The effect of avian eggshell membrane structure on microbial penetration: A simulation study.

Avian eggshells exhibit excellent antimicrobial properties. In this study, we conducted simulation experiments to explore the defense mechanisms of eggshell membranes with regards to their physical features. We developed a mathematical model for the movement of microorganisms and estimated their penetration ratio into eggshell membranes based on several factors, including membrane thickness, microbial size, directional drift, and attachment probability to membrane fibers. These results not only suggest that an eggshell membrane with multiple layers and low porosity indicates high antimicrobial performance, but also imply that the fibrous network structure of the membrane might contribute to effective defense. Our simulation results aligned with experimental findings, specifically in measuring the penetration time of Escherichia coli through the eggshell membrane. We briefly discuss the significance and limitations of this pilot study, as well as the potential for these results, to serve as a foundation for the development of antimicrobial materials.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

BACKGROUND: In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods. We aimed to evaluate the immunogenicity and safety of Euvichol-S (EuBiologics, Seoul, South Korea) compared with an active control vaccine, Shanchol (Sanofi Healthcare India, Telangana, India) in participants of various ages in Nepal. METHODS: We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Nepal. Eligible participants were healthy individuals aged 1-40 years without a history of cholera vaccination. Individuals with a history of hypersensitivity reactions to other preventive vaccines, severe chronic disease, previous cholera vaccination, receipt of blood or blood-derived products in the past 3 months or other vaccine within 4 weeks before enrolment, and pregnant or lactating women were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block sizes of two, four, six, or eight) to one of four groups (groups A-D); groups C and D were stratified by age (1-5, 6-17, and 18-40 years). Participants in groups A-C were assigned to receive two 1·5 mL doses of Euvichol-S (three different lots) and participants in group D were assigned to receive the active control vaccine, Shanchol. All participants and site staff (with the exception of those who prepared and administered the study vaccines) were masked to group assignment. The primary immunogenicity endpoint was non-inferiority of immunogenicity of Euvichol-S (group C) versus Shanchol (group D) at 2 weeks after the second vaccine dose, measured by the seroconversion rate, defined as the proportion of participants who had achieved seroconversion (defined as ≥four-fold increase in V cholerae O1 Inaba and Ogawa titres compared with baseline). The primary immunogenicity endpoint was assessed in the per-protocol analysis set, which included all participants who received all their planned vaccine administrations, had no important protocol deviations, and who provided blood samples for all immunogenicity assessments. The primary safety endpoint was the number of solicited adverse events, unsolicited adverse events, and serious adverse events after each vaccine dose in all ages and each age stratum, assessed in all participants who received at least one dose of the Euvichol-S or Shanchol. Non-inferiority of Euvichol-S compared with Shanchol was shown if the lower limit of the 95% CI for the difference between the seroconversion rates in Euvichol-S group C versus Shanchol group D was above the predefined non-inferiority margin of -10%. The trial was registered at ClinicalTrials.gov, NCT04760236. FINDINGS: Between Oct 6, 2021, and Jan 19, 2022, 2529 healthy participants (1261 [49·9%] males; 1268 [50·1%] females), were randomly assigned to group A (n=330; Euvichol-S lot number ES-2002), group B (n=331; Euvichol-S ES-2003), group C (n=934; Euvichol-S ES-2004]), or group D (n=934; Shanchol). Non-inferiority of Euvichol-S versus Shanchol in seroconversion rate for both serotypes at 2 weeks after the second dose was confirmed in all ages (difference in seroconversion rate for V cholerae O1 Inaba -0·00 [95% CI -1·86 to 1·86]; for V cholerae O1 Ogawa -1·62 [-4·80 to 1·56]). Treatment-emergent adverse events were reported in 244 (9·7%) of 2529 participants in the safety analysis set, with a total of 403 events; 247 events were reported among 151 (9·5%) of 1595 Euvichol-S recipients and 156 events among 93 (10·0%) of 934 Shanchol recipients. Pyrexia was the most common adverse event in both groups (57 events among 56 [3·5%] of 1595 Euvichol-S recipients and 37 events among 35 [3·7%] of 934 Shanchol recipients). No serious adverse events were deemed to be vaccine-related. INTERPRETATION: A two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.

Evaluation of Two Commercial Kits for Qualitative Detection of SARS-CoV-2 Antigens in Nasopharyngeal Specimens.

BACKGROUND: Two rapid antigen tests (RATs) for COVID-19 targeting the nucleocapsid protein of SARS-CoV-2 were compared with real-time RT-PCR as the reference method. METHODS: Ninety-six nasopharyngeal swab samples, comprising 56 positive and 40 negative samples confirmed through rRT-PCR were collected and retested to determine the reliability of the two nasopharyngeal RATs. RESULTS: The overall sensitivity and specificity of both RATs were 64.3% (95% confidence interval 50.4 - 76.6%) and 100% (95% confidence interval 91.2 - 100%), respectively. Cohen's kappa coefficient of agreement of both RATs to rRT-PCR was 0.600 (95% confidence interval 0.457 - 0.743) (p < 0.001), showing almost perfect agreement when the Ct values were less than 25 in rRT-PCR. A significant difference in Ct values between true positives and false negatives was observed (Mann-Whitney-Wilcoxon test; p < 0.001). CONCLUSIONS: Compared to rRT-PCR, RATs have fewer false negatives. In suspected COVID-19 cases, negative RAT results should be retested using either RAT or rRT-PCR.

Five-Day Spacing of Two Fractionated Ablative Radiotherapies Enhances Antitumor Immunity.

PURPOSE: This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS: FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS: Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.

Integrated approach for the isotope trophic position of black-tailed gull (Larus crassirostris) eggs over a decade: Combining stable isotopes of amino acids and fatty acids composition.

Recently, compound-specific isotope analysis (CSIA) using the amino acid nitrogen stable isotope ratio (δ15NAAs) has been widely used for accurate estimation of trophic position (TP). In addition, a quantitative fatty acid signature analysis (QFASA) offers insights into diet sources. In this study, we used these techniques to estimate the TP for seabirds that rely on diverse food sources across multiple ecosystems. This allows for the proper combination of factors used in TP calculation which are different for each ecosystem. The approach involved the application of a multi-mixing trophic discrimination factor (TDF) and mixing ß which is a Δδ15N between trophic and source amino acid of primary producer. Since the black-tailed gulls (BTGs) are income-breeding seabirds, which rely on energy sources obtained around their breeding sites, they and their eggs could be useful bioindicators for environmental monitoring. However, the ecological properties of BTGs such as habitats, diets, and TP are not well known due to their large migration range for wintering or breeding and their feeding habits on both aquatic and terrestrial prey. In this study, the eggs were used for estimating TP and for predicting TP of mother birds to overcome difficulties such as capturing birds and collecting non-invasive tissue samples. Eggs, sampled over a decade from three Korean islands, showed spatial differences in diet origin. Considering both the food chain and physiology of BTG, the TP of eggs was estimated to be 3.3-4.0. Notably, the TP was significantly higher at site H (3.8 ± 0.1) than at site B (3.5 ± 0.2), which indicated a higher contribution of marine diet as confirmed by QFASA. Using a reproductive shift of δ15NAAs, the TP of the mother birds was predicted to be 3.6-4.3, positioning them as the top predator in the food web. The advanced integration of multiple approaches provides valuable insights into bird ecology.

New insight into biomagnification factor of mercury based on food web structure using stable isotopes of amino acids.

Although many attempts have been carried out to elaborate trophic magnification factor (TMF) and biomagnification factor (BMF), such as normalizing the concentration of pollutants and averaging diet sources, the uncertainty of the indexes still need to be improved to assess the bioaccumulation of pollutants. This study first suggests an improved BMF (i.e., BMF') applied to mercury bioaccumulation in freshwater fish from four sites before and after rainfall. The diet source and TP of each fish were identified using nitrogen stable isotope of amino acids (δ15NAAs) combined with bulk carbon stable isotope (δ13C). The BMF' was calculated normalizing with TP and diet contributions derived from MixSIAR. The BMF' values (1.3-27.2 and 1.2-27.8), which are representative of the entire food web, were generally higher than TMF (1.5-13.9 and 1.5-14.5) for both total mercury and methyl mercury, respectively. The BMF' implying actual mercury transfer pathway is more reliable index than relatively underestimated TMF for risk assessment. The ecological approach for BMF calculations provides novel insight into the behavior and trophic transfer of pollutants like mercury.

Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Fiber-based quantum-dot pulse oximetry for wearable health monitoring with high wavelength selectivity and photoplethysmogram sensitivity.

Increasing demand for real-time healthcare monitoring is leading to advances in thin and flexible optoelectronic device-based wearable pulse oximetry. Most previous studies have used OLEDs for this purpose, but did not consider the side effects of broad full-width half-maximum (FWHM) characteristics and single substrates. In this study, we performed SpO2 measurement using a fiber-based quantum-dot pulse oximetry (FQPO) system capable of mass production with a transferable encapsulation technique, and a narrow FWHM of about 30 nm. Based on analyses we determined that uniform angular narrow FWHM-based light sources are important for accurate SpO2 measurements through multi-layer structures and human skin tissues. The FQPO was shown to have improved photoplethysmogram (PPG) signal sensitivity with no waveguide-mode noise signal, as is typically generated when using a single substrate (30-50%). We successfully demonstrate improved SpO2 measurement accuracy as well as all-in-one clothing-type pulse oximetry with FQPO.

The effects of visitors and social isolation from a peer on the behavior of a mixed-species pair of captive gibbons.

Human visitors affect the behavior of captive animals, which is the so-called visitor effect. The number and behavior of visitors may influence stress-related behaviors in captive animals, such as self-scratching, yawning, and visitor-directed vigilance. A social group setting can be applied to alleviate such negative visitor effects and facilitate social behavior and interactions between individuals. In this study, we examined how the number and behavior of visitors are related to stress-related behaviors of a captive mixed-species gibbon pair comprising a yellow-cheek gibbon (Nomascus gabriellae) and a white-handed gibbon (Hylobates lar). The two gibbons were separated during the study period, and we examined whether the social isolation stimulated the visitor effect. The frequency of stress-related behaviors of the gibbons increased and the social playing between them decreased proportionally to visitor number. In the indoor enclosure, the gibbons increased their visitor-directed vigilance when visitors shouted or struck the glass partition. Our findings indicate that the number and behavior of visitors negatively affect captive gibbons and that a mixed-species social setting can help gibbons reduce visitor-induced stress. Future studies with larger sample sizes will improve the understanding of the visitor effect and the social setting in the captivity.

HIF-1α Inhibition Improves Anti-Tumor Immunity and Promotes the Efficacy of Stereotactic Ablative Radiotherapy (SABR).

High-dose hypofractionated radiation such as SABR (stereotactic ablative radiotherapy) evokes an anti-tumor immune response by promoting a series of immune-stimulating processes, including the release of tumor-specific antigens from damaged tumor cells and the final effector phase of immune-mediated lysis of target tumor cells. High-dose hypofractionated radiation also causes vascular damage in tumors, thereby increasing tumor hypoxia and upregulation of hypoxia-inducible factors HIF-1α and HIF-2α, the master transcription factors for the cellular response to hypoxia. HIF-1α and HIF-2α are critical factors in the upregulation of immune suppression and are the master regulators of immune evasion of tumors. Consequently, SABR-induced increase in anti-tumor immunity is counterbalanced by the increase in immune suppression mediated by HIFα. Inhibition of HIF-1α with small molecules such as metformin downregulates immunosuppressive pathways, including the expression of immune checkpoints, and it improves or restores the anti-tumor immunity stimulated by irradiation. Combinations of HIFα inhibitors, particularly HIF-1α inhibitors, with immune checkpoint blocking antibodies may represent a novel approach to boost the overall anti-tumor immune profile in patients and thus enhance outcomes after SABR.

Potential of Colostrum-Derived Exosomes for Promoting Hair Regeneration Through the Transition From Telogen to Anagen Phase.

Human hair dermal papillary (DP) cells comprising mesenchymal stem cells in hair follicles contribute critically to hair growth and cycle regulation. The transition of hair follicles from telogen to anagen phase is the key to regulating hair growth, which relies heavily on the activation of DP cells. In this paper, we suggested exosomes derived from bovine colostrum (milk exosomes, Milk-exo) as a new effective non-surgical therapy for hair loss. Results showed that Milk-exo promoted the proliferation of hair DP cells and rescued dihydrotestosterone (DHT, androgen hormones)-induced arrest of follicle development. Milk-exo also induced dorsal hair re-growth in mice at the level comparable to minoxidil treatment, without associated adverse effects such as skin rashes. Our data demonstrated that Milk-exo accelerated the hair cycle transition from telogen to anagen phase by activating the Wnt/ß-catenin pathway. Interestingly, Milk-exo has been found to stably retain its original properties and efficacy for hair regeneration after freeze-drying and resuspension, which is considered critical to use it as a raw material applied in different types of alopecia medicines and treatments. Overall, this study highlights a great potential of an exosome from colostrum as a therapeutic modality for hair loss.

Bovine colostrum derived-exosomes prevent dextran sulfate sodium-induced intestinal colitis via suppression of inflammation and oxidative stress.

Despite the rise in the global burden of inflammatory bowel disease, there is a lack of safe and effective therapies that can meet the needs of clinical patients. In this study, we investigated the beneficial effects of bovine milk, especially colostrum-derived exosomes (Col-exo) in a murine model of ulcerative colitis induced by dextran sodium sulfate (DSS). Col-exo activated the proliferation of colonic epithelial cells and macrophages, and created an environment to relieve inflammation by effectively removing reactive oxygen species and regulating the expression of immune cytokines. Besides, Col-exo could pass through the gastrointestinal tract intact and efficiently deliver bioactive cargoes to the stomach, small intestine, and colon. Our results showed that oral gavage of Col-exo can alleviate colitis symptoms including weight loss, gastrointestinal bleeding, and chronic diarrhea by modulating intestinal inflammatory immune responses. Overall, bovine colostrum-derived exosomes with excellent structural and functional stability may offer great potential as natural therapeutics for the recovery of colitis.

PDL1-binding peptide/anti-miRNA21 conjugate as a therapeutic modality for PD-L1high tumors and TAMs.

Upregulation of oncogenic miRNA21 (miR-21) plays a pivotal role in proliferation, migration and invasion of cancer cells. In addition to cancer cells, tumor-associated macrophages (TAMs) also have high abundance of miR-21, which accelerates malignant progression of tumors in the late stages of carcinogenesis. Despite of the pro-tumorigenic functions of miR-21 in TAMs and cancer cells, reliable therapeutic strategies to simultaneously inhibit miR-21 activity in both types of cell have not yet been developed. In this study, we designed a dual-targeting drug delivery system of miR-21 inhibitors that could bind to both tumor cells and macrophages with overexpressed PD-L1 receptors. This peptide-oligonucleotide conjugate (Pep-21) consists of a PDL1-binding peptide covalently linked with an anti-miR-21 inhibitor via click chemistry. Pep-21 was preferentially internalized in both cell types, consequently depleting endogenous miR-21. Our studies found that Pep-21 treatment reduced tumor cell migration, reprogrammed immunosuppressive M2-type TAMs into M1-type macrophages, and restrained tumor progression. Collectively, neutralization of miR-21 activity in both cancer cells and TAMs can be a promising strategy for effective antitumor responses.

Environmental fate and trophic transfer of synthetic musk compounds and siloxanes in Geum River, Korea: Compound-specific nitrogen isotope analysis of amino acids for accurate trophic position estimation.

Despite the extensive usage of synthetic musk compounds (SMCs) and siloxanes in various personal care products (PCPs), trophic magnification of such chemicals in aquatic environments remains unexplored. In June and September 2020, eleven SMCs and nineteen siloxanes were measured in water, sediments, and biota. Samples were collected from two sites where levels were expected to be influenced by the distance from the wastewater treatment plant (WWTP) in the Geum River, Republic of Korea, were expected. High concentrations of SMCs and siloxanes entered through WWTP were measured in water, sediment, and biota at the both sites and both seasons. The δ15N of amino acids provided a high-resolution food web and accurate trophic position (TP), which is an important factor for determining the trophic magnification factor (TMF). Among 24 TMFs, 19 of them were <1, ranging 0.7-0.8 for 1,3,4,6,7,8­hexahydro­4,6,6,7,8,8­hexamethyl­cyclopenta­Î³­2­benzopyran (HHCB), 0.6-0.8 for 6-Acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), 0.7-0.8 for 4-tert-Butyl-3,5-dinitro-2,6-dimethylacetophenone (MK), 0.7-0.9 for octamethylcyclotetrasiloxane (D4), 0.1-0.4 for decamethylcyclopentasiloxane (D5), and 0.04-0.8 for dodecamethylcyclohexasiloxane (D6), and the remaining ones including HHCB, AHTN, MK, and D4 showed values close to 1 or slightly higher (TMF range: 1.0-2.3) indicating no or a little trophic magnification. The TMFs of these compounds were constant across sites and seasons. The TMF values of PCPs might be affected by species specificity and food web structure rather than by chemical properties such as log Kow, which describes a wide range of TMF values in various environments. This study presents valuable implications for assessing risk and managing environmental fate and trophic transfer of SMCs and siloxanes in freshwater environments.

Clinical application of an algorithm to screen for malignant cells in body fluids using an automated hematology analyzer.

INTRODUCTION: The detection of malignant cells in body fluids (BF) with an automated hematology analyzer has been proposed as an alternative to morphological examination owing to its various advantages; however, its limitations have also been highlighted. In this study, we devised a practical algorithm to screen for malignant cells in BFs using an automated hematology analyzer. METHODS: A total of 558 BF samples, including 232 cerebrospinal fluid (CSF) samples and 326 non-CSF samples, were consecutively collected. Thereafter, the results obtained using the BF mode of Sysmex XN-350 (Sysmex, Kobe, Japan) were compared with the cytological diagnosis. A cutoff was also established to screen for malignant cells using receiver operating characteristic (ROC) curve analysis based on the final clinical judgment. RESULTS: The automated hematology analyzer showed a moderate correlation or good agreement with the existing cytological diagnosis. Further, of the ROC curves for detecting malignant cells, the absolute value of highly fluorescent cells on BF (HF-BF) in total body fluids showed the highest area under the curve (0.85 [95% confidence interval 0.82-88], p < .0001, Youden index >7×106 /L, sensitivity 93%, and specificity 65%). CONCLUSION: An automated hematology analyzer could function as a complement to cytological examination. We propose a practical and comprehensive algorithm for cytological examination that requires low- and high-resolution microscopy based on the absolute value of HF-BF in BF samples suspected of malignancy. This algorithm can more usefully detect malignant cells while taking advantage of the automated analyzer and cytological examination.

Harnessing the Natural Healing Power of Colostrum: Bovine Milk-Derived Extracellular Vesicles from Colostrum Facilitating the Transition from Inflammation to Tissue Regeneration for Accelerating Cutaneous Wound Healing.

As wound healing is an extremely complicated process, consisting of a cascade of interlocking biological events, successful wound healing requires a multifaceted approach to support appropriate and rapid transitions from the inflammatory to proliferative and remodeling phases. In this regard, here the potential use of bovine milk extracellular vesicles (EVs) to enhance wound healing is investigated. The results show that milk EVs promote fibroblast proliferation, migration, and endothelial tube formation. In particular, milk EVs derived from colostrum (Colos EVs) contain various anti-inflammatory factors facilitating the transition from inflammation to proliferation phase, as well as factors for tissue remodeling and angiogenesis. In an excisional wound mouse model, Colos EVs promote re-epithelialization, activate angiogenesis, and enhance extracellular matrix maturation. Interestingly, Colos EVs are further found to be quite resistant to freeze-drying procedures, maintaining their original characteristics and efficacy for wound repair after lyophilization. These findings on the superior stability and excellent activity of milk Colos EVs indicate that they hold great promise to be developed as anti-inflammatory therapeutics, especially for the treatment of cutaneous wounds.

Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy.

Exosomes are a class of extracellular vesicles, with a size of about 100 nm, secreted by most cells and carrying various bioactive molecules such as nucleic acids, proteins, and lipids, and reflect the biological status of parent cells. Exosomes have natural advantages such as high biocompatibility and low immunogenicity for efficient delivery of therapeutic agents such as chemotherapeutic drugs, nucleic acids, and proteins. In this review, we introduce the latest explorations of exosome-based drug delivery systems for cancer therapy, with particular focus on the targeted delivery of various types of cargoes.

Germinated black soybean fermented with Lactobacillus pentosus SC65 alleviates DNFB-induced delayed-type hypersensitivity in C57BL/6N mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhynchosia nulubilis (black soybean) has many applications in oriental medicine. It is traditionally used to treat disease related with high blood pressure, diabetes, inflammation, and osteoporosis. Furthermore, fermented soybean foods have traditionally been used for immunity enhancement in East Asia. However, the anti-inflammatory effects of germinated R. nulubilis (GR) against delayed-type hypersensitivity (DTH) are not fully understood. AIM OF STUDY: This study aimed to investigate the anti-inflammatory effects of germinated Rhynchosia nulubilis (GR) fermented with the lactic acid bacterium Lactobacillus pentosus SC65 (GR-SC65) isolated from pickled burdock. MATERIALS AND METHODS: We investigated the effects of GR-SC65 (300 mg/kg/day) on ear thickness and immune cell infiltration in DNFB-induced DTH in mice. We used dexamethasone (3 mg/kg) as a reference drug. Changes in infiltration of CD4+ and CD8+ T cells and NK cells were examined by immunohistochemistry. In addition, we investigated cytokine and chemokine production related to DTH using reverse transcription-polymerase chain reaction. We also investigated DTH-related cytokine production using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. RESULTS: Two lactic acid bacterial strains (Lactobacillus pentosus SC65 and Pediococcus pentosaceus ON81A) were selected for fermenting GR due to their high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. The total polyphenol contents (TPCs) in GR-SC65 and GR-ON81A were higher than that in unfermented GR (∗∗∗P < 0.001 vs. GR). Content of daidzein, glycitein, and genistein, the deglycosylated form of isoflavonoids, was higher in GR-SC65 than in unfermented GR. The ethanol extracts of GR-SC65 exerted a stronger anti-inflammatory activity than GR by inhibiting pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in LPS-induced RAW264.7 macrophages. GR-SC65 reduced 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced ear swelling and hyperplasia as well as vascular permeability. Fewer infiltrated CD4+ and CD8+ T cells were observed in the ear tissue of the GR-SC65-treated mice than those of the unfermented GR-treated mice. Furthermore, fewer infiltrated NK cells were observed in the GR-SC65 treated mice, than in the GR-treated mice. GR-SC65 significantly diminished the levels of CCL5 and COX-2 mRNAs and increased the level of IL-10 mRNA. CONCLUSIONS: These data suggest that GR-SC65 can be used as a health supplement or a prophylactic against delayed-type hypersensitive inflammatory disease.

Fibertronic Organic Light-Emitting Diodes toward Fully Addressable, Environmentally Robust, Wearable Displays.

Significant potential of electronic textiles for wearable applications has triggered active studies of luminescent fibers toward smart textile displays. In spite of notable breakthroughs in the lighting fiber technology, a class of information displays with a luminescent fiber network is still underdeveloped due to several formidable challenges such as limited electroluminescence fiber performance, acute vulnerability to chemical and mechanical factors, and lack of decent engineering schemes to form fibers with robust interconnectable pixels for two-dimensional matrix addressing. Here, we present a highly feasible strategy for organic light-emitting diode (OLED) fiber-based textile displays that can overcome these issues by implementing prominent solution options including compatible fabrication method of OLED pixel arrays on adapted fiber configurations and chemically/mechanically sturdy but electrically conductive passivation system. To create solid interconnectable OLED fibers without compromising the high electroluminescence performance, phosphorescence OLED materials are deposited onto process-friendly fibers of rectangular stripes, where periodically patterned OLED pixels are selectively passivated with robust polymer and circumventing metal pads by a stamp-assisted printing method. A woven textile of interlaced interconnectable OLED fibers with perpendicularly arranged conductive fibers serves as a matrix-addressable two-dimensional network that can be operated by the passive matrix scheme. Successful demonstrations of stably working woven OLED textile in the water, as well as under the applied tensile force, support feasibility of the present approach to reify fully addressable, environmentally durable, fiber-based textile displays.