Search Results (822)

With rising global temperatures and increasing sustainability demands, the need for advanced pavement solutions has never been greater. This study breaks new ground by integrating phase change materials (PCMs), including paraffin-based wax (Rubitherm RT55), hydrated salt (Climator Salt S10), and fatty acid (lauric acid), as binder modifiers within warm mix asphalt (WMA) mixtures. Moving beyond the traditional focus on binder-only modifications, this research utilizes recycled cigarette filters (CFs) as a dual-purpose fiber additive, directly reinforcing the asphalt mixture while simultaneously transforming a major urban waste stream into valuable infrastructure. The performance of the developed WMA mixture has been evaluated in terms of stiffness behavior using an Indirect Tensile Strength Modulus (ITSM) test, permanent deformation using a static creep strain test, and rutting resistance using the Hamburg wheel-track test. Laboratory tests demonstrated that the incorporation of PCMs and recycled CFs into WMA mixtures led to remarkable improvements in stiffness, deformation resistance, and rutting performance. Modified mixes consistently outperformed the control, achieving up to 15% higher stiffness after 7 days of curing, 36% lower creep strain after 4000 s, and 64% reduction in rut depth at 20,000 passes. Cost–benefit analysis and service life prediction show that, despite costing USD 0.71 more per square meter with 5 cm thickness, the modified WMA mixture delivers much greater durability and rutting resistance, extending service life to 19–29 years compared to 10–15 years for the control. This highlights the value of these modifications for durable, sustainable pavements. Full article

Concern over the presence of pharmaceutical waste in the environment has prompted research into the management of emerging organic micropollutants (EOMs). In response, sustainable technologies have been applied as alternatives to reduce the effects of these contaminants. This study investigated the capacity of filamentous fungi isolated from iron mine soil in the Amazon region to biodegrade the drug chloroquine diphosphate. An initial screening assessed the growth of four fungal strains on solid media containing chloroquine diphosphate: Trichoderma pseudoasperelloides CBMAI 2752, Penicillium rolfsii CBMAI 2753, Talaromyces verruculosus CBMAI 2754, and Penicillium sp. cf. guaibinense CBMAI 2758. Among them, Penicillium sp. cf. guaibinense CBMAI 2758 was selected for further testing in liquid media. A Box–Behnken factorial design was applied with three variables, pH (5, 7, and 9), incubation time (5, 10, and 15 days), and chloroquine diphosphate concentration (50, 75, and 100 mg·L⁻¹), totaling 15 experiments. The samples were analyzed by gas chromatography–mass spectrometry (GC-MS). The most effective conditions for chloroquine biodegradation were pH 7, 100 mg·L⁻¹ concentration, and 10 days of incubation. Four metabolites were identified: one resulting from N-deethylation M1 (N4-(7-chloroquinolin-4-yl)-N1-ethylpentane-1,4-diamine), two from carbon–carbon bond cleavage M2 (7-chloro-N-ethylquinolin-4-amine) and M3 (N1,N1-diethylpentane-1,4-diamine), and one from aromatic deamination M4 (N1-ethylbutane-1,4-diamine) by enzymatic reactions. The toxicity analysis showed that the products obtained from the biodegradation of chloroquine were less toxic than the commercial formulation of this compound. These findings highlight the biotechnological potential of Amazonian fungi for drug biodegradation and decontamination. Full article

Background and Objectives: Malnutrition is one of the most common complications in patients undergoing hemodialysis (HD) and is closely linked to increased morbidity and mortality. This study aimed to investigate the nutritional status of HD patients and the clinical relevance of bioelectrical impedance analysis (BIA) parameters such as the percent body fat (PBF), skeletal muscle mass index (SMI), extracellular water-to-total body water ratio (ECW/TBW), and phase angle (PhA) in assessing malnutrition in Vietnamese HD patients. Materials and Methods: This cross-sectional study was conducted among 184 patients undergoing hemodialysis in Hanoi, Vietnam. The BIA parameters were measured by the InBody S10 body composition analyzer, while malnutrition was assessed by the geriatric nutritional risk index (GNRI), with a GNRI <92 classified as a high risk of malnutrition. The independent BIA variables for predicting malnutrition and its cut-off values were explored using logistic regression models and a receiver operating characteristic (ROC) curve analysis, respectively. Results: Among the study population, 42.9% (79/184) of patients were identified as being at a high risk of malnutrition. The multivariate logistic regression analysis revealed that a higher ECW/TBW was independently associated with an increased risk of malnutrition, while the PBF, SMI, and PhA expressed significant and inverse associations with the malnutrition risk after adjusting for multiple confounders. The cut-off values for predicting the high risk of malnutrition in overall HD patients were determined to be 20.45%, 7.75 kg/m², 5.45°, and 38.03% for the PBF, the SMI, the PhA, and the ECW/TBW ratio, respectively. Conclusions: BIA parameters, including the PBF, SMI, PhA, and ECW/TBW ratio, could serve as indicators of malnutrition in general Vietnamese patients with HD. Full article

Background and aim: ANGPTL3 is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL) through its N-terminal domain. Besides this activity, the C-terminal domain of ANGPTL3 interacts with integrin αVβ3. Since integrins are involved in inflammation and in the initiation of atherosclerotic plaque, the aim of our study was to evaluate the potential direct pro-inflammatory action of ANGPTL3 through the interaction of the fibrinogen-like domain and integrin αVβ3. Methods: We utilized cultured THP-1 human-derived macrophages and evaluated their pro-inflammatory phenotype in response to treatment with human recombinant ANGPTL3 (hANGPTL3). By Western blot, RT-qPCR, biochemical analysis, and ELISA assays, we determined the expression of genes and proteins involved in lipid metabolism and inflammatory response as well as intracellular cholesterol and triglyceride levels. In addition, we evaluated the effect of hANGPTL3 on the cellular cholesterol efflux process. Results: Incubation of THP-1-derived macrophages with 100 ng/mL of hANGPTL3 increased the mRNA expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα (respectively, 1.87 ± 0.08-fold, 1.35 ± 0.11-fold, and 2.49 ± 0.43-fold vs. control). The secretion of TNFα, determined by an ELISA assay, was also induced by hANGPTL3 (1.98 ± 0.4-fold vs. control). The pro-inflammatory effect of hANGPTL3 was partially counteracted by co-treatment with the integrin αVβ3 inhibitor RGD peptide, reducing the mRNA levels of IL-1β (3.35 ± 0.35-fold vs. 2.54 ± 0.25-fold for hANGPTL3 vs. hANGPTL3 + RGD, respectively). Moreover, hANGPTL3 reduced cholesterol efflux to apoA-I, with a parallel increase in the intracellular triglyceride and cholesterol contents by 31.2 ± 2.8% and 20.0 ± 4.1%, respectively, compared to the control. Conclusions: ANGPTL3 is an important liver-derived regulator of plasma lipoprotein metabolism, and overall, our results add a new important pro-inflammatory activity of this circulating protein. This new function of ANGPTL3 could also be related to triglyceride and cholesterol accumulation into macrophages. Full article

Human adipose-derived stem cells (hASCs) are widely used in regenerative medicine due to their accessibility and high proliferative capacity. Platelet lysate (PL) has recently emerged as a promising alternative to fetal bovine serum (FBS), offering superior cell expansion potential; however, the molecular basis for its efficacy remains insufficiently elucidated. In this study, we performed RNA sequencing to compare hASCs cultured with PL or FBS, revealing a significant upregulation of genes related to stress response and cell proliferation under PL conditions. These findings were validated by RT–qPCR and supported by functional assays demonstrating enhanced cellular resilience to oxidative and genotoxic stress, reduced doxorubicin-induced senescence, and improved antiapoptotic properties. In a murine wound model, PL-treated wounds showed accelerated healing, characterized by thicker dermis-like tissue formation and increased angiogenesis. Immunohistochemical analysis further revealed elevated expression of chk1, a DNA damage response kinase encoded by CHEK1, which plays a central role in maintaining genomic integrity during stress-induced repair. Collectively, these results highlight PL not only as a viable substitute for FBS in hASC expansion but also as a bioactive supplement that enhances regenerative efficacy by promoting proliferation, stress resistance, and antiaging functions. Full article

The mechanism by which quorum sensing (QS) enhances stress resistance in enterohemorrhagic Escherichia coli (E. coli) O157:H7 remains unclear. We employed optimized exogenous QS signal N-acyl-homoserinelactones (AHL) (100 μM 3-oxo-C6-AHL, 2 h) in EHEC O157:H7 strain EDL933, which was validated with endogenous yenI-derived AHL, to investigate QS-mediated protection against acid stress. RNA-seq transcriptomics identified key upregulated genes (e.g., rmf). Functional validation using isogenic rmf knockout mutants generated via λ-Red demonstrated abolished stress resistance and pan-stress vulnerability. Mechanistic studies employing qRT-PCR and stress survival assays established Ribosomal Hibernation Factor (RMF) as a non-redundant executor in a SdiA–RMF–RpoS axis, which activates ribosomal dormancy and SOS response to enhance EHEC survival under diverse stresses. For the first time, we define ribosomal hibernation as the core adaptive strategy linking QS to pathogen resilience, providing crucial mechanistic insights for developing EHEC control measures against foodborne threats. Full article

According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting such a lifestyle. Exercise induces complex molecular responses that mediate both acute metabolic stress and long-term physiological adaptations. FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15) are recognized as metabolic stress markers, while their receptors play critical roles in cellular signaling. However, the differential gene expression patterns of these molecules in trained and untrained individuals following exhaustive exercise remain poorly understood. This study aimed to examine the transcriptional and protein-level responses in trained and untrained individuals performed a treadmill maximal exercise test to voluntary exhaustion. Blood samples were collected at six time points (pre-exercise, immediately post-exercise, and 0.5 h, 6 h, 24 h, and 48 h post-exercise). Gene expression of FGF21, GDF15, FGFR1 (fibroblast growth factor receptors), FGFR3, FGFR4, KLB (β-klotho), and GFRAL (glial cell line-derived neurotrophic factor receptor alpha-like) was analyzed using RT-qPCR, while plasma protein levels of FGF21 and GDF15 were quantified via ELISA. The results obtained were statistically analyzed by using Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests in Statistica 13 software. Untrained individuals demonstrated significant post-exercise upregulation of FGFR3, FGFR4, KLB, and GFRAL. FGF21 and GDF15 protein levels were consistently lower in trained individuals (p < 0.01), with no significant correlations between gene and protein expression. Trained individuals showed more stable expression of genes, while untrained individuals exhibited transient upregulation of genes after exercise. Full article

In this article, we investigate the influence of viscosity on the evolution of the cosmos within the framework of the newly proposed $f(Q,L_m)$ gravity. We have considered a linear functional form $f(Q,L_m)=\alpha Q+\beta L_m$ with a bulk viscous coefficient $\zeta ={\zeta }_0+{\zeta }_{1}H$ for our analysis and obtained exact solutions to the field equations associated with a flat FLRW metric. In addition, we utilized Cosmic Chronometers (CC), CC + BAO, CC + BAO + GRB, and GRB data samples to determine the constrained values of independent parameters in the derived exact solution. The likelihood function and the Markov Chain Monte Carlo (MCMC) sampling technique are combined to yield the posterior probability using Bayesian statistical methods. Furthermore, by comparing our results with the standard cosmological model, we found that our considered model supports the acceleration of the universe in late time. Full article

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article

The control of following motion under mesoscale gap flow fields has important applications. The flexible characteristics of the plant, wideband time-varying disturbances caused by the flow field, and requirements of high precision and low overshoot make achieving submicron level accuracy a significant challenge for traditional control methods. This study adopts the control concept of Disturbance Observer Control (DOBC) and uses H_∞ mixed-sensitivity shaping technology to design a Q-filter. Simultaneously, multiple control techniques, such as high-order reference trajectory planning, Proportional-Integral-Derivative (PID) control, low-pass filtering, notch filtering, lead lag correction, and disturbance rejection filtering, are applied to obtain a control system with a high open-loop gain, sufficient phase margin, and stable closed-loop system. Compared to traditional control methods, the new method can increase the open-loop gain by 15 times and the open-loop bandwidth by 8%. We even observed a 150-time increase of the open-loop gain at the peak frequency. Ultimately, the method achieves submicron level accuracy, making important advances in solving the control problem of semiconductor equipment. Full article

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models. Full article

This work presents the synthesis, characterization and evaluation of physicochemical and biological properties of two new aminoporphyrazine derivatives bearing magnesium(II) cations in their cores and peripheral pyrrolyl groups. The synthesis was carried out in several stages, using classical methods and the Microwave-Assisted Organic Synthesis (MAOS) approach. The obtained compounds were characterized using spectral techniques: UV-Vis spectrophotometry, mass spectrometry, ¹H and ¹³C NMR spectroscopy. The porphyrazine derivatives were tested for their electrochemical properties (CV and DPV), which revealed four redox processes, of which in compound 7 positive shifts of oxidation potentials were observed, resulting from the presence of free phenolic hydroxyl groups. In spectroelectrochemical measurements, changes in UV-Vis spectra associated with the formation of positive-charged states were noted. Photophysical studies revealed the presence of characteristic absorption Q and Soret bands, low fluorescence quantum yields and small Stokes shifts. The efficiency of singlet oxygen generation (Φ_Δ) was higher for compound 6 (up to 0.06), but compound 7, despite its lower efficiency (0.02), was distinguished by a better biological activity profile. Toxicity tests using the Aliivibrio fischeri bacteria indicated the lower toxicity of 7 compared to 6. The most promising result was the strong photodynamic activity of porphyrazine 7 against the Methicillin-resistant Stapylococcus aureus (MRSA) strain, leading to a more-than-5.6-log decrease in viable counts after the colony forming units (CFU) after light irradiation. Compound 6 did not show any significant antibacterial activity. The obtained data indicate that porphyrazine 7 is a promising candidate for applications in photodynamic therapy of bacterial infections. Full article

Background/Objectives: To investigate the incidence of new-onset diabetic retinopathy (DR) in individuals with pre-existing type 2 diabetes (T2D) up to 3 years post SARS-CoV-2 infection. Methods: This retrospective study consisted of 5151 COVID-19 and 5151 propensity-matched non-COVID-19 patients with T2D in the Montefiore Health System between 1 March 2020 and 17 January 2023. The primary outcome was new-onset DR at least 2 months after the index date up to 17 January 2023. Matching for index date between groups was also used to ensure the same follow-up duration. Hazard ratios (HRs) were computed, adjusted for competing risks. Results: T2D patients with COVID-19 had a higher cumulative incidence of DR than T2D patients. The unadjusted HR for COVID-19 status for developing new DR was 2.44 [1.60, 3.73], p < 0.001. The adjusted HR was 1.70 [1.08, 2.70], p < 0.05, and the adjusted HR for prior insulin use was 3.28 [2.10, 5.12], p < 0.001. Sex, ethnicity, and major comorbidities had no significant association with outcome. Conclusions: T2D patients who contracted COVID-19 exhibited a significantly higher risk of developing DR within three years post infection compared to propensity-matched controls. The increased incidence was primarily driven by greater pre-existing insulin usage and SARS-CoV-2 infection in the COVID-19 positive cohort. Full article

To address the challenges of model uncertainty, strong nonlinearities, and controller tuning in high-precision trajectory tracking for hydraulic servo systems, this paper proposes a hierarchical GA-PID-MPC fusion strategy. The architecture integrates three functional layers: a Genetic Algorithm (GA) for online parameter optimization, a Model Predictive Controller (MPC) for future-oriented planning, and a Proportional–Integral–Derivative (PID) controller for fast feedback correction. These modules are dynamically coordinated through an adaptive cost-aware blending mechanism based on real-time performance evaluation. The MPC module operates on a linearized state–space model and performs receding-horizon control with weights and horizon length $\theta =[q,r,T_p]$ tuned by GA. In parallel, the PID controller is enhanced with online gain projection to mitigate nonlinear effects. The blending coefficient $\sigma \left(t\right)$ is adaptively updated to balance predictive accuracy and real-time responsiveness, forming a robust single-loop controller. Rigorous theoretical analysis establishes global input-to-state stability and $H_{\infty }$ performance under average dwell-time constraints. Full article

Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm² for 500 s, delivering an energy dose of 5 J/cm², followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article