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Although biocides are important materials in modern society and help protect human health and the environment, increasing exposure to combined biocides can cause severe side effects in the human body, such as lung fibrosis. In this study, we developed a receptonics system to screen for biocides in combined household chemical products based on biocides. The system contains transient receptor potential ankyrin 1 (TRPA1) nanovesicles (NVs) to sense biocides based on pain receptors and a side-gated field-effect transistor (SGFET) using a single-layer graphene (SLG) micropattern channel. The binding affinities between the TRPA1 receptor and the various biocides were estimated by performing biosimulation and using a calcium ion (Ca2+) assay, and the sensitivity of the system was compared with that of TRPA1 NV receptonics systems. Based on the results of the TRPA1 NV receptonics system, the antagonistic and potentiation effects of combined biocides and household chemical products depended on the concentration. Finally, the TRPA1 NV receptonics system was applied to screen for biocides in real products, and its performance was successful. Based on these results, the TRPA1 NV receptonics system can be utilized to perform risk evaluations and identify biocides in a simple and rapid manner.
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Desinfetantes , Canal de Cátion TRPA1 , Canal de Cátion TRPA1/metabolismo , Desinfetantes/toxicidade , Desinfetantes/química , Humanos , Grafite/toxicidade , Grafite/química , Células HEK293 , Cálcio/metabolismo , Transistores EletrônicosRESUMO
Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.
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Receptores ErbB , Proteínas Proto-Oncogênicas c-bcl-2 , Pontos Quânticos , RNA Interferente Pequeno , Pontos Quânticos/química , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , RNA Interferente Pequeno/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Lipídeos/química , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , MicelasRESUMO
[This corrects the article on p. 239 in vol. 18, PMID: 38584808.].
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BACKGROUND/OBJECTIVES: Over the past 10 yrs, the prevalence of diabetes in Korea has continued to incline, and the importance of lifestyle modification to manage diabetes has been highlighted. For patients with diabetes, carbohydrate intake reduction is effective in improving glycemic control; thus, we aimed to analyze the effect of carbohydrate intake ratio and suggest an appropriate carbohydrate intake ratio. SUBJECTS/METHODS: Using the 8th Korea National Health and Nutrition Examination Survey (2019-2021), we analyzed the data including participants aged 30 yrs or older with diabetes, and they were stratified into good and poor glycemic control groups. To analyze the correlation between the dietary behavior characteristics of participants with diabetes and the carbohydrate intake ratio, sociodemographic characteristics, dietary behavior, and health behavior were adjusted, and multivariate logistic regression analysis was conducted to present the adjusted odds ratio and 95% confidence interval (CI). RESULTS: In the unadjusted crude model, when carbohydrate intake ratio in total energy intake increased by 1%, the likelihood of poor glycemic control increased by 1.007-fold (95% CI, 0.998-1.016; P = 0.121). In model 1, which uses age and sex as adjustment variables, an increase of up to 1.011-fold was possible (95% CI, 1.001-1.021; P = 0.008). In model 2, which added variables such as diabetes duration, frequency of fruit consumption, frequency of lunch and, frequency of dinner, the risk of poor glycemic control increased by 1.010-fold as the carbohydrate intake ratio increased (95% CI, 0.998-1.022; P < 0.001). CONCLUSION: This study confirmed that as the ratio of carbohydrate intake to total energy intake increases the likelihood of poor glycemic control also increases in patients with diabetes. Therefore, to improve glycemic control in patients with diabetes, controlling the carbohydrate intake may be helpful.
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mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.
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Lipossomos , Nanopartículas , Vacinas , Animais , Camundongos , RNA Mensageiro/química , Vacinas de mRNA , Transfecção , Células Apresentadoras de Antígenos , Nanopartículas/químicaRESUMO
BACKGROUND: Smoking can reduce taste sensitivity, the ability to sense various tastes, and diet quality and can increase the incidence of diseases such as hypertension. This study aimed to analyze the association between the smoking amount, subjective salt preference, and salt-related eating behaviors. METHODS: Data of more than 16 million individuals from the Korean Community Health Survey were used. Forest plots were drawn to compare the cumulative odds ratios of salt taste preference and salt-related eating behaviors, adjusted for sex, age, body mass index, education level, household income, marital status, and drinking status at various smoking levels. RESULTS: Subjective salt preference and salt-related eating behaviors increased with smoking amount; the adjusted odds ratios (AORs) for smoking >20 cigarettes were higher than those for smoking <20 cigarettes. For daily smokers, the AOR was 1.27 (95% confidence interval [CI], 1.22-1.31) for 1-5 cigarettes per day and 1.68 (95% CI, 1.65-1.71) for 16-20 cigarettes per day (P<0.001). Smokers were more likely to have more frequent salt-related eating behaviors than nonsmokers. CONCLUSION: The subjective salt preference of smokers was higher than that of nonsmokers. Additionally, smokers used salt or soy sauce and dipped fried food in soy sauce more frequently than nonsmokers, which was also related to smoking amount.
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BACKGROUND: The goal of this study was to help prevent and control the spread of coronavirus disease 2019 (COVID-19) by identifying transmission routes and risk factors in livestock slaughtering and processing facilities (SPFs) and establishing an optimal intervention strategy for outbreaks. METHODS: This case series study was a demographic analysis of patients with confirmed COVID-19 associated with 5 SPFs in Korea between January and June 2021. Additionally, in a retrospective cohort study, the association between COVID-19 infection and risk factors was analyzed for SPFs at which outbreaks occurred. RESULTS: The COVID-19 attack rates were 11.2%, 24.5%, and 6.8% at 3 poultry SPFs (PSPFs) and 15.5% and 25.2% at 2 mammal SPFs (MSPFs). Regarding spatial risk factors, the COVID-19 risk levels were 12.1-, 5.2-, and 5.0-fold higher in the refrigeration/ freezing, by-product processing, and carcass cutting areas, respectively, than in the office area. The risk of COVID-19 infection was 2.1 times higher among employees of subcontractors than among employees of contractors. The COVID-19 risk levels were 5.3- and 3.0-fold higher in foreign workers than in native Korean workers in the PSPFs and MSPFs, respectively. CONCLUSION: As the COVID-19 pandemic continues, a detailed policy for infectious disease prevention and control intervention is needed, without interrupting economic activities. Thus, we propose an ideal intervention plan to prevent COVID-19 through disinfection and preemptive testing and to block its transmission through effective contact management during outbreaks at SPFs.
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BACKGROUND/OBJECTIVES: Excessive sodium intake, cigarette smoking, and alcohol consumption are risk factors for a wide range of diseases. This study aimed to determine whether smokers and drinkers are more likely to enjoy their food with more salt, and whether the combination of smoking and drinking is associated with salty taste preferences. SUBJECTS/METHODS: This study analyzed the data of over 16 million Koreans from two four-year Korean Community Health Survey cycles (i.e., 2010 to 2013 and 2014 to 2017). The respondents' preferences for salty foods (i.e., their salt intake levels, whether they added salt or soy sauce to foods served on the table, and whether they dipped fried foods in salt or soy sauce), and the odds ratio (OR) of their preference were examined among smokers and drinkers when adjusted for sex, age, body mass index, educational level, household income, marital status, and cigarette smoking or alcohol consumption status. RESULTS: Cigarette smoking and alcohol consumption were correlated with the consumption of salty food. Based on the adjusted model, cigarette smokers and alcohol drinkers preferred adding salt or soy sauce or dipping fried foods in soybean more than non-smokers and non-drinkers. In addition, people who smoked and consumed alcohol reported a more significant stacking effect regarding the salty taste preference. CONCLUSION: This large population-based study found that both cigarette smoking and alcohol consumption were correlated with salty taste preferences, which may cause excessive sodium intake.
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BACKGROUND/OBJECTIVES: This study aimed to compare 24-h diet recall (DR) and 24-h urine collection (UC) for estimating sodium and potassium intakes and their ratio (Na/K), identifying factors associated with sodium and potassium intakes and Na/K, and identifying those who were likely to underestimate sodium and potassium intakes by DR. SUBJECTS/METHODS: A total of 640 healthy adults aged 19-69 yrs completed a questionnaire survey, salty taste assessment, anthropometric measurement, two 24-h DRs, and two 24-h UCs. RESULTS: The mean sodium and potassium intakes and Na/K were 3,755 mg/d, 2,737 mg/d, and 1.45 according to DR, and 4,145 mg/d, 2,812 mg/d, and 1.57 according to UC, with percentage differences of -9.4%, -2.7%, and -7.6% in the values between the two methods, respectively. Men, older adults, smokers, obese individuals, those who consumed all the liquid in the soup, and those who were found to be salty in the salty taste assessment consumed significantly more sodium; older adults, the heavy- activity group, and obese individuals consumed more potassium; and men, younger adults, smokers, and obese individuals had a significantly higher Na/K, according to UC. Compared with UC, DR was more likely to underestimate sodium intake in older adults, smokers, obese individuals, those who consumed all the liquid in the soup, and those who consumed eating-out/delivery food at least once a day, and potassium intake in older adults, the heavy-activity group, and obese individuals. CONCLUSIONS: The mean sodium and potassium intakes and Na/K estimated by DR were comparable to those measured by UC. However, the association of sodium and potassium intakes with sociodemographic and health-related factors showed inconsistent results when estimated by DR and UC. Factors influencing the underestimation of sodium intake by DR compared to UC should be further investigated.
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The nanoscale spatiotemporal resolution of single-particle tracking (SPT) renders it a powerful method for exploring single-molecule dynamics in living cells or tissues, despite the disadvantages of using traditional organic fluorescence probes, such as the weak fluorescent signal against the strong cellular autofluorescence background coupled with a fast-photobleaching rate. Quantum dots (QDs), which enable tracking targets in multiple colors, have been proposed as an alternative to traditional organic fluorescence dyes; however, they are not ideally suitable for applying SPT due to their hydrophobicity, cytotoxicity, and blinking problems. This study reports an improved SPT method using silica-coated QD-embedded silica nanoparticles (QD2), which represent brighter fluorescence and are less toxic than single QDs. After treatment of QD2 in 10 µg/mL, the label was retained for 96 h with 83.76% of labeling efficiency, without impaired cell function such as angiogenesis. The improved stability of QD2 facilitates the visualization of in situ endothelial vessel formation without real-time staining. Cells retain QD2 fluorescence signal for 15 days at 4 °C without significant photobleaching, indicating that QD2 has overcome the limitations of SPT enabling long-term intracellular tracking. These results proved that QD2 could be used for SPT as a substitute for traditional organic fluorophores or single quantum dots, with its photostability, biocompatibility, and superior brightness.
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Nanopartículas , Pontos Quânticos , Humanos , Dióxido de Silício , Células Endoteliais da Veia Umbilical Humana , Linhagem Celular , Corantes FluorescentesRESUMO
Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.
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UBA6-specific E2 conjugation enzyme 1 (USE1) is frequently overexpressed in lung cancer patients. Moreover, the critical role of USE1 in the progression of human lung cancer is also indicated. As the next step, the authors aim to develop USE1-targeted therapeutic agents based on RNA interference (RNAi). In this study, a lipid-modified DNA carrier, namely U4T, which consists of four consecutive dodec-1-ynyluracil (U) nucleobases to increase the cell permeability of siRNA targeting of USE1 is introduced. The U4Ts aggregate to form micelles, and the USE1-silencing siRNA-incorporated soft spherical nucleic acid aggregate (siSNA) can be created simply through base-pairing with siRNA. Treatment with siSNA is effective in suppressing tumor growth in vivo as well as cell proliferation, migration, and invasion of lung cancer cells. Furthermore, siSNA inhibited tumor cell growth by inducing cell cycle arrest in the G1 phase and apoptosis. Thus, the anti-tumor efficacy of siSNA in lung cancer cell lines and that siSNA possesses effective cell-penetrating ability without using cationic transfection moieties are confirmed. Collectively, these results suggest that siSNA can be applied to the clinical application of RNAi-based therapeutics for lung cancer treatment.
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Neoplasias Pulmonares , Humanos , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Pontos de Checagem do Ciclo Celular , Interferência de RNA , Proliferação de Células , ApoptoseRESUMO
BACKGROUND/OBJECTIVES: South Korea has been conducting the Sodium Reduction Restaurant Project since 2015 to reduce sodium contents in restaurant menus. The purpose of this study was to analyze changes in the sodium content of menus as determined by the Daegu Sodium Reduction Restaurant Project between 2015 and 2019. MATERIALS/METHODS: Intervention was aimed at reducing the sodium contents of over 10% of menu items in participating restaurants. On-site inspections and evaluations were conducted using a checklist, and reductions in sodium contents were determined by analyzing the salinities and sodium contents of menus after intervention. RESULTS: Post-intervention salinities and sodium contents were significantly lower than baseline values in 2016 (P < 0.001), 2017 (P < 0.001), 2018 (P < 0.001), and 2019 (P < 0.001). However, sodium contents and salinities differences before and after intervention were not significant in 2015. Sodium contents of more than 20% of menu items offered by restaurants that participated in the Sodium Reduction Restaurant Project for 2 yrs starting in 2016 declined by 28.9%. On the other hand, the sodium reduction rate achieved by restaurants that participated for 4 yrs from 2015 reached 55.4%. The percentage of restaurants that participated in the project increased annually, though some failed to be designated as Sodium Reduction Restaurants because they did not meet sodium reduction rate requirements. CONCLUSIONS: Positive correlations were found between duration of participation in the project and sodium reduction and designation rates. Sustainable long-term support at the national level is required to expand the project to other regions.
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Introduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle. Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR. Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs. Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.
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BACKGROUND/OBJECTIVES: The purpose of this study was to develop a sodium index, which is a tool for estimating and assessing sodium intake easily and quickly, to assist in the prevention of various diseases induced by excess sodium intake in Korean adults. SUBJECTS/METHODS: The 24-h urine collection and dietary behavior surveys were performed on 640 healthy people in 4 regions of South Korea, and an equation for the estimation of 24-h sodium intake was developed. The validity and reliability of the equation were verified with 200 adults. The sodium index was developed by converting the estimated sodium intake using the equation. Finally, the sodium intake status of 1,600 adults was assessed using the sodium index. RESULTS: The equation included sex, age, body mass index, eating habit and dietary behaviors related to sodium intake. In validity test of the equation, the mean bias between sodium intake using 24-h urine analysis and using the equation from the Bland-Altman plots was -1.5 mg/day. The sensitivity and specificity of the equation for estimation of sodium intake were 80.5% and 64.4%, respectively. In the reliability test of the equation, there was no significant difference between the first and second sodium intakes calculated using the equations, and Spearman's correlation coefficient between the 2 sodium intakes was 0.98. Sodium intake can be assessed as 'very moderate' for 75-100 on the sodium index, 'moderate' for 100-150, 'careful' for less than 75 or 150-200, and 'severe' for 250 or more. When sodium intake was assessed using the sodium index in 1,600 subjects, 54.3% and 24.3% of the subjects were assessed to be in the 'careful' and 'severe' categories, respectively. CONCLUSIONS: Using a simple questionnaire, the sodium index can be used to monitor and assess sodium intake status, assisting in nutrition education and counseling in a large population.
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Sodium is a physiologically essential nutrient, but excessive intake is linked to the increased risk of various chronic diseases, particularly cardiovascular. It is, therefore, necessary to accomplish an evidence-based approach and establish the Korean Dietary Reference Intakes (KDRIs) index, to identify both the nutritional adequacy and health effects of sodium. This review presents the rationale for and the process of revising the KDRIs for sodium and, more importantly, establishing the sodium Chronic Disease Risk Reduction Intake (CDRR) level, which is a new specific set of values for chronic disease risk reduction. To establish the 2020 KDRIs for dietary sodium, the committee conducted a systematic literature review of the intake-response relationships between the selected indicators for sodium levels and human chronic diseases. In this review, 43 studies published from January 2014 to December 2018, using databases of PubMed and Web of Science, were finally included for evaluating the risk of bias and strength of evidence (SoE). We determined that SoE of the relationship between dietary sodium and cardiovascular diseases, cerebrovascular disease, and hypertension, was moderate to strong. However, due to insufficient scientific evidence, we were unable to establish the estimated average requirement and the recommended nutrient intake for dietary sodium. Therefore, the adequate intake of sodium for adults was established to be 1,500 mg/day, whereas the CDRR for dietary sodium was established at 2,300 mg/day for adults. Intake goal for dietary sodium established in the 2015 KDRIs instead of the tolerable upper intake level was not presented in the 2020 KDRIs. For the next revision of the KDRIs, there is a requirement to pursue further studies on nutritional adequacy and toxicity of dietary sodium, and their associations with chronic disease endpoint in the Korean population.
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Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, TI). However, little is known about the role of the prefrontal cortex for short- and long-term trace fear memory formation. Thus, we investigated how the prelimbic (PL) subregion within mPFC in rats contributes to short- and long-term trace fear memory formation using electrolytic lesions and d,l,-2-amino-5-phosphonovaleric acid (APV), an N-methyl-D-aspartate receptor (NMDAR) antagonist infusions into PL. In experiment 1, pre-conditioning lesions of PL impaired freezing to the CS as well as TI during the acquisition and retrieval sessions, indicating that PL is critically involved in trace fear memory formation. In experiment 2, temporary blockade of NMDA receptors in PL impaired the acquisition, but not the expression of short- and long-term trace fear memory. In addition, the inactivation of NMDAR in PL had little effect on locomotor activity, pre-pulse inhibition (PPI), or shock sensitivity. Taken together, these results suggest that NMDA receptor-mediated neurotransmission in PL is required for the acquisition of trace fear memory.
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The development of effective assay techniques for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently received research attention due to its rapid worldwide spread and considerable risk to human health. The receptor-binding domain (RBD) of the spike (S) protein in SARS-CoV-2, a key component for viral entry that has a unique sequence compared to other structural proteins, has been considered an important diagnostic target. In this respect, low-frequency vibrational modes have the advantage of providing information about compositional and structural dependencies at the peptide level. In this study, the sensitive and selective detection of peptides derived from the RBD in SARS-CoV-2 and SARS-CoV was investigated using metamaterial-based sensing chips with a terahertz time-domain spectroscopy (THz-TDS) system. Based on their RBD sequences, two pairs of peptides with 20 residues each were prepared. The sensitivity, specificity, and reproducibility of the proposed system were examined via quantitative analysis using THz metamaterials at three resonance frequencies, and it was found that the species could be discriminated based on their sequences. The THz signals were analyzed with regard to the major amino acid components of the peptides, and the molecular distributions were also investigated based on the hydropathy and net charge of the peptides.
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Técnicas Biossensoriais , COVID-19 , Humanos , Peptídeos/metabolismo , Ligação Proteica , Reprodutibilidade dos Testes , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.
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Necrose da Cabeça do Fêmur , Lúpus Eritematoso Sistêmico , Esteroides , Carboxipeptidases/genética , Proteínas de Transporte/genética , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/complicações , Necrose da Cabeça do Fêmur/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Cadeias Pesadas de Miosina/genética , Polimorfismo de Nucleotídeo Único , Esteroides/efeitos adversosRESUMO
OBJECTIVES: To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA). METHODS: Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population. RESULTS: Over the observation period, 225 deaths were reported. Total age- and sex-adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44-1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C-reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities. CONCLUSION: The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself.