Search Results (6,053)

This study presents an integrated approach to processing the heavy fraction of coal tar (HFCT) using oil shale (OS) from Shubarkol Komir JSC to simultaneously increase the yield of valuable hydrocarbon fractions and extract rare and dispersed trace elements. The lack of data on the effect of shale on the process and the kinetics of multi-component “tar + shale” systems limits the development of effective technologies. TG/DTG analysis was combined with the Friedman, Ozawa–Flynn–Wall, and Šesták–Berggren methods for the first time to evaluate the role of oil shale (OS). It was shown that the addition of 13% OS provides a sustained reduction in activation energy (~85–86 kJ/mol) and optimal conditions for hydrometallization. At 420 °C, an initial H₂ pressure of 4 MPa, and a reaction time of 60 min, the yield of light fractions reaches 62.6%, and the solid residue concentrates Ti, Mo, Ge, and other rare and dispersed elements reach up to 66,000 g/t in total. The possibility of extracting Ge using the Purolite C100 sorbent has also been confirmed. The novelty of the study lies in demonstrating the donor–catalytic effect of shale and the practical prospects of solid residue as a secondary mineral raw materials. Full article

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

Almond hulls and shells, the byproducts of the almond industry, were analyzed to assess their potential valorization pathways. Shells showed a higher content in lignin and polysaccharides, but very low levels of extractives and inorganics. Hull’s high polar extractives fraction showed poor phenolic preponderance and antioxidant activity, but high sugar and mineral contents, and its lipophilic extracts were highly enriched in triterpenes (from 73.5% to 91.3%), while shells presented more fatty acids (27.4% to 34.2%) and sterols (17.4% to 29.1%). Shells exhibited much higher S/G ratio (syringyl to guaiacyl units) in their lignin polymer (1.0 to 1.4), compared to hulls (0.5 to 0.6). After mineral analyses, hulls showed high amounts of potassium (3.7–4.9%). Fixed carbon content was similar for both materials, but shells showed a higher energetic content, ~20 MJ/kg. Finally, both hulls and pellets increased the water holding capacity (WHC) of the soil by 50%, when added in weight percentages of 6.25% (hulls) and 25% (pellets). With these results, the range of possibilities for these waste materials is exciting: shells could be used to obtain hemicellulose oligosaccharides, while hulls could be used in sugar extraction for biotransformation or as a soil amendment. Full article

The objective of this study was to investigate the effects of fractionation by sieving on cold-pressed camelina cake by separating it into particle-sized fractions and evaluating their nutritional and functional properties. Two Camelina sativa varieties, NS Zlatka and NS Slatka, were mechanically cold-pressed using a screw press then ground into flour. The resulting material was fractionated into three particle-sized fractions, >250 µm, 250–180 µm, and <180 µm, using a laboratory dry sieving system. Both the whole cake and the separated fractions were analyzed for proximate composition, amino acid and fatty acid profiles, tocopherol content, antioxidant potential, color characteristics, and water and oil absorption capacities. The results indicated that the finest cake fraction (<180 µm) from both camelina varieties contained the highest content of protein (~40%), fat (17–19%), essential amino acids (~17 g/100 g), γ-tocopherols (254–266 mg/kg), and the lowest content of condensed tannins (0.5–0.9 g/kg). It also displayed a lighter color and increased yellowness. However, it contained the highest concentrations of glucosinolates (24–27 μmol/g) and phytic acid (38–41 g/kg). In contrast, the coarsest fraction (>250 µm) had increased crude fiber content (13–15%), higher antioxidant potential, the greatest water absorption capacity, and a darker color with a more pronounced reddish color. It also contained the lowest levels of glucosinolates (19–21 μmol/g) and phytic acid (17–20 g/kg). In conclusion, whole camelina cake and its fractions demonstrate considerable potential for use in animal feed and a variety of human nutritional products, due to their favorable nutritional composition and functional properties. Fine fractions with high levels of antinutritional compounds could be used as a substrate for the extraction of bioactive compounds and may find further application in the cosmetic and pharmaceutical industries. Full article

Francisella tularensis is a pathogenic bacterium and the causative agent of the disease tularemia. Because of the virulence of this bacterium and the potential for weaponization, the Centers for Disease Control and Prevention (CDC) has classified F. tularensis as a Category A Bioterrorism Agent. Therefore, the need for new treatments for tularemia is critical. In this work, we screened a cataloged library of natural extracts to identify those that inhibit the growth of F. tularensis only during infection of THP-1 monocyte cells. One of the most promising extracts identified in this screen was derived from Foeniculum vulgare (fennel). Using bioassay-guided fractionation, the fennel extract was fractionated, and the bioactive compound was isolated and structurally elucidated as the phenylpropanoid dillapiole. We subsequently confirmed that dillapiole alone could limit the replication of F. tularensis in infected THP-1 cells, but not outside of this infection model. Investigations on host responses suggested that dillapiole was not substantially augmenting the immunity of these THP-1 cells. We then investigated the potential virulence modulation activity of dillapiole. To test this hypothesis, RNA-seq analysis was carried out on F. tularensis bacteria that were treated with dillapiole. This showed that dillapiole caused a significant downregulation of genes controlled by the transcriptional regulators MglA and SspA, including those encoded in the Francisella pathogenicity island. Western blotting validated these findings as both IglA and IglC expression was diminished in F. tularensis LVS bacteria treated with dillapiole. Because dillapiole dampens the virulence gene expression of F. tularensis, we concluded that this compound has potential to be used as a novel therapeutic for tularemia with a unique mechanism of action. Full article

Food spoilage and contamination are major global challenges, reducing food quality, safety, and availability, causing significant economic losses. This study evaluates the photodynamic and sonodynamic antibacterial activities of grape leaf extracts from Beer and Hanut Orcha varieties. The extracts were tested against Staphylococcus aureus and Escherichia coli under illumination and ultrasonic activation. The results demonstrated that the photodynamic and sonodynamic treatments significantly enhanced the antibacterial efficacy of the extracts when higher concentrations of the extracts and prolonged exposure led to complete bacterial eradication. Separation of the extracts using RP-18 cartridges (Yicozoo Energy Technology Co., Ltd., Xi’an, China) enabled us to get an active fraction containing components responsible for antimicrobial effects. Singlet oxygen generation measurements confirmed the involvement of reactive oxygen species in bacterial inactivation under illumination. Using HPLC/MS, the active components responsible for the photodynamic properties of the extracts were identified as quercetin 3’-O-glucuronide and pheophorbide a. The findings suggest that these natural extracts, in combination with photodynamic and sonodynamic activation, represent promising alternatives to conventional antibiotics. Further studies should focus on the isolation of active individual compounds, the improvement of treatment parameters, and the investigation of molecular mechanisms to facilitate the development of practical applications in medicine and food preservation. Full article

In this paper, the evaluation of the mechanical performance of novel, designed topologically optimized shin pads with advanced materials will be conducted with the aid of Finite Element Analysis (FEA) to assess the endurance of the final structure on impact phenomena extracted from actual real-life data acquired from contact sports. The main focus of the developed prototype is to have high-enough energy absorption capabilities and vibration isolation properties, crucial for the development of trustworthy protective equipment. The insertion of advanced materials with controlled weight fractions and lattice geometries aims to strategically improve those properties and provide tailored characteristics similar to the actual human skeleton. The final design is expected to be used as standalone protective equipment for athletes or as a protective shield for the development of human lower limb prosthetics. In this context, computational investigation of the dynamic mechanical response was conducted by replicating a real-life phenomenon of the impact during a contact sport in a median condition of a stud kick impact and an extreme case scenario to assess the dynamic response under shock-absorption conditions and the final design’s structural integrity by taking into consideration the injury prevention capabilities. The results demonstrate that the proposed lattice geometries positively influence the injury prevention capabilities by converting a severe injury to light one, especially in the gyroid structure where the prototype presented a unified pattern of stress distribution and a higher reduction in the transmitted force. The incorporation of the PA-12 matrix reinforced with the reused ground tire rubber results in a structure with high enough overall strength and crucial modifications on the absorption and damping capabilities vital for the integrity under dynamic conditions. Full article

The present work reports the bioguided isolation of constituents from the ethanol extract of Holarrhena floribunda stem bark, their identification by UHPLC-ESI-QTOF-MS/MS identification, and the in silico prediction of the pharmacokinetic and toxicity parameters. The crude extract, along with its n-hexane and alkaloid-rich fractions, displayed moderate to good antiplasmodial activity in vitro against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) strains of Plasmodium falciparum, with IC₅₀ values ranging from 6.54 to 43.54 µg/mL. Seventeen steroidal alkaloids (1–17) were identified in the most active fraction using UHPLC-ESI-QTOF-MS/MS, based on their fragmentation patterns and analysis with the Structural Similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS). Furthermore, bioguided isolation of the ethanol extract yielded twenty-one compounds (3, 5, 10, 14–16, 18–31), whose structures were elucidated by spectroscopic methods. Among them, compounds 5, 14, and 27 showed the highest potency against the two strains of P. falciparum, with IC₅₀ values between 25.97 and 55.78 µM. In addition, the in silico prediction of pharmacokinetic parameters and drug-likeness using the SwissADME web tool indicated that most of the evaluated compounds (1, 3–5, and 14–16) complied with Lipinski’s rule of five. Full article

This study investigates the anti-obesity and antidiabetic potential of P. palmata extracts produced through sequential enzymatic and alkaline treatments. Among the treatment groups, the extract treated solely with Alcalase^® (Alc) demonstrated the highest protein content (10.11 ± 0.15%) and degree of hydrolysis (30.36 ± 0.77%), significantly outperforming other treatments (p < 0.05). The Alc extract also exhibited superior inhibitory activity against porcine pancreatic lipase and α-amylase, achieving the lowest IC₅₀ for lipase (2.29 ± 0.87 mg.mL⁻¹) and showing significant enzyme inhibition across all tested concentrations (p < 0.05). Ultrafiltration of the Alc extract revealed that peptide fractions < 1 kDa and 1–3 kDa were most effective in enzyme inhibition, with IC₅₀ values of 3.25–3.55 mg.mL⁻¹ for both lipase and α-amylase. Peptides were identified via LC-MS/MS analysis and database searching using SequestHT, resulting in 536 sequences, of which bioinformatic screening yielded 51 non-toxic, non-allergenic candidates (PeptideRanker score > 0.6); four of these contained known inhibitory motifs for lipase and α-amylase. Molecular docking confirmed strong binding affinities between these peptides and their respective enzymes, supporting their potential as natural enzyme inhibitors. These findings indicate the functional food potential of Alcalase^®-derived P. palmata peptides for managing obesity and type 2 diabetes. Full article

Background: Marine macroalgae has been studied by our research group as alternative sources of bioactive compounds with promising antiparasitic activity, particularly against Schistosoma mansoni. Objectives: This study aimed to employ a metabolomics-based approach to identify anthelminthic active compounds from the macroalgae Laurencia aldingensis Saito and Womersley 1974 and Laurencia dendroidea J. Agardh 1852. Methods: The algae were extracted using a dichloromethane/methanol mixture, followed by liquid–liquid partitioning and sequential chromatographic fractionation using solvents of varying polarities. The resulting fractions were tested for biological activity against adult Schistosoma mansoni worms. Detailed chemical characterization of the extracts was conducted via HPLC-DAD-MS/MS, with subsequent data alignment and statistical analysis (Pearson correlation) to associate specific chemical compounds with the observed bioactivity. Results: Non-polar fractions (hexane and dichloromethane) exhibited significant anthelminthic activity, substantially reducing parasite viability and reproduction. Specific subfractions obtained from the dichloromethane fraction demonstrated notable activity. Metabolomic analysis revealed considerable chemical diversity, emphasizing the presence of bromophenols and halogenated sesquiterpenes, including potentially novel compounds with therapeutic potential against schistosomiasis. Conclusions: The metabolomics approach proved effective in identifying promising bioactive compounds from Laurencia spp. macroalgae with activity against S. mansoni. Full article

Background: Skin diseases of inflammatory origin, such as atopic dermatitis, psoriasis and acne, have a substantial prevalence in the world population. Natural products are particularly important at a topical level. Essential oils are examples of natural products and thyme in particular has been used for medicinal purposes due to its biological properties. Objectives: The aim of present work was to study the anti-inflammatory potential of Thymus mastichina essential oil, focusing on purified terpene-rich fractions. whose major compounds were thymol and linalool, eucalyptol and α-terpineol, and γ-terpinene and terpinolene, respectively. Additionally, a phytocannabinoid formulation containing cannabidiol (CBD) and cannabigerol (CBG) was evaluated to explore potential synergistic effects. Methods: Thymus mastichina essential oil was extracted and purified to obtain terpene-enriched fractions, which were used to develop three distinct formulations. These were screened for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and assessed for cytotoxicity in HaCaT human keratinocytes. Anti-inflammatory potential was evaluated via gene expression. Selected thyme formulations—alone or in combination with CBD/CBG—were also tested in vivo using a mouse model of acute skin inflammation. Results: The antioxidant activity of the three formulations showed a reduction in DPPH radicals. In addition, the formulations demonstrated to be safe in vitro in the human keratinocyte cell model HaCaT. Under PMA-induced inflammatory stress, the fractions modulated-inflammatory gene expression to varying degrees While terpene fractions alone showed moderate activity, their combination with CBD/CBG enhanced the anti-inflammatory response. In vivo, the gel formulations reduced oedema in a mouse model of acute inflammation. Conclusions: The data support the safe and effective use of Thymus mastichina-derived terpene fractions for topical anti-inflammatory applications. The synergistic effect observed with CBD and CBG suggests that combining essential oil terpenes with phytocannabinoids may offer a novel therapeutic strategy for managing inflammatory skin disorders. Full article

Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO₂) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO₂ (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO₂) was recorded when PaCO₂ was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO₂, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO₂ and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO₂, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO₂ and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article

Land degradation in Iraq’s Mesopotamian plain threatens food security and rural livelihoods, yet the relative roles of climatic water deficits versus anthropogenic pressures remain poorly attributed in space. We test the hypothesis that multi-timescale climatic water deficits (SPEI-03/-06/-12) exert a stronger effect on vegetation degradation risk than anthropogenic pressures, conditional on hydrological connectivity and irrigation. Using Babil and Al-Qadisiyah (2000–2023) as a case, we implement a four-part pipeline: (i) Fractional Vegetation Cover with Mann–Kendall/Sen’s slope to quantify greening/browning trends; (ii) LandTrendr to extract disturbance timing and magnitude; (iii) annual LULC maps from a Random Forest classifier to resolve transitions; and (iv) an XGBoost classifier to map degradation risk and attribute climate vs. anthropogenic influence via drop-group permutation (ΔAUC), grouped SHAP shares, and leave-group-out ablation, all under spatial block cross-validation. Driver attribution shows mid-term and short-term drought (SPEI-06, SPEI-03) as the strongest predictors, and conditional permutation yields a larger average AUC loss for the climate block than for the anthropogenic block, while grouped SHAP shares are comparable between the two, and ablation suggests a neutral to weak anthropogenic edge. The XGBoost model attains AUC = 0.884 (test) and maps 9.7% of the area as high risk (>0.70), concentrated away from perennial water bodies. Over 2000–2023, LULC change indicates CA +515 km², HO +129 km², UL +70 km², BL −697 km², WB −16.7 km². Trend analysis shows recovery across 51.5% of the landscape (+29.6% dec⁻¹ median) and severe decline over 2.5% (−22.0% dec⁻¹). The integrated design couples trend mapping with driver attribution, clarifying how compounded climatic stress and intensive land use shape contemporary desertification risk and providing spatial priorities for restoration and adaptive water management. Full article

Tuberculosis (TB) is still a significant public health threat, with rising drug resistance and high incidence in multiple areas worldwide. In the search for novel antitubercular agents, this study explores the application of a bioactivity-guided molecular networking approach to identify bioactive compounds from seven plant species (Curatella americana, Davilla nitida, Dipteryx punctata, Indigofera suffruticosa, Quassia amara, Tetradenia riparia, and Zingiber zerumbet) collected in French Guiana. Using ultrasound-assisted extraction followed by liquid–liquid partitioning and UHPLC-HRMS/MS analysis, a library of 72 samples was tested against Mycobacterium tuberculosis. The non-polar fractions from Indigofera suffruticosa, Tetradenia riparia, and Zingiber zerumbet showed the highest activity. The integration of metabolomic and bioassay data on molecular networks allowed the prioritization and annotation of active compounds, revealing flavonoids as contributors to the antitubercular activity of the active samples. In addition, the use of computational tools such as GNPS, SIRIUS, and TIMA-R enabled dereplication and increased the confidence in the structural prediction of active metabolites. This approach demonstrated its potential in accelerating the identification of both known and novel bioactive compounds without requiring exhaustive isolation, offering a robust strategy for natural product-based drug development against TB. Full article

The environmental fate of nickel (Ni) is dictated by its interaction with organic matter (OM), yet the specific roles of OM source and molecular size remain unclear. This study investigated the binding characteristics of Ni with size-fractionated dissolved OM (DOM) from the water column and alkaline-extractable OM (AEOM) from sediments in a tropical wetland. Using ultrafiltration and spectroscopy, we found that sedimentary AEOM was predominantly high-molecular-weight (HMW) and terrestrial compounds, whereas aquatic DOM was dominated by low-molecular-weight (LMW), microbial-derived compounds. Counterintuitively, the highest Ni binding affinity (NiBA) for both DOM and AEOM occurred in the smallest-molecular-weight fraction (<0.3 kDa). Predictive models confirmed this divergence: the model for the more chemically homogeneous AEOM was highly predictive (r = 0.89), while the model for the complex DOM was less robust (r = 0.70). Our findings demonstrate that LMW fractions are hotspots for Ni binding, challenging the common assumption that larger molecules are more reactive. We conclude that biogeochemical processing in sediments creates an OM pool that is chemically distinct and more predictable than that in the overlying water. This distinction is critical for accurately assessing Ni mobility and ecological risk in aquatic systems. Full article