Search Results (1,799)

Granulosa cells (GCs) and ovarian putative stem cells (oPSCs) represent distinct but complementary populations within the mammalian ovary. While GCs have long been considered terminally differentiated and hormonally specialized, emerging evidence indicates that they retain epigenetic plasticity and, under defined conditions, can be reprogrammed into cells exhibiting pluripotent-like features. In contrast, oPSCs, including oogonial stem cells (OSCs) and very small embryonic-like stem cells (VSELs), are naturally multipotent and capable of spontaneous or inducible differentiation into neural, endothelial, and other somatic lineages. Both cell types express stemness-related markers, such as OCT4, SOX2, and c-KIT, and demonstrate potential for self-renewal and lineage conversion. Recent advances in chemical modulation of epigenetic reprogramming, particularly with agents from the family of non-specific DNA methyltransferase (DNMT) inhibitors, such as 5-azacytidine (5-azaC), highlight the feasibility of generating functional, lineage-specific derivatives of GCs or oPSCs without genetic manipulation. Not without significance is also the fact that extended/high-dose 5-azaC-mediated modulation can induce cell senescence or apoptotic/necrotic death. Therefore, dosing must be carefully titrated, which strongly supports a dose- and/or time-dependent mechanism for 5-azaC-based epigenetic modification in treated cells. This study aims to summarize the molecular and functional properties of mammalian GCs and oPSCs, emphasizing their applicability in regenerative medicine and reproductive bioengineering, with a focus on safe, patient-specific cell-based therapies. Full article

Supramolecular hydrogels formed by the self-assembly of low-molecular-weight (LMW) agents are promising next-generation biomaterials for drug delivery, tissue engineering, and regenerative medicine. Phenylalanine (Phe) derivatives have emerged as a privileged class of LMW supramolecular gelators due to their strong propensity to self-assemble into emergent hydrogel networks with demonstrated biocompatibility. We have previously reported a series of cationic Phe-derived gelators in which fluorenylmethoxycarbonyl (Fmoc) phenylalanine (Phe), 3-fluorophenylalanine (3F-Phe), and pentafluorophenylalanine (F₅-Phe) are functionalized at the C-terminus with diaminopropane (DAP). These gelators (Fmoc-Phe-DAP, Fmoc-3F-Phe-DAP, and Fmoc-F₅-Phe-DAP) are water-soluble and undergo spontaneous self-assembly and gelation upon an increase in the ionic strength of the solution caused by addition of sodium chloride. Herein, we report the effects of pH on the self-assembly and gelation of Fmoc-Phe-DAP, Fmoc-3F-Phe-DAP, and Fmoc-F₅-Phe-DAP. We also describe the effects that pH has on the emergent properties of these hydrogel networks, including assembly morphology and hydrogel viscoelasticity. These studies indicate that pH has varying effects on the properties of the hydrogels that are also dependent on the molecular structure of the Fmoc-Phe-DAP derivative. Fmoc-Phe-DAP hydrogels are highly sensitive to changes in solvent pH, forming strong hydrogels only near neutral pH. In contrast, hydrogels of Phe derivatives with fluorinated side chains (Fmoc-3F-Phe-DAP and Fmoc-F5-Phe-DAP) have consistent emergent viscoelastic properties across a wider range of acidic to basic pH values. Full article

Counter-current, spontaneous imbibition of brine into oil-saturated rocks is a critical process for recovery of bypassed oil in carbonate reservoirs. However, the classic Amott-cell test introduces experimental artifacts that distort the true dynamics of oil recovery, complicating the interpretation and modeling of recovery histories. In this study, we applied a modified Amott procedure to eliminate these artifacts, producing smooth and reproducible recovery histories for both water-wet and mixed-wet carbonate core plugs saturated with brine and oil. By applying Generalized Extreme Value (GEV) statistics, we modeled cumulative oil production and showed that a GEV model is able to capture the essentially non-equilibrium nature of spontaneous imbibition. Our results demonstrate that water-wet systems exhibit faster recovery rates and shorter induction times due to favorable capillary forces, while mixed-wet samples have slower dynamics and longer induction times, reflecting the influence of wettability alterations. We demonstrate that the GEV fitting parameters systematically correlate with key rock–fluid properties, such as wettability, oil viscosity, and pore network characteristics, offering a semi-quantitative approach to analyze recovery behavior. This study demonstrates the potential of a GEV-based statistical model to deepen understanding of the spontaneous imbibition mechanisms and to enhance predictive capabilities for oil production dynamics. Full article

This study aimed to elucidate the vasorelaxant mechanism of action for apigenin 7-glucoside (A7G) by integrating computational and ex vivo pharmacological approaches. Molecular docking simulations were conducted to predict the binding affinities and interactions of A7G with key vascular proteins, specifically human endothelial nitric oxide synthase (eNOS-PDB ID: 1M9M), and human intermediate (IKCa-PDB ID: 9ED1) and small-conductance (SKCa-PDB ID: 6CNN) Ca2+-activated K+ channels. The vasodilatory properties of A7G were subsequently evaluated in isolated mesenteric vascular beds (MVBs) from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). The in silico analysis indicated that A7G possesses favorable binding affinities for the 1M9M, 9ED1, and 6CNN protein targets. Pharmacological assessments demonstrated that A7G induced a dose- and endothelium-dependent reduction in perfusion pressure in MVBs from WKY and SHR rats. The vasodilatory response to A7G was completely abrogated by perfusion with a high-potassium solution or a non-selective K+ channelblocker. Furthermore, co-administration of apamin and TRAM-34, selective inhibitors of SKCa and IKCa, respectively, also abolished the vasorelaxant effects of A7G. Collectively, these findings suggest that the vascular effects of A7G in both WKY and SHR rats involve an endothelium-dependent mechanism, likely initiated by the activation of the NO/cGMP pathway, which culminates in the opening of IKCa and SKCa channels. Full article

Background and Objectives: Transarterial embolization (TAE) serves as a valuable alternative for gastrointestinal bleeding when endoscopy fails or is inaccessible. Quick-soluble gelatin sponge particles (QS-GSPs) dissolve rapidly and may reduce ischemic complications compared to permanent embolic agents. This study evaluated the safety and effectiveness of TAE using QS-GSPs for acute lower gastrointestinal bleeding. Materials and Methods: This retrospective multicenter study analyzed patients who underwent TAE with QS-GSPs for acute nonvariceal lower GI bleeding between 2021 and 2024. Technical success (occlusion or stasis of blood flow in the target artery), clinical success (cessation of bleeding symptoms with hemodynamic stability during the week following TAE without major complications), and procedure-related complications were assessed. Results: A total of 29 patients (mean age 64.9 years) were included. Active bleeding was detected in 6 patients (20.7%) on angiography. Embolized arteries included jejunal (n = 7), ileal (n = 7), ileocolic anastomotic (n = 1), cecal (n = 2), colic (n = 7), and rectosigmoid (n = 5) arteries. QS-GSPs (150–350 μm (n = 10) or 350–560 μm (n = 19)), which dissolve completely within several hours, were used as the sole embolic agents. Technical and clinical success rates were 100% and 75.9% (22/29), respectively. Clinical failure occurred in seven patients (24.1%) due to persistent (n = 4) or recurrent (n = 3) bleeding within one week. Transient bowel ischemia occurred in two patients (6.9%) but resolved spontaneously. The clinical success rate did not differ significantly between patients with active bleeding (66.7%) versus those without (73.9%). Conclusions: TAE with QS-GSPs for acute lower GI bleeding demonstrated a favorable safety profile with clinical success exceeding 75%. Transient bowel ischemia occurred in 6.9% of patients with spontaneous resolution, and no bowel infarction was observed. Full article

Background: Hyperphosphorylated tau accumulation and neurofibrillary tangles (NFTs) are hallmarks of tauopathies, including Alzheimer’s disease (AD), and are strongly associated with cognitive decline. The rTg4510 mouse model, which expresses mutant human tau (P301L), develops progressive tauopathy in the absence of amyloid-β pathology, providing a valuable tool for investigating tau-driven neurodegeneration. Previous studies have demonstrated spatial and object-recognition memory deficits at six months of age, which can be prevented by doxycycline (DOX)-mediated suppression of tau expression. However, it remained unclear whether non-spatial hippocampal learning, particularly temporal associative learning, would be similarly affected. Methods: We evaluated six-month-old rTg4510 mice with or without DOX treatment. To control for potential motor confounds, we first assessed spontaneous home cage activity. We then tested hippocampus-dependent non-spatial learning using two paradigms: trace eyeblink conditioning (500-ms trace interval) and contextual fear conditioning. Results: General motor function remained intact; however, rTg4510 mice without DOX treatment exhibited increased rearing behavior. These mice demonstrated significant deficits in trace eyeblink conditioning acquisition, with particularly clear impairment on the final day of training. Contextual fear conditioning showed milder deficits. Analysis of response peak latency revealed subtle temporal processing abnormalities during early learning. Two months of DOX treatment initiated at four months of age prevented these learning deficits, confirming their association with tau overexpression. Conclusions: Our findings demonstrate that rTg4510 mice exhibit deficits in non-spatial temporal associative learning alongside previously reported spatial and object-recognition impairments. Trace eyeblink conditioning serves as a sensitive behavioral assay for detecting tau-related hippocampal dysfunction, and the prevention of learning deficits by DOX treatment highlights its potential utility as a translational biomarker for evaluating tau-targeted interventions. Full article

In Mediterranean semi-arid regions, rainfed olive groves are increasingly being abandoned due to drought, low profitability, and rural depopulation. The long-term impact of abandonment on soil conditions is debated, as it may promote vegetation recovery or lead to degradation. In contrast, some farmers are adopting low-disturbance management practices that allow spontaneous vegetation to establish. These contrasting scenarios offer valuable opportunities for comparison. This study aims to develop a framework to assess the impact of different management regimes on soil health and to investigate (1) the impact of spontaneous vegetation cover (SVC) and tillage regimes on soil organic carbon (SOC), and (2) the long-term ecological dynamics of abandoned groves, through a combination of field surveys, remote sensing, and object detection. SOC was assessed using both ground-based and remote sensing-derived indicators. Vegetation cover was quantified via a grid point intercept method. Field data were integrated with a land-use monitoring framework that includes abandonment assessment through historical orthophotos and a deep learning model (YOLOv12) to detect active and abandoned olive groves. Results show that abandoned zones are richer in SOC than active ones. In particular, the active groves with SVC exhibit a mean SOC of 1%, which is higher than that of tilled groves, where SOC is 0.45%, with no apparent moisture loss. Abandoned groves can be reliably identified from aerial imagery, achieving a recall of 0.833 for abandoned patches. Our results demonstrate the potential of YOLOv12 as an innovative and accessible tool for detecting zones undergoing ecological regeneration or degradation. The study underscores the ecological and agronomic potential of spontaneous vegetation in olive agroecosystems. Full article

Municipal solid waste incineration (MSWI) fly ash, classified as hazardous waste (HW18) due to the presence of heavy metals and dioxins, necessitates both harmless treatment and resource utilization. In this study, a Na-P1 zeolite adsorbent was synthesised from MSW incineration fly ash using its intrinsic Si and Al sources, supplemented by silica sol and sodium aluminate solution. The synthesised zeolite was employed for the adsorption removal of tetracycline hydrochloride (TCH) from wastewater. Under the optimised conditions (initial TCH concentration of 10 mg·L⁻¹, adsorbent dosage of 0.4 g·L⁻¹, pH 5.0, temperature 45 °C, and contact time 60 min), a maximum adsorption capacity of 14.8 mg·g⁻¹ and a removal efficiency of 59.1% were achieved. Kinetic analysis revealed that the adsorption process followed the pseudo-first-order model (R² = 0.975). The Langmuir isotherm provided a better fit than the Freundlich model (R² = 0.988), indicating monolayer adsorption on homogeneous sites. Thermodynamic parameters (ΔG < 0, ΔH > 0) confirmed that the adsorption was spontaneous and endothermic, with higher temperatures favoring enhanced TCH adsorption. This work demonstrates the feasibility of converting hazardous MSW incineration fly ash into a value-added Na-P1 zeolite adsorbent with excellent performance for antibiotic wastewater treatment, thereby offering a sustainable strategy for fly ash resource recovery and environmental remediation. Full article

Background/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal (TA-CVS) and transvaginal (TV-CVS) techniques, focusing on procedure-related fetal loss and diagnostic yield. Methods: In this 15-year, single-operator prospective study, a total of 5500 women underwent CVS between 10 and 14 weeks of gestation at a single center. Sampling was performed via TA-CVS (n = 4500), TC-CVS (n = 850), or TV-CVS (n = 150). Outcomes assessed included fetal loss rates, sample adequacy, early complications and hemodynamic changes measured by Doppler ultrasound. A p-value < 0.05 (two-tailed) was considered statistically significant. Results: Spontaneous abortion rates were significantly lower following TA-CVS (0.18%; 8/4500) compared to TC-CVS (0.6%; 5/850) and TV-CVS (1.3%; 2/150) (χ² = 24.56, p < 0.001). Post hoc pairwise analysis showed significantly lower fetal loss in TA-CVS compared to TC-CVS, but not between TA-CVS and TV-CVS. Cytogenetic abnormalities were detected in 220 cases (4.0%), and clinically significant copy number variants (CNVs) were confirmed in fetuses with major structural malformations. Five-year follow-up showed no diagnosed intellectual disability among assessed children. Optimal tissue weight (10–20 mg) was more frequent with TA-CVS (66.7%) than TC-CVS (35.3%) or TV-CVS (36.7%) (χ² = 350.92, p < 0.001). In a Doppler subset (n = 400), uterine, spiral, and interplacental artery PI changes were non-significant; the umbilical (p = 0.032) and middle cerebral arteries (p < 0.001) showed transient PI reductions after sampling. Conclusions: Transabdominal CVS demonstrated the most favorable balance of safety and diagnostic quality, suggesting it should be the preferred first-line technique in early prenatal diagnosis. Standardized technique and operator training remain critical to optimize outcomes. Full article

A previous study demonstrated that spontaneous forest recovery can result in the development of functional mixed forests in post-mining areas. A critical step in this process is the establishment of climax woody species in the understory of pioneer trees. In this case study, we utilise repeated sampling to evaluate the establishment, initial survival, and growth of pedunculate oak (Quercus robur) and European beech (Fagus sylvatica) seedlings, and to newly assess Norway spruce (Picea abies) during unassisted forest recovery on a post-mining site after coal mining near Sokolov in North Bohemia. Detailed mapping of beech and oak seedlings was conducted in 2009 and 2012 (i.e., 14 and 11 years after the site was reclaimed). Now, we have resurveyed these seedlings, which has allowed us to evaluate their survival and growth. We have also mapped spruce seedlings and estimated their age from annual branch whorls. In the original study, most seedlings were found on the northern site near the edge of the post-mining area and the surrounding landscape, which serve as seed sources. Beech shows the best survival and growth on the northern site, where the greatest number of new seedlings also appear. In contrast, oaks demonstrate much higher mortality than beech overall, with the highest mortality observed on the northern site and the highest survival on the southern site, where most of the new seedlings also appeared. Interestingly, however, surviving oaks grew faster on the northern site. Across microtopography, seedlings of all three tree species were most frequent on the slopes of micro-undulations. Beech individuals were taller in depressions, whereas oaks did not consistently demonstrate a size advantage across microhabitats. Spruce colonised vigorously and was the most abundant of the three species across microhabitats. Age-frequency analyses suggest an annual mortality rate of 3%–9%. Browsing damage was observed on 19% of beech seedlings and 9% of oak seedlings. The study shows that pioneer tree stands are suitable nursing sites for studied climax tree species, which can colonise these sites several kilometres away from mature trees, and their establishment involves a complex interplay between distance to seed source and local microclimatic conditions. Our resurvey indicates that later successional stages may increasingly be shaped by shade-tolerant beech and spruce under the developing canopy. Full article

Studying the luminescent properties and the light amplification capabilities are fundamental investigations for newly synthesized organic compounds intended to act as chromophores. These studies are conducted for compounds in the form of solutions, solids, and also molecules stabilized with the aid of polymers. One of the methods used to study amplification is the generation of amplified spontaneous emission (ASE) using stripe-shaped light beam excitation. This process can lead to the generation of ASE, but also, with the coexistence of microcrystals and scatterers, to the generation of laser action with random feedback, known as random lasing (RL). However, when the degree of light scattering is too high, it can lead to the inhibition of laser emission. Therefore, as an alternative in studying amplification properties, we developed a protocol that allows the investigation of laser action generation using rapidly prototyped polymer waveguides with an embedded dye. The setup used was based on Direct Laser Writing (DLW), which enables the controlled fabrication of multimode optical waveguides. We demonstrated that the use of this technique will allow for the study of the performance of dyes from strictly structured resonators, enabling measurements of gain and lasing threshold. This allowed us to lower the lasing thresholds while maintaining the directionality of emission. Full article

Background/Objectives: Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major global health challenge and a leading cause of neonatal mortality. PTB is broadly classified into spontaneous and medically indicated (iatrogenic), which have distinct etiologies. While prediction is key to improving outcomes, there is a lack of models that specifically differentiate between spontaneous and iatrogenic PTB subtypes. This study aimed to develop and validate predictive models for the prediction of spontaneous and iatrogenic PTB at <32, <34, and <37 weeks’ gestation using medical history and readily available second-trimester data. Methods: This was a retrospective cohort study on singleton pregnancies from a single tertiary institution (2012–2025). Predictor variables included maternal characteristics, obstetric history, and second-trimester ultrasound markers. Four algorithms, including multivariable Logistic Regression and three machine learning methods (Random Forest, XGBoost, and a Neural Network), were trained and evaluated on a held-out test set (20% of the data). Model performance was primarily assessed by the Area Under the Curve (AUC). Results: In total, 9805 singleton pregnancies were included. The models performed significantly better for iatrogenic PTB than for spontaneous PTB. For delivery <37 weeks, the highest AUC for iatrogenic PTB was 0.764 (Random Forest), while for spontaneous PTB it was 0.609 (Neural Network). Predictive accuracy improved for earlier gestations; for delivery <32 weeks, the best model for iatrogenic PTB achieved an AUC of 0.862 (Neural Network), and the best model for spontaneous PTB achieved an AUC of 0.749 (Random Forest). Model interpretation revealed that iatrogenic PTB was primarily driven by markers of placental dysfunction, such as estimated fetal weight by ultrasound scan and uterine artery pulsatility index, while spontaneous PTB was most associated with a history of PTB and a short cervical length. Conclusions: Models using routine mid-gestation data demonstrate effective prediction for iatrogenic PTB, with accuracy improving for earlier, more severe cases. In contrast, performance for spontaneous PTB was modest. Traditional Logistic Regression performed comparably to complex machine learning algorithms, highlighting that the clinical value is rooted in the subtype-specific modeling approach rather than in algorithmic complexity. Full article

As global copper demand continues to grow, China, being the largest copper consumer, faces increasingly complex challenges in ensuring the security of its supply chain. However, a substantive gap remains: prevailing assessments rely on static index systems and discrete scenario analyses that seldom model uncertainty-driven, continuous-time strategic interactions, leaving the conditions for self-enforcing cooperation and the attendant policy trade-offs insufficiently identified. This study models the interaction between Chinese copper importers and foreign suppliers as a continuous-time stochastic differential game, with feedback Nash equilibria derived from a Hamilton–Jacobi–Bellman system. The supply security utility is specified as a diffusion process perturbed by Brownian shocks, while regulatory intensity and profit-sharing are treated as structural parameters shaping its drift and volatility—thereby delineating the parameter region for self-enforcing cooperation and clarifying how sudden disturbances reconfigure equilibrium security. The research findings reveal the following: (i) the mean and variance of supply security utility progressively strengthen over time under the influence of both parties’ maintenance efforts, while stochastic disturbances causing actual fluctuations remain controllable within the contract period; (ii) spontaneous cooperation can be achieved under scenarios featuring strong regulation of domestic importers, weak regulation of foreign suppliers, and a profit distribution ratio slightly favoring foreign suppliers, thereby reducing regulatory costs; this asymmetry is beneficial because stricter oversight of domestic importers curbs the primary deviation risk, lighter oversight of foreign suppliers avoids cross-border enforcement frictions, and a modest supplier-favored profit-sharing ratio sustains participation—together expanding the self-enforcing cooperation set; (iii) sudden events exert only short-term impacts on supply security with controllable long-term effects; however, an excessively stringent regulatory environment can paradoxically reduce long-term supply security. Security effort levels demonstrate positive correlation with supply security, while regulatory intensity must be maintained within a moderate range to balance incentives and constraints. Full article

Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom C-type lectin-like protein, mediates this effect ex vivo. Here, we extended our study of the antithrombotic potential of this protein in vivo using a mouse model of ferric chloride (FeCl₃)-induced carotid artery thrombosis. Prior to inducing thrombus formation, the mice received 1, 5, 10, 20, or 50 μg/kg Vaa-snaclec-3/2 intravenously. Afterward, the arterial blood flow was monitored with a perivascular Doppler probe. Additionally, the platelet count in the peripheral venous blood; tail bleeding time; and liver, lung, kidney, spleen, and heart histology were evaluated. The lowest dose of Vaa-snaclec-3/2 that we showed to cause severe thrombocytopenia and completely inhibit FeCl₃-induced thrombus formation was 20 µg/kg. This dose prolonged the median tail bleeding time from 86.5 to 153.5 s but did not induce acute spontaneous hemorrhage, as demonstrated by histological analysis. Histology revealed no signs of apoptosis, necrosis or other degenerative changes in the inspected organs of mice exposed to 20 μg/kg Vaa-snaclec-3/2. Platelet clusters were observed only in the lungs, which appear to be the primary site of platelet sequestration and the cause of thrombocytopenia. Taken together, our findings highlight the high potential of Vaa-snaclec-3/2 as a safe and effective antithrombotic agent for the transient prevention of thrombosis in acute clinical settings. Full article

This study synthesizes three new composites: chitin-cross-linked poly(ortho-phenylenediamine)-grafted silicon dioxide (CT-PoPD-grafted SiO₂), chitosan-cross-linked PoPD-grafted SiO₂ (CS-PoP-grafted SiO₂), and guar-gum-cross-linked PoPD-grafted SiO₂ (GG-PoPD-grafted SiO₂). These biopolymer-based materials were developed as cost-effective, biocompatible adsorbents with increased surface area for removing Acid Red 1 AR1) and Crystal Violet (CV) dyes. Structural and morphological analyses through Fourier-transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy (XPS) confirmed their successful synthesis. Adsorption studies were conducted under various conditions, including adsorbent dosage, pH, temperature, and contact time. Among the composites, GG-PoPD-grafted SiO₂ demonstrated superior performance, achieving 99.1% and 95.6% removal of AR1 and CV, respectively. Kinetic analysis revealed a pseudo-second-order model, while thermodynamic results indicated a spontaneous and endothermic adsorption process. In conclusion, the GG-PoPD-grafted SiO₂ composite exhibits significant potential as an effective and sustainable material for wastewater treatment. Full article