1 expression profiles differed between the model plant and the crop plant under varying Fe availability. The expression of other genes involved in chloroplast Fe homeostasis, including iron acquisition, trafficking, and storage, was affected to some extent in both AtMFL1 knockout and overexpressing plants. Moreover, root growth and photosynthetic parameters changed unfavorably in the mutant lines. The obtained results imply that AtMFL1 and CsMFL1, as putative chloroplast iron transporters, play a role in both iron management and the proper functioning of the plant. Full article

Compressed sensing is widely used in modern resource-constrained sensor networks. However, achieving high-quality and robust signal reconstruction under low sampling rates and noise interference remains challenging. Traditional CS methods have limited performance, so many deep learning-based CS models have been proposed. Although these models show strong fitting capabilities, they often lack the ability to handle complex noise in sensor networks, which affects their performance stability. To address these challenges, this paper proposes SBCS-Net. This framework innovatively expands the iterative process of sparse Bayesian compressed sensing using convolutional neural networks and Transformer. The core of SBCS-Net is to optimize key SBL parameters through end-to-end learning. This can adaptively improve signal sparsity and probabilistically process measurement noise, while fully leveraging the powerful feature extraction and global context modeling capabilities of deep learning modules. To comprehensively evaluate its performance, we conduct systematic experiments on multiple public benchmark datasets. These studies include comparisons with various advanced and traditional compressed sensing methods, comprehensive noise robustness tests, ablation studies of key components, computational complexity analysis, and rigorous statistical significance tests. Extensive experimental results consistently show that SBCS-Net outperforms many mainstream methods in both reconstruction accuracy and visual quality. In particular, it exhibits excellent robustness under challenging conditions such as extremely low sampling rates and strong noise. Therefore, SBCS-Net provides an effective solution for high-fidelity, robust signal recovery in sensor networks and related fields. Full article

Background: Total hip arthroplasty (THA) is a well-established surgical procedure for end-stage hip arthrosis. Innovations such as minimally invasive approaches and new technologies have improved outcomes and reduced invasiveness. The introduction of short-stem prostheses, which offer potential benefits in bone preservation, has been a significant development in recent years. This prospective case series study aims to compare invasiveness of the short-stem (SS) and conventional-stem (CS) prostheses in THA with a posterolateral approach (PLA) by assessing perioperative serum markers. Methods: A prospective case series was conducted involving consecutive patients who underwent primary THA from January 2022 to December 2023. Demographics and preoperative, postoperative day 1 (POD1), and postoperative day 2 (POD2) serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and white blood cells (WBCs) were measured. Results: The study included 21 patients with CS and 19 with SS, with no significant differences between groups in demographic. No statistically significant differences were found in serum markers between SS and CS groups at any time point. Both groups showed significant increases in ESR, CRP, and PCT from preoperative levels to POD2 (p < 0.001), while WBC values increased from preoperative to POD1 but decreased between POD1 and POD2. Conclusion: The short-stem prosthesis does not exhibit significantly different perioperative serum marker profiles compared to the conventional stem, suggesting similar levels of surgical invasiveness between the two implants. Further studies with larger sample sizes are needed to validate these findings and explore other aspects of short-stem THA. Full article

Enteroendocrine cells (EECs) are specialized secretory cells in the gut epithelium that differentiate from intestinal stem cells (ISCs). Mature EECs secrete incretin hormones that stimulate pancreatic insulin secretion and regulate appetite. Decreased EEC numbers and impaired secretion of the incretin glucagon-like peptide-1 (GLP1) have been implicated in obesity-associated metabolic complications. Gut microbial metabolites of dietary tryptophan (TRP) were recently shown to modulate ISC proliferation and differentiation. However, their specific effects on EEC differentiation are not known. We hypothesized that the gut microbial metabolites of dietary tryptophan counteract impaired GLP1 production and function in obesity by stimulating EEC differentiation from ISCs. We utilized complementary models of human and rat intestines to determine the effects of obesity or TRP metabolites on EEC differentiation. EEC differentiation was assessed by the EEC marker chromogranin A (CHGA) levels in the intestinal mucosa of normal versus obese rats. The effects of TRP metabolites on EEC differentiation were determined in human intestinal organoids treated with indole, a primary TRP metabolite, or the culture supernatant of Lactobacillus acidophilus grown in TRP media (LA-CS-TRP). Our results showed that the mRNA and protein levels of CHGA, the EEC marker, were significantly decreased (~60%) in the intestinal mucosa of high-fat-diet-induced obese rat intestines. The expression of the transcription factors that direct the ISC differentiation towards the EEC lineage was also decreased in obesity. In human organoids, treatment with indole or LA-CS-TRP significantly increased (more than 2-fold) CHGA levels, which were blocked by the aryl hydrocarbon receptor (AhR) antagonist CH-223191. Thus, the stimulation of EEC differentiation by colonic microbial metabolites highlights a novel therapeutic role of TRP metabolites in obesity and associated metabolic disorders. Full article

Hypoxia represents a critical environmental stressor in aquaculture, significantly disrupting aquatic organisms’ physiological homeostasis and thereby constraining the sustainable development of aquaculture industries. To elucidate the mechanisms underlying hypoxia-induced metabolic regulation in aquatic species, this study employed hybrid yellow catfish (Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂) as a model organism to systematically investigate the multidimensional physiological responses in brain, liver, and muscle tissues under hypoxia (0.7 mg/L) and reoxygenation (7.0 mg/L) conditions. Through qRT-PCR and enzymatic activity analyses, we comprehensively assessed molecular alterations associated with oxygen sensing (HIF-1α gene), respiratory metabolism (PFKL, HK1, PK, CS, and LDHA genes and corresponding enzyme activities), oxidative stress (SOD1, SOD2, GSH-PX, and CAT genes, along with LPO, MDA, PCO, T-SOD, GSH-PX, and CAT levels), apoptosis (Caspase-3, Bax/Bcl-2), inflammatory response (IL-1β, IKKβ), and mitochondrial function (COXIV, PGC-1α, ATP5A1). Key findings demonstrated pronounced HIF-1α activation across all examined tissues. Hepatic tissues exhibited adaptive metabolic reprogramming from aerobic to anaerobic metabolism, whereas cerebral tissues displayed suppressed anaerobic glycolysis during prolonged hypoxia, and muscular tissues manifested concurrent inhibition of both glycolytic and aerobic metabolic pathways. Notably, skeletal muscle exhibited marked oxidative stress accompanied by mitochondrial dysfunction, exacerbated inflammation, and apoptosis activation during hypoxia/reoxygenation cycles. This study delineates tissue-specific adaptive mechanisms to hypoxia in yellow catfish, providing theoretical foundations for both piscine hypoxia physiology research and aquaculture practices. Full article

Background: We previously reported an interim safety and immunogenicity analysis of a Phase 3 trial in the Philippines of the EuCorVac-19 (ECV-19) COVID-19 vaccine with the COVISHIELD^TM (CS) comparator (ClinicalTrials.gov identifier NCT05572879). Here, we present full-year humoral immunogenicity analysis. Methods: Healthy adults over 18 years of age received two injections of ECV-19 or CS vaccines, with 4 weeks between prime and boost. Analysis was carried out in individuals with immunogenicity measurements available at all 4 timepoints (weeks 0, 6, 30, and 56; n = 535 for ECV-19 and n = 260 for CS). Results: 2 weeks after boosting (week 6), ECV-19 elicited higher median anti-RBD IgG (1512 vs. 340 BAU/mL, p < 0.001) and neutralizing antibodies (1280 vs. 453 median microneutralization (MN) titer, p < 0.001) compared to CS. Anti-RBD IgG remained higher for ECV-19 compared to CS through week 30 (412 vs. 238 BAU/mL, p < 0.001) and 56 (425 vs. 260 BAU/mL, p < 0.001). MN titers remained higher for ECV-19 compared to CS through week 30 (640 vs. 453, p < 0.001) and 56 (453 vs. 320, p < 0.001). Correlation between anti-RBD IgG and neutralization titers persisted throughout the study. Women generally exhibited greater antibody responses than men. In the first six months following immunization, the ECV-19 group had a median antibody half-life of 80 days for anti-RBD IgG and 112 days for MN titer. In the subsequent six months, antibody half-life increased to 237 days for anti-RBD IgG and 168 days for MN titer. Conclusions: Following initial prime-boost vaccination, ECV-19 maintained higher anti-RBD IgG and neutralizing antibody titers relative to the CS comparator over a full-year period. Full article

The rubber plantations in Sankuru province, located in the Democratic Republic of Congo (DRC), have historically been pivotal to the regional economy. However, the absence of suitable silvicultural practices has promoted self-regeneration, resulting in the proliferation of diverse species. This study aims to characterize species richness and plant structure of these plantations. To this end, 80 subplots measuring 0.25 hectares were meticulously established, with a proportionate division between state-owned and farmer plantations. The results obtained from this study indicate that these plantations are home to approximately 105 species, classified into 33 distinct botanical families, with dominant families such as Fabaceae, Meliaceae, Euphorbiaceae, Olacaceae, Clusiaceae, and Moraceae. Despite the similarity between the two types of plantations (Cs = 58%), significant disparities were observed in terms of individuals, 635 ± 84.06 and 828 ± 144.62 (p < 10⁻³); species, 41 ± 7.49 and 28 ± 4.59 (p < 10⁻³); families, 19 ± 3.06 and 16 ± 1.62 (p < 10⁻²); and basal area, 29.88 ± 5.8 and 41.37 ± 7.57 (p < 10⁻²) for state and peasant plantations, respectively. State plantations exhibited greater diversity (H′ = 1.87) and enhanced equity (J’ = 0.43) than peasant plantations. The diametric structure exhibited an inverted J-shaped distribution, indicating constant and regular regeneration of these plantations. The upper canopy dominates the vertical structure in both types of plantations, with a significantly higher proportion in peasant plantations (83.60%) than in state plantations (73.8%), ANOVA (F (2.24 = 21.78), df = 24; p = 4.03 × 10⁻⁶). The findings indicate that the sustainable management of these plantations could incorporate agroecological principles to promote the coexistence of rubber production and biodiversity conservation while contributing to the restoration of degraded ecosystems and the well-being of local communities. Full article

The development of non-noble metal catalysts for gas-phase propylene epoxidation with H₂/O₂ remains challenging due to their inadequate activity and stability. Herein, we report a Cs⁺-modified Ni/TS-1 catalyst (9%Ni-Cs/TS-1), which exhibits unprecedented catalytic performance, giving a state-of-the-art PO formation rate of 382.9 g_PO·kg_cat⁻¹·h⁻¹ with 87.8% selectivity at 200 °C. The catalyst stability was sustainable for 150 h, far surpassing reported Ni-based catalysts. Ni/TS-1 exhibited low catalytic activity. However, the Cs modification significantly enhanced the performance of Ni/TS-1. Furthermore, the intrinsic reason for the enhanced performance was elucidated by multiple techniques such as XPS, N₂ physisorption, TEM, ²⁹Si NMR, NH₃-TPD-MS, UV–vis, and so on. The findings indicated that the incorporation of Cs⁺ markedly boosted the reduction of Ni, enhanced Ni⁰ formation, strengthened Ni-Ti interactions, reduced acid sites to inhibit PO isomerization, improved the dispersion of Ni nanoparticles, reduced particle size, and improved the hydrophobicity of Ni/TS-1 to facilitate propylene adsorption/PO desorption. The 9%Ni-Cs/TS-1 catalyst demonstrated exceptional performance characterized by a low cost, high activity, and long-term stability, offering a viable alternative to Au-based systems. Full article

Cellulite, characterised by cutaneous dimpling, surface irregularities, and dermal atrophy skin texture, affects up to 90% of post-pubertal females. It is a multifactorial condition involving anatomical, hormonal, and metabolic components, primarily affecting the thighs and buttocks. Despite numerous available therapies, there remains a high demand for effective, non-invasive, and well-tolerated treatment options. This single-centre, in vivo, prospective study evaluated the efficacy of a non-pharmacological, thermogenic topical cream-gel combined with manual massage in women with symmetrical grade II or III cellulite (Nürnberger–Müller scale). A total of 56 female participants (aged 18–55 years) were enrolled and instructed to apply the product twice daily for eight weeks to the thighs and buttocks. Efficacy was assessed using instrumental skin profilometry (ANTERA^® 3D CS imaging system), dermatological clinical grading, and patient self-assessment questionnaires. Quantitative analysis showed a mean reduction of 23.5% in skin indentation volume (p < 0.01) and a mean decrease of 1.1 points on the cellulite severity scale by week 8. Patient-reported outcomes revealed 85.7% satisfaction with visible results and 91% satisfaction with product texture and ease of application. Dermatological evaluation confirmed no clinically significant adverse reactions, and only 3.5% of participants reported mild and transient skin sensitivity. These findings suggest that this topical cream-gel formulation, when used in conjunction with manual massage, represents a well-tolerated and non-invasive option for the cosmetic improvement of moderate to severe cellulite. Full article

Polycarboxylate superplasticizer (PCE) is an important part of improving the overall performance of concrete. However, its synthetic raw materials are overly dependent on petrochemical products, and it also causes problems such as environmental pollution. With the development of the building material industry, the demand for petrochemical resources required for synthetic water-reducing agents will increase rapidly. Therefore, there is an urgent need to transition the synthetic raw materials of PCE from petrochemicals to biomass materials to reduce the consumption of nonrenewable resources as well as the burden on the environment. Biomass materials are inexpensive, readily available and renewable. Utilizing biomass resources to develop good-performing water-reducing agents can reduce the consumption of fossil resources. This is conducive to carbon emission reduction in the concrete material industry. In addition, it promotes the high-value utilization of biomass resources. Therefore, in this study, a biomass polyether monomer, acryloyl hydroxyethyl cellulose (AHEC), was synthesized from cellulose via the reaction route of ethylene oxide (EO) etherification and acrylic acid (AA) esterification. Biomass polycarboxylate superplasticizers (PCE-Cs) were synthesized through free radical polymerization by substituting AHEC for a portion of the frequently utilized polyether monomer isopentenyl polyoxyethylene ether (TPEG). This study primarily focused on the properties of PCE-Cs in relation to cement. The findings of this study indicated that the synthesized PCE-C5 at a dosing of 0.4% (expressed as mass fraction of cement) when the AHEC substitution ratio was 5% achieved good water reduction properties and significant delays. With the same fluidity, PCE-C5 could enhance the mechanical strength of cement mortar by 30% to 40%. This study utilized green and low-carbon biomass resources to develop synthetic raw materials for water-reducing agents, which exhibited effective water-reducing performance and enhanced the utilization rate of biomass resources, demonstrating significant application value. Full article