Search Results (685)

Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. Tumor-derived organoids are valuable tools for drug screening; however, their clinical relevance relies on how accurately they recapitulate the phenotypic and functional characteristics of the original tumors. In this study, we present a quantitative analysis of how hydrogel composition influences the phenotype, tissue remodeling, metabolism, and drug resistance of PDAC organoids. Organoids were cultured within three types of hydrogels: Matrigel, collagen-I, and a mixture of collagen-I and Matrigel. Our results demonstrate that: (i) PDAC organoids grown in Matrigel exhibit a classical phenotype, with metabolic and drug response profiles similar to those of low-physiological two-dimensional cultures; (ii) Organoids grown in collagen-containing hydrogels, particularly those in collagen-Matrigel composites, faithfully recapitulate basal-like tumors, characterized by epithelial-to-mesenchymal transition, tissue remodeling, metabolic activity, and drug resistance; (iii) TGFβ induces an exacerbated, highly invasive basal-like phenotype. Summarizing, our findings highlight the importance of 3D hydrogel composition in modulating PDAC organoid phenotype and behavior and suggest collagen-Matrigel hydrogels as the most suitable matrix for modeling PDAC biology. Full article

Maintenance dredging produces large volumes of fine sediments that are commonly discarded, despite increasing pressure for beneficial reuse. Lime–cement stabilization offers one pathway, yet field performance is highly variable. This study juxtaposes two French marine dredged sediments—DS-F (low plasticity, organic matter (OM) ≈ 2 wt.%) and DS-M (high plasticity, OM ≈ 18 wt.%)—treated with practical hydraulic road binder (HRB) dosages. This is the first French study that directly contrasts two different DS types under identical HRB treatment and proposes practical boundary thresholds. Physical indexes (particle size, methylene-blue value, Atterberg limits, OM) were measured; mixtures were compacted (Modified Proctor) and tested for immediate bearing index (IBI). IBI, unconfined compressive strength, indirect tensile strength, and elastic modulus were determined. DS-F reached IBI ≈ 90–125%, UCS ≈ 4.7–5.9 MPa, and ITS ≈ 0.40–0.47 MPa with only 6–8 wt.% HRB, satisfying LCPC-SETRA class S2–S3 requirements for road subgrades. DS-M never exceeded IBI ≈ 8%, despite 3 wt.% lime + 6 wt.% cement. A decision matrix distilled from these cases and recent literature shows that successful stabilization requires MBV < 3 g/100 g, plastic index < 25%, OM < 7 wt.%, and fine particles < 35%. These thresholds permit rapid screening of dredged lots before costly treatment. Highlighting both positive and negative evidence clarifies the realistic performance envelope of soil–cement reuse and supports circular-economy management of DS. Full article

Dysphagia is a common clinical condition, especially among older adults, associated with an increased risk of malnutrition, aspiration, and respiratory complications. A key therapeutic approach involves modifying liquid consistency using thickening agents to achieve safer swallowing. Although rotational rheometry offers accurate viscosity characterization, its complexity and cost limit routine application in clinical or domestic settings. This study evaluates and correlates different methods for measuring the viscosity of thickened liquids, comparing rheological data with empirical techniques such as the Ford cup, Bostwick consistometer, and Line-Spread Test (LST). Several thickeners were tested—guar gum, xanthan gum, a guar/xanthan blend, maltodextrin-based mixtures, and a commercial thickener—across a range of concentrations, temperatures, and preparation times. The results demonstrate that simple methods, particularly the Bostwick consistometer and LST, show strong correlations with rheometer measurements within the International Dysphagia Diet Standardisation Initiative (IDDSI) Level 2 (mildly thick) and Level 3 (moderately thick) ranges. However, limitations were observed at extreme viscosities, where certain methods lacked sensitivity or operational feasibility. These findings support the potential of empirical tools for practical viscosity screening in dysphagia management, especially where rheometry is unavailable. This work provides evidence-based guidance for clinicians, caregivers, and food service professionals seeking safe, reproducible, and standardized approaches to fluid consistency assessment. Full article

The use of astaxanthin (AST) is expanding from its origins as a food coloring to health-related applications. This paper evaluates the efficiency of its extraction from dried Xanthophyllomyces dendrorhous using two combined and consecutive techniques. First, cell membrane permeation is achieved with the application of pulsed electric fields (PEFs). Solid–liquid extraction is then performed with hydrophobic eutectic solvents (hESs) prepared by mixing components of essential oils (linalool, l-menthol, eugenol, geraniol, cinnamyl alcohol, or thymol) and oleic acid. The hESs were characterized by measuring of several thermophysical properties at 25 °C and 0.1 MPa. An initial screening was performed to choose the best solvent and the extraction conditions (composition, extraction time, and temperature) were evaluated using the response surface methodology. The results showed the importance of the electroporation as a preliminary step to the extraction. The more hydrophobic and less compact the hES, the more effective the solvent. Thus, the equimolar mixture of l-menthol and oleic acid achieved an efficiency of 77% for untreated biomass, 83% for that treated with PEF, and 92% for that treated with PEF and later incubated. Molecular dynamics simulations demonstrated the importance of the hydrophobic interactions between AST and the components of the best solvent. Full article

Heracleum sosnowskyi Manden. (Sosnowsky’s hogweed), originally introduced to Central and Eastern Europe as a fodder crop, has become a highly invasive species due to its ecological adaptability, high reproductive capacity, and efficient seed dispersal. Despite its negative impact on native flora and its health risks to humans and animals, the species also represents a valuable source of biologically active compounds. In this study, we demonstrate that the leaves of H. sosnowskyi contain substantial amounts of furanocoumarins—phototoxic compounds with notable therapeutic potential, particularly as natural photosensitizers in anticancer therapies. To extract furanocoumarins from H. sosnowskyi, microwave-assisted extraction (MAE) was employed, with optimization of key parameters including extraction solvent (hexane), temperature (70 °C), extraction time (10 min), and solvent-to-solid ratio (20:1). Four major compounds—angelicin (2.3 mg/g), psoralen (0.15 mg/g), methoxsalen (0.76 mg/g), and bergapten (3.14 mg/g)—were identified and quantified using gas chromatography–mass spectrometry and gas chromatography with flame ionization detection. To purify the extract and selectively isolate the target compounds, a solid-phase extraction method was developed using a Strata Eco-Screen sorbent and stepwise elution with a hexane–acetone mixture. As a result, pure angelicin, pure methoxsalen, and various mixtures of the furanocoumarins were obtained. These findings highlight the potential of H. sosnowskyi as a sustainable source of furanocoumarins for pharmaceutical applications. Full article

Background/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-β-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug. Full article

Background/Objectives: Aneuploidy is near-ubiquitous in cancer and can decrease chemotherapy efficacy while also sensitizing cells to other drugs. Methods: To systematically identify treatment strategies that target aneuploid cancers, data were integrated from The Cancer Genome Atlas (TCGA; 10,967 samples, 16,948 aneuploidy events) and the Broad Institute’s Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) screen of 578 cancer cell lines and 4518 compounds. Results: Our analyses uncovered 37,720 significant positive and negative associations linking specific aneuploidies and treatments with patient prognosis or cell viability. Within TCGA data, 22 treatments correlated with improved 5-year survival for specific aneuploid cancers, whereas 46 were linked to worse outcomes. A complementary analysis of PRISM identified 17,946 compound–aneuploidy associations and 16,189 mechanism of action (MOA)–aneuploidy associations. Pathway-altering compounds that selectively reduce viability in cells with aneuploidy profiles were discovered, including an unexpectedly prominent number of glucocorticoid receptor agonists. Conclusions: This integrated dataset provides a resource for designing therapeutic decision hypotheses, identifying drug-repurposing opportunities, and informing future studies aimed at targeting aneuploidy-induced vulnerabilities in cancer. Full article

This study employs molecular dynamics simulations to investigate counterion effects (Li⁺, Na⁺, K⁺) on the interfacial aggregation of mixed short-chain fluorocarbon, Perfluorohexanoic acid (PFH_XA), and Sodium dodecyl sulfate (SDS) surfactants. Motivated by the need for greener surfactant alternatives and a fundamental understanding of molecular interactions governing their behavior, we demonstrate that counterion hydration radius critically modulates system organization. K⁺ ions induce superior monolayer condensation and interfacial performance compared to Li⁺ and Na⁺ counterparts, as evidenced by threefold analysis: (1) RMSD/MSD-confirmed equilibrium attainment ensures data reliability; (2) 1D/2D density profiles and surface tension measurements reveal K⁺-enhanced packing density (lower solvent-accessible surface area versus Na⁺ and Li⁺ systems); (3) Electrostatic potential analysis identifies synergistic complementarity between SDS’s hydrophobic stabilization via dodecyl chain interactions and PFH_XA’s charge uniformity, optimizing molecular-level charge screening. Radial distribution function analysis demonstrates K⁺’s stronger affinity for SDS head groups, with preferential sulfate coordination reducing surfactant-water hydration interactions. This behavior correlates with hydrogen-bond population reduction, attributed to SDS groups functioning as multidentate ligands—their tetrahedral oxygen arrangement facilitates cooperative hydrogen-bond networks, while counterion-specific charge screening competitively modulates bond formation. The resultant interfacial restructuring enables ordered molecular arrangements with lower system curvature than those observed in Li⁺ and Na⁺-containing systems. These findings elucidate counterion-mediated interfacial modulation mechanisms and establish K⁺ as an optimal candidate for enhancing PFH_XA/SDS mixture performance through hydration-radius screening. The work provides molecular-level guidelines for designing eco-friendly surfactant systems with tailored interfacial properties. Full article

Background: The identification of body fluids collected from crime scenes is crucial for determining the type and nature of assaults and for advancing the resolution of crimes. Objectives: The primary aim of this study was to investigate tissue-specific DNA methylation markers that can effectively distinguish buccal samples from blood, semen, and vaginal epithelial tissue. Methods: We screened various markers and selected four genomic locations for further analysis. Genomic DNA was extracted from tissue samples, followed by bisulfite conversion, locus-specific polymerase chain reaction (PCR) amplification, and pyrosequencing. Results: Four loci—cg-9652652, cg-11536474, cg-3867465, and cg-10122865—along with several adjacent CpG sites, were found to be hypermethylated in buccal samples compared to other tissue types. The difference in DNA methylation of buccal samples was statistically significant (p < 0.0001) compared to other tissues, indicating the potential usefulness of these loci for forensic tissue identification. Two additional studies were conducted: (a) a species specificity study and (b) a mixture study involving two different tissue types. The species specificity study showed that the primers used in the assay were specific to primates and humans. They did not amplify five non-primate samples, while the two primate samples—chimpanzee and rhesus—provided usable methylation data. The mixture study involved DNA from two different tissues—buccal samples and semen—combined in varying proportions. The results showed a decrease in the overall percentage of DNA methylation at the locus cg-9652652 as well as five adjacent CpG sites when the amount of buccal cell DNA in the mixture was reduced. Conclusion: The specificity of the primers and the significant differences in percent DNA methylation between buccal cells and other tissues make these markers excellent candidates for forensic tissue identification. Full article

Cryptochrome is an important class of blue-light receptors involved in various physiological activities such as photomorphogenesis and abiotic stress regulation in plants. In order to investigate the molecular mechanism of blue-light-induced color change in Chimonobambusa sichuanensis, we screened and cloned the gene encoding the blue-light receptor Cryptochrome. In order to investigate the molecular mechanism of blue-light-induced color change in Chimonobambusa sichuanensis, we screened and cloned the gene encoding the blue-light receptor Cryptochrome in Ch.sichuanensis, and analyzed the expression characteristics of the Cryptochrome gene in Ch.sichuanensis under different light intensities, light quality, and temperatures by qRT-PCR. Through homologous cloning, a total of four CsCRY genes were obtained in the Ch.sichuanensis genome, namely, CsCRY1a, CsCRY1b, CsCRY2, and CsCRY3. Structural domain analyses of the encoded proteins of the four genes revealed that all CsCRYs proteins had the typical photoreceptor structural domain, PRK (protein kinase C-related kinase). Phylogenetic tree analyses revealed that the four genes CsCRY1a, CsCRY1b, CsCRY2, and CsCRY3 could be categorized into three subfamilies, with CsCRY1a and CsCRY1b clustered in subfamily I, CsCRY2 classified in subfamily II, and CsCRY3 belonging to subfamily III. All CsCRYs proteins lacked signal peptides and the instability index was higher than 40, among which the isoelectric points of CsCRY1a, CsCRY1b, and CsCRY2 were around five. qRT-PCR analysis revealed that the expression of all four CsCRYs genes was up-regulated at 75 µmol·m⁻²·s⁻¹ blue-light illumination for 4 h. In addition, under treatments of different light quality, the expression of CsCRY2 genes was significantly higher under blue light than under red light and a mixture of red light and blue light with a light intensity of 1:1; the expression of CsCRY1a and CsCSY1b was significantly higher in the mixed light of red and blue light than in the single light treatment, while under different temperature gradients, CsCRYs genes were highly expressed under low-temperature stress at −5 °C and 0 °C. This study provides a basis for further research on blue-light-induced color change in Ch.sichuanensis and expands the scope of Cryptochrome gene research. Full article

Background/Objectives: Proteolysis-targeting chimeras (PROTACs) have shown significant potential in the treatment of intractable diseases. However, their clinical applications are limited by poor water solubility and permeability. In this study, the cyclodextrin inclusion method was employed for the first time to prepare the PROTAC-CD complex with the aim of improving the dissolution of a PROTAC drug (LC001). Methods: Initially, sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was selected to improve the solubility of LC001. The polymer TPGS was screened based on the phase solubility method to enhance the efficiency of complexation and solubilization capacity, and its ratio with SBE-β-CD was optimized. The ternary complex was prepared by lyophilization with an SBE-β-CD/TPGS molar ratio of 1:0.03. Differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy results confirmed the formation of an amorphous complex. Fourier-transform infrared and molecular docking simulations indicated the formation of hydrogen bond interactions between components. Results: The results showed that the ternary complexes significantly improved the dissolution rate and release amount of LC001 in PBS (pH 6.8) and were unaffected by changes in gastric pH compared to the binary complexes and physical mixtures. The lack of crystal structure in the lyophilized particles and the formation of nano aggregates in solution may be the reasons for the improved dissolution of the ternary complex. Conclusions: In conclusion, the addition of TPGS to the LC001-SBE-β-CD binary system has a synergistic effect on improving the solubility and dissolution of LC001. This ternary complex is a promising formulation for enhancing the dissolution of LC001. Full article

Background: Inhibition of intestinal α-glucosidase is a key strategy for controlling postprandial hyperglycemia in diabetes. Astragali Radix (AR), a traditional medicinal and dietary herb widely consumed in China, is rich in flavonoids that are believed to exhibit hypoglycemic properties. Methods: A total of 29 AR-related flavonoids, including both original constituents and metabolites, were screened for α-glucosidase inhibitory activity using in vitro enzymatic assays. Mechanistic investigations were conducted through enzyme kinetics, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), and molecular docking. The in vivo hypoglycemic effects were assessed using a postprandial hyperglycemic mouse model. Additionally, potential mixture effects of flavonoid combinations were evaluated. Results: Of the 29 flavonoids, 16 demonstrated significant α-glucosidase inhibitory activity, with five (C3, C17, C19, C28, and C29) identified as novel inhibitors. Structure–activity relationship (SAR) analysis revealed that hydroxylation, particularly at the C-3 position, enhanced activity, while glycosylation and methoxylation reduced it. Mechanistic studies demonstrated that these compounds bind to distinct amino acid residues within the active site of α-glucosidase, inducing conformational changes and exerting different types of inhibition, leading to varying inhibitory mechanisms. Additionally, 15 compounds reduced postprandial blood glucose levels, with C3, C16, C17, C19, and C28 confirmed as novel in vivo inhibitors. Notably, two compositions of flavonoids combined at their individually ineffective concentrations exhibited significant inhibitory effects. Conclusions: This study provides a comprehensive evaluation of AR-related flavonoids as α-glucosidase inhibitors and offers valuable insights for the development of highly effective, low-toxicity, flavonoid-based, antidiabetic therapeutics and functional foods. Full article

Formaldehyde is the most abundant carbonyl globally and the biggest driver of cancer risk in the United States among hazardous air pollutants. Ambient formaldehyde concentration measurements are generally sparse due to high measurement costs and limited measurement infrastructure. Recent studies have used low-cost air quality sensors to affordably improve spatial coverage and provide real-time measurements. Our previous research evaluated the laboratory performance of a low-cost electrochemical formaldehyde sensor (Sensirion SFA30) over formaldehyde concentrations ranging from 0 to 76 ppb. The sensors exhibited good linearity of response, a low limit of detection, and good accuracy in detecting formaldehyde. This study evaluated the cross-sensitivity of the SFA30 and the Gravity sensors (electrochemical formaldehyde sensors) over formaldehyde concentrations ranging from 0 to 326 ppb in a laboratory evaluation system, with broadband cavity-enhanced absorption spectroscopy used to obtain the reference measurements. We evaluated the sensors in a mixture of formaldehyde with five outdoor trace gases (CO, NO, NO₂, O₃, and isobutylene) and two indoor VOCs (methanol and isopropyl alcohol). The results suggest that the Gravity sensors may be useful for outdoor formaldehyde measurements when formaldehyde levels are well above background levels and that the SFA30 sensors may be useful screening tools for indoor environments, if properly calibrated. Full article

The presence of substandard and falsified (SF) medicines poses a significant challenge in resource-limited countries. Low-quality antibiotics are commonly reported in low-income countries. The present study aimed to develop and validate a liquid chromatography method with ultraviolet detection (LC-UV) for the identity screening and assay of 13 different injectable antibiotics, i.e., cefepime, amoxicillin, cefazolin, ampicillin, chloramphenicol, ceftazidime, ceftriaxone, cefotaxime, vancomycin, flucloxacillin, cloxacillin, benzylpenicillin, and meropenem in pharmaceutical formulations. Separation was performed using an XBridge C18 column and gradient elution. Mixtures of acetonitrile and 20 mM phosphate buffer (pH 8.0) were used as the mobile phases. The screening method was validated in terms of specificity and robustness, while linearity, precision, accuracy, and sensitivity were checked for the quantification method. The determination coefficients (R²) following linear regression were all greater than 0.999. The method showed good precision, with relative standard deviation values below 1%. The percentage recovery values were close to 100%. The method was applied to analyze 17 injectable antibiotics collected from the Ethiopian market. All commercial samples analyzed contained the correct API and met USP content specifications. Full article

A biosensor for the determination of glucose, lactate, ethanol and starch in beverages has been developed using enzymes immobilized by a redox-active gel on a screen-printed electrode. A significant improvement proposed for multichannel biosensors, overcoming stability and sensitivity issues by covalently binding phenazine mediators to a biocompatible protein hydrogel, enhancing the packaging of the enzyme. Glucose oxidase (GOx), alcohol oxidase (AOx) and lactate oxidase (LOx) were used as biological materials, as well as a mixture of GOx with γ-amylase (Am). Redox gels were synthesized from bovine serum albumin (BSA) and phenazine derivatives. It was shown that a neutral red-based redox gel combined with single-walled carbon nanotubes is more promising than other substrates for enzyme immobilization. The lower limit of quantification for glucose, ethanol, lactate and starch using these systems is 0.035 mM, 2.3 mM, 15 mM and 2 mg/L, respectively. Biosensors were used to analyze the content of these substances in alcoholic, kvass and fermentation mass. Statistical analysis of the results showed that the values of glucose, ethanol, lactic acid and starch determined using biosensors and obtained by reference methods differ insignificantly. A set of biosensors developed on the basis of specifically selected enzymes is effective for controlling biotechnological processes and can be used as an alternative to classical analytical methods. Full article