RESUMO

Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and ß isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.

RESUMO

Traumatic brain injury (TBI) results from sudden accidents, leading to brain damage, subsequent organ dysfunction, and potentially death. Despite extensive studies on rodent TBI models, there is still high variability in terms of target points, and this results in significantly different symptoms between models. In this study, we established a more concise and effective TBI mouse model, which included locomotor dysfunctions with increased apoptosis, based on the controlled cortical impact method. Behavioral tests, such as elevated body swing, rotarod, and cylinder tests were performed to assess the validity of our model. To investigate the underlying mechanisms of injury, we analyzed the expression of proteins associated with immune response and the apoptosis signaling pathway via western blotting analysis and immunohistochemistry. Upon TBI induction, the mouse subjects showed motor dysfunctions and asymmetric behavioral assessment. The expression of Bax gradually increased over time and reached its maximum 3 days post-surgery, and then declined. The expression of Mcl-1 showed a similar trend to Bax. Furthermore, the expression of caspase-3, ROCK1, and p53 were highly elevated by 3 days post-surgery and then declined by 7 days post-surgery. Importantly, immunohistochemistry revealed an immediate increase in the level of Bcl-2 at the lesion site upon TBI induction. Also, we found that the expression of neuronal markers, such as NeuN and MAP2, decreased after the surgery. Interestingly, the increase in NFH level was in line with the symptoms of TBI in humans. Collectively, our study demonstrated that the established TBI model induces motor dysfunction, hemorrhaging, infarctions, and apoptosis, closely resembling TBI in humans. Therefore, we predict that our model may be useful for developing effective treatment option for TBI.

Assuntos

Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Animais , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/fisiopatologia , Camundongos , Masculino , Apoptose , Fatores de Tempo , Camundongos Endogâmicos C57BL , Atividade Motora

RESUMO

Peptide-based therapeutics have traditionally faced challenges, including instability in the bloodstream and limited cell membrane permeability. However, recent advancements in α-helix stapled peptide modification techniques have rekindled interest in their efficacy. Notably, these developments ensure a highly effective method for improving peptide stability and enhancing cell membrane penetration. Particularly in the realm of antimicrobial peptides (AMPs), the application of stapled peptide techniques has significantly increased peptide stability and has been successfully applied to many peptides. Furthermore, constraining the secondary structure of peptides has also been proven to enhance their biological activity. In this review, the entire process through which hydrocarbon-stapled antimicrobial peptides attain improved drug-like properties is examined. First, the essential secondary structural elements required for their activity as drugs are validated, specific residues are identified using alanine scanning, and stapling techniques are strategically incorporated at precise locations. Additionally, the mechanisms by which these structure-based stapled peptides function as AMPs are explored, providing a comprehensive and engaging discussion.

RESUMO

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

Assuntos

Proteínas de Bactérias , Proteínas Repressoras , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Ferro/metabolismo , Ferro/química , Sítios de Ligação , Metais/metabolismo , Metais/química , Ligação Proteica

RESUMO

BACKGROUND: Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. METHODS: To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. RESULTS: Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2's inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. CONCLUSIONS: We propose TPST2's novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.

Assuntos

Receptor de Morte Celular Programada 1 , Sulfotransferases , Animais , Humanos , Camundongos , Sulfotransferases/genética , Sulfotransferases/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Linhagem Celular Tumoral , Interferon gama/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Sistemas CRISPR-Cas , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/metabolismo , Modelos Animais de Doenças

RESUMO

Lipids, as multifunctional molecules, play a crucial role in a variety of cellular processes. These include regulating membrane glycoprotein functions, controlling membrane trafficking, influencing apoptotic pathways, and affecting drug transport. In addition, lipid metabolites can alter the surrounding microenvironment in ways that might encourage tumor progression. The reprogramming of lipid metabolism is pivotal in promoting tumorigenesis and cancer progression, with tumors often displaying significant changes in lipid profiles. This review concentrates on the essential factors that drive lipid metabolic reprogramming, which contributes to the advancement and drug resistance in melanoma. Moreover, we discuss recent advances and current therapeutic strategies that employ small-molecule inhibitors to target lipid metabolism in skin cancers, particularly those associated with inflammation and melanoma.

RESUMO

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer.

Assuntos

Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2 , Inflamação , Humanos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Animais , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Neoplasias Intestinais/prevenção & controle , Neoplasias Intestinais/metabolismo , Quimioprevenção/métodos , Quimioprevenção/tendências

RESUMO

Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.

Assuntos

Antibacterianos , Peptídeos Catiônicos Antimicrobianos , Hemólise , Lisina , Testes de Sensibilidade Microbiana , Lisina/química , Lisina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Hemólise/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Relação Estrutura-Atividade , Proteólise/efeitos dos fármacos , Humanos , Estrutura Molecular

RESUMO

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

RESUMO

Front-of-package (FOP) is one of the most direct communication channels connecting manufacturers and consumers, as it displays crucial information such as certification, nutrition, and health. Traditional methods for obtaining information from FOPs often involved manual collection and analysis. To overcome these labor-intensive characteristics, new methods using two artificial intelligence (AI) approaches were applied for information monitoring of FOPs. In order to provide practical implementations, a case study was conducted on infant food products. First, FOP images were collected from Amazon.com. Then, from the FOP images, 1) the certification usage status of the infant food group was obtained by recognizing the certification marks using object detection. Moreover, 2) the nutrition and health-related texts written on the images were automatically extracted based on optical character recognition (OCR), and the associations between health-related texts were identified by network analysis. The model attained a 94.9% accuracy in identifying certification marks, unveiling prevalent certifications like Kosher. Frequency and network analysis revealed common nutrients and health associations, providing valuable insights into consumer perception. These methods enable fast and efficient monitoring capabilities, which can significantly benefit various food industries. Moreover, the AI-based approaches used in the study are believed to offer insights for related industries regarding the swift transformations in product information status.

Assuntos

Inteligência Artificial , Alimentos Infantis , Humanos , Lactente , Rotulagem de Alimentos , Embalagem de Alimentos

RESUMO

The purpose of this study was to analyze the mediating role of digital health literacy and the moderating effect of parasocial relationships on the relationship between the viewing experience of health exercise-related YouTube content and the intention for health exercise behavior. Based on the health action process approach, this study established a foundational theoretical model to analyze how digital health literacy mediates the impact of media viewing experience on health exercise behavior intention. Additionally, this study examined the moderating effect of parasocial relationships with YouTube creators. For empirical analysis, variables were measured using a self-administration method among 409 randomly sampled consumers of YouTube health exercise content. The collected data were analyzed using a structural equation model incorporating mediation parameters, and a multigroup model analysis was conducted to understand differences based on parasocial relationships. The results revealed that increased YouTube viewing experience enhanced cognitive, skill, and evaluative components of digital health literacy, which were significant factors in increasing health exercise behavior intention. Notably, the mediating effect of cognition played a crucial role, and the strengthening effect of parasocial relationships on this relationship was confirmed. These findings can be utilized as practical foundational data for designing digital health communication strategies, particularly in developing motivational mechanisms that encourage consumers to engage voluntarily and consistently in health behaviors based on online health information.

RESUMO

The potential of monolithic 3D integration technology is largely dependent on the enhancement of interconnect characteristics which can lead to thinner stacks, better heat dissipation, and reduced signal delays. Carbon materials such as graphene, characterized by sp2 hybridized carbons, are promising candidates for future interconnects due to their exceptional electrical, thermal conductivity and resistance to electromigration. However, a significant challenge lies in achieving low contact resistance between extremely thin semiconductor channels and graphitic materials. To address this issue, an innovative wafer-scale synthesis approach is proposed that enables low contact resistance between dry-transferred 2D semiconductors and the as-grown nanocrystalline graphitic interconnects. A hybrid graphitic interconnect with metal doping reduces the sheet resistance by 84% compared to an equivalent thickness metal film. Furthermore, the introduction of a buried graphitic contact results in a contact resistance that is 17 times lower than that of bulk metal contacts (>40 nm). Transistors with this optimal structure are used to successfully demonstrate a simple logic function. The thickness of active layer is maintained within sub-7 nm range, encompassing both channels and contacts. The ultrathin transistor and interconnect stack developed here, characterized by a readily etchable interlayer and low parasitic resistance, leads to heterogeneous integration of future 3D integrated circuits (ICs).

RESUMO

ß-lactam antibiotics are the most successful and commonly used antibacterial agents, but the emergence of resistance to these drugs has become a global health threat. The expression of ß-lactamase enzymes produced by pathogens, which hydrolyze the amide bond of the ß-lactam ring, is the major mechanism for bacterial resistance to ß-lactams. In particular, among class A, B, C and D ß-lactamases, metallo-ß-lactamases (MBLs, class B ß-lactamases) are considered crucial contributors to resistance in gram-negative bacteria. To combat ß-lactamase-mediated resistance, great efforts have been made to develop ß-lactamase inhibitors that restore the activity of ß-lactams. Some ß-lactamase inhibitors, such as diazabicyclooctanes (DBOs) and boronic acid derivatives, have also been approved by the FDA. Inhibitors used in the clinic can inactivate mostly serine-ß-lactamases (SBLs, class A, C, and D ß-lactamases) but have not been effective against MBLs until now. In order to develop new inhibitors particularly for MBLs, various attempts have been suggested. Based on structural and mechanical studies of MBL enzymes, several MBL inhibitor candidates, including taniborbactam in phase 3 and xeruborbactam in phase 1, have been introduced in recent years. However, designing potent inhibitors that are effective against all subclasses of MBLs is still extremely challenging. This review summarizes not only the types of ß-lactamase and mechanisms by which ß-lactam antibiotics are inactivated, but also the research finding on ß-lactamase inhibitors targeting these enzymes. These detailed information on ß-lactamases and their inhibitors could give valuable information for novel ß-lactamase inhibitors design.

Assuntos

Antibacterianos , Inibidores de beta-Lactamases , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/química , beta-Lactamas/metabolismo , beta-Lactamas/farmacologia , beta-Lactamases , Resistência Microbiana a Medicamentos

RESUMO

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as gefitinib and osimertinib have primarily been used as first-line treatments for patients with EGFR-activating mutations in non-small cell lung cancer (NSCLC). Novel biomarkers are required to distinguish patients with lung cancer who are resistant to EGFR-TKIs. The aim of the study is to investigate the expression and functional role of YES1, one of the Src-family kinases, in EGFR-TKI-resistant NSCLC. YES1 expression was elevated in gefitinib-resistant HCC827 (HCC827/GR) cells, harboring EGFR mutations. Moreover, HCC827/GR cells exhibited increased reactive oxygen species (ROS) levels compared to those of the parent cells, resulting in the phosphorylation/activation of YES1 due to oxidation of the cysteine residue. HCC827/GR cells showed elevated expression levels of YES1-associated protein 1 (YAP1), NF-E2-related factor 2 (Nrf2), cancer stemness-related markers, and antioxidant proteins compared to those of the parent cells. Knockdown of YES1 in HCC827/GR cells suppressed YAP1 phosphorylation, leading to the inhibition of Bcl-2, Bcl-xL, and Cyclin D1 expression. Silencing YES1 markedly attenuated the proliferation, migration, and tumorigenicity of HCC827/GR cells. Dasatinib inhibited the proliferation of HCC827/GR cells by targeting YES1-mediated signaling pathways. Furthermore, the combination of gefitinib and dasatinib demonstrated a synergistic effect in suppressing the proliferation of HCC827/GR cells. Notably, YES1- and Nrf2-regulated genes showed a positive regulatory relationship in patients with lung cancer and in TKI-resistant NSCLC cell lines. Taken together, these findings suggest that modulation of YES1 expression and activity may be an attractive therapeutic strategy for the treatment of drug-resistant NSCLC.

Assuntos

Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Proliferação de Células , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Proteínas Proto-Oncogênicas c-yes/genética

RESUMO

Src family kinases (SFKs) are non-receptor tyrosine kinases that are recognized as proto-oncogenic products. Among SFKs, YES1 is frequently amplified and overexpressed in a variety of human tumors, including lung, breast, ovarian, and skin cancers. YES1 plays a pivotal role in promoting cell proliferation, survival, and invasiveness during tumor development. Recent findings indicate that YES1 expression and activation are associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors in human malignancies. YES1 undergoes post-translational modifications, such as lipidation and nitrosylation, which can modulate its catalytic activity, subcellular localization, and binding affinity for substrate proteins. Therefore, we investigated the diverse mechanisms governing YES1 activation and its impact on critical intracellular signal transduction pathways. We emphasized the function of YES1 as a potential mechanism contributing to the anticancer drug resistance emergence.

Assuntos

Neoplasias , Quinases da Família src , Humanos , Proteínas Proto-Oncogênicas c-yes , Linhagem Celular Tumoral , Quinases da Família src/metabolismo , Transdução de Sinais , Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Neoplasias/genética

RESUMO

Mycobacterium tuberculosis, a major cause of mortality from a single infectious agent, possesses a remarkable mycobacterial cell envelope. Penicillin-Binding Proteins (PBPs) are a family of bacterial enzymes involved in the biosynthesis of peptidoglycan. PBP4 (DacB) from M. tuberculosis (MtbPBP4) has been known to function as a carboxypeptidase, and the role and significance of carboxypeptidases as targets for anti-tuberculosis drugs or antibiotics have been extensively investigated over the past decade. However, their precise involvement remains incompletely understood. In this study, we employed predictive modeling and analyzed the three-dimensional structure of MtbPBP4. Interestingly, MtbPBP4 displayed a distinct domain structure compared to its homologs. Docking studies with meropenem verified the presence of active site residues conserved in PBPs. These findings establish a structural foundation for comprehending the molecular function of MtbPBP4 and offer a platform for the exploration of novel antibiotics.

Assuntos

Mycobacterium tuberculosis , Proteínas de Ligação às Penicilinas/genética , Antituberculosos , Membrana Celular , Parede Celular

RESUMO

The reprogramming of lipid metabolism and its association with oncogenic signaling pathways within the tumor microenvironment (TME) have emerged as significant hallmarks of cancer. Lipid metabolism is defined as a complex set of molecular processes including lipid uptake, synthesis, transport, and degradation. The dysregulation of lipid metabolism is affected by enzymes and signaling molecules directly or indirectly involved in the lipid metabolic process. Regulation of lipid metabolizing enzymes has been shown to modulate cancer development and to avoid resistance to anticancer drugs in tumors and the TME. Because of this, understanding the metabolic reprogramming associated with oncogenic progression is important to develop strategies for cancer treatment. Recent advances provide insight into fundamental mechanisms and the connections between altered lipid metabolism and tumorigenesis. In this review, we explore alterations to lipid metabolism and the pivotal factors driving lipid metabolic reprogramming, which exacerbate cancer progression. We also shed light on the latest insights and current therapeutic approaches based on small molecular inhibitors and phytochemicals targeting lipid metabolism for cancer treatment. Further investigations are worthwhile to fully understand the underlying mechanisms and the correlation between altered lipid metabolism and carcinogenesis.

Assuntos

Antineoplásicos , Neoplasias , Humanos , Metabolismo dos Lipídeos , Microambiente Tumoral , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese , Lipídeos

RESUMO

OBJECTIVE: To describe the oral health of older people by region and family status using data from the National Health and Nutrition Survey. BACKGROUND: As the ageing of Korean society intensifies, health inequalities based on region and family status are also deepening. METHODS: Data from the 8th National Health and Nutrition Survey (2020-2021) conducted by the Korea Centers for Disease Control and Prevention were used, and a total of 3437 older people aged 65 or older were selected as study participants. Chewing discomfort and oral health behaviours were assessed by region and family status using multivariable logistic regression analysis with the complex sample survey design. RESULTS: We found an association between living alone and greater chewing discomfort. Residing in rural areas was also associated with a higher prevalence of this. In urban areas, chewing discomfort was 1.27 times higher among older people living alone than in those not living alone, while in rural areas, the discomfort was 1.52 times higher among the older people who lived alone. CONCLUSIONS: Region and family status were associated with greater chewing discomfort in older people. In Korean society, where the number of single-person older people households is increasing, along with the ageing population, attention to resolving the disparities in oral health in older people is needed.

RESUMO

Time-series forecasting (TSF) is a traditional problem in the field of artificial intelligence, and models such as recurrent neural network, long short-term memory, and gate recurrent units have contributed to improving its predictive accuracy. Furthermore, model structures have been proposed to combine time-series decomposition methods such as seasonal-trend decomposition using LOESS. However, this approach is learned in an independent model for each component, and therefore, it cannot learn the relationships between the time-series components. In this study, we propose a new neural architecture called a correlation recurrent unit (CRU) that can perform time-series decomposition within a neural cell and learn correlations (autocorrelation and correlation) between each decomposition component. The proposed neural architecture was evaluated through comparative experiments with previous studies using four univariate and four multivariate time-series datasets. The results showed that long- and short-term predictive performance was improved by more than 10%. The experimental results indicate that the proposed CRU is an excellent method for TSF problems compared to other neural architectures.

RESUMO

Calcium hydroxide is a widely used endodontic medicament with antibacterial activity. When excessive pressure is applied during injection of calcium hydroxide paste or apical perforation occurs, calcium hydroxide can leak into the maxillary sinus and is adsorbed onto the sinus membrane. Although a leakage of calcium hydroxide may not usually cause clinical symptoms, when a large amount of leakage occurs, it can cause degeneration of adjacent tissue and functional disorder, requiring immediate surgical removal. However, due to adsorption to the sinus membrane, calcium hydroxide leaked into the maxillary sinus is difficult to remove completely. Here, we describe the case of a 47-year-old patient in whom a large amount of calcium hydroxide leaked into the maxillary sinus and was successfully removed using modified endoscopic-assisted sinus surgery, and favorable bone regeneration and sinus membrane regeneration were achieved. In addition, histological and ultrastructural changes of the membrane resulted from the calcium hydroxide were presented.