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High dielectric constant organic semiconductors, often obtained by the use of ethylene glycol (EG) side chains, have gained attention in recent years in the efforts of improving the device performance for various applications. Dielectric constant enhancements due to EGs have been demonstrated extensively, but various effects, such as the choice of the particular molecule and the frequency and temperature regime, that determine the extent of this enhancement require further understanding. In this work, we study these effects by means of polarizable molecular dynamics simulations on a carefully selected set of fullerene derivatives with EG side chains. The selection allows studying the dielectric response in terms of both the number and length of EG chains and also the choice of the group connecting the fullerene to the EG chain. The computed time- and frequency-dependent dielectric responses reveal that the experimentally observed rise of the dielectric constant within the kilo/megahertz regime for some molecules is likely due to the highly stretched dielectric response of the EGs: the initial sharp increase over the first few nanoseconds is followed by a smaller but persistent increase in the range of microseconds. Additionally, our computational protocol allows the separation of different factors that contribute to the overall dielectric constant, providing insights to make several molecular design guides for future organic materials in order to enhance their dielectric constant further.

Prion diseases or transmissible spongiform encephalopathies are fatal, progressive, neurodegenerative, protein-misfolding disorders. Prion diseases may arise spontaneously, be inherited genetically or be acquired by infection and affect a variety of mammalian species including humans. Prion infections in the central nervous system (CNS) cause extensive neuropathology, including abnormal accumulations of misfolded host prion protein, vacuolar change resulting in sponge-like (spongiform) appearance of CNS tissue, neurodegeneration and reactive glial responses. Many different prion agent strains exist and these can differ based on disease duration, clinical signs and the targeting and distribution of the neuropathology in distinct brain areas. Reactive astrocytes are a prominent feature in the prion disease affected CNS as revealed by distinct morphological changes and upregulation of glial fibrillary acidic protein (GFAP). The CD44 antigen is a transmembrane glycoprotein involved in cell-cell interactions, cell adhesion and migration. Here we show that CD44 is also highly expressed in a subset of reactive astrocytes in regions of the CNS targeted by prions. Astrocyte heterogeneity revealed by differential CD44 upregulation occurs coincident with the earliest neuropathological changes during the pre-clinical phase of disease, and is not affected by the route of infection. The expression and distribution of CD44 was compared in brains from a large collection of 15 distinct prion agent strains transmitted to mice of different prion protein (Prnp) genotype backgrounds. Our data show that the pattern of CD44 upregulation observed in the hippocampus in each prion agent strain and host Prnp genotype combination was unique. Many mouse-adapted prion strains and hosts have previously been characterized based on the pattern of the distribution of the spongiform pathology or the misfolded PrP deposition within the brain. Our data show that CD44 expression also provides a reliable discriminatory marker of prion infection with a greater dynamic range than misfolded prion protein deposition, aiding strain identification. Together, our data reveal CD44 as a novel marker to detect reactive astrocyte heterogeneity during CNS prion disease and for enhanced identification of distinct prion agent strains.

Introduction. This study was conducted to identify the factors that influence user satisfaction to determine the quality of the website (online system) for quality assurance in vocational education from the user’s point of view and to provide the best recommendations for improving the quality of the vocational school quality assurance online system.Aim. This study aims to analyse the quality of the vocational school quality assurance website that affects user satisfaction using the WebQual model.Methodology and research methods. This research used structural equation modelling – partial least square (PLS-SEM) analysis. The purposive sampling technique was chosen to determine the sample of respondents from operators or users of the quality assurance website from 36 vocational schools in Yogyakarta Province, Indonesia.Results. Based on the analysis results, it was found that the service interaction quality factor significantly influenced the e-service quality of the vocational school website for quality assurance, which then directly affected website user satisfaction.Practical significance. This research has implications for developing vocational school website for quality assurance to optimise the website function. This research also has implications for schools to facilitate performance reporting through quality assurance website.

This research aims to reveal the experience profile of future Physics teachers in developing simple multi-loaded life skill project. The research method used was a descriptive method with 62 future Physics teachers as the research subject. Based on observations, interviews, and questionnaires, it was drawn descriptions of the future teachers’ experiences in developing a simple project. The future teachers were assessed based on some Physics indicators such as project design, project creation, data collection, data analysis, and creativity. The results of the project preparation descriptions obtained by the experience data of future Physics teachers indicate the highest score of 4.8 (96%) on the indicator of schedule making, while the lowest score was 2.9 (58%) on the indicators of formulating the product benefits, preparing the feasibility analysis and analyzing the environmental impact. The results show that future Physics teachers got the highest score of 4.6 (93%) on data adjustment for experimental purposes indicator, and the lowest score of 2.8 (55%) on designing tools and materials indicator. Based on the Physics props trial, it was obtained the highest score of 4.5 (89%) on the indicator of analyzing the baseline data, while the lowest score of 2.9 (58%) was on the variation test variables. Positive feedback about time-management in completing the project, the ability to identify the topic of the project, the ability to find ideas to support the completion of the project, the ability to test the tools, and the ability to make progress reports on project completion were derived from the interviews. The highest score of students’ responses to project completion was 4.8 (95%) on the second data collection indicator and the lowest was 3.2 (64%) on the instrument material design indicator.

Spatial distribution of land properties and its susceptibility to degradation is essential for watershed management planning. Therefore, a study was carried out to assess spatial distribution of land susceptibity to degradation and provide some recommendations for its improvement. The location of the study was in the upper Solo sub-watershed which majority located in Central Java Province. To classify degree of land susceptibility, a watershed typhology was applied. The typhology of watershed was based on land system and land cover type. Data of land cover and slope steepness were derived from sattelite images. Land system was obtained from Regional Physical Planning Programme for Transmigration (RePPProT). The results show that 36% of the study area is covered by highly susceptible and 55% moderate susceptible to degradation. The rest are classified as very high, low, and very low suceptible to degradation. Improvement of the degraded land can be achieved by applying land use planning which is suitable with its capability, in fact agricultural areas are found at land use capability classes VI and VII which have to use for production forest and limited production forest. In addition, conservation practices need to be applied, especially for agricultural land at Vst of land capability class.

Background: Hemodialysis (HD) is the modality of renal replacement therapy (RRT) with the highest mortality rate. The identification of prognostic factors will help achieve better outcomes among HD patients. In this study, we sought to conduct a survival analysis and determine the predictors of mortality among adult Indonesian HD patients using data obtained from Indonesian Renal Registry (IRR)., Methods: This is a retrospective cohort study which reviewed all adult hemodialysis patients in Indonesia based on the records of IRR during 2007-2022. Variables analyzed in this study include age, sex, etiology of CKD, cause of death, HD frequency, and initial vascular access. A 5-year follow-up was performed until the outcome of death or drop out was found., Results: Among 99,552 eligible patients, the mean survival length was 1536.21 ± 2.50 days. The 5-year survival rate was 77%. Cox proportional hazard regression model revealed demographic and clinical characteristics that are significantly associated with mortality: male sex (HR: 1.038, 95% CI 1.002-1.075), age of 60 years or older (HR: 1.329, 95% CI 1.281-1.379), diabetic nephropathy (HR: 1.347, 95% CI 1.249-1.452), twice-weekly hemodialysis frequency (HR: 1.080, 95% CI 1.011-1.155), initial vascular accesses with femoral vein puncture (HR: 2.710, 95% CI 2.568-2.860), and CVC (HR: 2.992, 95% CI 2.848-3.144)., Conclusions: The 5-year survival rate of Indonesian HD patients is 77. Male sex, age of HD onset at 60 years or older, diabetic nephropathy, twice-weekly HD frequency, and the initial vascular accesses with femoral vein puncture and CVC are associated with increased risk of mortality., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Hypoxia remains a challenge for the therapeutic management of head and neck squamous cell carcinoma (HNSCC). The combination of radiotherapy with nimorazole has shown treatment benefit in HNSCC, but the precise underlying molecular mechanisms remain unclear., Purpose: To assess and to characterize the transcriptomic/epigenetic landscape of HNSCC tumor models showing differential therapeutic response to fractionated radiochemotherapy (RCTx) combined with nimorazole., Materials/methods: Bulk RNA-sequencing and DNA methylation experiments were conducted using untreated and treated HNSCC xenografts after 10 fractions of RCTx with and without nimorazole. These tumor models (FaDu, SAS, Cal33, SAT and UT-SCC-45) previously showed a heterogeneous response to RCTx with nimorazole. The prognostic impact of candidate genes was assessed using clinical and gene expression data from HNSCC patients treated with primary RCTx within the DKTK-ROG., Results: Nimorazole responder and non-responder tumor models showed no differences in hypoxia gene signatures However, non-responder models showed upregulation of metabolic pathways. From that, a subset of 15 differentially expressed genes stratified HNSCC patients into low and high-risk groups with distinct outcome., Conclusion: In the present study, we found that nimorazole non-responder models were characterized by upregulation of genes involved in Retinol metabolism and xenobiotic metabolic process pathways, which might contribute to identify mechanisms of resistance to nitroimidazole compounds and potentially expand the repertoire of therapeutic options to treat HNSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Survivin, an important inhibitor of apoptosis protein, contributes to cancer cells' resistance to apoptosis, proliferation, and survival. It is a promising biomarker and therapeutic target due to being highly expressed in cancer cells relative to normal cells and universally expressed in almost all cancer types. Cancer cells release survivin to the tumour microenvironment (TME) not only as a free protein but also encapsulated in extracellular vesicles (EVs), especially small EVs (sEVs). The release of encapsulated survivin from cancer cells can be taken up by neighbouring cells, eliciting pathological responses such as tumorigenesis and metastasis. Consequently, EV survivin holds potential as a diagnostic, prognostic, and therapeutic biomarker for several types of cancer, including breast cancer, prostate cancer, pancreatic cancer, and glioblastoma. EV survivin expression is significantly elevated in cancer patients and correlates with unfavourable clinicopathologic parameters. Although no clinical studies have explored EV survivin as a therapeutic target, future research should explore survivin-based therapies in combination with EV-targeting therapies to effectively disrupt its roles in tumorigenesis and metastasis., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Eribulin is a non-taxane synthetic analogue approved in many countries as third-line treatment for the treatment of patients with metastatic breast cancer. In addition to its mitotic property, eribulin has non-mitotic properties including but not limited to, its ability to induce phenotypic reversal of epithelial to mesenchymal transition, vascular remodelling, reduction in immunosuppressive tumour microenvironment. Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Context: Antibiotics have been suggested to diminish the efficacy of immune checkpoint inhibitors (ICIs) by alterations of the gut microbiota., Objective: To perform a meta-analysis summarizing the effect of antibiotics on the overall survival (OS) and progression-free survival (PFS) of urothelial cancer (UC) patients receiving ICI., Evidence Acquisition: PubMed, EMBASE (Ovid), and the Cochrane Library were searched to identify studies published up to July 14, 2023. Studies reporting the associations between antibiotics use and OS and PFS in UC patients treated with ICI were included in this systematic review and meta-analysis. The random-effect model was used to pool the Hazard Ratios (HRs) for OS and PFS with 95% confidence interval (95%CI). The ROBINS-I was used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform the quality of evidence., Evidence Synthesis: Thirteen nonrandomized studies involving a total of 5,095 ICI-treated UC patients were included in this review, of which 1434 (28%) received antibiotics. Overall, compared to patients who did not receive antibiotics, the pooled HRs for OS and PFS in those who received antibiotics were 1.45 [95% CI 1.25-1.68] and 1.40 [95% CI 1.05-1.87], respectively. Subgroup analysis revealed that the types of ICI and timing of antibiotic initiation did not influence the effect of antibiotics on OS and PFS in UC patients (P > 0.05)., Conclusions: Antibiotic use significantly reduced OS and PFS in UC patients receiving ICI. While antibiotics remain crucial for the treatment of infections in UC patients, antibiotics should be prescribed cautiously in UC patients receiving ICI., Patient Summary: Antibiotic use is associated with worsened survival in UC patients receiving immune checkpoint inhibitors., Competing Interests: Declaration of Competing Interest All the authors hereby declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Combined hemodialysis (HD) and hemadsorption (HA) therapy has shown the highest clearance rates for middle and large-sized uremic toxin molecules and reduced mortality rates among maintenance HD (MHD) patients. This study aimed to investigate the effectiveness of combined HD and HA therapy in patients undergoing MHD., Methods: Forty patients with end-stage renal disease (ESRD) were divided into three groups: HD only (14), HD + biweekly HA (14), and HD + weekly HA (12). The duration of the study was 8 weeks. Uremic toxins (β2-microglobulin, leptin, parathyroid hormone), inflammatory markers (interleukin-6, C-reactive protein), and symptoms (appetite, pruritus, sleep quality) were assessed before the start and at the completion of therapy. Changes in the parameters were compared between the three groups. Mean differences of parameters in each group were also compared between before and after therapy., Results: Decrease in BUN level (-61.34 mg/dL [95% CI: -71.33 to -51.34], p < 0.0001) and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p = 0.013) was significantly larger in HD + biweekly HA group compared to the others. Only HD + biweekly HA group showed significant reductions in CRP level (-0.10 mg/L [95%: -0.18 to -0.01], p = 0.034), VAS appetite score (10.43 [95% CI: 4.99-15.87], p = 0.001), and pruritus score (-3.93 [95% CI: -6.89 to -0.97], p = 0.013) after therapy. Both HD + biweekly HA (-2.79 [95% CI: -4.97 to -0.60], p = 0.016) and HD + weekly HA group (-2.33 [95% CI: -4.59 to -0.08], p = 0.044) exhibited a significant improvement in sleep quality score after therapy., Conclusions: HD combined with a biweekly HA is associated with a greater reduction in BUN level and better improvement of pruritus in ESRD patients compared to HD alone. HD + biweekly HA can significantly reduce CRP levels, alleviate pruritus, improve appetite, and enhance sleep quality., (© 2024 S. Karger AG, Basel.)

End-stage renal disease patients on haemodialysis (HD) have been largely excluded from SARS-CoV-2 vaccine trials due to safety reasons and shown to mount lower responses to vaccination. This study aims to evaluate the immunogenicity and safety of inactivated COVID-19 vaccine among HD patients compared to healthy controls. All subjects who received the primary inactivated COVID-19 vaccination had their blood samples tested 21 days after the second dose. We report the immunogenicity based on anti-RBD IgG titre (IU/mL), the inhibition rate of neutralizing antibodies (NAbs) (%) to RBD, and seroconversion rates. Adverse events were assessed within 30 min and on the 7th day after each dose. Among 75 HD patients and 71 healthy controls, we observed no significant difference in all immunogenicity measures: anti-RBD IgG GMT (277.91 ± 7.13 IU/mL vs. 315.50 ± 3.50 IU/mL, p = 0.645), NAbs inhibition rate (82% [53-96] vs. 84% [39-98], p = 0.654), and seroconversion rates (anti-RBD IgG: 86.7% vs. 85.9%, p = 0.895; NAbs: 45.3% vs. 60.6%, p = 0.065). The number of adverse events is not significantly different between the two groups. The primary inactivated SARS-CoV-2 vaccination elicits an adequate antibody response and can be safely administered in haemodialysis patients., (© 2023. The Author(s).)

The Johor Strait separates the island of Singapore from Peninsular Malaysia. A 1-kilometer causeway built in the early 1920s in the middle of the strait effectively blocks water flowing to/from either side, resulting in low water turnover rates and build-up of nutrients in the inner Strait. We have previously shown that short-term rather than seasonal environmental changes influence microbial community composition in the Johor Strait. Here, we present a temporally-intensive study that uncovers the factors keeping the microbial populations in check. We sampled the surface water at four sites in the inner Eastern Johor Strait every other day for two months, while measuring various water quality parameters, and analysed 16S amplicon sequences and flow-cytometric counts. We discovered that microbial community succession revolves around a common stable state resulting from frequent pulse disturbances. Among these, sporadic riverine freshwater input and regular tidal currents influence bottom-up controls including the availability of the limiting nutrient nitrogen and its biological release in readily available forms. From the top-down, marine viruses and predatory bacteria limit the proliferation of microbes in the water. Harmful algal blooms, which have been observed historically in these waters, may occur only when there are simultaneous gaps in the top-down and bottom-up controls. This study gains insight into complex interactions between multiple factors contributing to a low-resistance but high-resilience microbial community and speculate about rare events that could lead to the occurrence of an algal bloom., (© 2023. The Author(s).)

Background: A significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients., Methods: Patients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs)., Results: The geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89-9,571.94) U/mL (p =  < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63-27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported., Conclusions: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events., (© 2023. The Author(s).)

Due to the nature of the disease, end-stage renal disease (ESRD) patients suffer from dysfunction of the adaptive immune system, which leads to a poorer response to vaccination. Accordingly, it is crucial to evaluate the efficacy and safety of management strategies, including vaccinations, which could potentially reduce the risk of respiratory diseases, such as pneumonia, influenza, or COVID-19, and its associated outcomes. We searched PubMed, CENTRAL, ScienceDirect, Scopus, ProQuest, and Google Scholar databases using designated MeSH keywords. The risk of bias was assessed using ROBINS-I. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Relative risk (RR) and 95% confidence interval (CI) were calculated. Heterogeneity was investigated using forest plots and I2 statistics. This systematic review included a total of 48 studies, with 13 studies of influenza (H1N1 and H3N2) vaccination and 35 studies of COVID-19 vaccination. H1N1 vaccination in ESRD patients undergoing hemodialysis induced lower seroconversion rates (RR 0.62, 95% CI: 0.56-0.68, p <0.00001) and lower seroprotection rates (RR 0.76, 95% CI: 0.70-0.83, p <0.00001) compared to controls. H3N2 vaccination in ESRD patients undergoing hemodialysis yielded lower seroconversion rates (RR 0.76, 95% CI: 0.68-0.85, p <0.00001) and lower seroprotection rates (RR 0.84, 95% CI: 0.77-0.90, p <0.00001) compared to controls. Twenty-nine studies demonstrate significantly lower antibody levels in ESRD patients undergoing hemodialysis compared to the controls following COVID-19 vaccination. This review presents evidence of lower seroconversion and seroprotection rates after vaccination against viral respiratory diseases in patients with ESRD undergoing hemodialysis. Since hemodialysis patients are more susceptible to infection and severe disease progression, a weakened yet substantial serological response can be considered adequate to recommend vaccination against respiratory diseases in this population. Vaccination dose, schedule, or strategy adjustments should be considered in stable ESRD patients on maintenance hemodialysis. Trial registration: Systematic review registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021255983, identifier: CRD42021255983., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Puspitasari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

DNA methylomes of Helicobacter pylori strains are complex due to the large number of DNA methyltransferases (MTases) they possess. H. pylori J99 M.Hpy99III is a 5-methylcytosine ( m5 C) MTase that converts GCGC motifs to G m5 CGC. Homologs of M.Hpy99III are found in essentially all H. pylori strains. Most of these homologs are orphan MTases that lack a cognate restriction endonuclease, and their retention in H. pylori strains suggest they have roles in gene regulation. To address this hypothesis, green fluorescent protein (GFP) reporter genes were constructed with six putative promoters that had a GCGC motif in the extended -10 region, and the expression of the reporter genes was compared in wild-type H. pylori G27 and a mutant lacking the M.Hpy99III homolog (M.HpyGIII). The expression of three of the GFP reporter genes was decreased significantly in the mutant lacking M.HpyGIII. In addition, the growth rate of the H. pylori G27 mutant lacking M.HpyGIII was reduced markedly compared to that of the wild type. These findings suggest that the methylation of the GCGC motif in many H. pylori GCGC-containing promoters is required for the robust expression of genes controlled by these promoters, which may account for the universal retention of M.Hpy99III homologs in H. pylori strains.

As a phenolic terpenoid, carnosic acid (CA) mainly exists in rosemary, which can be effectively used for the treatment of degenerative and chronic diseases by taking advantage of its health-promoting bioactivities. However, the low solubility and dissolution of CA in aqueous solutions at ambient and body temperatures result in low stability and bioaccessibility during the digestion process, which limits its application scope in the functional foods industry. In this regard, a lecithin based nanoemulsion system (CA-NE) is employed in the present work to enhance the bioaccessibility and bioactivities of CA. It is revealed that the CA-NE under investigation exhibits high loading capacity (2.80 ± 0.15%), small particle size (172.0 ± 3.5 nm) with homogeneous particle distribution (polydispersity index (PDI) of 0.231± 0.025) and high repulsive force (zeta potential = -57.2 ± 0.24 mV). More importantly, the bioaccessibility of CA-NE is improved by 2.8-fold compared to that of CA in MCT oil. In addition, the cellular antioxidant assay (CAA) and cellular uptake study of the CA-NE in HepG2 cell models demonstrate a longer endocytosis process, suggesting the well-controlled release of CA from CA-NE. Furthermore, an improved anti-inflammatory activity was evaluated via the inhibition of the pro-inflammatory cytokines, nitric oxide (NO) and TNF-α production in LPS-stimulated RAW 264.7 macrophage cells. The results clearly demonstrated a promising application of CA-NE as a functional food.

Carnosic acid (CA) represents one of the most effective antioxidants that can be applied for the prevention of degenerative and chronic diseases. However, the intrinsic hydrophobic nature of CA results in low solubility and poor dissolution in the gastrointestinal (GI) tract, which limits its applications in a variety of functional food systems. In order to address these issues, we encapsulated CA in a lecithin-based nanoemulsion (CA-NE) to improve its bioaccessibility and bioavailability which are evaluated using in vitro and in vivo digestion models. The CA-NE demonstrated a loading capacity of 2.6-3.0%, an average particle size of 165 nm, a ζ-potential value of -57.2 mV, and good stability during 4-weeks of storage at 4, 25, and 37 °C. The in vitro static pH-stat lipolysis model and dynamic TNO gastrointestinal (TIM-1) model demonstrated a 12.6 and 5.6 fold increase in the total bioaccessibility of CA encapsulated in nanoemulsion, respectively, as opposed to CA in suspension form. Moreover, the in vivo pharmacokinetics study on a rat model (Male Sprague Dawley) confirmed that the bioavailability of CA in nanoemulsion showed a 2.2 fold increase, as compared to that of CA in suspension form. In conclusion, the bioaccessibility and bioavailability of CA were remarkably improved by encapsulation of CA in a lecithin-based nanoemulsion. Moreover, the combined in vitro and in vivo study could serve as a useful approach for the comprehensive evaluation of oral lipid-based delivery systems.

The present study aimed to assemble protein fibril-polysaccharide hydrogels as nutraceutical delivery vehicles. Turbidity titrations confirmed that complexations between ovotransferrin (OVT) fibrils and xanthan gum (XG) indeed occurred, and electrostatic interaction was the major driving force of OVT fibril-XG complexation. After optimization of the pH and acidifier, stable OVT fibril-XG hydrogels could be fabricated by adjusting the pH to 4.0 with glucono delta-lactone. To better understand the physicochemical properties of OVT fibril-XG gel, characterization of XG gel was also conducted. Scanning electron microscopy indicated that OVT fibril-XG gel had a denser network than XG gel. Rheological measurements revealed that OVT fibril-XG gel had higher gel strength and viscosity than XG gel. OVT fibril-XG gel and XG gel could be used as dihydromyricetin (DMY) delivery vehicles with a higher DMY loading (2 mg mL-1). DMY release was investigated using an in vitro gastrointestinal digestion model. All DMY was released from OVT fibril-XG gel after gastrointestinal digestion, and only 41.7% of DMY was released from XG gel after gastrointestinal digestion, indicating that OVT fibril-XG gel was more efficient in DMY delivery. DMY was released via a non-Fickian transport mechanism in both OVT fibril-XG gel and XG gel. The results of this study could provide new insight into the assembly of protein fibril-polysaccharide hydrogels and rational design of hydrogels as nutraceutical delivery vehicles.

In this work, the bioaccessibility of polymethoxyflavones (PMFs) loaded in high internal phase emulsions (HIPE, ϕ oil  = 0.82) stabilized by whey protein isolate (WPI)-low methoxy pectin (LMP) complexes was evaluated using in vitro lipolysis and dynamic in vitro intestinal digestion studies. PMFs loaded HIPE was prepared by using aqueous dispersion of pre-formed biopolymeric complexes (WPI-LMP, 2:1 ratio) as the external phase and medium chain triglycerides oil (containing PMFs extracted from citrus peel) as the dispersed phase. The in vitro lipolysis study revealed that PMFs in HIPE became bioaccessible much higher than PMFs in medium chain triacylglycerols oil (MCT oil). In addition, by simulating the entire human gastrointestinal (GI) tract, the GI model TIM-1 demonstrated a 5- and 2-fold increase in the total bioaccessibility for two major PMFs encapsulated in HIPE, i.e. tangeretin (TAN) and nobiletin (NOB), respectively, as opposed to PMFs in MCT oil. Together these results from the digestion study showed that the incorporation of a high amount of PMFs into the viscoelastic matrix of HIPE could represent an innovative and effective way to design an oral delivery system. Such a system could be used to control and to improve the delivery of lipophilic bioactive compounds within the different compartments of the digestive tract, especially the human upper GI tract., Competing Interests: We have no conflict of interest in this research., (© 2019 The Author(s).)