Search Results (17,237)

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. Full article

One of the advantages of the EPR spectroscopy method in assessing structural defects caused by irradiation is the fact that using this method it is possible to determine not only the concentration dependences of the defect structure but to also establish their type, which is not possible with methods such as X-ray diffraction or scanning electron microscopy. Based on the data obtained, the role of variation in the ratio of components in Li₄SiO₄–Li₂TiO₃ ceramics on the processes of softening under high-dose irradiation with protons simulating the accumulation of hydrogen in the damaged layer, as well as the concentration of structural defects in the form of oxygen vacancies and radiolysis products on the processes of high-temperature degradation of ceramics, was determined. It was found that the main changes in the defect structure during the prolonged thermal exposure of irradiated samples are associated with the accumulation of oxygen vacancies, the density of which was estimated by the change in the intensity of singlet lithium, characterizing the presence of E-centers. At the same time, it was found that the formation of interphase boundaries in the structure of Li₄SiO₄–Li₂TiO₃ ceramics leads to the inhibition of high-temperature degradation processes in the case of post-radiation thermal exposure for a long time. Also, during the conducted studies, the role of thermal effects on the structural damage accumulation rate in Li₄SiO₄–Li₂TiO₃ ceramics was determined in the case when irradiation is carried out at different temperatures. During the experiments, it was determined that the main contribution of thermal action in the process of proton irradiation at a fluence of 5 × 10¹⁷ proton/cm² is an increase in the concentration of radiolysis products, described by changes in the intensities of spectral maxima, characterized by the presence of defects such as ≡Si–O, SiO₄³⁻ and Ti³⁺ defects. Full article

The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Due to the stroke-protective effects of dietary fiber and anthocyanin together with the synergistic interaction, we hypothesized that the functional drink containing the anthocyanins and dietary fiber-enriched functional ingredient from banana and germinated black Jasmine rice (BR) should protect against ischemic stroke. BR at doses of 300, 600, and 900 mg/kg body weight (BW) was orally given to male Wistar rats weighing 290–350 g once daily for 21 days, and they were subjected to ischemic reperfusion injury induced by temporary occlusion of the middle cerebral artery (MCAO/IR) for 90 min. The treatment was prolonged for 21 days after MCAO/IR. They were assessed for brain infarction volume, neuron density, Nrf2, MDA, and catalase in the cortex together with serum TNF-α and IL-6. Lactobacillus and Bifidobacterium spp. in feces were also assessed. Our results showed that BR improved the increase in brain infarcted volume, MDA, TNF-α, and IL-6 and the decrease in neuron density, Nrf2, catalase, and both bacteria spp. induced by MCAO/IR. These data suggest the stroke-protective effect of the novel functional drink, and the action may involve the improvement of Nrf2, oxidative stress, inflammation, and the amount of Lactobacillus and Bifidobacterium spp. Full article

High-viscosity stratified strata, characterized by complex geotechnical properties such as strong cohesion, low permeability, and pronounced layered structures, exhibit significant lateral friction resistance and high-end resistance during steel sheet pile installation. These factors substantially increase construction difficulty and may even cause structural damage. This study addresses two critical mechanical challenges during vibratory pile driving in Fujian Province’s hydraulic engineering project: prolonged high-frequency driving durations, and severe U-shaped steel sheet pile head damage in high-viscosity stratified soils. Employing the Coupled Eulerian–Lagrangian (CEL) numerical method, a systematic investigation was conducted into the penetration resistance, stress distribution, and damage patterns during vibratory pile driving under varying conditions of cohesive soil layer thickness, predrilled hole spacing, and aperture dimensions. The correlation between pile stress and penetration depth was established, with the influence mechanisms of key factors on driving-induced damage in high-viscosity stratified strata under multi-factor coupling effects elucidated. Finally, the feasibility of predrilling techniques for resistance reduction was explored. This study applies the damage prediction model based on the CEL method to U-shaped sheet piles in high-viscosity stratified formations, solving the problem of mesh distortion in traditional finite element methods. The findings provide scientific guidance for steel sheet pile construction in high-viscosity stratified formations, offering significant implications for enhancing construction efficiency, ensuring operational safety, and reducing costs in such challenging geological conditions. Full article

Water scarcity and spatial variability in soil fertility are key constraints to stable grain production in the Huang-Huai-Hai Plain. However, the interaction mechanisms between regulated deficit irrigation and soil fertility influencing yield formation and water-nitrogen use efficiency in winter wheat remain unclear. In this study, a two-year field experiment (2022–2024) was conducted to investigate the effects of two irrigation regimes—regulated deficit irrigation during the heading to grain filling stage (D) and full irrigation (W)—under four soil fertility levels: F1 (N: P: K = 201.84: 97.65: 199.05 kg ha⁻¹), F2 (278.52: 135: 275.4 kg ha⁻¹), F3 (348.15: 168.75: 344.25 kg ha⁻¹), and CK (no fertilization). The results show that aboveground dry matter accumulation, total nitrogen content, pre-anthesis dry matter and nitrogen translocation, and post-anthesis accumulation significantly increased with fertility level (p < 0.05). Regulated deficit irrigation promoted the contribution of post-anthesis dry matter to grain yield under the CK and F1 treatments, but suppressed it under the F2 and F3 treatments. However, it consistently enhanced the contribution of post-anthesis nitrogen to grain yield (p < 0.05) across all fertility levels. Higher fertility levels prolonged the grain filling duration by 18.04% but reduced the mean grain filling rate by 15.05%, whereas regulated deficit irrigation shortened the grain filling duration by 3.28% and increased the mean grain filling rate by 12.83% (p < 0.05). Grain yield significantly increased with improved fertility level (p < 0.05), reaching a maximum of 9361.98 kg·ha⁻¹ under the F3 treatment. Regulated deficit irrigation increased yield under the CK and F1 treatments but reduced it under the F2 and F3 treatments. Additionally, water use efficiency exhibited a parabolic response to fertility level and was significantly enhanced by regulated deficit irrigation. Nitrogen partial factor productivity (NPFP) declined with increasing fertility level (p < 0.05); Regulated deficit irrigation improved NPFP under the F1 treatment but reduced it under the F2 and F3 treatments. The highest NPFP (41.63 kg·kg⁻¹) was achieved under the DF1 treatment, which was 54.81% higher than that under the F3 treatment. TOPSIS analysis showed that regulated deficit irrigation combined with the F1 fertility level provided the optimal balance among yield, WUE, and NPFP. Therefore, implementing regulated deficit irrigation during the heading–grain filling stage under moderate fertility (F1) is recommended as the most effective strategy for achieving high yield and efficient resource utilization in winter wheat production in this region. Full article

Relict fern species, confined to microhabitats with stable historical conditions, are especially vulnerable to climate change. The Alboran Arc hosts a unique relict fern flora, including Culcita macrocarpa, Diplazium caudatum, and Pteris incompleta, and functions as a major Pleistocene refuge. This study assesses the population trends and climate sensitivity of these species in Los Alcornocales Natural Park using annual abundance time series for a decade, empirical survival projections, and principal component analysis to identify key climatic drivers. Results reveal distinct climate response clusters among populations, though intra-specific variation highlights the importance of local conditions. Climate change is already impacting population viability, especially for P. incompleta, which shows high sensitivity to rising maximum temperatures and prolonged heatwaves. Climate-driven models forecast more severe declines than empirical ones, particularly for C. macrocarpa and P. incompleta, with the latter showing a projected collapse by the mid-century. In contrast, D. caudatum exhibits moderate vulnerability. Crucially, the divergence between models underscores the impact of conservation efforts: without reinforcement and reintroduction actions, projected declines would likely be more severe. These results project a decline in the populations of the studied ferns, highlighting the urgent need to continue implementing both in situ and ex situ conservation measures. Full article

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

While boreal forests constitute 30% of the Earth’s forested area and are responsible for 20% of the global carbon sink, there is considerable concern about their sustainability. This paper focuses on the role of elevated CO₂, examining whether wood volume in these forests has responded to increased CO₂ over the last 60 years. To accomplish this, we use a rich set of wood volume measurement data from the Province of Alberta, Canada, and deploy quasi-experimental techniques to determine the effect of elevated CO₂. While the few experimental studies that have examined boreal forests have found almost no effect of elevated CO₂, our results indicate that a 1.0% increase in lifetime exposure to CO₂ leads to a 1.1% increase in aboveground wood volume in these boreal forests. This study showcases the value of research designs that use natural settings to better account for the effects of prolonged exposure to elevated CO₂. Our results should enable improved delineation of the drivers of historical changes in wood volume and carbon storage in boreal forests. In addition, when combined with other studies, these results will likely aid policymakers in designing management or policy approaches that will enhance the sustainability of forests in boreal regions. Full article

Subsurface mass concrete infrastructure—including immersed tunnels, dams, and nuclear waste containment systems—frequently faces calcium-leaching risks from prolonged groundwater exposure. An anisotropic stress-leaching damage model incorporating microcrack propagation is developed for underground concrete’s chemo–mechanical coupling. This model investigates stress-induced anisotropy in concrete through the evolution of oriented microcrack networks. The model incorporates nonlinear anisotropic plastic strain from coupled chemical–mechanical damage. Unlike conventional concrete rheology, this model characterizes chemical creep through stress-chemical coupled damage mechanics. The numerical model is incorporated within COMSOL Multiphysics to perform coupled multiphysics simulations. A close match is observed between the numerical predictions and experimental findings. Under high stress loads, calcium leaching and mechanical stress exhibit significant coupling effects. Regarding concrete durability, chemical degradation has a more pronounced effect on concrete’s stiffness and strength reduction compared with stress-generated microcracking. Full article

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

In early May 2025, extreme wildfires swept across Manitoba, Canada, fueled by unseasonably warm temperatures, prolonged drought, and stressed vegetation. We explore how multi-source satellite indicators—such as anomalies in snow cover, precipitation, temperature, vegetation indices, and soil moisture in April–May—jointly signal landscape preconditioning for fire, highlighting the potential of these compound anomalies to inform fire risk awareness in boreal regions. Results indicate that rainfall deficits and diminished snowpack significantly reduced soil moisture, which subsequently decreased vegetative greenness and created a flammable environment prior to ignition. This concept captures how multiple moderate anomalies, when occurring simultaneously, can converge to create high-impact fire conditions that would not be flagged by individual thresholds alone. These findings underscore the importance of integrating climate and biosphere anomalies into wildfire risk monitoring to enhance preparedness in boreal regions under accelerating climate change. Full article

This research demonstrates the potential of plant waste cellulose as a remarkable biomaterial for multilayer tablet formulation. Rice husks (RC) and orange peels (OC) were used as cellulose sources and characterized for a comparison with commercial cellulose. The FTIR characterization shows minimal differences in their chemical components, making them equivalent for compression into tablets containing ibuprofen. TGA measurements indicate that the RC is slightly better for multilayer formulations due to its favorable degradation profile. This is corroborated by an XRD analysis that reveals its higher crystalline fraction (~55%). The use of a heat press at combined high pressures and temperatures allows the layer-by-layer tablet formulation of ibuprofen, taken as a model drug. Additionally, this study compares the release profile of three types of tablets compressed with cellulose: mixed (MIX), two-layer (BL), and three-layer (TL). The MIX tablet shows a profile like that of conventional ibuprofen tablets. Although both BL and TL tablets significantly reduce their release percentage in the first hours, the TL ones have proven to be better in the long run. In fact, formulations made of extracted cellulose sandwiching ibuprofen display a zero-order release profile and prolonged release since the drug release amounts to ~70% after 120 h. This makes the TL formulations ideal for maintaining the therapeutic effect of the drug and improving patients’ wellbeing and compliance while reducing adverse effects. Full article