Search Results (5,060)

Background: Neurodegeneration and dementia are key factors in Alzheimer’s disease (AD). The deposition of amyloid-ß into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. Methods: AD transgenic APP23 mice were analyzed in experimental AMI using the closed-chest model. Results: APP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. The analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI. Conclusions: These results suggest that AD patients are at higher risk for cardiac damage after AMI. This implies the need for a personalized therapy of AMI in AD patients. Full article

This study aimed to investigate the effects of r-type exopolysaccharides (EPSs) produced by the symbiotic bacteria Rhizobium tropici on soil aggregate formation and stability in loess sandy soil and to elucidate the independent and synergistic roles of EPSs in soil structure development. Experiments were conducted under both sterile and non-sterile soil conditions to distinguish the direct effects of EPSs from their interactions with indigenous soil microorganisms. Soil samples were treated with varying concentrations of EPSs and compared with untreated controls after undergoing a simulated weathering process. Aggregates were classified into four size fractions: <53 μm, 53–250 μm, 250–2000 μm, and 2000–5000 μm. Aggregate distribution and soil stability indicators, including the percentage of water-stable aggregates larger than 0.25 mm, mean weight diameter (MWD), geometric mean diameter (GMD), and fractal dimension (D), were analyzed. EPS application significantly promoted the formation of larger soil aggregates (>53 μm), with approximately 80% increases in the number of aggregates in the 53–250 μm and 2000–5000 μm fractions compared to the control. Soil stability was markedly enhanced, with a 41.7% increase in >0.25 mm water-stable aggregates, a 36.4% rise in MWD, and a 0.3% increase in GMD. The D decreased by 1.2% under 0.2‰ EPS treatment, indicating a more ordered soil structure. EPSs play a key role in promoting soil aggregate formation and enhancing soil stability. While microbial presence has a limited short-term effect on aggregation, the synergistic interaction between microorganisms and EPSs over time significantly enhances soil stability. This study provides new insights into understanding the independent and synergistic roles of EPSs in soil structure formation. Full article

This paper addresses the limitations of conventional single-stage direct-control maximum power point tracking (MPPT) methods, such as the Perturb and Observe (P&O) algorithm. Fixed-step-size duty-cycle perturbations cause a trade-off between slow tracking with small oscillations and fast tracking with large oscillations, along with poor responsiveness to rapid weather variations and output voltage fluctuations. Two main contributions are presented. First, a fractional-order DC–DC boost converter (FOBC) is introduced, incorporating fractional-order dynamics to enhance system performance beyond improvements in control algorithms alone. Second, a novel indirect-control MPPT strategy based on a two-stage architecture is developed, where the P&O algorithm generates the optimal voltage reference and a fractional-order linear-quadratic-integral (FOLQI) controller—designed using a fractional-order small-signal model—regulates the PV module voltage to generate the FOBC duty cycle. Hardware-in-the-loop simulations confirm substantial performance improvements. The proposed FOLQI-based indirect-control approach with FOBC achieves a maximum MPPT efficiency of 99.26%. An alternative indirect method using a classical linear-quadratic-integral (LQI) controller with an integer-order boost converter reaches 98.38%, while the conventional direct-control P&O method achieves only 94.21%, demonstrating the superiority of the proposed fractional-order framework. Full article

This study investigated the combined influence of hydrothermal treatment and particle size on the techno-functional properties of defatted coconut residue (DCR) to optimize its use as a hydrocolloid fat replacer. A 3 × 2 factorial design evaluated boiling and autoclaving treatments in combination with coarse and fine milling. Fine particle fractions (boiling-fine [BF] and autoclaved-fine [AF]) were identified as optimal, exhibiting peak water-holding capacity (WHC) (10.95 g/g) and oil-holding capacity (4.57 g/g) due to maximized surface area and thermal unblocking of capillary networks. When incorporated into cookies, all DCR formulations qualified as “reduced-fat” (30% reduction) and “high-fiber” (6 g/100 g) products. Crucially, the extreme WHC of fine fractions induced severe water competition within the dough, leading to a direct inverse correlation with quality, characterized by a restricted spread ratio (6.9) and increased hardness (27 N). Furthermore, thermal leaching of Maillard precursors suppressed excessive browning, improving cookie color. While the BF fraction provided the best functional balance, future research should optimize dough moisture to mitigate the impact of high fiber hydration on texture. These findings demonstrate DCR’s potential for agro-food valorization and improved human health. Full article

Coastal lakes are highly vulnerable transitional systems in which sedimentological processes and benthic ecological conditions jointly control contaminant accumulation and preservation, particularly in densely urbanized settings. A robust understanding of the physical and ecological characteristics of bottom sediments is therefore essential for the correct interpretation of contaminant distributions, including those of potentially toxic metals. In this study, an integrated sedimentological–ecological approach was applied to Lake Ganzirri, a Mediterranean shallow coastal lake located in northeastern Sicily (Italy), where recent investigations have identified localized heavy metal anomalies in surface sediments. Sediment texture, petrographic and mineralogical composition, malacofaunal assemblages, and lake-floor morpho-bathymetry were systematically analysed using grain-size statistics, faunistic determinations, GIS-based spatial mapping, and bivariate and multivariate statistical methods. The modern lake bottom is dominated by bioclastic quartzo-lithic sands with low fine-grained fractions and variable but locally high contents of calcareous skeletal remains, mainly derived from molluscs. Sediments are texturally heterogeneous, consisting predominantly of coarse-grained sands with lenses of very coarse sand, along with gravel and subordinate medium-grained sands. Both sedimentological features and malacofaunal death assemblages indicate deposition under open-lagoon conditions characterized by brackish waters and relatively high hydrodynamic energy. Spatial comparison between sedimentological–ecological parameters and previously published heavy metal distributions reveals no significant correlations with metal hotspots. The generally low metal concentrations, mostly below regulatory threshold values, are interpreted as being favoured by the high permeability and mobility of coarse sediments and by energetic hydrodynamic conditions limiting fine-particle accumulation. Overall, the integration of sedimentological and ecological data provides a robust framework for interpreting contaminant patterns and offers valuable insights for the environmental assessment and management of vulnerable coastal lake systems, as well as for the understanding of modern lagoonal sedimentary processes. Full article

Background: To overcome the gastrointestinal and hepatic toxicity of oral pirfenidone (PFD) in the treatment of idiopathic pulmonary fibrosis (IPF), this study systematically constructed a minimal-component, buffer-free pirfenidone aerosol inhalation solution (PFD-AIS), achieving lung-targeted delivery, reduced systemic exposure, and maintained antifibrotic efficacy. Methods: Analytical methods for PFD-AIS, covering content, related substances, aerodynamic particle size distribution (APSD), and delivered dose uniformity, were established. The prescription and preparation process of the formulation was optimized by evaluating its key quality attributes. Pharmacodynamic and pharmacokinetic evaluations of PFD-AIS were performed in a mouse lung-fibrosis model and SD rats. Results: The final specification of PFD-AIS was set to 40 mg:4 mL, containing 40 mg of PFD, 28 mg of sodium chloride, and 4 mL of injection water with a preparation process of 40 °C for 60 min and a pH range of 4–8. The PFD-AIS exhibited a fine particle fraction (FPF) of 56.1%, meeting the requirements for deep lung deposition. The delivered dose and delivery rate were 17.52 mg and 2.48 mg/min, respectively, both complying with inhalation formulation standards. In the bleomycin-induced IPF mouse model, the PFD-AIS markedly improved pulmonary fibrosis pathology, reduced the lung coefficient, and significantly lowered serum ALT/AST levels, indicating hepatic protection. In the SD rats, compared with oral dosing, PFD-AIS administration resulted in significantly lower AUC_0−t (−63%) and AUC_0–∞ (−67%) values, demonstrating a substantial reduction in systemic drug exposure. Conclusion: This work presents a complete, systematic chain—from formulation, process, and quality control to pharmacodynamics and pharmacokinetics—of a PFD-AIS. The PFD-AIS is effective and feasible, featuring a stable preparation process and controllable quality. Lung-directed drug delivery enhances PFD’s therapeutic efficacy, reduces systemic exposure and liver toxicity, and offers significant clinical advantages. Full article

Background: Occupational exposure to aerosol particles can pose a substantial health risk. The study aimed to characterise the deposition of occupationally relevant aerosols in a 3D anatomical adult nasal cavity model under steady and unsteady flows. Materials: The deposition of aerosolised wheat flour, pine wood sanding dust, carbon black, and Arizona Test Dust A3 was quantified under steady flows (5, 7.5, and 20 L/min per nostril) and an unsteady breathing pattern generated by the commercial breathing simulator. Image analysis with custom software quantified the area covered by deposited particles. The Downstream Penetration Index (DPI) was determined from the outlet mass. Results: The highest segmental deposition occurred in the anterior segment of the lateral wall (WA) and septum (SA), with moderate values in the middle lateral wall (WM) and the lowest in the posterior lateral wall (WP, nasopharynx) and septum (SP). Arizona Test Dust A3 and carbon black demonstrated higher middle-posterior deposition and DPI, consistent with finer particle size distributions (PSD) and greater sub-10 µm fractions. In contrast, wheat flour and pine wood dust, with larger median particle sizes and lower sub-10 µm fractions, showed stronger anterior filtration and lower DPI. Increased flow enhanced anterior filtration of coarse particles and shifted deposition forward, aligning with increased inertial impaction, but elevated DPI for fine particles. Under unsteady flow, deposition was intermediate between 7.5 and 20 L/min. Conclusions: This study shows that PSD, morphology, and flow conditions influence nasal deposition. Coarse aerosols were filtered in the anterior nose, while fine-rich aerosols showed relatively greater middle-posterior deposition and higher DPI. These findings are essential for assessing occupational exposure and developing interventions and prevention strategies. Full article

The Cheng-gang crystalline graphite deposit is a recently discovered medium-to-large-sized deposit within the Tan-Lu Fault Zone (TLFZ), East China. However, the knowledge on this deposit remains limited, resulting in a poor understanding of its genesis. In this study, this deposit is chosen to elucidate the degree of graphite mineralization, the nature and depositional environments of the protoliths, and the carbon source of graphite through geochemical and stable isotope investigations, and mineralogical analysis. The fixed carbon contents in the graphite-ore-bearing layers range from 2% to 3%. X-ray diffraction analyses reveal a high degree of graphitization. Analyses of elemental ratios indicate that the protoliths of metamorphic rocks predominantly consist of felsic rocks derived from the upper crust and deposited in brackish-water and reducing environments (anoxic to dysoxic). Stable carbon isotope analyses show that CH₄ with lighter carbon isotopes released from the decomposition of pristine organic matter was trapped into adjacent inorganic reservoirs and the residual fraction with heavy carbon isotopes evolved to become graphite under metamorphism. Assuming the existence of isotope exchange between carbonate minerals and graphite, the temperature of peak metamorphism is estimated to be 580–860 °C, corresponding to amphibolite–granulite facies during regional metamorphism. The direct mixing of organic fluids and adjacent inorganic reservoirs may have contributed to graphite ore formation and needs to be further explored in future studies. The findings shed light on the genesis of the TLFZ graphite deposits, providing practical implications for local mineral exploration. Full article

Glass wool waste constitutes a rapidly increasing fraction of construction and demolition residues, yet it remains one of the most challenging insulation materials to recycle. Its non-combustible nature, extremely low bulk density, and high fibre elasticity preclude energy recovery and severely limit conventional mechanical recycling routes, resulting in long-term landfilling and loss of mineral resources. Converting glass wool waste into a fine mineral powder represents a potentially viable pathway for its integration into low-carbon construction materials, provided that industrial scalability, particle-size control, and chemical compatibility with cementitious binders are ensured. This study investigates the industrial-scale milling of end-of-life glass wool waste in a ventilated horizontal ball mill. It compares two grinding routes: a corundum-free route (BK) and an abrasive-assisted route (ZK) employing α-Al₂O₃ corundum to intensify fibre fragmentation. Particle size distribution was quantified by laser diffraction using cumulative and differential analyses, as well as characteristic diameters. The results confirm that abrasive-assisted milling significantly enhances fragmentation efficiency and reduces the coarse fibre fraction. However, the study demonstrates that this gain in fineness is inherently coupled with the incorporation of α-Al₂O₃ into the milled powder, introducing a chemically foreign crystalline phase that cannot be removed by post-processing. From a cement-oriented perspective, this contamination represents a critical limitation, as α-Al₂O₃ may interfere with hydration reactions, aluminate–sulfate equilibria, and microstructural development in Portland and calcium sulfoaluminate binders. In contrast, the corundum-free milling route yields a slightly coarser, chemically unmodified powder, offering improved process robustness, lower operational complexity, and greater compatibility with circular economy objectives. The study establishes that, for the circular reuse of fibrous insulation waste in cementitious systems, particle fineness alone is insufficient as an optimization criterion. Instead, the combined consideration of fineness, chemical purity, and binder compatibility governs the realistic and sustainable reuse potential of recycled glass wool powders. Full article

A novel polysaccharide from Cynanchum auriculatum Royle ex Wight was isolated, structurally characterized, and its antioxidant activity was evaluated. The crude extract was purified by ion exchange and size exclusion chromatography to obtain a homogeneous fraction, CAP2-1. CAP2-1 displayed a weight-average molecular mass of 184.17 kDa and is mainly composed of galactose, arabinose, and galacturonic acid. Structural analysis revealed that CAP2-1 is a highly branched acidic arabinogalactan-type polysaccharide with a backbone of →6)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and →4)-α-D-GalpA-(1→ units, and side chains enriched in α-L-arabino furanose residues. Ultrasonic degradation produced a lower-molecular-weight derivative, UCAP2-1, which exhibited significantly stronger free radical scavenging ability compared with CAP2-1 (p < 0.01). These findings suggest that molecular weight reduction enhances antioxidant properties by improving electron-donating capacity and accessibility to reactive sites. This study reveals the structure–antioxidant relationship of CAP2-1 and UCAP2-1 and highlights UCAP2-1 as a promising natural antioxidant. Full article

The structural origin of the germanate anomaly in glasses, which involves complex Ge–O coordination environments, is frequently studied using crystalline analogs. This study aims to provide reliable spectroscopic fingerprints by performing a detailed structural and thermal analysis of crystalline A₄Ge₉O₂₀ model systems with A = Li, Na, K. The compounds were synthesized via melt crystallization and characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Raman spectroscopy techniques. The results demonstrate clear cation-dependent crystallization pathways. The Li-containing system predominantly forms Li₂Ge₇O₁₅ in mixture with Li₄Ge₉O₂₀, indicating a preference for thermodynamically stable phases. The Na-system successfully yields the target Na₄Ge₉O₂₀ compound. In contrast, the K-system primarily produces the likely metastable K₂Ge₄O₉ phase with a significant amorphous fraction, highlighting the role of kinetic limitations. This comparative study demonstrates that the size of the alkali cation is a critical factor for controlling phase formation under identical stoichiometric and thermal conditions. Full article

Exercise training has demonstrated potential benefits in addressing the adverse effects of cardiovascular diseases, particularly myocardial infarction (MI). This study analyzed the cardioprotective effects of moderate exercise before and after MI in rats subjected to isoproterenol (ISO)-induced heart damage. Wistar rats were assigned to five groups: controls (CTRL), isoproterenol-treated (ISO), swimming before ISO (PRE + ISO), swimming after ISO (ISO + POST), and swimming both before and after ISO (PRE + ISO + POST). Cardiac function was assessed through echocardiography, while oxidative stress markers, Heme Oxygenase-1 (HO-1) and Myeloperoxidase (MPO), were quantified using biochemical assays and enzyme-linked immunosorbent assay (ELISA). Statistical analyses were conducted by one-way analysis of variance (ANOVA), accompanied by Tukey’s post hoc test. Exercise performed post-MI and both pre- and post-MI significantly reduced ISO-induced infarct size and improved left ventricular function (stroke volume (SV), ejection fraction (EF), and Tei index). HO-1 protein concentration and HO enzyme activity were restored, while swim training reduced the activity of MPO compared to the ISO group. Moderate exercise training, when appropriately timed, provides cardioprotection against ISO-induced myocardial damage by reducing oxidative stress and cardiac dysfunction. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

We develop a unified likelihood-based framework for limited outcomes built on the two-piece normal family. The framework includes a censored specification that accommodates boundary inflation, a doubly truncated specification on $(0,1)$ for rates and proportions, and a survival formulation with a log-two-piece normal baseline and Gamma frailty to account for unobserved heterogeneity. We derive closed-form building blocks (pdf, cdf, survival, hazard, and cumulative hazard), full log-likelihoods with score functions and observed information, and stable reparameterizations that enable routine optimization. Monte Carlo experiments show a small bias and declining RMSE with increasing sample size; censoring primarily inflates the variability of regression coefficients; the scale parameter remains comparatively stable, and the shape parameter is most sensitive under heavy censoring. Applications to HIV-1 RNA with a detection limit, household food expenditure on $(0,1)$, labor-supply hours with a corner solution, and childhood cancer times to hospitalization demonstrate improved fit over Gaussian, skew-normal, and beta benchmarks according to AIC/BIC/CAIC and goodness-of-fit diagnostics, with model-implied censoring closely matching the observed fraction. The proposed formulations are tractable, flexible, and readily implementable with standard software. Full article

The presence of the brittle β/B2 phase in TiAl alloys often deteriorates their mechanical properties, posing a significant challenge for manufacturing large-sized, high-performance sheets. To address this issue, this study systematically investigates the synergistic effect of pack rolling and subsequent heat treatment on the microstructure evolution and mechanical properties of a Ti-44Al-4Nb-1.5Mo-0.1B-0.1Y alloy. Sheets with two different deformation levels (R7: 69.8% and R11: 83.0% reduction) were prepared via pack rolling. This was followed by a series of heat treatments at different temperatures (1150–1350 °C) and cyclic heat treatments at 1250 °C (3, 6, and 9 cycles). The results demonstrate that the higher deformation level (R11) promoted extensive dynamic recrystallization, resulting in a uniform microstructure of equiaxed γ, α₂, and β phases, while the lower deformation (R7) retained a significant fraction of deformed γ/α₂ lamellae. Heat treatment at 1250 °C was identified as optimal for transforming the microstructure into fine lamellar colonies while effectively reducing the β/B2 phase. Cyclic heat treatment at this temperature further decreased the β-phase content to 4.1% after 9 cycles. The elimination mechanism was determined to follow the β→ α → γ + α₂ phase transformation sequence, driven by the combined effect of rolling-induced defects and cyclic thermal stress. Cyclic heat treatment at this temperature was particularly effective in generating a high density of nucleation sites within the lamellar colonies, leading to significant refinement of the lamellar structure. Consequently, the R11 sheet subjected to 9 cycles of heat treatment exhibited a 15.5% increase in tensile strength and an 8.3% improvement in elongation compared to the hot-isostatically pressed state. This enhancement is primarily attributed to the significant refinement of lamellar colonies and the reduction in interlamellar spacing. This work presents an effective integrated processing strategy for fabricating high-performance TiAl alloy sheets with superior strength and toughness. Full article