Search Results (107)

This narrative review explores the intricate relationship between the plasminogen activator system (PAS), comprising urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), and a range of neuropsychiatric disorders, including depression and anxiety. By synthesizing existing preclinical and clinical evidence, we clarify the roles of uPA and tPA in the pathogenesis and potential treatments of these conditions. This narrative review emphasizes their involvement in modulating neuronal plasticity, synaptic remodeling, and neurotransmitter systems, which are pivotal in maintaining brain function and behavior. Additionally, this review highlights key mechanisms by which these activators influence the neurobiological processes underlying mood and cognitive dysfunction. Critical analysis identifies areas of consensus, such as the role of plasminogen activators in neuroinflammation and stress responses, while also addressing gaps and controversies in the literature. The findings underscore the therapeutic potential of targeting the uPA/tPA system for innovative interventions. By offering a nuanced understanding of their contributions to mood disorders, this review aims to inspire future research toward developing novel, mechanism-based treatment strategies that harness the PAS’ capacity to restore neural homeostasis and improve patient outcomes. Full article

In the absence of fully effective therapies and preventive strategies against the development of urosepsis, a deeper understanding of the virulence mechanisms of Uropathogenic Escherichia coli (UPEC) strains is needed. UPEC strains employ a wide range of virulence factors (VFs) to persist in the urinary tract and bloodstream. UPEC strains were isolated from patients with sepsis and a control group without sepsis. PCR was used to detect 36 genes encoding various groups of virulence and fitness factors. Profiling of both intracellular and extracellular bacterial proteins was also included in our approach. Bacterial metabolites were identified and quantified using GC-MS and LC-MS techniques. The UpaG autotransporter, a trimeric E. coli AT adhesin, was significantly more prevalent in urosepsis strains (p = 0.00001). Iron uptake via aerobactin and the Iha protein also appeared to be predictive of urosepsis (p = 0.03 and p = 0.002, respectively). While some studies suggest an association between S fimbriae and the risk of urosepsis, we observed no such correlation (p = 0.0001). Proteomic and metabolomic analyses indicated that elevated levels of bacterial citrate, malate, coenzyme Q10, pectinesterase (YbhC), and glutamate transport proteins, as well as the regulators PhoP two-component system, CpxR two-component system, Nitrate/nitrite response regulator protein NarL, and the Ferrienterobactin receptor FepA, may play a role in sepsis. These genetic biomarkers, proteins, and metabolites derived from UPEC could potentially serve as indicators for assessing the risk of developing sepsis. Full article

Background: This study examined the incidence of acute complications within the first year following combat-related lower extremity injuries in United States (U.S.) Service members (SMs). The research compared outcomes between primary amputation (PA), limb salvage (LS), and non-threatening limb trauma (NTLT) groups, and conducted a subgroup analysis within the LS group, differentiating between SM who underwent a secondary amputation (LS-SA) and those who did not (LS-NA). Methods: A retrospective analysis of combat-related lower extremity injuries sustained between January 2001 and October 2015 was performed using data from the Military Health System Medical Data Repository. Chi-square tests and adjusted logistic regression analysis were used to compare complication frequencies by injury severity. Results: The analysis of the 4275 SM revealed that 21% had undergone PA, 47% LS (with 13% experiencing LS-SA and 87% LS-NA), and NTLT was observed in 32% of cases. The PA group exhibited higher rates of most acute complications compared to other groups, with three exceptions—i.e., non-union fractures, compartment syndrome, and orthopedic device complications were more prevalent in the LS group than the PA group. The LS-SA group had higher complication rates than the LS-NA group for most complications. Notably, the PA group was associated with the highest rates of post-hemorrhagic anemia and heterotopic ossification, while the LS-SA group exhibited the highest rates of osteomyelitis, non-union fractures, non-healing wounds, and compartment syndrome. Conclusions: Individuals with amputation (PA or LS-SA) were more likely to experience acute complications compared to their counterparts (PA vs. LS and NTLT; LS-SA vs. LS-NA), with the exception of non-union fractures, which were more frequent in the LS group than the PA group. These findings highlight the need for close monitoring and targeted interventions to address post-surgical complications in Service members with limb salvage. Full article

Introduction: This study assessed healthcare utilization in the first year after combat-related lower extremity injuries in 4275 U.S. Service members. Varying injury severity was hypothesized to correlate with different utilization patterns, with the limb salvage with secondary amputation (LS-SA) group expected to have the highest resource use. Methods: Data on inpatient admissions and outpatient visits were analyzed across four injury groups: primary amputation (PA), LS-SA, limb salvage with no amputation (LS-NA), and non-threatened limb trauma (NTLT). The LS-SA group had the highest mean total bed days and intensive care unit (ICU) days, with over 40% requiring four or more hospitalizations. The sample averaged 208.9 outpatient visits. Physical therapy, orthopedics, and social work had the highest clinic engagement. Result: Initial engagement in therapy clinics was high for PA and LS-SA but decreased for LS-NA and NTLT after the first quarter, while primary care engagement was more consistent. Physical therapy had the highest mean clinic utilization. Most initial inpatient admissions were at Landstuhl Regional Medical Center. PA and LS-SA received the majority of outpatient care at three Advanced Rehabilitation Centers, while care was more distributed for LS-NA and NTLT. This study underscores the substantial healthcare burden of combat-related lower extremity injuries, with the LS-SA group exhibiting the greatest resource utilization. Conclusions: The findings emphasize the need to optimize extremity trauma care across the Military Healthcare System as Service members with these injuries require significant healthcare resources, necessitating optimization of both care delivery and the military healthcare system. Full article

Bovine mastitis is a condition typically induced by various pathogens, with Escherichia coli (E. coli) being a common causative agent known for its propensity to cause persistent infections. In experimental models of bovine mastitis, lipopolysaccharide (LPS), a key component of the E. coli cell wall, is frequently employed as an inducer. The extracellular matrix (ECM) is regulated by MMPs, TIMPs, and the uPA system. They collectively participate in ECM degradation and remodeling and have been identified as promising targets for mastitis treatment. However, investigations into the precise mechanisms underlying E. coli and LPS-induced mastitis, as well as the relationship between bovine mastitis and the MAPK signaling pathway, remain limited. In this study, bovine mammary epithelial cells (BMECs) were treated in vitro with 10⁶ CFU/mL heat-inactivated E. coli, 7.5 µg/mL LPS, or a combination of both. The treatments resulted in varying degrees of activation of the MAPK signaling pathway, specifically ERK1/2, JNK, and P38. BMECs were exposed to MAPK inhibitors (the JNK inhibitor SP600125, the ERK inhibitor PD98059, and the P38 inhibitor SB203580) after treatments with heat-inactivated E. coli (10⁶ CFU/mL), LPS (7.5 µg/mL), or a combination of the two for 6, 12, 24, and 48 h. The mRNA and protein levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, uPA, uPAR, and PAI-1 were assessed using RT-qPCR and Western blot analysis. The findings indicated that heat-inactivated E. coli and LPS stimulated the expression of MAPK mRNAs (ERK1/2, P38, and JNK) in BMECs, along with corresponding increases in the phosphorylated proteins. Furthermore, MAPK inhibitors substantially upregulated the expression of TIMP-1, TIMP-2, and PAI-1. However, no significant changes were observed in the mRNA and protein levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, uPA, or uPAR. In conclusion, heat-inactivated E. coli and LPS can activate the MAPK signaling pathway in BMECs. Inhibiting this signaling pathway can modulate the expression of TIMP-1, TIMP -2, and PAI-1 at both mRNA and protein levels. Full article

This study addresses the urgent need for transitioning to clean energy systems to achieve net-zero emissions and mitigate climate change. It introduces an algebraic modeling framework inspired by the nuclear fission six-factor formula to optimize the construction rates of clean power plants, with a focus on Small Modular Reactors (SMRs). The framework integrates four key factors affecting SMR deployment: Public Acceptance (PA), Supply Chain Readiness (SC), Human Resource (HR) Availability, and Land Availability (LA), including their associated sub-factors. The proposed algebraic formula optimizes projections from the existing Dynamic Integrated Climate-Economy (DICE) model. By capturing socio-economic and environmental constraints, the model enhances the accuracy of clean energy transition scenarios. In the case of Ontario’s pathway to achieving net-zero emissions, the results indicate that incorporating the algebraic formula reduces the SMR construction rate projected by the DICE model from 5.2 to 3.7 units per year by 2050 and from 2.7 to 1.9 units per year by 2100. This reduction highlights the need for accelerated readiness in key deployment factors to avoid delays in reaching net zero targets, reinforcing the importance of strategic investments in PA, SC, HR, and LA. Validation against historical nuclear deployment data from the U.S., Japan, and Canada confirms the model’s ability to reflect real-world trends, with PA and SC emerging as the most influential factors. In addition to informing SMR planning, this approach offers a structured tool for prioritizing policy actions and can be adapted to other clean technologies, enhancing strategic decision making in support of net-zero goals. Full article

Automated damage segmentation for concrete bridges is a fundamental task in infrastructure maintenance, yet existing systems often depend heavily on large annotated datasets, which are costly and time-consuming to produce. This paper presents an innovative framework for concrete bridge damage segmentation, leveraging the Segment Anything Model (SAM) to reduce the reliance on extensive annotated data while enhancing segmentation accuracy and efficiency. Firstly, a SAM-guided mask generation network is introduced, which utilizes the SAM’s segmentation capabilities to generate supplementary supervision labels for damage segmentation. Then, a novel point-prompting strategy, incorporating saliency information, is proposed to refine SAM’s prompts, ensuring accurate mask generation for complex damage patterns. Next, a trainable semantic segmentation network is designed, integrating MambaVision and ResNet as dual backbones to capture multi-level features from concrete bridge damages. To fuse these features effectively, a Hierarchical Attention Fusion (HAF) mechanism is introduced. Finally, a Polarized Self-Attention (PSA) decoder is employed to improve segmentation precision. Experiments on a dataset of 10,000 concrete bridge images with box-level annotations achieved state-of-the-art performance, with an MIoU of 60.13%, PA of 74.02%, and MDice of 75.40%, outperforming existing segmentation models. In summary, this study improves the accuracy of concrete bridge damage segmentation through a series of innovative methods and strategies, and the concrete bridge damage segmentation algorithm opens up new horizons and directions. Full article

Cadmium (Cd) is a toxic, non-essential metal that primarily enters animal bodies through the digestive and respiratory systems, leading to damage to multiple organs and tissues. Cd can accumulate in cartilage and induce damage to chondrocytes. Procyanidins (PAs), also known as concentrated tannic acid or oligomeric proanthocyanidins (OPCs), exhibit diverse biological and pharmacological activities. However, the mechanism of OPCs alleviates Cd-induced damage to chondrocytes in chickens remains to be further explored in vitro. Chondrocytes were isolated from both ends of the tibia of 17-day-old SPF chicken embryos, and then subsequently treated with various concentrations of Cd (0, 1, 2.5, 5, and 10 μmol/L) or OPCs (0, 5, 10, 20, and 40 μmol/L) to investigate the mechanism underlying extracellular matrix (ECM) degradation and damage. Cd reduced cell viability, glycosaminoglycan (GAG) secretion, and ECM degradation in chondrocytes by decreasing the expression of type II collagen alpha 1 (COL2A1) and aggrecan (ACAN) while increasing the release of cartilage oligomeric matrix protein (COMP), along with elevated levels of matrix-degrading enzymes, such as matrix metalloproteinases 1 (MMP1), MMP10, and MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5. Cd induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and the expression of matrix-degrading enzymes, impairing ECM synthesis, an effect that could be alleviated by ERK1/2 inhibitor U0126. Chondrocytes were treated with 5 μmol/L Cd and 10 μmol/L OPCs, and it was found that OPCs inhibited the activation of the ERK1/2 signaling pathway and the expression of matrix-degrading enzymes, while promoting ECM synthesis and alleviating Cd-induced ECM damage in chickens. This study provides a theoretical basis for clinical research on OPCs with respect to the prevention and treatment of Cd-induced chondrogenic diseases in poultry. Full article

Uranium–niobium (U-Nb) alloys, used in a variety of industrial and energy applications that require high density, ductility, and good corrosion resistance, comprise a highly complex, multiphasic system with a phase diagram well established through decades of extensive experimental and theoretical research. They are also one of the best candidates for a metallic fuel alloy with high-temperature strength sufficient to support the core, acceptable nuclear properties, good fabricability, and compatibility with usable coolant media. The key factor determining the performance and safety of a metallic fuel such as U-Nb is its operational limits in the application environment, which are closely related to material’s structure and thermodynamic stability. They are in turn closely related to the ambient (zero-pressure) melting point $\left(T_m\right);$ thus, $T_m$ is an important engineering parameter. However, the current knowledge of $T_m$ of the U-Nb system is limited, as the only experimental study of its Nb-rich portion dates back to 1958. In addition, it has not yet been adequately modeled based on general thermodynamics principles or using an equation-of-state approach. In this study, we present a theoretical model for the melting curve (liquidus) of a mixture, and apply it to U-Nb, which is considered as a mixture of pure U and pure Nb. The model uses the known melting curves of pure constituents as an input and predicts the melting curve of their mixture. It has only one free parameter, which must be determined independently. The ambient liquidus of U-Nb predicted by the model appears to be in good agreement with the available experimental data. We calculate the melting curve (the pressure dependence of $T_m$) of pure U using ab initio quantum molecular dynamics (QMD), the knowledge of which is required for obtaining the model parameters for U. We also generalize the new model to nonzero pressure and consider the melting curve of U-6 wt.% Nb (U-6Nb) alloy as an example. The melting curve of U-6Nb alloy predicted by the model appears to be in good agreement with the ab initio melting curve obtained from our QMD simulations. We suggest that the U-18Nb alloy can be considered as a proxy for protactinium (Pa) and demonstrate that the melting curves of U-18Nb and Pa are in good agreement with each other. Full article

Water extraction from Synthetic Aperture Radar (SAR) images is crucial for water resource management and maintaining the sustainability of ecosystems. Though great progress has been achieved, there are still some challenges, such as an insufficient ability to extract water edge details, an inability to detect small water bodies, and a weak ability to suppress background noise. To address these problems, we propose the Global Context Attention Feature Fusion Network (GCAFF-Net) in this article. It includes an encoder module for hierarchical feature extraction and a decoder module for merging multi-scale features. The encoder utilizes ResNet-101 as the backbone network to generate four-level features of different resolutions. In the middle-level feature fusion stage, the Attention Feature Fusion module (AFFM) is presented for multi-scale feature learning to improve the performance of fine water segmentation. In the advanced feature encoding stage, the Global Context Atrous Spatial Pyramid Pooling (GCASPP) is constructed to adaptively integrate the water information in SAR images from a global perspective, thereby enhancing the network’s ability to express water boundaries. In the decoder module, an attention modulation module (AMM) is introduced to rearrange the distribution of feature importance from the channel-space sequence perspective, so as to better extract the detailed features of water bodies. In the experiment, SAR images from Sentinel-1 system are utilized, and three different water areas with different features and scales are selected for independent testing. The Pixel Accuracy (PA) and Intersection over Union (IoU) values for water extraction are 95.24% and 91.63%, respectively. The results indicate that the network can extract more integral water edges and better detailed features, enhancing the accuracy and generalization of water body extraction. Compared with the several existing classical semantic segmentation models, GCAFF-Net embodies superior performance, which can also be used for typical target segmentation from SAR images. Full article

Metropolitan areas increasingly confront complex challenges related to food security, social inequality, environmental degradation, and resource scarcity, exacerbated by rapid urbanization, climate change, and the reliance on extended, fragile supply chains. Urban and peri-urban agriculture (UPA) is recognized as a promising approach to mitigate these issues. For example, it enhances food security and nutrition by strengthening local food supply systems, improves livelihoods by providing employment and income for local residents, and promotes environmental sustainability through the creation of greening spaces and reduction of food miles. However, the full potential of UPA remains constrained by various technological, economic, and social barriers, such as limited growing spaces, lack of land tenure security, low economic efficiency, and insufficient public awareness and acceptance. Given that the technological innovations are critical in overcoming these barriers and maximizing the positive impacts of UPA, this review provides a state-of-the-art overview of advanced technologies and tools applicable to UPA, aiming to inform how these innovations can be better enabled to enhance UPA’s contributions to sustainable urban food systems. The review begins by defining UPA, categorizing its various forms, and exploring its multifunctional roles within urban contexts. It then presents a thorough analysis of a range of UPA technologies that serve specific purposes, including productivity and product quality improvement, space utilization optimization, resource recycling, and land use management. Furthermore, the review evaluates the current challenges faced by these technologies throughout the stages of research and development (R&D), dissemination and extension, and application and commercialization, employing an analytical framework adapted from Technology Life Cycle theories. In conclusion, the review emphasizes the crucial roles that UPA and relevant technological innovations play in transforming food systems and urban environments. It proposes four key recommendations: (1) enhancing funding mechanisms and fostering interdisciplinary collaboration for UPA R&D, (2) strengthening UPA technology dissemination systems, (3) promoting economic feasibility and market integration within UPA business models, and (4) establishing supportive environments among all stakeholders in the innovation process. These targeted strategies are essential for scaling UPA technologies, thereby strengthening food security, environmental sustainability, and socio-economic resilience in metropolitan areas. Full article

Background: Coronary and carotid artery diseases are manifestations of a systemic atherosclerotic process, often coexisting in patients affected by both conditions. This association emphasizes the importance of evaluating both coronary and carotid atherosclerosis in high-risk individuals. Ultrasound 2D shear-wave elastography (2D-SWE) has shown promise as a noninvasive technique for assessing carotid plaque stiffness. This prospective pilot study aimed to assess carotid plaque stiffness in patients undergoing coronary artery bypass grafting (CABG) and those not scheduled for the procedure as a control group. Methods: 32 patients (17 CABG and 15 controls) were recruited, collectively presenting 43 carotid plaques. Bilateral carotid ultrasound was performed using a high-resolution linear transducer. Plaque stiffness was quantified via 2D-SWE, expressed in shear-wave velocity (SWV, m/s) and Young’s modulus (YM, kPa). Plaque characteristics, including GSM, were quantified. Intra-observer reproducibility was evaluated with intraclass correlation coefficients (ICCs) and Bland–Altman plots. Statistical differences and correlations were assessed using Mann–Whitney U and Spearman’s correlation tests. Results: Carotid plaques in the CABG group exhibited significantly lower stiffness compared to controls (median stiffness SWV: 3.64 m/s vs. 4.91 m/s, p < 0.0001; YM: 20.96 kPa vs. 72.54 kPa, p < 0.0001). ICCs demonstrated excellent reproducibility for stiffness measurements (SWV: ICC = 0.992; YM: ICC = 0.992), with minimal bias in measurements. A positive correlation was observed between 2D-SWE and GSM values (SWV: r = 0.343, p = 0.024; YM: r = 0.340, p = 0.026). Conclusions: Ultrasound 2D-SWE has shown promise as a reliable tool for quantifying carotid plaque stiffness, demonstrating high reproducibility and a significant correlation with GSM. The observed reduction in plaque stiffness among CABG patients highlights its potential as a valuable parameter for identifying high-risk plaques and assessing cerebrovascular risk in patients undergoing CABG. Full article

The degradation of pastures in tropical regions, particularly in sandy soils, poses significant challenges to sustainable agricultural practices. Crop–livestock integration (CLI) systems have emerged as a promising strategy to restore these degraded soils. This study evaluated the impact of land-use transitions on soil health in Western São Paulo, Brazil, focusing on the conversion from pasture (Urochloa brizantha) to CLI systems with U. brizantha (CLI-u) and M. maximum (CLI-m). A comprehensive set of chemicals (pH, phosphorus, potassium), physical (aggregate stability, bulk density), and biological (β-glucosidase activity, soil organic carbon) indicators were assessed across four land-use types: native vegetation (NV), pasture (PA), CLI-u, and CLI-m. The Soil Management Assessment Framework (SMAF) was applied to calculate the Soil Health Index (SHI) across three soil depths (0–0.1 m, 0.1–0.2 m, 0.2–0.3 m). At the surface layer (0–0.1 m), PA and NV exhibited the highest SHI values (0.65 and 0.63, respectively), while CLI-m showed a lower SHI (0.56). In the subsurface layer (0.1–0.2 m), CLI-m and NV presented the highest SHI values (0.66 and 0.67, respectively), whereas PA and CLI-u had lower values (0.52 and 0.58). At the deepest layer (0.2–0.3 m), SHI values in CLI systems were comparable to NV (0.56), while PA recorded the lowest SHI (0.48). These results demonstrate that land-use transitions and management practices significantly affect soil health in sandy soils. The findings underscore the potential of CLI systems, particularly those incorporating M. maximum, to enhance biological and chemical soil health indicators in tropical agroecosystems. Further refinement of CLI management strategies is essential to optimize soil health recovery in sandy soil ecosystems. Full article

The role of the plasminogen activation system is to regulate the activity of the extracellular protease plasmin. It comprises the urokinase plasminogen activator (uPA), a specific extracellular protease which activates plasminogen, its inhibitor PAI1, and the urokinase plasminogen activator receptor, uPAR, which localizes the urokinase activity. The plasminogen activation system is involved in tissue remodeling through extracellular matrix degradation, and therefore participates in numerous physiological and pathological processes, which make it a potential biomarker. To investigate the role of these molecules in the cellular processes, we cloned human uPA, PAI1, and uPAR and overexpressed them in two cell lines, the glioblastoma line A1235 and the transformed human embryonal kidney cells HEK 293. We analyzed the urokinase activity and the expression of plasminogen activation system elements on the protein and RNA level by Western blot analysis and RTqPCR. Cell proliferation was followed up by cell counting, cell migration and invasion by wound-healing and the transwell assays, respectively, and cell adhesion and dispersal by spheroid formation. The cells transfected with urokinase sequence had increased urokinase activity and uPA expression, while the PAI1-transfected cells decreased urokinase activity, increased PAI1 expression, and decreased cell migration. HEK 293 cells expressing PAI formed only small spheroids. The effects of the uPA system molecules depended on their interactions with each other and with other molecules in the microenvironment, as well as on the cell-type-specific signaling. Full article

Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBL^wt/wt, LND1^wt/wt, Hmel1^V600K/wt and M3^V600E/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h–48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1^wt/wt (p < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAF^mut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAF^wt/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAF^wt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells. Full article