Search Results (4,561)

Hydrophilic Interaction Liquid Chromatography (HILIC) has emerged as a powerful and versatile analytical technique for the separation and quantification of polar and ionizable compounds, particularly in the field of pharmaceutical impurity profiling. Over the past two decades, HILIC has gained increasing attention due to its compatibility with mass spectrometry, enhanced retention of hydrophilic impurities, and ability to resolve structurally similar degradation products and process-related impurities that are often inadequately retained by reversed-phase chromatography. This comprehensive review presents a critical overview of HILIC-based methodologies applied to impurity profiling in pharmaceutical analysis from early 2005 to the present. Emphasis is placed on the application of HILIC to both small-molecule drugs and large biomolecules. Additionally, the review categorizes analytical configurations into four main groups based on their operational principles and use cases, offering insights into method selection and performance characteristics. This article serves as a valuable resource for researchers and regulatory scientists seeking to apply HILIC in modern impurity profiling and quality control of pharmaceutical products. Full article

Alzheimer’s disease (AD) is marked by the pathological aggregation of amyloid β (Aβ) and tau proteins. Emerging research reveals that these proteins undergo liquid–liquid phase separation (LLPS), forming biomolecular condensates that promote aggregation and neurotoxicity. These phase-separated structures reshape the intracellular environment, facilitating protein misfolding and spreading. This review highlights recent advances in understanding the role of condensates in AD pathogenesis and explores novel therapeutic strategies targeting condensate dynamics. Promising approaches include small molecules that disrupt LLPS, epigenetic drugs influencing nuclear condensates, and compounds like DDL 920 and RI AG03 that modulate tau phase separation and neuroinflammation, respectively. Additionally, anti-inflammatory agents, such as nucleotide reverse transcriptase inhibitors (NRTIs), offer potential for upstream intervention. Targeting biomolecular condensates presents a next-generation strategy for AD treatment. Future research should focus on in vivo profiling of condensate composition, biomarker development, and the development of patient-specific therapies to enable early, disease-modifying interventions. Full article

Ammonia (NH₃) emissions from swine manure pits contribute significantly to odor nuisance, health risks, and secondary PM_2.5 formation. This study assessed the pilot-scale performance of three source-control technologies: surface sealing with surfactant-based foam system (FOAM SYSTEM), swine manure wiping and removing system (WIPING SYSTEM), and belt-conveyor-based solid–liquid separator system (BELT SYSTEM). Each technology targets a different pathway in the ammonia generation process. The FOAM SYSTEM suppresses volatilization by forming a foam barrier at the air–liquid interface. The WIPING SYSTEM reduces precursor contact time by periodically removing feces. The BELT SYSTEM separates feces and urine upon excretion, inhibiting enzymatic ammonia formation. Among the individual systems, the BELT SYSTEM achieved the highest ammonia reduction efficiency of 91.7%, followed by the FOAM SYSTEM (73.6%) and WIPING SYSTEM (64.4%). The combined FOAM SYSTEM + BELT SYSTEM yielded the best performance with an ammonia reduction efficiency of 94.4%, showing modest synergy without operational interference. In contrast, the FOAM SYSTEM + WIPING SYSTEM configuration achieved 71.1%, slightly lower than the FOAM SYSTEM alone, likely due to foam disruption. Environmental sensitivity tests revealed that higher temperatures and alkaline pH elevated NH₃ emissions, whereas systems that maintained near-neutral pH, like the FOAM SYSTEM, demonstrated greater stability. These findings highlight the importance of integrating physical and source-control mechanisms while considering environmental variability for effective on-farm ammonia mitigation. Full article

Efficient xylene isomers’ separation remains a challenge due to their similar kinetic diameter and boiling points, particularly for the separation of the immediate size of meta-xylene (MX). A metal–organic framework (MOF) membrane offers the opportunity to realize the isomers’ separation due to the highly tunable pore size and pore environment. Herein, an In-based hierarchic MOF (MIL-100) with a size of 0.77 nm was screened, aiming at the realization for isomer separation through pore size matching. Meanwhile, the polar microenvironment in the MOF channel built through trimesic acid ligands contributes to the higher affinity to the MX relative to the PX. With the equimolar feed mixture of MX/PX, the optimal membrane demonstrated a total flux of 7.6 kg·m⁻²·h⁻¹ and an MX/PX separation factor of 2.54 at room temperature through pervaporation. Such performance highly indicates the possibility for efficient liquid xylene separation in future. Full article

The aim of this study was to improve screening efficiency by establishing reasonable interpretation criteria for the use of flow injection analysis tandem mass spectrometry (FIA-MS/MS) in newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD). FIA-MS/MS was employed to analyze very-long-chain acylcarnitines (ACs) and lysophosphatidylcholines (LPCs) and their ratios in dried blood spot (DBS) obtained from five X-ALD patients in the neonatal period (0–7 days old) and 7123 healthy neonate controls. By comparing these results and analyzing receiver operating characteristic (ROC) curves, we identified sensitive indicators for X-ALD screening in newborns. To evaluate the performance of different FIA-MS/MS screening indicators, we simultaneously analyzed 7712 neonatal DBS samples obtained for X-ALD screening using FIA-MS/MS and the established liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitative detection of C26:0-lysophosphatidylcholine (C26:0-LPC). Furthermore, 84,268 newborn X-ALD screening results were retrospectively analyzed to further evaluate the screening performance of FIA-MS/MS. After the three-step optimization evaluation, the optimized first-tier sensitive screening indicators of FIA-MS/MS were C24:0-AC, C26:0LPC, and C24:0/C22:0-AC. Among the 7712 newborns screened, one case was confirmed to be double-positive. Within separate statistical analyses, based on LC-MS/MS screening alone (positive cutoff > 0.17 µmol/L), only seven cases (0.09%) were initially positive, with a positive predictive value (PPV) of 42.8%, and two additional ABCD1 VUS hemizygous males were detected. Through the retrospective analysis of 84,268 newborns, eight ABCD1 variants (six hemizygous males and two heterozygous females) were ultimately identified. Our study showed that the optimization of first-tier screening performance is particularly important if second-tier screening is not performed. Using LC-MS/MS for second-tier screening for X-ALD can significantly reduce the number of false positives, but the method still misses some false negatives. If it is used as a first-tier assessment, more VUS variant neonates can be detected. Full article

Wnt/β-catenin signaling is hyper-activated in several cancer cells and cancer stem cells. Dishevelled/Dvl is a key adapter protein that acts as a bridge between the Wnt receptor Frizzled (Fzd) and other cytosolic factors. In detail, the C-terminal cytosolic region is the ligand of the PSD-95, disks large, and zonula occludens-1 (PDZ) domain of Dvl. Therefore, the PDZ domain (Dvl-PDZ) is thought to be a potential drug target. In this paper, we determined the first crystal structure of the PDZ domain of human Dvl1 (hDvl1-PDZ) at a 2.4 Å resolution. The domain was adapted into a unique trimeric form in which all the canonical ligand-binding clefts were occupied by the β2-β3 loop of the neighbor molecule, like an auto-inhibiting trimer. We used solution nuclear magnetic resonance (NMR) experiments to assess the presence of the self-associated oligomer of hDvl1-PDZ in the solution. Introducing the Ala substitution at Asp 272, the key residue of the β2-β3 loop, partly abolished the concentration-dependent chemical shift change, which suggests that this residue is one of the key residues for formation. Based on these observations, we propose an auto-inhibiting trimer formation of Dvl-PDZ in a Dvl-Axin hetero-oligomerization model of Wnt/β-catenin signal transduction. Full article

Protaetia brevitarsis seulensis (Kolbe, 1886) larvae have traditionally been used in East Asian medicine and have recently attracted attention as functional food ingredients because of their pharmacological potential. However, chemical investigations remain limited, and no marker compounds have been established for quality control. This study aimed to isolate and identify a primary constituent from the 70% ethanol extract of P. brevitarsis (PBE) and to develop an analytical method for its quantification. Among the solvent-partitioned fractions, the n-butanol fraction (PBE-B) exhibited a major peak in HPLC analysis. The compound was purified through a combination of vacuum liquid chromatography (VLC), medium-pressure liquid chromatography (MPLC), and recycling preparative HPLC. Its structure was identified as L-tryptophan based on HR-ESI-MS and NMR spectroscopy. Quantitative analysis was conducted using HPLC-DAD under optimized analytical conditions, employing a Thermo Scientific™ Acclaim™ Polar Advantage II column and an acidified mobile phase (0.1% formic acid in water and methanol) to improve resolution. The method demonstrated excellent linearity (r² > 0.9999), and the L-tryptophan content in PBE was determined to be 1.93 ± 0.05 μg/mg. The analyte was well separated with minimal interference, supporting the reproducibility of the method. These results indicate that L-tryptophan is a promising candidate Q-marker for the quality control of P. brevitarsis extracts. Full article

This study investigates the behavior of phosphorus during high-temperature smelting of hydrogen-reduced high-phosphorus oolitic iron ore from the Lisakovsk deposit. The preliminary reduction was carried out at temperatures ranging from 600 to 900 °C using hydrogen, aiming to selectively reduce iron to the metallic phase while retaining phosphorus in the oxide form. The resulting reduced products were subjected to wet magnetic separation and liquid-phase separation. It was found that neither method provides effective separation of phosphorus from iron: phosphorus partially enters the magnetic fraction and, during smelting, transfers into the metallic phase. To confirm the mechanism of phosphate reduction by metallic iron, a control experiment was conducted, in which a mixture of reduced iron and raw ore was smelted at 1650 °C. Microstructural and elemental analyses confirmed the redistribution of phosphorus into the metallic phase. These findings indicate that effective separation of iron and phosphorus cannot be achieved by reduction roasting alone and highlight the need for further studies on slag formation conditions and phase separation kinetics. Full article

Flexible polyurethane foams (PUFs) are widely used materials whose crosslinked chemical structure hinders conventional recycling, leading to significant environmental challenges. This study presents a selective and scalable depolymerization strategy for polyurethane foam waste (PUFW), utilizing a combination of 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]) as water-miscible ionic liquid (IL) and a strong organic base to enable hydrolytic cleavage of urethane bonds under mild reaction conditions (98 °C, atmospheric pressure). The approach was evaluated across different PUFW formulations and successfully scaled up to a 1 kg reaction mass, maintaining high efficiency in both the depolymerization and separation steps. The recovered polyols exhibited high purity and structural fidelity, comparable to those of virgin polyols. The recycled products were integrated into a new foam formulation, resulting in a PUF with mechanical and morphological properties, as revelated by scanning electron microscopy (SEM), which closely resemble those of virgin polyol-based references and surpass those of foams produced using commercially recycled polyols. These findings support the feasibility of closed-loop polyurethane recycling and represent the transition towards circular polymer economy strategies. Full article

This study investigates the valorisation of sour orange (Citrus aurantium L.) flowers using supercritical antisolvent fractionation (SAF) with CO₂ as an antisolvent. SAF was applied to selectively recover bioactive compounds from ethanolic extracts, using supercritical CO₂ to induce precipitation. Response Surface Methodology (RSM) was employed to optimize operational conditions across a pressure range of 8.7–15 MPa and CO₂ flow rates of 0.6–1.8 kg/h, at a constant temperature of 40 °C. Pressure showed a statistically significant positive effect on precipitate yield, while higher CO₂ flow rates led to reduced recovery. High-performance liquid chromatography (HPLC) analysis identified naringin (33.7%), neohesperidin (21.6%), and synephrine (9.0%) as the main components of the enriched fractions. SAF enabled the selective concentration of these compounds, supporting its application as a green separation technique. As a complementary evaluation, preliminary in silico predictions of ADMET properties and skin permeability were performed. The results indicated favourable absorption, low predicted toxicity, and limited dermal permeation for the major flavonoids. These findings are consistent with available experimental and regulatory safety data. Overall, the study demonstrates the potential of SAF as an effective green technology for the selective extraction and enrichment of high-value bioactive compounds derived from Citrus aurantium flowers, with promising applications in cosmetic, nutraceutical, and pharmaceutical formulations. Full article

To investigate the effects of the endophytic fungus Setophoma terrestris (isolated from Panax notoginseng roots) on the growth and rhizosphere microbiota of understory-cultivated P. notoginseng, we prepared liquid and solid fermentates of the fungus and applied them separately via irrigation. Rhizosphere soil of P. notoginseng was subjected to non-targeted metabolomics and microbiome sequencing for detection and analysis. Relative to the control, P. notoginseng treated with liquid and solid fermentates exhibited increases in plant height (3.5% and 0.7%), chlorophyll content (23.4% and 20.4%), and total saponin content (14.6% and 17.0%), respectively. Non-targeted metabolomics identified 3855 metabolites across 23 classes, with amino acids and their derivatives (21.54%) and benzene derivatives (14.21%) as the primary components. The significantly altered metabolic pathways shared by the two treatment groups included ABC transporters, purine metabolism, and the biosynthesis of various other secondary metabolites. Exogenous addition of S. terrestris significantly affected the composition of the rhizosphere soil microbial community of P. notoginseng and increased the relative abundance of genera such as Bradyrhizobium. In conclusion, the endophytic fungus S. terrestris enhances P. notoginseng growth and modulates both rhizosphere soil metabolites and microbial abundance. This study can provide certain data support for research on endophytic fungi of P. notoginseng. Full article

The mechanism of separating the small chiral drug molecules on large soft polymers is essential in pharmaceutical science. As a case study, the differentiation mechanism of ibuprofen, (R,S)-2-(4-isobutylphenyl)propanoic acid, with cellulose tris(4-methylbenzoate) (CMB) as the chiral stationary phase (CSP) was investigated by combining the molecular docking simulation and multi-level layered terminal-to-center elongation (ML-T2C-ELG) method. Our results demonstrated that, based on the optimized geometry using the ML-T2C-ELG method, the complexation energy of S-ibuprofen with CMB obtained at B3LYP-D3(BJ)/6-311G(d) level is more negative than that of R-ibuprofen, which is caused by the greater hydrogen bonding and π-π stacking interactions between CMB and S-ibuprofen. The results are in line with the experimental observations of high-performance liquid chromatography (HPLC) that the retention time of S-ibuprofen on CMB is longer than that of R-ibuprofen. Moreover, the ML-T2C-ELG method was found to be valuable for optimizing the geometries of such flexible and large systems, which allows for a more accurate description of interactions between soft polymers and small molecules when coupled with the docking simulation. It is anticipated that this study can provide beneficial insights for future optical resolution mechanisms of other chiral drugs. Full article

The absence of parental presence has a direct impact on the emotional stability and social routines of children, especially during extended periods of separation from their family environment, as in the case of daycare centers, hospitals, or when they remain alone at home. At the same time, the technology currently available to provide emotional support in these contexts remains limited. In response to the growing need for emotional support and companionship in child care, this project proposes the development of a multi-platform software architecture based on artificial intelligence (AI), designed to be integrated into humanoid robots that assist children between the ages of 6 and 14. The system enables daily verbal and non-verbal interactions intended to foster a sense of presence and personalized connection through conversations, games, and empathetic gestures. Built on the Robot Operating System (ROS), the software incorporates modular components for voice command processing, real-time facial expression generation, and joint movement control. These modules allow the robot to hold natural conversations, display dynamic facial expressions on its LCD (Liquid Crystal Display) screen, and synchronize gestures with spoken responses. Additionally, a graphical interface enhances the coherence between dialogue and movement, thereby improving the quality of human–robot interaction. Initial evaluations conducted in controlled environments assessed the system’s fluency, responsiveness, and expressive behavior. Subsequently, it was implemented in a pediatric hospital in Guayaquil, Ecuador, where it accompanied children during their recovery. It was observed that this type of artificial intelligence-based software, can significantly enhance the experience of children, opening promising opportunities for its application in clinical, educational, recreational, and other child-centered settings. Full article

This study presents a strategy to develop crayfish shell peptides with enhanced antioxidant and angiotensin-I-converting enzyme (ACE) inhibitory properties. Crayfish shell protein hydrolysates (CSPH1–3) with different molecular weights were analyzed. CSPH2 (3–5 kDa) exhibited the strongest antioxidant activities, which could scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2,2′-azobis(3-ethylbenzothiazoline-6-sulfonic acid) sodium salt (ABTS) radical by (77.40 ± 4.54)% and (91.59 ± 0.30)%, respectively, and ACE inhibition activity of (64.74 ± 0.64)%. CSPH2 was further separated into three fractions, and CSPHF2 showed the maximum biological activity. The sequences of the purified antioxidant peptide (APAPLPPPAP) and ACE inhibitory peptide (QGPDDPLIPIM) were identified by liquid chromatography–tandem mass spectrometry (LC-MS/MS) in CSPHF2. These peptides increased the nitric oxide (NO) concentration and decreased the endothelin-1 (ET-1) content in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, while also inhibiting reactive oxygen species (ROS). In addition, CSPH showed protective effects in terms of oxidative damage to HepG2 cells induced by H₂O₂. These findings suggest that crayfish shell peptides have potential applications as ingredients in antihypertensive agents and antioxidants, offering significant health benefits when consumed. Full article

Waste animal fat (WAF) can be converted to distillate fractions similar to petroleum solvents and used as solvents via pyrolysis and fractional distillation. Pyrolysis oil from triglyceride materials presents adequate viscosity and volatility, compared to petroleum fuels, but shows acid values between 60–140 mg KOH/g, impeding its direct use as biofuels without considerable purification of its distillates. Fractional distillation can be applied for the purification of bio-oil, but only a few studies accurately describe the process. The purpose of this study was to evaluate the effect of temperature in the conversion of waste animal fat into fuel-like fractions by pyrolysis and fractional distillation in a semi-batch stirred bed reactor (2 L) according to reaction time. Waste animal fat was extracted (rendering) from disposed meat cuts obtained from butcher shops and pyrolyzed in a stainless-steel stirred bed reactor operating in semi-batch mode at 400–500 °C. The obtained liquid fraction was separated according to reaction time. The pyrolysis bio-oil at 400 °C was separated into four distinct fractions (gasoline, kerosene, diesel, and heavy phase) by fractional distillation with reflux. The bio-oil and distillate fractions were analyzed by density, kinematic viscosity, acid value, and chemical composition by gas chromatography coupled to mass spectra (GC-MS). The results show that, for semi-batch reactors with no inert gas flow, higher temperature is associated with low residence time, reducing the conversion of fatty acids to hydrocarbons. The distillate fractions were tested in a common application not sensible to the fatty acid concentration as a diluent in the preparation of diluted asphalt cutback for the priming of base pavements in road construction. Kerosene and diesel fractions can be successfully applied in the preparation of asphalt cutbacks, even with a high acid value. Full article