Search Results (267)

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31⁺/CD146⁺ ratio among viable CD45⁻ cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness. Full article

Heavy metal pollution poses a serious threat to soil ecosystems worldwide, as long-term exposure can alter microbial community functioning and reduce overall ecosystem resilience. This study investigated the impact of heavy metal contamination in technogenic industrial areas of the East Kazakhstan Region on soil microbial communities. Soil samples were collected for chemical and metagenomic analyses. Concentrations of Zn, Pb, Cu, and Cd were quantified by flame atomic absorption spectrometry (FAAS). Using long-read whole-metagenome nanopore sequencing, we conducted strain-level profiling of soils with different levels of metal contamination. This approach provided high-resolution taxonomic data, enabling detailed characterization of microbial community structure. Heavy metal exposure did not significantly reduce microbial diversity or richness but influences the quality of community composition. Metal-resistant taxa dominated contaminated soils. Overall, the results highlight the value of long-read sequencing for resolving strain-level responses to environmental contamination. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

Background/Objectives: This study examined the metabolic, oxidative, immunological, and histomorphological effects of the multicomponent fermented biological product derived from camel milk, Inullact-Fito, in comparison to metformin in a rat model of alloxan-induced diabetes resulting from insulin insufficiency. The model was chosen as an experimental system that replicates pancreatic β-cell damage induced by oxidative stress rather than insulin resistance. Methods: Alloxan-induced diabetes was used to evaluate metabolic, oxidative, immunological, and histomorphological alterations. Metformin was utilized as a pharmacological comparator. Blood glucose levels, circulating insulin concentrations, markers of oxidative stress and lipid peroxidation, immunoglobulin levels, CD4⁺/CD8⁺ T cell balance, and pancreatic histostructure were assessed. Results: Alloxan administration led to substantial hyperglycemia, oxidative stress, immunological imbalance, and structural damage to pancreatic tissue. Following therapy with Inullact-Fito, blood glucose levels reduced dramatically (from 21.9 ± 0.22 to 9.85 ± 0.10 mmol/L, p < 0.05), circulating insulin concentrations were largely corrected, oxidative stress and lipid peroxidation markers decreased. Immunological evaluation revealed decreased serum immunoglobulin M and IgG levels (p < 0.05) and partial normalization of the CD4⁺/CD8⁺ T cell balance. Metformin showed comparative effects; however, its activity in this model is limited by its primary mechanism related to insulin resistance. Conclusions: Overall, the data reveal that Inullact-Fito combines metabolic, antioxidant, and immunomodulatory actions under experimental oxidative and metabolic stress conditions. Further research using models of insulin resistance and type 2 diabetes, as well as long-term clinical trials, is needed to fully evaluate the therapeutic potential, safety profile, and translational importance of this fermented dairy product as a functional nutritional intervention. Full article

Cadmium (Cd) is a typical pollutant with strong toxicity even at low concentrations. In the marine environment, Cd is a problem of magnitude and ecological significance due to its high toxicity and accumulation in living organisms. The clam Meretrix meretrix is a useful bioindicator species for evaluating heavy-metal stress. This study investigated the extent of recovery from Cd²⁺-induced oxidative and immune impairments in M. meretrix gills achieved by short-term depuration. Clams were exposed to 3 mg/L Cd²⁺ for six days or three days followed by three days of depuration, and the Cd contents, morphological structure, osmoregulation, oxidative stress, and immune responses in the gills were evaluated. The results showed that gill Cd contents increased with exposure, reaching 9.857 ± 0.074 mg·kg⁻¹ on day 3 but decreased slightly to 8.294 ± 0.056 mg·kg⁻¹ after depuration, while reaching 18.665 ± 0.040 mg·kg⁻¹ on day 6 after continuous exposure. Histological lesions, including lamellar fusion, hemolymphatic sinus dilation, and ciliary degeneration, partially recovered after depuration. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels decreased significantly, while DNA-protein crosslinking rate (DPC) and protein carbonyl (PCO) showed minor reductions. Total antioxidant capacity (T-AOC) and the activities of Ca²⁺/Mg²⁺-ATPase (CMA), cytochrome c oxidase (COX), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) increased by over 10% during depuration, though these changes were not statistically significant. Lysozyme (LZM) activity and MT transcript levels increased progressively with Cd exposure, indicating their suitability as biomarkers of Cd stress. Acid and alkaline phosphatase (ACP, AKP) activities and Hsp70 and Nrf2 mRNA transcripts exhibited inverted U-shaped response consistent with hormetic response. ACP and AKP activity levels rose by more than 20% after depuration, suggesting partial restoration of immune capacity. Overall, Cd exposure induced oxidative damage, metabolic disruption, and immune suppression in M. meretrix gills, yet short-term depuration allowed partial recovery. These findings enhance understanding of Cd toxicity and reversibility in marine bivalves and reinforce the usage of biochemical and molecular markers for monitoring Cd contamination and assessing depuration efficiency in aquaculture environments. Full article

Change detection plays a crucial role in geological disaster tasks such as landslide identification, post-earthquake building reconstruction assessment, and unstable rock mass monitoring. However, real-world scenarios often pose significant challenges, including complex surface backgrounds, illumination and seasonal variations between temporal phases, and diverse change patterns. To address these issues, this paper proposes a multi-stage model for geological disaster change detection, termed MSMCD, which integrates strategies of global dependency modeling, local difference enhancement, edge constraint, and frequency-domain fusion to achieve precise perception and delineation of change regions. Specifically, the model first employs a DualTimeMamba (DTM) module for two-dimensional selective scanning state-space modeling, explicitly capturing cross-temporal long-range dependencies to learn robust shared representations. Subsequently, a Multi-Scale Perception (MSP) module highlights fine-grained differences to enhance local discrimination. The Edge–Change Interaction (ECI) module then constructs bidirectional coupling between the change and edge branches with edge supervision, improving boundary accuracy and geometric consistency. Finally, the Frequency-domain Change Fusion (FCF) module performs weighted modulation on multi-layer, channel-joint spectra, balancing low-frequency structural consistency with high-frequency detail fidelity. Experiments conducted on the landslide change detection dataset (GVLM-CD), post-earthquake building change detection dataset (WHU-CD), and a self-constructed unstable rock mass change detection dataset (TGRM-CD) demonstrate that MSMCD achieves state-of-the-art performance across all benchmarks. These results confirm its strong cross-scenario generalization ability and effectiveness in multiple geological disaster tasks. Full article

Background: Electrochemotherapy (ECT) is a clinically validated local ablative treatment increasingly recognized for its ability to induce immunogenic cell death and stimulate antitumor immunity. Its combination with immune checkpoint inhibitors, such as anti-PD-1 antibodies, may enhance systemic immune responses and improve therapeutic efficacy, particularly in poorly immunogenic tumors. Methods: We evaluated the antitumor effectiveness of ECT combined with a murine analog of the anti-PD-1 antibody in four syngeneic murine tumor models with differing histology and immune status: WEHI fibrosarcoma, CT26 and MC38 colorectal carcinoma, and 4T1 mammary carcinoma. In vitro cytotoxicity assays assessed tumor cell sensitivity to ECT, while in vivo experiments evaluated complete response (CR) rates, immune cell infiltration, and long-term immune memory through secondary tumor challenge. Immunohistochemical analysis of CD4⁺, CD8⁺, and granzyme B⁺ effector cells. Results: In vitro, WEHI cells exhibited the highest sensitivity to ECT. In vivo, ECT monotherapy induced CRs in 100% of WEHI tumors, 60% of CT26, 17% of 4T1, and 15% of MC38. The addition of anti-PD-1 significantly enhanced outcomes in less responsive models, increasing CRs to 90% in CT26, 91% in MC38, and 53% in 4T1. Combination therapy promoted pronounced infiltration of CD4⁺, CD8⁺, and granzyme B⁺ T cells and the formation of tertiary lymphoid structure, particularly in MC38 tumors. Secondary challenge experiments confirmed long-term immune memory in CT26 and MC38 models and induced memory in 4T1, which was absent following monotherapy. Conclusions: ECT synergizes with PD-1 blockade to potentiate local and systemic antitumor immunity, overcoming immune resistance in poorly immunogenic tumors. These findings support further clinical development of ECT in combination with immune checkpoint inhibitors as a component of personalized cancer immunotherapy. Full article

We report a novel approach to fabricating high-performance and robust quantum dot light-emitting diodes (QLEDs) utilizing sputtered SnO₂ thin films as the electron transport layer (ETL). While conventional solution-processed ZnMgO NP ETLs face limitations in mass production, the sputtering process offers advantages for uniform and reproducible thin film deposition. Herein, the structural, optical, and electrical properties of SnO₂ thin films were optimized by controlling the Ar/O₂ ratio and substrate heating temperature during sputtering. SnO₂ thin films with O₂ gas improve charge balancing in QLEDs by lowering the conduction band minimum. Furthermore, it was observed that oxygen vacancies in SnO₂ function as exciton quenching sites, which directly impacts the long-term stability of the device. QLEDs fabricated under optimal conditions (Ar/O₂ = 35:5, 200 °C heating) achieved a peak luminance of 99,212 cd/m² and a current efficiency of 21.17 cd/A with excellent device stability. The findings suggest that sputtered SnO₂ ETLs are a highly promising technology for the commercial production of QLEDs. Full article

Creatinine (Crn) is a clinically relevant biomarker commonly used for the diagnosis and monitoring of kidney disease. In this work, we report the fabrication of reduced-graphene-oxide-based field-effect transistors (rGO FETs) for Crn detection. These devices were functionalized using a layer-by-layer (LbL) assembly, in which polyethyleneimine (PEI) and creatinine deiminase (CD) were alternately deposited. This LbL strategy allows for the effective incorporation of CD without compromising its structural or functional integrity, while also taking advantage of the local pH changes caused by creatinine hydrolysis. It also benefits from the use of a polyelectrolyte that can amplify the enzymatic signal. Furthermore, it enables scalable and efficient fabrication. These transistors also address the challenges of point-of-care implementation in single-use cartridges. It is worth noting that the devices showed a linear relationship between the Dirac-point shift and the logarithm of the creatinine concentration in the 20–500 µM range in diluted simulated urine. The sensor response improved with increasing numbers of PEI/CD bilayers. Furthermore, the functionalized FETs demonstrated rapid detection dynamics and good long-term stability. Present results confirm the potential of these devices as practical biosensors for sample analysis under real-world conditions, making them ideal for implementation in practical settings. Full article

Carbon dots (CDs) have recently emerged as a novel class of eco-friendly and multifunctional corrosion inhibitors owing to their nanoscale dimensions, tunable surface functionalities, and sustainable synthesis pathways. This review summarizes the latest progress in CD-based inhibitors, focusing on synthesis methods, applications, and inhibition mechanisms. Various strategies—including hydrothermal/solvothermal treatment, microwave irradiation, pyrolysis, electrochemical synthesis, and chemical oxidation—have been employed to obtain CDs with tailored size, heteroatom doping, and surface groups, thereby enhancing their inhibition efficiency. CDs have demonstrated remarkable applicability across diverse corrosive environments, including acidic, neutral chloride, CO₂-saturated, microbiologically influenced, and alkaline systems, often achieving inhibition efficiencies exceeding 90%. Mechanistically, their performance arises from strong adsorption and compact film formation, heteroatom-induced electronic modulation, suppression of anodic and cathodic reactions, and synergistic effects of particle size and structural configuration. Compared with conventional inhibitors, CDs offer higher efficiency, environmental compatibility, and multifunctionality. Despite significant progress, challenges remain regarding precise structural control, scalability of synthesis, and deeper mechanistic understanding. The effectiveness of CDs inhibitors is highly dependent on factors such as pH, temperature, inhibitor concentration, and exposure time, which should be tailored for specific applications to maximize performance. Future research should focus on integrating sustainable synthesis with rational heteroatom engineering and advanced characterization to achieve long-term, cost-effective, and environmentally benign corrosion protection solutions. Compared to earlier reviews, this review discusses the emerging trends in the field of CDs as corrosion inhibitors. Full article

Osteosarcoma (OS) remains the most common primary malignant bone tumor in adolescents, with conventional treatments yielding only modest improvements in long-term survival. Immunotherapy has emerged as a promising strategy to overcome these limitations. B7-H3 (CD276) stands apart from other potential targets due to its high expression in tumors cells, as well as its strong association with tumor aggressiveness and poor prognosis. This review provides a comprehensive overview of B7-H3, covering its molecular structure, regulatory mechanisms, biological functions, and expression patterns in tumor tissues. We emphasize the dual roles of B7-H3—both immunoregulatory and non-immunoregulatory—in shaping the tumor microenvironment (TME) and facilitating immune evasion. Building on these insights, we summarize current immunotherapeutic strategies targeting B7-H3 in OS, including monoclonal antibodies (mAbs), chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). These four strategies have their own advantages and deficiencies. Excitingly, rapid advances in nanoparticle-based systems offer promising solutions to overcome the limitations, especially to develop more effective drug delivery systems and to reshape the TME by targeting immune cells. Despite promising progress, significant challenges remain. These include the absence of an identified B7-H3 receptor, the immunosuppressive and heterogeneous nature of the OS TME, and the need for improved targeting specificity and safety. Addressing these challenges through optimization of delivery systems, combination strategies, and the integration of nanotechnology may unlock the full potential of B7-H3-based immunotherapy in the treatment of OS. Full article

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which ocular involvement represents a clinically significant yet frequently underrecognized contributor to morbidity. Ocular manifestations in SLE may arise from disease activity itself, but also as adverse effects of long-term pharmacological therapy. With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways. These advances have improved systemic disease control and survival; however, their ophthalmological safety profiles remain only partially defined. This review synthesizes current evidence on ocular adverse events associated with both traditional and emerging SLE therapies. Established agents, particularly hydroxychloroquine and corticosteroids, are consistently linked to complications including retinopathy, posterior subcapsular cataracts, steroid-induced glaucoma, and central serous chorioretinopathy. In contrast, recently approved or investigational therapies—such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies—have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains. Although ocular complications appear infrequent in clinical trials, underdetection in real-world practice and insufficient long-term monitoring may underestimate their true incidence. These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient population. Full article

Urban building change detection (UBCD) is essential for urban planning, land-use monitoring, and smart city analytics, yet bi-temporal optical methods remain limited by spectral confusion, occlusions, and weak sensitivity to structural change. To overcome these challenges, we propose DDDMNet, a lightweight deep learning framework that fuses multi-source inputs—including DSM, dnDSM, DOM, and NDVI—to jointly model geometric, spectral, and environmental cues. A core component of the network is the DSM Difference Normalization Module (DDDM), which explicitly normalizes elevation differences and directs the model to focus on height-related structural variations such as rooftop additions and demolition. Embedded into a TinyCD backbone, DDDMNet achieves efficient inference with low memory cost while preserving detail-level change fidelity. Across LEVIR-CD, WHU-CD, and DSIFN, DDDMNet achieves up to 93.32% F1-score, 89.05% Intersection over Union (IoU), and 99.61% Overall Accuracy (OA), demonstrating consistently strong performance across diverse benchmarks. Ablation analysis further shows that removing multi-source fusion, DDDM, dnDSM, or morphological refinement causes notable drops in performance—for example, removing DDDM reduces IoU from 88.12% to 74.62%, underscoring its critical role in geometric normalization. These results demonstrate that DDDMNet is not only accurate but also practically deployable, offering strong potential for scalable 3D city updates and long-term urban monitoring under diverse data conditions. Full article

This study proposes a novel framework for analyzing Vehicle-Integrated Photovoltaic (VIPV) systems, integrating optical, thermal, and electrical models. The model modifies existing fixed PV methodologies for VIPV applications to assess received irradiance, PV module temperature, and energy production, and is available as an open-source MATLAB tool (VIPVLIB) enabling simulations via a smartphone. A key innovation is the integration of meteorological data and real-time driving, dynamically updating vehicle position and orientation every second. Different time resolutions were explored to balance accuracy and computational efficiency for optical model, while the thermal model, enhanced by vehicle speed, wind effects, and thermal inertia, improved temperature and power predictions. Validation on a minibus operating within the University of Palermo campus confirmed the applicability of the proposed framework. The roof received 45–47% of total annual irradiation, and the total yearly energy yield reached about 4.3 MWh/Year for crystalline-silicon, 3.7 MWh/Year for CdTe, and 3.1 MWh/Year for CIGS, with the roof alone producing up to 2.1 MWh/Year (c-Si). Under hourly operation, the generated solar energy was sufficient to fully meet daily demand from April to August, while during continuous operation it supplied up to 60% of total consumption. The corresponding CO₂-emission reduction ranged from about 3.5 ton/Year for internal-combustion vehicles to around 2 ton/Year for electric ones. The framework provides a structured, data-driven approach for VIPV analysis, capable of simulating dynamic optical, thermal, and electrical behaviors under actual driving conditions. Its modular architecture ensures both immediate applicability and long-term adaptability, serving as a solid foundation for advanced VIPV design, fleet-scale optimization, and sustainability-oriented policy assessment. Full article

Background/Objectives: Three-dimensional (3D) in vitro cell culture models have recently stimulated great interest since they may have more pre-clinical value than conventional in vitro 2D models. In fact, 3D culture models may mimic the in vivo biophysical 3D structure of tumors and cell-to-cell interaction, thereby representing a more useful approach to testing drug responses. In this study we have developed a 3D culture model of an EBV+/CD30+cell line, D430B, previously characterized as an Anaplastic Large Cell Lymphoma of B phenotype (B-ALCL), to determine the cytotoxic activity of the antibody–drug conjugate Brentuximab Vedotin. Methods: By using of ultra-low attachment plates, we developed D430B spheroids that appeared particularly homogenous in terms of growth and size. Results: Brentuximab Vedotin treatment (1 to 20 μg/mL) turned out to be significantly cytotoxic to these cells, while the addition of the anti-CD20 chimeric antibody Rituximab (10 μg/mL) appeared almost ineffective, even though these cells express CD20. Moreover, when we co-cultured D430B cells with stromal cells (HS5), to re-create a microenvironment representative of neoplastic cell/mesenchymal cell interactions within the lymph node, we observed a significant, although faint, protective effect. Conclusions: This simple and reproducible method of generating D430B-ALCL spheroids to evaluate their response to Brentuximab Vedotin treatment, as here described, may provide a valuable preliminary tool for the future pre-clinical screening of patients’ primary lymphoma cells or the development of novel therapies for this type of pathology and related diseases. Full article