Rational design of polymer-based particulate vaccine adjuvants.

Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life-threatening infectious diseases. Vaccine adjuvants are a key component of many vaccines, serving to steer antigen-specific immune responses and increase their magnitude. Despite major advances in the field of adjuvant research over recent decades, our understanding of their mechanism of action remains incomplete. This hinders our capacity to further improve these adjuvant technologies, so addressing how adjuvants induce and control the induction of innate and adaptive immunity is a priority. Investigating how adjuvant physicochemical properties, such as size and charge, exert immunomodulatory effects can provide valuable insights and serve as the foundation for the rational design of vaccine adjuvants. Most clinically applied adjuvants are particulate in nature and polymeric particulate adjuvants present advantages due to stability, biocompatibility profiles, and flexibility in terms of formulation. These properties can impact on antigen release kinetics and biodistribution, cellular uptake and targeting, and drainage to the lymphatics, consequently dictating the induction of innate, cellular, and humoral adaptive immunity. A current focus is to apply rational design principles to the development of adjuvants capable of eliciting robust cellular immune responses including CD8+ cytotoxic T-cell and Th1-biased CD4+ T-cell responses, which are required for vaccines against intracellular pathogens and cancer. This review highlights recent advances in our understanding of how particulate adjuvants, especially polymer-based particulates, modulate immune responses and how this can be used as a guide for improved adjuvant design.

Pine has two glutamine synthetase paralogs, GS1b.1 and GS1b.2, exhibiting distinct biochemical properties.

The enzyme glutamine synthetase (EC 6.3.1.2) is mainly responsible for the incorporation of inorganic nitrogen into organic molecules in plants. In the present work, a pine (Pinus pinaster) GS1 (PpGS1b.2) gene was identified, showing a high sequence identity with the GS1b.1 gene previously characterized in conifers. Phylogenetic analysis revealed that the presence of PpGS1b.2 is restricted to the genera Pinus and Picea and is not found in other conifers. Gene expression data suggest a putative role of PpGS1b.2 in plant development, similar to other GS1b genes from angiosperms, suggesting evolutionary convergence. The characterization of GS1b.1 and GS1b.2 at the structural, physicochemical, and kinetic levels has shown differences even though they have high sequence homology. GS1b.2 had a lower optimum pH (6 vs. 6.5) and was less thermally stable than GS1b.1. GS1b.2 exhibited positive cooperativity for glutamate and substrate inhibition for ammonium. However, GS1b.1 exhibited substrate inhibition behavior for glutamate and ATP. Alterations in the kinetic characteristics produced by site-directed mutagenesis carried out in this work strongly suggest an implication of amino acids at positions 264 and 267 in the active center of pine GS1b.1 and GS1b.2 being involved in affinity toward ammonium. Therefore, the amino acid differences between GS1b.1 and GS1b.2 would support the functioning of both enzymes to meet distinct plant needs.

Nanoparticle Toxicology.

Nanoparticles from natural and anthropogenic sources are abundant in the environment, thus human exposure to nanoparticles is inevitable. Due to this constant exposure, it is critically important to understand the potential acute and chronic adverse effects that nanoparticles may cause to humans. In this review, we explore and highlight the current state of nanotoxicology research with a focus on mechanistic understanding of nanoparticle toxicity at organ, tissue, cell, and biomolecular levels. We discuss nanotoxicity mechanisms, including generation of reactive oxygen species, nanoparticle disintegration, modulation of cell signaling pathways, protein corona formation, and poly(ethylene glycol)-mediated immunogenicity. We conclude with a perspective on potential approaches to advance current understanding of nanoparticle toxicity. Such improved understanding may lead to mitigation strategies that could enable safe application of nanoparticles in humans. Advances in nanotoxicity research will ultimately inform efforts to establish standardized regulatory frameworks with the goal of fully exploiting the potential of nanotechnology while minimizing harm to humans.

Single extracellular vesicle research: From cell population to a single cell.

Extracellular vesicles (EVs) are secreted by cells with a membrane structure and complex components such as DNA, RNA and proteins. These biomolecules play an important role in cell communication, cell proliferation, cell migration, vascularization, immune response and other physiological and pathological processes. Most current research on EVs focused on populations of EVs. Heterogeneity of EVs is neglected. Considering the heterogeneity of single EVs may offer critical molecular insights into cell-cell interactions, it is necessary to enhance our understanding about molecular characteristics from EVs derived from cell population to a single EV of derived from a single cell. This transformation is expected to provide a new insight into the understanding of cellular biology and the accurate description of the law of disease progress. In this article, we review the current research progress of single EV analysis technology for single EVs derived from cell population (SECP) and discuss its main applications in biological and clinical medicine research. After that, we propose the development direction, main difficulties and application prospect of single EV analysis technology for single EVs derived from single cells (SESC) according to our own research work, to provide new perspectives for the field of EV research.

The effect of white grub (Maladera Verticalis) larvae feeding on rhizosphere microbial characterization of aerobic rice (Oryza sativa L.) in Puer City, Yunnan Province, China.

BACKGROUND: Rhizosphere microorganisms are vital in plants' growth and development and these beneficial microbes are recruited to the root-zone soil when experiencing various environmental stresses. However, the effect of white grub (Maladera verticalis) larvae feeding on the structure and function of rhizosphere microbial communities of aerobic rice (Oryza sativa L.) is unclear. RESULTS: In this study, we compared physicochemical properties, enzyme activities, and microbial communities using 18 samples under healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soils at the Yunnan of China. 16 S rRNA and ITS amplicons were sequenced using Illumina high throughput sequencing. M. verticalis larvae feeding on aerobic rice can influence rhizosphere soil physicochemical properties and enzyme activities, which also change rhizosphere microbial communities. The healthy and M. verticalis larvae-feeding aerobic rice rhizosphere soil microorganisms had distinct genus signatures, such as possible_genus_04 and Knoellia genera in healthy aerobic rice rhizosphere soils and norank_f__SC - I-84 and norank_f__Roseiflexaceae genera in M. verticalis larvae-feeding aerobic rice rhizosphere soils. The pathway of the metabolism of terpenoids and polyketides and carbohydrate metabolism in rhizosphere bacteria were significantly decreased after M. verticalis larvae feeding. Fungal parasite-wood saprotroph and fungal parasites were significantly decreased after M. verticalis larvae feeding, and plant pathogen-wood saprotroph and animal pathogen-undefined saprotroph were increased after larvae feeding. Additionally, the relative abundance of Bradyrhizobium and Talaromyces genera gradually increased with the elevation of the larvae density. Bacterial and fungal communities significantly correlated with soil physicochemical properties and enzyme activities, respectively. CONCLUSIONS: Based on the results we provide new insight for understanding the adaptation of aerobic rice to M. verticalis larvae feeding via regulating the rhizosphere environment, which would allow us to facilitate translation to more effective measures.

Preparation of Activated Biocarbons from Cones and their Potential Application for Adsorption of Antibiotics (Tetracycline).

The pine cones (PC), spruce cones (SC) and fir cones (FC) were used for biocarbons preparation. Chemical activation with sodium hydroxide was applied to prepare activated biocarbons. All the materials under investigation were characterized by the N2 adsorption, scanning electron microscopy (SEM), elemental analysis (CHNS), infrared spectroscopy (ATR FT-IR), and the Boehm's titration method. Moreover, pHpzc (the point of zero charge) was determined. It was shown that cones are a good, cheap precursor from which biocarbons with a developed porous structure, characterized by good adsorption properties, can be obtained. All the obtained adsorbents are characterized mainly by a microporous structure. Moreover, they contain both acidic and basic surface functional groups (acidic ones prevail over basic ones). The tested activated biocarbons have large specific surface area values ranging from 578 to 1182 m2 g-1. The efficacy of selected materials in the adsorption of an essential contaminant of increasing concern, tetracycline (TC), was investigated. The experimental data were described using the Langmuir and Freundlich adsorption isotherm models. The maximum adsorption capacity of the tested biocarbons ranges from 200 to 392 mg g-1. Thermodynamic studies proved that adsorption is a spontaneous and endothermic process. In summary, economical and environmentally friendly adsorbents were obtained.

Stability and integrity of self-assembled bovine parvovirus virus­like particles (BPV­VLPs) of VP2 and combination of VP1VP2 assisted by baculovirus-insect cell expression: a potential logistical platform for vaccine deployment.

BACKGROUND: Bovine parvovirus (BPV) is an autonomous DNA virus with a smaller molecular size and subtle differences in its structural proteins, unlike other animal parvoviruses. More importantly, this virus has the potential to produce visible to silent economic catastrophes in the livestock business, despite receiving very little attention. Parvoviral virus-like particles (VLPs) as vaccines and as logistical platforms for vaccine deployment are well studied. However, no single experimental report on the role of VP1 in the assembly and stability of BPV-VLPs is available. Furthermore, the self-assembly, integrity and stability of the VLPs of recombinant BPV VP2 in comparison to VP1 VP2 Cap proteins using any expression method has not been studied previously. In this study, we experimentally evaluated the self-assembling ability with which BPV virus-like particles (VLPs) could be synthesized from a single structural protein (VP2) and by integrating both VP2 and VP1 amino acid sequences. METHODS: In silico and experimental cloning methods were carried out. His-tagged and without-His-tag VP2 and V1VP2-encoding amino acid sequences were cloned and inserted into pFastbacdual, and insect cell-generated recombinant protein was evaluated by SDS‒PAGE and western blot. Period of infectivity and expression level were determined by IFA. The integrity and stability of the BPV VLPs were evaluated by transmission electron microscopy. The secondary structure of the BPV VLPs from both VP2 and V1VP2 was analyzed by circular dichroism. RESULTS: Our findings show that VP2 alone was equally expressed and purified into detectable proteins, and the stability at different temperatures and pH values was not appreciably different between the two kinds of VLPs. Furthermore, BPV-VP2 VLPs were praised for their greater purity and integrity than BPV-VP1VP2 VLPs, as indicated by SDS‒PAGE. Therefore, our research demonstrates that the function of VP1 has no bearing on the stability or integrity of BPV-VLPs. CONCLUSIONS: In summary, incredible physiochemically stable BPV VP2-derived VLPs have been found to be promising candidates for the development of multivalent vaccines and immunodiagnostic kits against enteric viruses and to carry heterogeneous epitopes for various economically important livestock diseases.

Optimizing Drug Development: Harnessing the Sustainability of Pharmaceutical Cocrystals.

Environmental impacts of the industrial revolution necessitate adoption of sustainable practices in all areas of development. The pharmaceutical industry faces increasing pressure to minimize its ecological footprint due to its significant contribution to environmental pollution. Over the past two decades, pharmaceutical cocrystals have received immense popularity due to their ability to optimize the critical attributes of active pharmaceutical ingredients and presented an avenue to bring improved drug products to the market. This review explores the potential of pharmaceutical cocrystals as an ecofriendly alternative to traditional solid forms, offering a sustainable approach to drug development. From reducing the number of required doses to improving the stability of actives, from eliminating synthetic operations to using pharmaceutically approved chemicals, from the use of continuous and solvent-free manufacturing methods to leveraging published data on the safety and toxicology, the cocrystallization approach contributes to sustainability of drug development. The latest trends suggest a promising role of pharmaceutical cocrystals in bringing novel and improved medicines to the market, which has been further fuelled by the recent guidance from the major regulatory agencies.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

AIMS: The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. METHODS: Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. RESULTS: For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). CONCLUSION: The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

Hydrochar and Its Dissolved Organic Matter Aged in a 30-Month Rice-Wheat Rotation System: Do Primary Aging Factors Alter at Different Stages?

Hydrochar, recognized as a green and sustainable soil amendment, has garnered significant attention. However, information on the aging process in soil and the temporal variability of hydrochar remains limited. This study delves deeper into the interaction between hydrochar and soil, focusing on primary factors influencing hydrochar aging during a 30-month rice-wheat rotation system. The results showed that the initial aging of hydrochar (0-16 months) is accompanied by the development of specific surface area and leaching of hydrochar-derived dissolved organic matter (HDOM), resulting in a smaller particle size and reduced carbon content. The initial aging also features a mineral shield, while the later aging (16 to 30 months) involves surface oxidation. These processes collectively alter the surface charge, hydrophilicity, and composition of aged hydrochar. Furthermore, this study reveals a dynamic interaction between the HDOM and DOM derived from soil, plants, and microbes at different aging stages. Initially, there is a preference for decomposing labile carbon, whereas later stages involve the formation of components with higher aromaticity and molecular weight. These insights are crucial for understanding the soil aging effects on hydrochar and HDOM as well as evaluating the interfacial behavior of hydrochar as a sustainable soil amendment.

PICKAPEP: An application for parameter calculation and visualization of cyclized and modified peptidomimetics.

The interest in peptides and especially in peptidomimetic structures has risen enormously in the past few years. Novel modification strategies including nonnatural amino acids, sophisticated cyclization strategies, and side chain modifications to improve the pharmacokinetic properties of peptides are continuously arising. However, a calculator tool accompanying the current development in peptide sciences towards modified peptides is missing. Herein, we present the application PICKAPEP, enabling the virtual construction and visualization of peptidomimetics ranging from well-known cyclized and modified peptides such as ciclosporin A up to fully self-designed peptide-based structures with custom amino acids. Calculated parameters include the molecular weight, the water-octanol partition coefficient, the topological polar surface area, the number of rotatable bonds, and the peptide SMILES code. To our knowledge, PICKAPEP is the first tool allowing users to add custom amino acids as building blocks and also the only tool giving the possibility to process large peptide libraries and calculate parameters for multiple peptides at once. We believe that PICKAPEP will support peptide researchers in their work and will find wide application in current as well as future peptide drug development processes. PICKAPEP is available open source for Windows and Mac operating systems (https://urldefense.com/v3/__https://www.research-collection.ethz.ch/handle/20.500.11850/681174__;!!N11eV2iwtfs!qt5f_2lNd6IZUDH1HVSVwg0zYzS8-nFazQ8c61jS5GaD5vkVS5C3igyfh3haJRnaX8ugW7o9VWUiCihPqcptmaWoqwYf9LvZTQ$).

Influence of herbaceous litter thickness on bacterial community structure and physicochemical properties of aeolian sand.

The change and mechanism of soil and soil bacterial diversity during the change of herbaceous litter thickness in desert areas is crucial to understand. In the study, the dominant herbaceous litter mixture in Baijitan National Nature Reserve was selected as the research material, and an experiment was established by adjusting the litter depth. The results showed that the measured values of soil physicochemical factors (total nitrogen, total protein, total potassium, available phosphorus, available potassium, pH, and soil water content) increased with the increase of herbaceous litter mixture thickness in 0-5 cm soil layer. Actinobacteria, Proteobacteria, Acidobacteria, Chloroflexi, and Gemmatimonadetes were the dominant bacterial phyla under different thicknesses of herbaceous litter in 0-5 and 5-10 cm soil layers. Balneimonas, Rubrobacter, and Geodermatophilus were the dominant bacterial genera under different thicknesses of herbaceous litter in 0-5 and 5-10 cm soil layers. There was no obvious change in the α-diversity index of bacterial community the same soil layer, but the α-diversity index in the 0-5 cm soil layer was lower compared to the 5-10 cm soil layer. The results of this study revealed that the change of herbaceous litter thickness had no significant effect on soil bacterial community structure in desert areas.

Microbial dynamics and quality characteristics of spontaneously fermented salamis produced by replacing pork fat with avocado pulp.

The aim of this study was to develop a novel and healthier fermented meat product by replacing pork fat with avocado pulp (AVP) during salami production. Experimental salamis were produced under laboratory conditions by substituting pork fat with AVP partially (10-AVP) and totally (20-AVP), while control salamis (CTR) remained AVP-free. The microbial composition of control and experimental salamis was assessed using a combined culture-dependent and -independent approach. Over a 20-days ripening period, lactic acid bacteria, coagulase-negative staphylococci, and yeasts dominated the microbial community, with approximate levels of 9.0, 7.0 and 6.0 log CFU/g, respectively. Illumina technology identified 26 taxonomic groups, with leuconostocs being the predominant group across all trials [constituting 31.26-59.12 % of relative abundance (RA)]. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed changes in fatty acid composition and volatile organic compounds due to the substitution of pork fat with AVP. Specifically, monounsaturated fatty acids and terpene compounds increased, while saturated fatty acids and lipid oxidation products decreased. Although AVP influenced the sensory characteristics of the salamis, the highest overall satisfaction ratings were observed for the 10-AVP salamis. Consequently, substituting pork fat with AVP emerges as a viable strategy for producing healthier salamis and diversifying the meat product portfolio.

Koumiss and immunity: A thorough investigation of fermentation parameters and their impact on health benefits.

The aim of this study was to determine the components and cytokine and immunoglobulin levels of koumiss during different fermentation periods, and to reveal the interrelation between these parameters. For achieving this objective, 10 samples of koumiss were prepared and randomly divided into 2 groups: the first group was sampled at 0, 1, 5, 12, and 24 h of incubation at room temperature for analysis. The second group was stored at +4°C, and samples were taken on d 5, 10, 15, and 20. The counts of Enterobacteriaceae spp., Staphylococcus, and Micrococcus spp. progressively decreased with the period of fermentation until becoming undetectable in the final samples of both groups. We fond positive or negative correlations between cytokine and immunoglobulin levels and the physicochemical and microbiological parameters in the koumiss samples in both groups. However, the levels of IFN-γ, IL-2, TNF-α, and IgG did not change significantly over time in both groups. Overall, it is clear that traditionally prepared koumiss under different fermentation times and temperatures does not show any differences in cytokine and immunoglobulin concentrations.

Physicochemical properties, antioxidant and antidiabetic activities of different hydrolysates of goat milk protein.

There is growing interest in the origin, preparation, and application of bioactive peptides. This study investigated the impact of 6 enzymes on the structural, physicochemical properties, antioxidant activities, and antidiabetic potential of defatted fresh goat milk. Structural and functional changes resulting from enzymatic hydrolysis were assessed using gel electrophoresis, laser particle size analysis, multi-spectroscopy, and evaluations of foaming and emulsification properties. Antioxidant capacity was determined through free radical scavenging, Fe2+ chelation, and reducing ability experiments. Additionally, the inhibitory effects of the hydrolysates on α-glucosidase and α-amylase were measured to evaluate antidiabetic activity. Results showed that enzymatic hydrolysis disrupted the spatial structure of goat milk protein and reduced its molecular weight. Papain hydrolysate exhibited the highest degree of hydrolysis (32.87 ± 0.11%) and smallest particle size (294.75 ± 3.33 nm), followed by alcalase hydrolysate (29.12 ± 0.09%, 302.03 ± 7.28 nm). Alcalase hydrolysate showed the best foaming properties, while papain hydrolysate demonstrated the strongest DPPH and hydroxyl radical scavenging activity, Fe2+ chelation, and antidiabetic potential. These findings provide solid theoretical basis for utilizing defatted goat milk as functional ingredients or excipients in the food, medical, and cosmetic industries.

Soils in distress: The impacts and ecological risks of (micro)plastic pollution in the terrestrial environment.

Plastics have revolutionised human industries, thanks to their versatility and durability. However, their extensive use, coupled with inadequate waste disposal, has resulted in plastic becoming ubiquitous in every environmental compartment, posing potential risks to the economy, human health and the environment. Additionally, under natural conditions, plastic waste breaks down into microplastics (MPs<5 mm). The increasing quantity of MPs exerts a significant burden on the soil environment, particularly in agroecosystems, presenting a new stressor for soil-dwelling organisms. In this review, we delve into the effects of MP pollution on soil ecosystems, with a specific attention to (a) MP transport to soils, (b) potential changes of MPs under environmental conditions, (c) and their interaction with the physical, chemical and biological components of the soil. We aim to shed light on the alterations in the distribution, activity, physiology and growth of soil flora, fauna and microorganisms in response to MPs, offering an ecotoxicological perspective for environmental risk assessment of plastics. The effects of MPs are strongly influenced by their intrinsic traits, including polymer type, shape, size and abundance. By exploring the multifaceted interactions between MPs and the soil environment, we provide critical insights into the consequences of plastic contamination. Despite the growing body of research, there remain substantial knowledge gaps regarding the long-term impact of MPs on the soil. Our work underscores the importance of continued research efforts and the adoption of standardised approaches to address plastic pollution and ensure a sustainable future for our planet.

Assessment of metal pollution and effects of physicochemical factors on soil microbial communities around a landfill.

The physicochemical properties, chemical fractions of six metals (Cu, Zn, Pb, Cd, Cr, and Mn), and microbial communities of soil around a typical sanitary landfill were analyzed. The results indicate that soils around the landfill were from neutral to weak alkalinity. The contents of organic matter (OM), total nitrogen (TN), total phosphorous (TP), and activities of catalase, cellulase, and urease were significantly higher in landfill soils than those in background soils. Negative correlations were found between pH and metals. Cr was the dominant metal. Cu, Pb, Cr, and Mn were accumulated in the nearby farmland soils. Cd had the highest percentage of exchangeable fraction (33.7%-51.8%) in landfill and farmland soils, suggesting a high bioavailability to the soil environment affected by the landfill. Pb, Cr, and Mn existed mostly in oxidable fraction, and Cu and Zn were dominant in residual fraction. There was a low risk of soil metals around the landfill based on the RI values, while according to RAC classification, Cd had high to very high environmental risk. The MisSeq sequencing results showed that Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria were the dominant phyla of bacteria, and the most abundant phylum of fungi was Ascomycota. The NMDS analysis revealed that the landfill could influence soil fungal communities more intensely than bacterial communities. TN, cellulase, and bioavailable metals (Pb-Bio and Cr-Bio) were identified to have main influences on microbial communities. Pb-Bio was the most dominant driving factor for bacterial community structures. For fungi, Pb-Bio was significantly negatively related to Olpidiomycota and Cr-Bio had a significantly negative correlation with Ascomycota. It manifests that bioavailable metals play important roles in assessing environmental risks and microbial community structures of soil around landfill.

Design, synthesis, anti-cancer, anti-inflammatory and in silico studies of 3-substituted-2-oxindole derivatives.

This study focuses on the design and multistep synthesis of diverse structural and functional 3-substituted-2-oxindole derivatives aimed at being dual-active molecules with anti-cancer and anti-inflammatory properties. In vitro evaluations confirmed the dual activity of these derivatives. 4a exhibited GI50 value 3.00E-05 against MDA-MB-231; 4b has shown GI50 value 2E-05 against MDA-MB-231; 4c has shown GI50 value 6E-05 against VERO; and 4d has shown GI50 value 8E-05 each against both MDA-MB-231 and MCF-7. 4e has shown GI50 values 2E-05 and 5E-05 each against both the MCF-7 and VERO. The analysis indicates that compounds 3c (71.19%), 3e (66.84%), and 3g (63.04%) exhibited significant anti-inflammatory activity. Additionally, in silico binding free energy analysis and interaction studies revealed significant correlations between in vitro and computational data, identifying compounds 4d, 4e, 3b, 3i, and 3e as promising candidates. Key residues such as Glu917, Cys919, Lys920, Glu850, Lys838, and Asp1046 were found to play critical roles in ligand binding and kinase inhibition, providing valuable insights for designing potent VEGFR2 inhibitors. The quantum mechanics-based independent gradient model analysis further highlighted the electronic interaction landscape, showing larger attractive peaks and higher electron density gradients for compounds 4d and 4e compared to Sunitinib, suggesting stronger and diverse attractive forces.

Ultrasound-assisted ethanol/K2HPO4 aqueous two-phase extraction of polysaccharides from Plantago asiatica L. seeds: Process optimization, physicochemical properties, and antioxidant activity.

INTRODUCTION: The seeds of Plantago asiatica L., a folk herb, are rich in polysaccharides that possess antioxidant, antidiabetic, and anti-inflammatory properties. Polysaccharides with lower molecular weights generally exhibit higher biological activity, so a method to efficiently extract low-molecular-weight polysaccharides from P. asiatica L. seeds (PLPs) is needed. OBJECTIVES: The aim was to establish an efficient method for extracting polysaccharides from P. asiatica L. seeds while preserving their activity. MATERIALS AND METHODS: Response surface methodology was applied to determine the optimal polysaccharide extraction conditions. Subsequently, the extracted polysaccharides were characterized to determine their monosaccharide composition, physicochemical properties, and molecular weight. Their antioxidant activity was evaluated by measuring their ability to scavenge DPPH and ABTS free radicals. RESULTS: An extraction yield of 9.17% was achieved under an ethanol concentration of 18.0% (w/w), a K2HPO4 concentration of 27.8% (w/w), a solvent-to-material ratio of 30:1 (mL/g), an ultrasound power of 203 W, and an extraction time of 39 min. Structural analyses indicated that this method might cause physicochemical changes in the conformation of PLPs and induce the degradation of PLP side chains but not the backbone. The antioxidant assay results showed that the DPPH and ABTS radical scavenging rates of PLPs were 48.3% and 49.2%, respectively, while in the control group the radical scavenging rates were 35.5% and 37.1%, respectively. CONCLUSION: The established method for extracting polysaccharides from P. asiatica L. seeds is efficient and reliable. The polysaccharides could be used as an important resource with antioxidant activity.

Physicochemical and mechanical properties of preheated composite resins for luting ceramic laminates.

This study analyzed and compared the physicochemical and mechanical properties of preheated resin composite with light-cured resin cement for luting indirect restorations. 210 specimens of resin cement/resin composite were prepared according to preheating treatment heated (Htd) or not (NHtd). Light-cured resin cement (Variolink Veneer, Ivoclar), and resin composite (Microhybrid-Z100, 3 M; Nanohybrid-Empress direct, Ivoclar; and Bulk fill-Filtek One, 3 M) were used (n = 10). Resin cement specimens were not preheated. The response variables were (n = 10): film thickness, microhardness, liquid sorption and solubility. Data were analyzed by 2-way ANOVA and Tukey HSD post-test (α = 0.05). Bulk fill NHtd resin had the highest film thickness values (p < 0.001). Microhybrid and nanohybrid Htd resins had the smallest thicknesses and did not differ from the cement (p > 0.05). The highest microhardness values were found for Bulk fill NHtd and Bulk fill Htd resins. The nanohybrid and microhybrid Htd resins showed the lowest microhardness values, with no difference in cement (p > 0.05). For liquid sorption, there was no significant difference between the groups (p = 0.1941). The microhybrid Htd resin showed higher solubility values than the other materials (p = 0.0023), but it did not differ statistically from resin cement (p > 0.05). Preheating composite resins reduced the film thickness. After heating, nanohybrid and Bulk fill resins retained stable microhardness, sorption, and solubility values.