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BACKGROUND: Preventative self-care can reduce dental disease that disproportionately burdens vulnerable populations. Personalized digital oral self-care behavioral interventions offer a promising solution. However, the success of these digital interventions depends on toothbrushing data collection e-platforms attuned to the needs and preferences of vulnerable communities. OBJECTIVE: The aim of this study is to assess the usability and feasibility of the Remote Oral Behaviors Assessment System (ROBAS), which has been adapted to address the unique requirements of socioeconomically disadvantaged minority individuals. METHODS: A cohort of 53 community-clinic participants, including 31 (58%) Latino and 22 (42%) Black individuals with no prior experience using electric toothbrushes, were recruited to use ROBAS, with planned assessments at baseline, 2 months, and 4 months. Beyond evaluating ROBAS's technical performance, extensive feedback was gathered to gauge users' experiences, viewpoints, and overall contentment. The System Usability Scale (SUS) served as a primary metric for assessing user satisfaction and acceptability. RESULTS: ROBAS exhibited largely reliable and consistent data-gathering capabilities. SUS scores (mean 75.6, SD 14.5) reflected participant contentment within a range of values for other commonly used digital devices and technologies. Among participants who answered questions about willingness to pay for ROBAS, 97% (30/31) indicated that they were willing to pay for ROBAS either as a one-time payment or as a subscription-based service. Additionally, 87.5% of participants expressed that they would endorse it to acquaintances. Most participants expressed no reservations about privacy; among those who expressed privacy concerns (n=20, 50%), the concerns included exposure of information (n=18, 45%), monitoring of brushing habits (n=12, 30%), and collection of information (n=14, 35%), although these concerns did not significantly correlate with specific participant traits. In qualitative terms, users valued ROBAS's ability to monitor brushing habits but called for refinements, especially in Wi-Fi and application connectivity. Recommendations for system improvements encompassed enhanced app functionality, individualized coaching, more comprehensive brushing data, and the addition of flossing activity tracking. CONCLUSIONS: The research highlights ROBAS's promise as a digital platform for unobtrusively tracking daily oral self-care activities in marginalized communities. The system proved to be both feasible, as evidenced by its stable and accurate data capture of brushing behaviors, and user-friendly, as reflected by strong SUS scores and positive user feedback. Influential factors for its uptake included ease of learning and operation, and the feedback provided.
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The voluntary introduction of defects can be considered an effective strategy for enhancing the electrochemical properties of metal oxide electrodes. In this study, the enhanced pseudocapacitive properties of an acceptor (Gd) doped cerium oxide nanoparticle-a sustainable metal oxide with low environmental and human toxicity-are investigated in depth using ex situ X-ray photoemission spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Interestingly, with 15 at% Gd doping (15GDC), the specific capacitance of the nanoparticles measured at 1 A g-1 enhanced to 547.8 F g-1, which is fivefold higher than undoped CeO2 (98.7 F g-1 at 1 A g-1). The rate-dependent capacitance is also improved for 15GDC, which showed a 31.0% decrease in the specific capacitance upon a tenfold increase in the current density, while CeO2 showed a 49.9% decrease. The enhanced electrochemical properties are studied in depth via ex situ XPS and EIS analysis, which revealed that the oxygen vacancies at the surface of the nanoparticles played important roles in enhancing both the specific capacitance and the high-rate performance of 15GDC by acting as the active site for pseudocapacitive redox reaction and allowing fast diffusion of oxygen ions at the surface of 15GDC nanoparticles.
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Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.
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Transportador 1 de Cassete de Ligação de ATP , Colesterol , Células Espumosas , Lipoproteínas LDL , Receptores X do Fígado , Receptores Toll-Like , Humanos , Células Espumosas/metabolismo , Células Espumosas/efeitos dos fármacos , Colesterol/metabolismo , Receptores X do Fígado/metabolismo , Receptores Toll-Like/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , PPAR gama/metabolismo , Células THP-1 , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Lipopolissacarídeos/farmacologia , Receptores Depuradores Classe B/metabolismo , Receptores Depuradores Classe B/genéticaRESUMO
In order to manipulate the complex behavior of cells in a 3-dimensional (3D) environment, it is important to provide the microenvironment that can accurately portray the complexity of highly anisotropic tissue structures. However, it is technically challenging to generate a complex microenvironment using conventional biomaterials that are mostly isotropic with limited bioactivity. In this study, the gelatin-hyaluronic acid hydrogel incorporated with aqueous-dispersible, short nanofibers capable of in situ alignment is developed to emulate the native heterogeneous extracellular matrix consisting of fibrous and non-fibrous components. The gelatin nanofibers containing magnetic nanoparticles, which could be aligned by external magnetic field, are dispersed and embedded in gelatin-hyaluronic acid hydrogel encapsulated with dermal fibroblasts. The aligned nanofibers via magnetic field could be safely integrated into the hydrogel, and the process could be repeated to generate larger 3D hydrogels with variable nanofiber alignments. The aligned nanofibers in the hydrogel can more effectively guide the anisotropic morphology (e.g., elongation) of dermal fibroblasts than random nanofibers, whereas myofibroblastic differentiation is more prominent in random nanofibers. At a given nanofiber configuration, the hydrogel composition having intermediate hyaluronic acid content induces myofibroblastic differentiation. These results indicate that modulating the degree of nanofiber alignment and the hyaluronic acid content of the hydrogel are crucial factors that critically influence the fibroblast phenotypes. The nanofiber-composite hydrogel capable of directional nanofiber alignment and tunable material composition can effectively induce a wide array of phenotypic plasticity in 3D cell culture.
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A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).
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Anticorpos Antivirais , Galinhas , Patos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Vírus da Doença de Newcastle , Vacinas de Produtos Inativados , Vacinas Sintéticas , Eliminação de Partículas Virais , Animais , Galinhas/imunologia , Influenza Aviária/prevenção & controle , Influenza Aviária/imunologia , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/genética , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Patos/virologia , Patos/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Organismos Livres de Patógenos Específicos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Doença de Newcastle/prevenção & controle , Doença de Newcastle/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
OBJECTIVES: To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS. METHODS: Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated. RESULTS: MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12 % in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45 % and 56 %, respectively. CONCLUSIONS: NCP containing 0.15 % MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties. CLINICAL SIGNIFICANCE: NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration.
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Aderência Bacteriana , Biofilmes , Cerâmica , Desenho Assistido por Computador , Resistência à Flexão , Teste de Materiais , Metacrilatos , Fosforilcolina , Propriedades de Superfície , Cerâmica/química , Metacrilatos/química , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacologia , Materiais Dentários/química , Polímeros/química , Humanos , Dureza , Solubilidade , Porphyromonas gingivalis/efeitos dos fármacosRESUMO
KRAS plays a crucial role in regulating cell survival and proliferation and is one of the most commonly mutated oncogenes in human cancers. The novel KRASG12D inhibitor, MRTX1133, demonstrates promising antitumor efficacy in vitro and in vivo. However, the development of acquired resistance in treated patients presents a considerable challenge to sustained therapeutic effectiveness. In response to this challenge, we conducted site-specific mutagenesis screening to identify potential secondary mutations that could induce resistance to MRTX1133. We screened a range of KRASG12D variants harboring potential secondary mutations, and 44 representative variants were selected for in-depth validation of the pooled screening outcomes. We identified eight variants (G12D with V9E, V9W, V9Q, G13P, T58Y, R68G, Y96W, and Q99L) that exhibited substantial resistance, with V9W showing notable resistance, and downstream signaling analyses and structural modeling were conducted. We observed that secondary mutations in KRASG12D can lead to acquired resistance to MRTX1133 and BI-2865, a novel pan-KRAS inhibitor, in human cancer cell lines. This evidence is critical for devising new strategies to counteract resistance mechanisms and, ultimately, enhance treatment outcomes in patients with KRASG12D-mutant cancers.
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Resistencia a Medicamentos Antineoplásicos , Mutagênese Sítio-Dirigida , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacosRESUMO
Abdominal obesity (AO) and dynapenia (DP) are associated with cognitive decline, and the relationship between dynapenic abdominal obesity (DAO), a combination of DP and AO, and mild cognitive impairment (MCI) has been confirmed. This study aims to determine whether this relationship exhibits potential sex differences. The relationship between MCI and DAO was confirmed in 1309 community elderly individuals aged 65 years or older who were not diagnosed with dementia. The MCI was defined as a Korean mini-mental state examination (K-MMSE) score of 18-23 points. Multiple logistic regression analyses were conducted, categorizing participants into groups: a control group without AO or DP, an AO group, a DP group, and a DAO group. The study results showed that in women, both DP and DAO were significantly associated with MCI not only in the unadjusted Model 1 but also in Model 2, which adjusted for general characteristics and health behaviors, and Model 3, which additionally adjusted for chronic diseases and disease-related characteristics. In men, DP was associated with MCI in the unadjusted Model 1. The findings highlight sex differences in the impact of the DAO on MCI. These differences should be considered when studying the factors related to MCI in old age.
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Clade 2.3.4.4b highly pathogenic avian influenza A (HPAI) viruses have been detected in wild birds worldwide, causing recurrent outbreaks since 2016. During the winter of 2021-2022, we detected one H5N8 and forty-three H5N1 clade 2.3.4.4b HPAI viruses from wild birds in South Korea. Phylogenetic analysis revealed that HA gene of H5N1 viruses was divided into two genetically distinct groups (N1.G1 and N1.G2). Bayesian phylodynamic analysis demonstrated that wild birds play a vital role in viral transmission and long-term maintenance. We identified five genotypes (N1.G1.1, N1.G2, N1.G2.1, N1.G2.2, and N1.G2.2.1) having distinct gene segment constellations most probably produced by reassortments with low-pathogenic avian influenza viruses. Our results suggest that clade 2.3.4.4b persists in wild birds for a long time, causing continuous outbreaks, compared with previous clades of H5 HPAI viruses. Our study emphasizes the need for enhancing control measures in response to the changing viral epidemiology.
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BACKGROUND/AIM: Phloretin is a natural flavonoid compound found in some plants, such as apples and pears, as well as in the bark of apple trees. Phloretin has been shown to have inhibitory effects on glucose transporters in cells and can potentially inhibit the growth of cancer cells. However, the mechanism by which phloretin regulates the expression of estrogen receptor alpha (ERα), a key transcription factor in breast cancer, is still unclear. This study investigated how phloretin affects the growth of ERα positive human breast cancer cells. MATERIALS AND METHODS: The growth of breast cancer cell lines, including MCF7 and T47D, was examined using cell proliferation and colony formation assays. Western blotting and semi-quantitative RT-PCR were used to examine protein and mRNA levels, respectively. Localization of cellular proteins was analyzed using subcellular fractionation. Transient transfection and reported gene assays were used to elucidate the impact of phloretin on cell proliferation and ERα transactivation. RESULTS: Phloretin decreased ERα expression at the mRNA and protein levels in MCF7 and T47D cells. It also inhibited the binding of ERα to the estrogen response element present in the promoter of target genes. Moreover, treatment with phloretin inhibited the expression of cyclin D1 and breast cancer marker gene pS2, which are known ERα target genes. Consequently, it inhibited the growth of ERα-positive human breast cancer cells. Furthermore, inhibition of breast cancer growth by phloretin was found to be mediated through both the ERα and ERK1/ERK2 pathways. CONCLUSION: Phloretin, a dihydrochalcone extracted from natural sources, exhibits the ability to regulate ERα function and suppress breast cancer cell proliferation.
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Neoplasias da Mama , Receptor alfa de Estrogênio , Humanos , Feminino , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação para Baixo , Floretina/farmacologia , Proliferação de Células , RNA Mensageiro/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Infectious bronchitis virus (IBV), an avian coronavirus, has caused considerable damage to the poultry industry. In Korea, indigenous KM91-like and newly introduced QX-like lineages belonging to the GI-19 lineage have been prevalent despite constant vaccination. In this study, complete genome sequences of 23 IBV isolates in Korea from 2010 to 2020 were obtained using next-generation sequencing, and their phylogenetic relationship and recombination events were analyzed. Phylogenetic analysis based on the S1 gene showed that all isolates belonged to the GI-19 lineage and were divided into five subgroups (KM91-like, K40/09-like, and QX-like II to IV). Among the 23 isolates, 14 recombinants were found, including frequent recombination between KM91-like and QX-like strains. In addition, it was observed that other lineages, such as GI-1, GI-13, and GI-16, were involved in recombination. Most recombination breakpoints were detected in the ORF1ab gene, particularly nsp3. However, when considering the size of each genome, recombination occurred more frequently in the 3a, E and 5a genes. Taken together, genetic recombination frequently occurred throughout the entire genome between various IBV strains in Korea, including live attenuated vaccine strain. Our study suggests the necessity of further research on the contribution of recombination of genomes outside the spike region to the biological characteristics of IBV.
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Gammacoronavirus , Vírus da Bronquite Infecciosa , Filogenia , República da Coreia/epidemiologia , Vírus da Bronquite Infecciosa/genética , Vacinas Atenuadas , Recombinação GenéticaRESUMO
Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.
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Implantes Absorvíveis , Magnetismo , Medicina de Precisão , Tecnologia sem Fio , Papel , Medicina de Precisão/instrumentação , Humanos , Masculino , Animais , Ratos , Encéfalo , Eletrônica Médica/instrumentaçãoRESUMO
Human affects such as emotions, moods, feelings are increasingly being considered as key parameter to enhance the interaction of human with diverse machines and systems. However, their intrinsically abstract and ambiguous nature make it challenging to accurately extract and exploit the emotional information. Here, we develop a multi-modal human emotion recognition system which can efficiently utilize comprehensive emotional information by combining verbal and non-verbal expression data. This system is composed of personalized skin-integrated facial interface (PSiFI) system that is self-powered, facile, stretchable, transparent, featuring a first bidirectional triboelectric strain and vibration sensor enabling us to sense and combine the verbal and non-verbal expression data for the first time. It is fully integrated with a data processing circuit for wireless data transfer allowing real-time emotion recognition to be performed. With the help of machine learning, various human emotion recognition tasks are done accurately in real time even while wearing mask and demonstrated digital concierge application in VR environment.