Search Results (7,134)

Egypt has the highest global prevalence of hepatitis C virus (HCV), with genotype 4 (G4) in over 94% of cases. Direct-acting antivirals (DAAs) yield sustained virologic response (SVR) rates above 95%. Second-generation DAAs are recommended for patients with virological failure, achieving over 90% eradication. This study aimed to classify and evaluate the pattern of HCV resistance-associated substitutions (RASs) in patients who failed DAA treatment in Egypt. A total of 1778 chronically infected HCV patients from Egypt’s Nile Delta were enrolled (2016–2018). Among them, 37 relapsed, and high-quality serum samples from 22 patients were available, including 6 cases with pre- and post-treatment samples. Next-generation sequencing (NGS) was performed for HCV subtyping and RAS identification. Among the 22 analyzed cases, 21 (95.4%) were G4: 11 were classified as subtype G4a, seven G4o, and three G4m. One patient (4.5%) was identified as G1g. One case shifted from G4a pre- to G4o post-treatment, suggesting reinfection. The RAS pattern in rare G4 subtypes (G4m/G4o) differs from the G4a subtype. The combination of L28M/L30S mutations was detected in 8/11 G4a samples; in contrast, RASs in G4o were characterized by T30S or Y93C/H/N/S substitutions. Notably, some substitutions identified as RASs may represent fixed polymorphisms in regional viral populations, such as those in Egypt’s Nile Delta. HCV subtypes significantly influence the RAS pattern, particularly within the NS5A region, after DAA-treatment failure. The RAS pattern differs among G4 subtypes, particularly in rare ones, predisposing patients to resistance and underscoring the importance of NGS in regional populations to optimize treatment strategies. Full article

Reinforced alumina ceramics are renowned for their high hardness and strength among common oxide ceramics. However, high-temperature or high-pressure treatment is necessary for maximizing values of strength and hardness. In this paper, liquid-phase-assisted pressureless sintering of alumina reinforced with zirconia was studied. Sintering of dense ceramic bodies in relatively low temperatures (up to 1100 °C) was possible with the usage of CuO-TiO₂-Nb₂O₅-based additive, together with an intense milling process. By using the XRD method, the formation of dominant α-Al₂O₃ and m-ZrO₂ phases with small concentrations of secondary ones in experimental samples was confirmed. SEM studies showed that uniform distribution of components in the composite was achieved in samples sintered from intensively milled powders. The significant increase in the values of Vickers hardness and biaxial flexural strength (by 2.6 times) in samples from intensively milled powders at a sintering temperature of 1050 °C was explained by reduced porosity, improved grain distribution, and the formation of the t-ZrO₂ phase in the alumina-reinforced composite. The study clearly showed high potential of the proposed low-temperature sintering method for zirconia-toughened aluminum oxide, which can be used in manufacturing of advanced ceramics. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles, which synergistically accelerate disease progression. Since Aβ plaques and tau tangles are key factors in the development of AD, dual-targeting of Aβ and tau aggregation represents a promising therapeutic strategy. Amodiaquine (AQ), a quinoline-based antimalarial, has recently attracted attention for its ability to suppress protein aggregation. However, direct effects of AQ on both Aβ and tau aggregation remain unclear. Methods: The effects of AQ on the aggregation and dissociation of Aβ and tau were examined using a thioflavin T (ThT) assays. Molecular docking and molecular dynamics (MD) simulations were performed to examine binding characteristics and structural interactions. The effects of AQ on the expression of pro-inflammatory cytokines induced by Aβ and tau aggregation in BV2 microglial cells were analyzed by qRT-PCR. Results: ThT assay demonstrated a dose-dependent dual effect of AQ on Aβ, where 25 μM inhibited aggregation after 36 h, while 250 μM markedly accelerated it, reaching a plateau within 12 h. All concentrations of AQ promoted the disassembly of mature Aβ fibrils within 12 h. Molecular docking revealed stronger binding of AQ to aggregated Aβ (−45.17 and −23.32 kcal/mol for pentameric 2BEG and hexameric 2NAO) than to monomeric Aβ (−4.81 and −7.29 kcal/mol for 1Z0Q and 2BEG). MD simulation suggested that AQ disrupted the cross-β-sheet interactions of Aβ aggregates. In the case of tau, ThT assay showed that all concentrations of AQ inhibited tau aggregation from 6 h, and 350 μM AQ promoted the disassembly of mature fibrils from 6 h. Molecular docking indicated stronger binding of AQ to aggregated tau (−27.95 and −12.13 kcal/mol for the pentameric and decameric 5O3L) than to monomeric tau (−3.05 kcal/mol for 8Q96). MD simulations revealed no major structural changes in the aggregates. In BV2 cells, 1 and 10 μM AQ significantly reduced Aβ and tau-induced TNF-α and IL-6 mRNA expressions. In APP-H4 cells, 10 μM AQ decreased the level of Aβ compared to the control. Conclusions: AQ modulates both Aβ and tau aggregation and attenuates neuroinflammation and reduces Aβ pathology, supporting its potential as a dual-target therapeutic candidate for AD. Full article

Hybrid PV-TEG systems can harvest both solar electrical and thermoelectric power, but their operating point drifts with irradiance, temperature gradients, partial shading, and load changes—often yielding multi-peak P-V characteristics. Conventional MPPT (e.g., P&O) and fixed-structure integer-order PID struggle to remain fast, stable, and globally optimal in these conditions. To address fast, robust tracking in these conditions, we propose an adaptive fractional-order PID (FOPID) MPPT whose parameters (K_p, K_i, K_d, λ, μ) are auto-tuned by the red-billed blue magpie optimizer (RBBMO). RBBMO is used offline to set the controller’s search ranges and weighting; the adaptive law then refines the gains online from the measured ΔV, ΔI slope error to maximize the hybrid PV-TEG output. The method is validated in MATLAB R2024b/Simulink 2024b, on a boost-converter–interfaced PV-TEG using five testbeds: (i) start-up/search, (ii) stepwise irradiance, (iii) partial shading with multiple local peaks, (iv) load steps, and (v) field-measured irradiance/temperature from Shanxi Province for spring/summer/autumn/winter. Compared with AOS, PSO, MFO, SSA, GHO, RSA, AOA, and P&O, the proposed tracker is consistently the fastest and most energy-efficient: 0.06 s to reach 95% MPP and 0.12 s settling at start-up with 1950 W·s harvested (vs. 1910 W·s AOS, 1880 W·s PSO, 200 W·s P&O). Under stepwise irradiance, it delivers 0.95–0.98 kJ at t = 1 s and under partial shading, 1.95–2.00 kJ, both with ±1% steady ripple. Daily field energies reach 0.88 × 10⁻³, 2.95 × 10⁻³, 2.90 × 10⁻³, 1.55 × 10⁻³ kWh in spring–winter, outperforming the best baselines by 3–10% and P&O by 20–30%. Robustness tests show only 2.74% power derating across 0–40 °C and low variability (Δv^max typically ≤ 1–1.5%), confirming rapid, low-ripple tracking with superior energy yield. Finally, the RBBMO-tuned adaptive FOPID offers a superior efficiency–stability trade-off and robust GMPP tracking across all five cases, with modest computational overhead. Full article

Rape is one of the most widely cultivated and highest-yielding fruit crops in the world. However, research on its precise nutrient diagnosis and fertilization theory is severely lacking, significantly restricting the development of the grape industry. In this study, an L₁₆(4⁵) orthogonal experimental design was applied to determine the effects of varying ratios of nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) on the fruit quality of ‘87-1’ grape (Vitis vinifera L.) cultivated in a facility, aiming to optimize nutrient application rates and improve fruit quality. Among the treatments T5 (N2P1K2Ca3Mg4), T14 (N4P2K3Ca1Mg4), and T9 (N3P1K3Ca4Mg2), treatment T9 had the most significant effect on single fruit weight, total soluble solids (TSS) content, fruit firmness (FF), and fruit quality index (FQI) and was conducive to the positive accumulation of the above quality indicators. Based on a comprehensive multi-factor analysis of variance, the optimal fertilization combination for achieving a high FQI was N3P1K2Ca1Mg2, corresponding to application rates of 375.0, 0, 168.8, 0, and 70.5 kg·hm⁻² for N, P₂O₅, K₂O, CaO, and MgO, respectively. Furthermore, to establish standards for multivariate compositional nutrient diagnosis (CND) and define the nutrient sufficiency range for ‘87-1’ grape fruit cultivated in a facility, the nutrient concentrations in various plant tissues and the soil and the FQI were measured across 80 treatments over five consecutive years. The nutritional status of the grapes cultivated under these treatments was calculated using the Technique for Order Preference by Similarity to Ideal Solution and the CND method. Based on the optimal nutrient ranges for high FQI sub-populations, a precise fertilization model was developed to facilitate economic fertilizer savings, quality improvement, and standardized grape cultivation in a facility. Full article

In this article, we investigate the impact of T6 heat treatment on Al/Mg/PPA composites’ microstructure, densification, wear, and mechanical properties. The samples were synthesized using a ball milling machine and spark plasma sintering (SPS). Microstructural analysis revealed homogeneously distributed Al, Mg, and PPA particles. However, microstructural defects such as micro-pores and cracks increased due to prolonged heating. Precipitations such as Al₂O₃, MgO, and MgAl₂O₄ were present in the composites, and no new phase was detected after the heat treatment. The grain size analysis showed that no significant grain growth occurred. The porosity of the composite samples increased significantly, with sample H4 (Al/2Mg/15PPA) displaying the highest porosity of 148.55% after the heat treatment. The composites’ hardness improved after the T6 heat treatment, with sample H2 (Al/2Mg/5PPA) displaying the maximum hardness of 69.4 HV, representing an increase of 12.48%. More significantly, the compressive strength of all the samples reinforced with PPA, dropped at a percentage range of 42.30–51.50% after the heat treatment. It can, therefore, be inferred from this investigation that the T6 heat treatment is most suitable for improving the hardness of heat-treatable aluminum alloys and composites rather than improving their overall properties. Full article

Research on the Mesozoic–Cenozoic magmatism and the tectonic framework within the Lhasa Terrane is voluminous. However, the sparse documentation of Early Cretaceous magmatism in this region fuels ongoing debate over the prevailing tectonic regime during this time period (i.e., normal subduction vs. flat subduction). The present study investigates the Luerma pyroxenite and Boyun granitoid in the Western Lhasa Terrane through zircon U-Pb dating, whole-rock geochemistry, mineral chemistry, and Sr-Nd-Hf isotopes. The findings date the formation of Luerma pyroxenite at 115 Ma and Boyun granites at 113 Ma to the Early Cretaceous period (115–113 Ma). SiO₂ content of pyroxenite is relatively low (34.27–44.16 wt.%), characterized by an enrichment in large ion lithophile elements (LILEs), light rare earth elements (LREEs), and a depletion in heavy field strength elements (HSFEs), indicative of a metasomatic origin. The εNd (t) and εHf (t) values of the Early Cretaceous ultrabasic rocks range from +2.1 to +2.7 and −0.8 to +10.1, respectively, suggesting their derivation from an enriched mantle source with asthenospheric material incorporation. The Early Cretaceous granodiorites and their mafic enclaves belong to the high-K calc-alkaline series, and show enrichment in LILEs (e.g., Rb, Ba, U, and Th) and depletion in HFSEs (e.g., Nb, Ta, Ti, and Zr). The acidic rocks and their developed mafic enclaves exhibit the geochemical characteristics of trace elements found in island arc magmas. Their εNd (t) values are (−6.0–−5.0), while their εHf (t) values are (−11.7–−1.8); the MMEs εHf (t) values are (−4.1–+0.9). In summary, the Early Cretaceous pyroxenite in the Gangdese Belt originated from a combination of asthenospheric and enriched lithospheric mantle melts, while the granitoids were generated by partial melting of the mantle wedge, a process driven by metasomatism resulting from the slab-derived fluids. At the same time, heat from upwelling mantle-derived melts induced the partial melting of lower crustal materials, leading to the formation of acidic magmas through varying degrees of mixing with basic magmas. This study suggests that Early Cretaceous magmatic activity occurred within a northward subduction setting, characterized by the rotation and fragmentation of the Neo-Tethys oceanic crust. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits marked resistance to immunotherapy. Beyond its characteristically low tumor mutational burden, post-translational modifications (PTMs) remodel the immunopeptidome and promote immune escape through reversible, enzyme-driven programs. Subject Matter: We synthesize evidence that aberrant glycosylation, O-GlcNAcylation, phosphorylation, and citrullination constitute core determinants of antigen visibility operating within spatially discrete tumor niches and a desmoplastic stroma. In hypoxic regions, HIF-linked hexosamine metabolism and OGT activity stabilize immune checkpoints and attenuate antigen processing; at tumor margins, sialylated mucins engage inhibitory Siglec receptors on innate and adaptive lymphocytes; within the stroma, PAD4-dependent NET formation enforces T cell exclusion. We also delineate technical barriers to discovering PTM antigens labile chemistry, low stoichiometry, and method-embedded biases and outline practical solutions: ETD/EThcD/AI-ETD fragmentation, PTM-aware database searching and machine-learning models, and autologous validation in patient-derived organoid–T cell co-cultures. Finally, we highlight therapeutic strategies that either immunize against PTM neoepitopes or inhibit PTM machinery (e.g., PAD4, OGT, ST6GAL1), with stromal remodeling as an enabling adjunct. Conclusions: PTM biology, spatial omics, and patient sample models can uncover targetable niches and speed up PDAC vaccination, TCR, and enzyme-directed treatment development. Full article

The uptake and accumulation of nanoplastics by plants have emerged as a major research focus. Exogenous selenium nanoparticles (SeNPs) are widely used to mitigate the toxicity of abiotic stresses, such as nanoplastics (NPs) and polyethylene (PE—NPs) nanoplastics, and represent a feasible strategy to enhance plant performance. However, the molecular mechanisms by which SeNPs alleviate the phytotoxicity of microplastics and nanoplastics remain poorly defined. To address this gap, we used Pistia stratiotes L. (P. stratiotes) as a model and silicon dioxide nanoparticles (SiO₂NPs) as a comparator, integrating physiological assays, ultrastructural observations, and proteomic analyses. We found that NP stress caused ultrastructural damage in root tips, exacerbated oxidative stress, and intensified membrane lipid peroxidation. SeNPs treatment significantly mitigated NP-induced oxidative injury and metabolic suppression. Compared to the NPs group, SeNPs increased T-AOC by 38.2% while reducing MDA and ·OH by 33.3% and 89.6%, respectively. Antioxidant enzymes were also elevated, with CAT and POD rising by 47.1% and 39.2%. SeNPs further enhanced the photosynthetic capacity and osmotic adjustment, reflected by increases in chlorophyll a, chlorophyll b, and soluble sugar by 49.7%, 43.8%, and 27.0%, respectively. In contrast, proline decreased by 17.4%, indicating stress alleviation rather than an osmotic compensation response. Overall, SeNPs outperformed SiO₂NPs. These results indicate that SeNPs broadly strengthen anti-oxidative defenses and metabolic regulation in P. stratiotes, effectively alleviating NP-induced oxidative damage. Proteomics further showed that SeNPs specifically activated the MAPK signaling cascade, phenylpropanoid biosynthesis, and energy metabolic pathways, enhancing cell-wall lignification to improve the mechanical barrier and limiting NPs translocation via a phytochelatin-mediated vacuolar sequestration mechanism. SiO₂NPs produced similar but weaker alleviative effects. Collectively, these findings elucidate the molecular basis by which SeNPs mitigate NPs’ phytotoxicity and provide a theoretical foundation and practical outlook for using nanomaterials to enhance phytoremediation in aquatic systems. Full article

Large-scale Mesozoic granites are widespread in the offshore area of eastern Shandong Province, China. This study aims to refine the granite classification and explore the degree of granite differentiation and ore-bearing potential in the study area. We conducted field investigations in Dazhushan, Xiaozhushan, and Laoshan plutons. The analytical methods included petrography, whole-rock geochemistry, Sr–Nd–Pb–Li isotopes, zircon U–Pb dating, in situ Hf isotopes, and microanalysis (LA-ICP-MS) of plagioclase. The results reveal high-silica (SiO₂ > 70%), highly differentiated (DI > 90) granites emplaced during the Early Cretaceous (113.12–121.78 Ma). Sr–Nd–Pb isotopes indicate magma derived from a crustal source (I_Sr = 0.7032–0.7242; εNd(t) = −12.45~−20.46). Critically, the spodumene-bearing Dazhushan granites exhibit high Li content with limited isotopic fractionation (δ⁷Li = 1.00–4.62‰; Li = 8.64–93 ppm), signaling high ore potential. In contrast, the Xiaozhushan granites are barren (δ⁷Li = 3.31–4.92‰; Li = 0.66–4.01 ppm). This study identified I-type (Laoshan) and I-S type (Dazhushan and Xiaozhushan) highly differentiated granites formed by plagioclase fractionation, with Dazhushan being the most promising for mineralization. Full article

Background: Endometrioma recurrence after laparoscopic cystectomy remains a clinical challenge in the long-term management of endometriosis. The Empressin Injection Technique (EIT), which involves the use of a vasopressin analog during surgery, may reduce recurrence by improving the completeness of cyst removal. This study aimed to evaluate the impact of the EIT on recurrence rates compared to standard cystectomy without Empressin. Methods: We conducted a retrospective case–control study of 263 patients who underwent laparoscopic cystectomy for unilateral or bilateral endometriomas between 2014 and 2024 at a tertiary endometriosis referral center. The patients were divided into two groups: EIT (n = 110) and control (n = 153). In the EIT group, 10 mL of diluted Empressin (1 mL in 100 mL NaCl 0.9%) was injected at the cyst capsule–ovarian cortex interface prior to stripping. Demographic and clinical variables were analyzed using descriptive statistics (chi-square test and the Mann–Whitney t-test) and logistic regression to identify factors associated with recurrence between the two groups. Results: No significant differences were found between the groups regarding age, BMI, #ENZIAN O score, or r-ASRM stage. No intraoperative or postoperative complications were reported. Recurrence was significantly lower in the EIT group (5.5%) compared to the control group (19.6%) (p = 0.001; OR 0.2, 95% CI: 0.08–0.55). Hormonal therapy was administered postoperatively in 69.1% of EIT patients and 62.5% of controls. Pregnancy rates were comparable between the groups. Repeat surgery for recurrence was required only in the control group (4.2%, p = 0.004). Conclusions: Use of Empressin during laparoscopic cystectomy significantly reduces endometrioma recurrence without adverse effects, particularly when combined with postoperative hormonal therapy. Full article

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) represents a significant global health burden, frequently leading to severe complications such as peripheral neuropathy and both micro- and macrovascular dysfunctions. These complications are integral to the pathology of diabetic foot ulcers (DFUs) and are associated with an elevated risk of lower limb amputations. This study investigated lower extremity skeletal muscle perfusion in patients with T2DM and DFUs using [¹⁵O]H₂O PET imaging, in comparison to healthy controls. Methods: A total of 10 healthy controls and 26 patients with T2DM and DFUs were enrolled. Resting skeletal muscle perfusion was quantified using [¹⁵O]H₂O PET. Regional perfusion was assessed in multiple lower leg and foot muscle groups. Distal blood pressure was measured, and foot/leg perfusion ratios were calculated. Results: Patients with T2DM and DFUs exhibited a 58% higher median global foot resting perfusion compared to healthy controls. At the individual muscle level, median perfusion in the flexor hallucis brevis was elevated by up to 210% in the ulcerated foot compared to controls. No significant differences in perfusion were observed in the non-ulcerated foot. The foot/leg perfusion ratio was up to 58% higher in the ulcerated limb of T2DM patients compared to the controls. Conclusions: This study demonstrates localized alterations in skeletal muscle perfusion in patients with T2DM and DFUs, characterized by elevated resting foot perfusion in muscles adjacent to ulcerations. Understanding these perfusion dynamics may contribute to refined DFU management strategies. However, further research is needed to validate the clinical utility of [¹⁵O]H₂O PET imaging in guiding interventions and predicting treatment outcomes for DFUs. Full article

Biochar has been widely recognized for its potential to improve soil quality and mitigate greenhouse gas (GHG) emissions. A field experiment was conducted in a temperate climate zone of Slovakia on Haplic Luvisol and evaluated the long-term impact of biochar on soil properties, nitrous oxide (N₂O) emissions, and winter wheat (Triticum aestivum L.) yield. Biochar was applied in 2014 at rates of 0, 10, and 20 t ha⁻¹ and reapplied in 2018 at the same rates, combined with nitrogen (N) fertilization (0, 140, and 210 kg N ha⁻¹). Measurements, conducted from March to October 2021, showed that biochar improved soil water content, increased soil pH, and enhanced soil organic carbon content. However, the concentrations of NH₄⁺-N and NO₃⁻-N generally decreased across all the treatments compared to their respective controls. Biochar reapplication rate at 20 t ha⁻¹, especially combined with second level of N-fertilization, led to a significant reduction in cumulative N₂O emissions by 38.40%. Winter wheat yield was positively correlated with both biochar application (10 and 20 t ha⁻¹) and N levels (140 and 210 kg N ha⁻¹), but these differences were not statistically significant (p > 0.05). The positive effects of biochar on soil properties and yield declined over time, with no significant yield differences observed 7 years after the initial application and 3 years after reapplication. These findings suggest that while biochar can enhance soil conditions and reduce GHG emissions in the short term, its long-term effectiveness remains uncertain. Further research is needed to explore alternative biochar feedstocks, application methods, and strategies to sustain its benefits in agricultural systems. Full article

Background: The increase in potentially toxic elements (PTEs) in the soil is worrying, especially in agricultural soils due to the bioaccumulation factor. Copper (Cu) and iron (Fe) are micronutrients, responsible for important functions in the plant body, but the high availability of these elements in the soil can cause soil contamination and toxicity in plants; consequently, they can be considered PTEs. Objectives: The focus of this study is to understand the physiological responses (pigments, gas exchange, growth, biomass, accumulation) of Canavalia ensiformis to high levels of Cu and Fe in the soil, in isolation, and to identify which PTE is most harmful to its development. Methods: Two experiments (Cu and Fe) were conducted simultaneously in a greenhouse. Treatments of 50, 150, 250, and 350 mg dm⁻³ of soil for each element (CuSO₄*5H₂O and FeSO₄*7H₂O) were incorporated into the soil (Oxisol) of each experimental unit (4 dm³ pot), in addition to the control. C. ensiformis seeds were sown directly in soil enriched with Cu and Fe, respectively, and after emergence they were cultivated for 90 days. Results: Changes in chlorophyll levels caused direct effects on gas exchange, shoot biomass, root development, nodulation, and total plant biomass. The tolerance of the species is dependent on chlorophyll levels and gas exchange. There was accumulation of both PTEs in the roots and low translocation to the shoot. Conclusions: The plants were tolerant to Fe treatments; however, they were not tolerant to Cu treatments (T150–T350). Excess Cu was more detrimental to plant development. Full article

Olfactory dysfunction (OD) is an early symptom associated with a variety of diseases, including COVID-19, Alzheimer’s disease, and Parkinson’s disease, where patients commonly experience hyposmia or anosmia. Effective restoration of olfactory function is therefore crucial for disease diagnosis and management, and improving overall quality of life. Traditional treatment approaches have primarily relied on medication and surgical intervention. However, recent advances in bionic sensing and brain–computer interface (BCI) technologies have opened up novel avenues for olfactory rehabilitation, facilitating the reconstruction of neural circuits and the enhancement of connectivity within the central nervous system. This review provides an overview of the current research landscape on OD-related diseases and highlights emerging olfactory restoration strategies, including olfactory training (OT), electrical stimulation, neural regeneration, and BCI-based approaches. These developments lay a theoretical foundation for achieving more rapid and reliable clinical recovery of olfactory function. Full article