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Genetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element, using convolutional neural network. The enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits. Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.
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BACKGROUND: Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aß) in Alzheimer's disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aß-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aß-induced autophagy-associated genes are involved Aß clearance in astrocytes of animal model of AD. METHODS: Whole RNA sequencing (RNA-seq) was performed to detect gene expression patterns in Aß-treated human astrocytes in a time-dependent manner. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) and Sequestosome1 (SQSTM1) based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD (APP/PS1) mice was determined. Neuropathological alterations of AD mice with astrocytic autophagy dysfunction were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through novel object recognition test (NOR) and novel object place recognition test (NOPR). RESULTS: Here, we show that astrocytes, unlike neurons, undergo plastic changes in autophagic processes to remove Aß. Aß transiently induces expression of LC3B gene and turns on a prolonged transcription of SQSTM1 gene. The Aß-induced astrocytic autophagy accelerates urea cycle and putrescine degradation pathway. Pharmacological inhibition of autophagy exacerbates mitochondrial dysfunction and oxidative stress in astrocytes. Astrocyte-specific knockdown of LC3B and SQSTM1 significantly increases Aß plaque formation and GFAP-positive astrocytes in APP/PS1 mice, along with a significant reduction of neuronal marker and cognitive function. In contrast, astrocyte-specific overexpression of LC3B reduced Aß aggregates in the brain of APP/PS1 mice. An increase of LC3B and SQSTM1 protein is found in astrocytes of the hippocampus in AD patients. CONCLUSIONS: Taken together, our data indicates that Aß-induced astrocytic autophagic plasticity is an important cellular event to modulate Aß clearance and maintain cognitive function in AD mice.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Astrocitos , Autofagia , Ratones Transgénicos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Autofagia/fisiología , Astrocitos/metabolismo , Péptidos beta-Amiloides/metabolismo , Ratones , Humanos , Modelos Animales de Enfermedad , Cognición/fisiologíaRESUMEN
Branched-chain hydroxy acids (BCHAs), produced by lactic acid bacteria, have recently been suggested as bioactive compounds contributing to the systemic metabolism and modulation of the gut microbiome. However, the relationship between BCHAs and gut microbiome remains unclear. In this study, we investigated the effects of BCHAs on the growth of seven different families in the gut microbiota. Based on in vitro screening, both 2-hydroxyisovaleric acid (HIVA) and 2-hydroxyisocaproic acid (HICA) stimulated the growth of Lactobacillaceae and Bifidobacteriaceae, with HIVA showing a significant growth promotion. Additionally, we observed not only the growth promotion of probiotic Lactobacillaceae strains but also growth inhibition of pathogenic B. fragilis in a dosedependent manner. The production of HIVA and HICA varied depending on the family of the gut microbiota and was relatively high in case of Lactobacillaceae and Lachnosporaceae. Furthermore, HIVA and HICA production by each strain positively correlated with their growth variation. These results demonstrated gut microbiota-derived BCHAs as active metabolites that have bacterial growth modulatory effects. We suggest that BCHAs can be utilized as active metabolites, potentially contributing to the treatment of diseases associated with gut dysbiosis.
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Microbioma Gastrointestinal , Hidroxiácidos , Microbioma Gastrointestinal/efectos de los fármacos , Hidroxiácidos/metabolismo , Hidroxiácidos/farmacología , Probióticos , Caproatos/metabolismo , Caproatos/farmacología , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Bacterias/crecimiento & desarrollo , Bacterias/genética , Bacterias/clasificación , Lactobacillaceae/metabolismo , Humanos , Ácidos Pentanoicos/metabolismoRESUMEN
During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as 'maskne' (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either 'pathogen helper (PH)' or 'pathogen inhibitor (PIn)' strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.
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COVID-19 , Máscaras , Microbiota , Piel , Animales , Ratones , Humanos , COVID-19/microbiología , COVID-19/virología , Piel/microbiología , Acné Vulgar/microbiología , SARS-CoV-2 , Femenino , Metagenómica/métodos , Modelos Animales de Enfermedad , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Interacciones Microbianas , Dermatitis por Contacto/etiologíaRESUMEN
The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis. The likelihood of BM was evaluated using multivariate analysis and a predictive nomogram. Additionally, we prospectively monitored 177 samples from 46 LC patients initially without BM. Patients with BMs (n= 135) had significantly higher median sNfL (52.5 pg/mL) and sGFAP (239.2 pg/mL) levels compared to those without BMs (n = 565), with medians of 17.8 pg/mL and 141.1 pg/mL, respectively (p < 0.001 for both). The nomogram, incorporating age, sNfL, and sGFAP, predicted BM with an area under the curve (AUC) of 0.877 (95% CI 0.84-0.914), showing 74.8% sensitivity and 83.5% specificity. Over nine months, 93% of samples from patients without BM remained below the cutoff, while all patients developing BMs showed increased levels at detection. A nomogram incorporating age, sNfL, and sGFAP provides a valuable tool for identifying LC patients at high risk for BM, thereby enabling targeted MRI screenings and enhancing diagnostic efficiency.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Proteína Ácida Fibrilar de la Glía , Neoplasias Pulmonares , Proteínas de Neurofilamentos , Humanos , Proteínas de Neurofilamentos/sangre , Femenino , Masculino , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Proteína Ácida Fibrilar de la Glía/sangre , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/sangre , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico , Estudios Retrospectivos , Nomogramas , Adulto , Imagen por Resonancia Magnética/métodos , Anciano de 80 o más AñosRESUMEN
The emergence of multidrug-resistant pathogens has outpaced the development of new antibiotics, leading to renewed interest in endolysins. Endolysins have been investigated as novel biocontrol agents for Gram-positive bacteria. However, their efficacy against Gram-negative species is limited by the barrier presented by their outer membrane, which prevents endolysin access to the peptidoglycan substrate. Here, we used the translocation domain of botulinum neurotoxin to deliver endolysin across the outer membrane of Gram-negative bacteria. The translocation domain selectively interacts with and penetrates membranes composed of anionic lipids, which have been used in nature to deliver various proteins into animal cells. In addition to the botulinum neurotoxin translocation domain, we have fused bacteriophage-derived receptor binding protein to endolysins. This allows the attached protein to efficiently bind to a broad spectrum of Gram-negative bacteria. By attaching these target-binding and translocation machineries to endolysins, we aimed to develop an engineered endolysin with broad-spectrum targeting and enhanced antibacterial activity against Gram-negative species. To validate our strategy, we designed engineered endolysins using two well-known endolysins, T5 and LysPA26, and tested them against 23 strains from six species of Gram-negative bacteria, confirming that our machinery can act broadly. In particular, we observed a 2.32 log reduction in 30 min with only 0.5 µM against an Acinetobacter baumannii isolate. We also used the SpyTag/SpyCatcher system to easily attach target-binding proteins, thereby improving its target-binding ability. Overall, our newly developed endolysin engineering strategy may be a promising approach to control multidrug-resistant Gram-negative bacterial strains.
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Antibacterianos , Membrana Externa Bacteriana , Endopeptidasas , Bacterias Gramnegativas , Endopeptidasas/farmacología , Endopeptidasas/metabolismo , Endopeptidasas/química , Bacterias Gramnegativas/efectos de los fármacos , Antibacterianos/farmacología , Membrana Externa Bacteriana/efectos de los fármacos , Membrana Externa Bacteriana/metabolismo , Pruebas de Sensibilidad Microbiana , Transporte de Proteínas , Toxinas Botulínicas Tipo A/química , Toxinas Botulínicas Tipo A/metabolismo , Acinetobacter baumannii/efectos de los fármacosRESUMEN
We developed a novel quadratic resampling method for summing up γ-ray spectra with different calibration parameters. We investigated a long-term environmental background γ-ray spectrum by summing up 114 spectra measured using a 30% HPGe detector between 2017 and 2021. Gain variations in different measurement periods shift γ-ray peak positions by a fractional pulse-height bin size up to around 2 keV. The resampling method was applied to measure low-level background γ-ray peaks in the γ-ray spectrum in a wide energy range from 50 keV to 3 MeV. We additionally document temporal variations in the activities of major γ-ray peaks, such as 40K (1461 keV), 208Tl (2615 keV), and other typical nuclides, along with contributions from cosmic rays. The normal distribution of γ-ray background count rates, as evidenced by quantile-quantile plots, indicates consistent data collection throughout the measurement period. Consequently, we assert that the quadratic resampling method for accumulating γ-ray spectra surpasses the linear method (Bossew, 2005) in various aspects.
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BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.
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Developing web-based education sexual and reproductive health (SRH) programs for immigrant women is crucial. This scoping review aims to provide basic data for developing more advanced programs by examining web-based educational program literature. This review considers web-based SRH education programs for adult immigrant women and focuses on their characteristics, instructional strategies, and outcome evaluations. Data will be extracted following the Minimum Initial Service Package (MISP) and Kirkpatrick level and summarized to show future-oriented results while documenting web-based approach evidence for educating immigrant women on SRH. It is expected to provide information for web-based education programs to meet the MISP and develop various evaluation methods. As such, the findings can be used to determine the direction and level of SRH education.
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Emigrantes e Inmigrantes , Internet , Salud Reproductiva , Salud Sexual , Humanos , Femenino , Salud Sexual/educación , Educación Sexual/métodos , Educación en Salud/métodosRESUMEN
We aimed to develop a substantive theory according to the associations between adaptation experience-related factors identified in male nurses after turnover to community institutions. From April through August 2019, data were collected through direct observations and in-depth interviews of 22 male nurse participants who were recruited purposively and analyzed simultaneously with the method proposed by Strauss and Corbin. Furthermore, 29 subcategories were derived from 11 categories, including: (1) leaving the clinical sector and changing jobs, (2) shaking while settling, (3) characteristics of the new job, (4) personal disposition, (5) support system, (6) finding my place, (7) solidifying my place, (8) demonstrating my professional competence, (9) stable settlement in my place, (10) preparing for a better future, and (11) still confused. The core category was identified as "putting down roots in another place for myself." The verification of this theory in this study's results indicates a need for research into the evaluation and development of professional development programs and related policies to provide support to male nurses who are pursuing opportunities in community institutions to maintain their nursing identity and further their efforts for developing a nursing specialty.
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Adaptación Psicológica , Teoría Fundamentada , Enfermeros , Reorganización del Personal , Humanos , Masculino , Adulto , República de Corea , Enfermeros/psicología , Persona de Mediana EdadRESUMEN
BACKGROUND: Lumbar spinal stenosis (LSS) and spondylolisthesis (SPL) are characterized as degenerative spinal pathologies and share considerable similarities. However, opinions vary on whether to recommend exercise or restrict it for these diseases. Few studies have objectively compared the effects of daily physical activity on LSS and SPL because it is impossible to restrict activities ethnically and practically. We investigated the effect of restricting physical activity due to social distancing (SoD) on LSS and SPL, focusing on the aspect of healthcare burden changes during the pandemic period. METHODS: We included first-visit patients diagnosed exclusively with LSS and SPL in 2017 and followed them up for two years before and after the implementation of the SoD policy. As controls, patients who first visited in 2015 and were followed for four years without SoD were analyzed. The common data model was employed to analyze each patient's diagnostic codes and treatments. Hospital visits and medical costs were analyzed by regression discontinuity in time to control for temporal effects on dependent variables. RESULTS: Among 33,484 patients, 2,615 with LSS and 446 with SPL were included. A significant decrease in hospital visits was observed in the LSS (difference, -3.94 times/month·100 patients; p = 0.023) and SPL (difference, -3.44 times/month·100 patients; p = 0.026) groups after SoD. This decrease was not observed in the data from the control group. Concerning medical costs, the LSS group showed a statistically significant reduction in median copayment (difference, -$45/month·patient; p < 0.001) after SoD, whereas a significant change was not observed in the SPL group (difference, -$19/month·patient; p = 0.160). CONCLUSION: Restricted physical activity during the SoD period decreased the healthcare burden for patients with LSS or, conversely, it did not significantly affect patients with SPL. Under circumstances of physical inactivity, patients with LSS may underrate their symptoms, while maintaining an appropriate activity level may be beneficial for patients with SPL.
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COVID-19 , Ejercicio Físico , Vértebras Lumbares , Estenosis Espinal , Espondilolistesis , Humanos , COVID-19/epidemiología , Espondilolistesis/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Costos de la Atención en Salud/estadística & datos numéricos , SARS-CoV-2 , Distanciamiento Físico , Hospitalización/estadística & datos numéricos , Hospitalización/economía , PandemiasRESUMEN
Angiogenesis is an indispensable mechanism in cancer progression, as cancer cells need to establish blood vessels to supply oxygen and nutrients. Extracellular vesicles (EVs) derived from cancer cells act as messengers in the tumor microenvironment and induce resistance to anti-angiogenic cancer treatment. EVs can be classified into two categories: exosomes and microvesicles (MVs). Although exosomes are involved in angiogenesis, the role of MVs in angiogenesis and cancer progression remains unclear. CD133 plays a key role in MV formation and oncoprotein trafficking. In this study, we investigated the role of CD133-containing MVs derived from colorectal cancer (CRC) in angiogenesis and cancer progression. CRC-derived MVs were incorporated into endothelial cells and increased the mesh area and tube length of endothelial cells. CD133-containing MVs also stimulate vessel sprouting in endothelial cell spheroids and mouse thoracic aortas. However, MVs derived from CD133-knockdown CRC cells exerted a limited effect on tube formation and vessel sprouting. CD133-containing MVs induced angiogenesis through p38 activation and angiogenesis induced by CD133-containing MVs was insensitive to the anti-vascular endothelial growth factor antibody bevacizumab. Survival analysis revealed that high expression level of CD133 correlated with poor prognosis in patients with metastatic CRC. These findings suggest that CD133-containing MVs act as key regulators of angiogenesis and are related to the prognosis of CRC patients.
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Adhesion has attracted great interest in science and engineering especially in the field pertaining to nano-science because every form of physical contact is fundamentally a macroscopic observation of interactions between nano-asperities under the adhesion phenomenon. Despite its importance, no practical adhesion prediction model has been developed due to the complexity of examining contact between nano-asperities. Here, we scrutinized the contact phenomenon and developed a contact model, reflecting the physical sequence in which adhesion develops. For the first time ever, our model analyzes the adhesion force and contact properties, such as separation distance, contact location, actual contact area, and the physical deformation of the asperities, between rough surfaces. Through experiments using atomic force microscopy, we demonstrated a low absolute percentage error of 2.8% and 6.55% between the experimental and derived data for Si-Si and Mo-Mo contacts, respectively, and proved the accuracy and practicality of our model in the analysis of the adhesion phenomenon.
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The pathophysiology of functional bowel disorders is complex, involving disruptions in gut motility, visceral hypersensitivity, gut-brain-microbiota interactions, and psychosocial factors. Light pollution, as an environmental stressor, has been associated with disruptions in circadian rhythms and the aggravation of stress-related conditions. In this study, we investigated the effects of environmental stress, particularly continuous light exposure, on intestinal motility and inflammation using zebrafish larvae as a model system. We also evaluated the efficacy of probiotics, specifically Bifidobacterium longum (B. longum), at alleviating stress-induced constipation. Our results showed that continuous light exposure in zebrafish larvae increased the cortisol levels and reduced the intestinal motility, establishing a stress-induced-constipation model. We observed increased inflammatory markers and decreased intestinal neural activity in response to stress. Furthermore, the expressions of aquaporins and vasoactive intestinal peptide, crucial for regulating water transport and intestinal motility, were altered in the light-induced constipation model. Administration of probiotics, specifically B. longum, ameliorated the stress-induced constipation by reducing the cortisol levels, modulating the intestinal inflammation, and restoring the intestinal motility and neural activity. These findings highlight the potential of probiotics to modulate the gut-brain axis and alleviate stress-induced constipation. Therefore, this study provides a valuable understanding of the complex interplay among environmental stressors, gut function, and potential therapeutic strategies.
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Bifidobacterium longum , Probióticos , Animales , Pez Cebra , Hidrocortisona , Estreñimiento/etiología , Estreñimiento/terapia , Probióticos/farmacología , Probióticos/uso terapéutico , Inflamación , LarvaRESUMEN
Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.
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Neuromielitis Óptica , Humanos , Acuaporina 4 , Complemento C1q , Complemento C3b , Proteínas del Sistema Complemento , Inmunoglobulina G , Glicoproteína Mielina-OligodendrócitoRESUMEN
Decentralized Identifiers have recently expanded into Internet of Things devices and are crucial in securing users' digital identities and data. However, Decentralized Identifiers face challenges in scenarios necessitating authority delegation and anonymity, such as when dealing with legal guardianship for minors, device loss or damage, and specific medical contexts involving patient information. This paper aims to strengthen data sovereignty within the Decentralized Identifier system by implementing a secure authority delegation and anonymity scheme. It suggests optimizing verifiable presentations by utilizing a sequential aggregate signature, a Non-Interactive Zero-Knowledge Proof, and a Merkle tree to prevent against linkage and Sybil attacks while facilitating delegation. This strategy mitigates security risks related to delegation and anonymity, efficiently reduces the computational and verification efforts for signatures, and reduces the size of verifiable presentations by about 1.2 to 2 times.
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Negative-differential-resistance (NDR) devices offer a promising pathway for developing future computing technologies characterized by exceptionally low energy consumption, especially multivalued logic computing. Nevertheless, conventional approaches aimed at attaining the NDR phenomenon involve intricate junction configurations and/or external doping processes in the channel region, impeding the progress of NDR devices to the circuit and system levels. Here, an NDR device is presented that incorporates a channel without junctions. The NDR phenomenon is achieved by introducing a metal-insulator-semiconductor capacitor to a portion of the channel area. This approach establishes partial potential barrier and well that effectively restrict the movement of hole and electron carriers within specific voltage ranges. Consequently, this facilitates the implementation of both a ternary inverter and a ternary static-random-access-memory, which are essential components in the development of multivalued logic computing technology.
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Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.
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Limosilactobacillus fermentum , Psidium , Antioxidantes/metabolismo , Psidium/química , Fenoles/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Evidence-based practice (EBP) is crucial for delivering high-quality healthcare and effective self-care. Enhancing clinical nurses' research competencies through structured mentorship is key to the widespread application of EBP. This study evaluated a newly developed Research Competency Enhancement Program (RCEP), aimed at bolstering EBP among experienced nurses. METHODS: Conducted in a tertiary university hospital in Korea, this single-group study employed a pretest-post-test design and a mixed-methods approach. The RCEP involved 11 experienced clinical nurses in an 8-week intervention, featuring mentor-led workshops, interactive sessions, and resource-driven activities. Data were collected using the Evidence-Based Practice Beliefs Scale (EBPB), the Evidence-Based Practice Attitude Scale (EBPA), and the Research Practice Ability (RPA) tool, alongside qualitative feedback. These measures assessed the program's feasibility, acceptability, and preliminary effectiveness. RESULTS: The quantitative analysis indicated significant improvements in research competency post-intervention. Mean scores on the EBPB and RPA scales increased (Z = -2.53, p = .011; Z = -2.66, p = .008). Participants described the RCEP as inspirational and challenging, creating an environment conducive to research. Facilitators included mentor support and innovative learning tools, while barriers were internet connectivity and scheduling conflicts. Suggestions for improvement included more hands-on sessions, small team collaborations, and integration with academic institutions. CONCLUSION: The RCEP, facilitated by EBP mentors, significantly improved the research competencies and attitudes of clinical nurses towards EBP. The study underscores the importance of continual RCEP refinement, integrating structured, interactive, and collaborative elements to further empower nurses in evidence-based practice. The program shows promise in enhancing research competencies and fostering a commitment to EBP in clinical settings.
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Although functional changes of the frontal and (para)limbic area for emotional hyper-reactivity and emotional dysregulation are well documented in social anxiety disorder (SAD), prior studies on structural changes have shown mixed results. This study aimed to identify differences in cortical thickness between SAD and healthy controls (CON). Thirty-five patients with SAD and forty-two matched CON underwent structural magnetic resonance imaging. A vertex-based whole brain and regional analyses were conducted for between-group comparison. The whole-brain analysis revealed increased cortical thickness in the left insula, left superior parietal lobule, left superior temporal gyrus, and left frontopolar cortex in patients with SAD compared to CON, as well as decreased thickness in the left superior/middle frontal gyrus and left fusiform gyrus in patients (after multiple-correction). The results from the ROI analysis did not align with these findings at the statistically significant level after multiple corrections. Changes in cortical thickness were not correlated with social anxiety symptoms. While consistent results were not obtained from different analysis methods, the results from the whole-brain analysis suggest that patients with SAD exhibit distinct neural deficits in areas involved in salience, attention, and socioemotional processing.