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This study presents a thorough investigation of the novel application of graphene oxide (GO) modified with melamine formaldehyde to fabricate granular three-dimensional GO (3D-GO), followed by the introduction of UiO-66 doping (3D-GO/U) for high uranium (U) adsorption. The U(VI) adsorption isotherms revealed that 3D-GO/U-10 with 10 % UiO-66 incorporation exhibited an impressive adsorption capacity of 375.5 mg g-1 and remained high U(VI) sorption performance in wide pH range. The introduction of UiO-66 to 3D-GO (3D-GO/U-10) led to the deagglomeration of the UiO-66 particles. The in situ surface-enhanced-Raman-spectroscopy-analysis and density-functional-theory simulations showed the symmetric metal center site Zr-O2 on UiO-66 was discovered to exhibit the highest adsorption energy (-3.21 eV) for U(VI) species due to the electrons transfer from the oxygen atom to U(VI) drives the covalent bonding between the symmetric metal center sites Zr-O2 and U(VI) on 3D-GO/U-10. The 3D-GO/U-10 was regenerated using a 0.1 M Na2CO3/0.01 M H2O2 solution and achieved up to 89.7 % U(VI) removal in the 5th cycle. The continuous flow column experiments results revealed 3D-GO/U-10 can regenerate and maintain a U(VI) removal capacity of â¼76 % for up to 4 cycles column experiments. Therefore, 3D-GO/U-10 exhibits great potential for removing U(VI) from water bodies.
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Polymer nanocomposites exhibiting remarkable mechanical properties are a focus of research for decades in structural applications. However, their practical application faces challenges due to poor interfacial load transfer, nanofiller dispersion, and processing limitations. These issues are critical in achieving stiff, strong, lightweight, and structurally integrated materials. Additionally, they often suffer from predetermined properties, which may not be effective under specific loading conditions. Addressing these challenges, the development of design strategies for mechano-responsive materials has advanced, enabling self-adaptive properties that respond to various mechanical stimuli. Drawing inspiration from natural systems, these approaches have been implemented in synthetic material systems, leveraging the design flexibility of nanocomposites as needed. Key focus areas include exploring mechanoradical reactions for dynamic mechano-responsiveness, as well as utilizing biomimetic mineralization and mechanical training for self-strengthening. This work also examines multistability, enabling on-demand deformation of materials and structures. Recent advancements in viscoelastic damping and nonreciprocal materials are discussed, highlighting their potential for directional energy absorption, transmission, and vibration control. Despite the need for significant improvements for real-world applications, mechano-responsive polymers and nanocomposites are expected to offer enormous opportunities not only in structural applications but also in other fields such as biomedical engineering, energy harvesting, and soft robotics.
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BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
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Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons , Hormônios Tireóideos , Proteínas tau , Humanos , Masculino , Feminino , Idoso , Proteínas tau/sangue , Proteínas tau/metabolismo , Estudos Transversais , Hormônios Tireóideos/sangue , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/sangue , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Tiroxina/sangue , Tireotropina/sangue , Estudos de CoortesRESUMO
OBJECTIVE: To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION: Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.
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Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression-free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432. We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis.
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The contamination of water sources by pharmaceutical compounds presents global environmental and health risks, necessitating the development of efficient water treatment technologies. In this study, the synthesis, characterization, and evaluation of a novel graphitic carbon nitride-calcined (Fe-Ca) layered double hydroxide (gC3N4-CLDH) composite for electrochemical degradation of sulfamethoxazole (SMX) in water yielded significant outcomes are reported. SEM, XRD, FTIR, and XPS analyses confirmed well-defined composite structures with unique morphology and crystalline properties. Electrochemical degradation experiments demonstrated >98% SMX removal and >75% TOC removal under optimized conditions, highlighting its effectiveness. The composite exhibited excellent mineralization efficiency across various pH levels, with superoxide radicals (O2â-) and hydroxyl radicals (âOH) identified as primary reactive oxygen species. With remarkable regeneration capability for up to 7 cycles, the gC3N4-CLDH composite emerges as a highly promising solution for sustainable water treatment. Humic acid (HA) in water significantly slows SMX degradation, suggests complicating SMX degradation with natural organic matter. Despite this, the gC3N4-CLDH composite effectively degrades SMX in groundwater and industrial wastewater, with slight efficiency reduction in the latter due to higher impurity levels. These findings highlight the complexities of treating pharmaceutical pollutants in various water types. Overall, gC3N4-CLDH's high removal efficiency, broad pH applicability, sustainability, and mechanistic insights provide a solid foundation for future research and real-world environmental applications.
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Grafite , Sulfametoxazol , Poluentes Químicos da Água , Purificação da Água , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Sulfametoxazol/química , Grafite/química , Águas Residuárias/química , Hidróxidos/química , Água Subterrânea/química , Técnicas Eletroquímicas , Substâncias Húmicas/análise , Compostos de Nitrogênio/química , Compostos de Nitrogênio/análiseRESUMO
BACKGROUND: Early detection of cancer and provision of appropriate treatment can increase the cancer cure rate and reduce cancer-related deaths. Early detection requires improving the cancer screening quality of each medical institution and enhancing the capabilities of health professionals through tailored education in each field. However, during the COVID-19 pandemic, regional disparities in educational infrastructure emerged, and educational accessibility was restricted. The demand for remote cancer education services to address these issues has increased, and in this study, we considered medical metaverses as a potential means of meeting these needs. In 2022, we used Metaverse Educational Center, developed for the virtual training of health professionals, to train radiologic technologists remotely in mammography positioning. OBJECTIVE: This study aims to investigate the user experience of the Metaverse Educational Center subplatform and the factors associated with the intention for continuous use by focusing on cases of using the subplatform in a remote mammography positioning training project. METHODS: We conducted a multicenter, cross-sectional survey between July and December 2022. We performed a descriptive analysis to examine the Metaverse Educational Center user experience and a logistic regression analysis to clarify factors closely related to the intention to use the subplatform continuously. In addition, a supplementary open-ended question was used to obtain feedback from users to improve Metaverse Educational Center. RESULTS: Responses from 192 Korean participants (male participants: n=16, 8.3%; female participants: n=176, 91.7%) were analyzed. Most participants were satisfied with Metaverse Educational Center (178/192, 92.7%) and wanted to continue using the subplatform in the future (157/192, 81.8%). Less than half of the participants (85/192, 44.3%) had no difficulty in wearing the device. Logistic regression analysis results showed that intention for continuous use was associated with satisfaction (adjusted odds ratio 3.542, 95% CI 1.037-12.097; P=.04), immersion (adjusted odds ratio 2.803, 95% CI 1.201-6.539; P=.02), and no difficulty in wearing the device (adjusted odds ratio 2.020, 95% CI 1.004-4.062; P=.049). However, intention for continuous use was not associated with interest (adjusted odds ratio 0.736, 95% CI 0.303-1.789; P=.50) or perceived ease of use (adjusted odds ratio 1.284, 95% CI 0.614-2.685; P=.51). According to the qualitative feedback, Metaverse Educational Center was useful in cancer education, but the experience of wearing the device and the types and qualities of the content still need to be improved. CONCLUSIONS: Our results demonstrate the positive user experience of Metaverse Educational Center by focusing on cases of using the subplatform in a remote mammography positioning training project. Our results also suggest that improving users' satisfaction and immersion and ensuring the lack of difficulty in wearing the device may enhance their intention for continuous use of the subplatform.
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COVID-19 , Humanos , Feminino , COVID-19/prevenção & controle , Estudos Transversais , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Mamografia/estatística & dados numéricos , Mamografia/métodos , Masculino , Neoplasias da Mama/diagnóstico por imagem , Adulto , Educação a Distância/métodos , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 µg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.
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Caprilatos , Fluorocarbonos , Complexo de Golgi , Fígado , Reprodução , Animais , Fluorocarbonos/toxicidade , Feminino , Masculino , Caprilatos/toxicidade , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Reprodução/efeitos dos fármacos , Administração Oral , Tamanho do Órgão/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
The remediation of diesel-contaminated soil is a critical environmental concern, driving the need for effective solutions. Recently, the methodology of Non-thermal Atmospheric Plasma (NTAP) technology, which is equipped with a Dielectric Barrier Discharge (DBD) electrode and has become a feasible approach, was proven to be viable. The reactive species from the plasma were exposed to the contaminated soil in this investigation using the NTAP technique. The reacted soil was then extracted using dichloromethane, and the amount of Total Petroleum Hydrocarbon (TPH) removed was assessed. Investigation into varying power levels, treatment durations, and hydrogen peroxide integration revealed significant findings. With an initial concentration of 3086 mg of diesel/kg of soil and a pH of 5.0, 83% of the diesel was removed from the soil at 150 W in under 20 min. Extended exposure to NTAP further improved removal rates, highlighting the importance of treatment duration optimization. Additionally, combining hydrogen peroxide (H2O2) with NTAP enhanced removal efficiency by facilitating diesel breakdown. This synergy offers a promising avenue for comprehensive soil decontamination. Further analysis considered the impact of soil characteristics on removal efficacy. Mechanistically, NTAP generates reactive species that degrade diesel into less harmful compounds, aiding subsequent removal. Overall, NTAP advances environmental restoration efforts by offering a quick, economical, and environmentally benign method of remediating diesel-contaminated soil especially when used in tandem with hydrogen peroxide.
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Recuperação e Remediação Ambiental , Gasolina , Peróxido de Hidrogênio , Gases em Plasma , Poluentes do Solo , Solo , Recuperação e Remediação Ambiental/métodos , Poluentes do Solo/análise , Gases em Plasma/química , Solo/química , Peróxido de Hidrogênio/química , Gasolina/análise , Petróleo/análise , Hidrocarbonetos/análiseRESUMO
The objective of this study was to investigate the physicochemical, structural, and in vitro release properties of carboxymethyl cellulose (CMC)-based cryogel beads incorporating resveratrol-loaded microparticles (MP) for colon-targeted delivery system. CMC-based cryogel beads were produced by ionic cross-linking with different concentrations (2%, 3%, and 4%) of AlCl3. Based on FE-SEM images, CMC-based cryogel beads showed a smoother surface and more compact internal structure with increasing AlCl3 concentrations, which was proven to be due to the new cross-linking between the -COO- group of CMC and Al3+ by FT-IR analysis. The encapsulation efficiency of the cryogel beads was significantly increased from 79.48% to 85.74% by elevating the concentrations of AlCl3 from 2% to 4%, respectively. In vitro release study showed that all CMC-based cryogel beads had higher stability for resveratrol than MP in simulated gastric conditions and can efficiently deliver resveratrol to colon without the premature release.
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Carboximetilcelulose Sódica , Colo , Criogéis , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Resveratrol , Resveratrol/química , Resveratrol/administração & dosagem , Carboximetilcelulose Sódica/química , Criogéis/química , Colo/metabolismo , Colo/química , Portadores de Fármacos/química , Humanos , Liberação Controlada de Fármacos , Tamanho da Partícula , MicroesferasRESUMO
BACKGROUND: There is an unmet surgical burden among people living with rheumatic heart disease (RHD) in Uganda. Nevertheless, risk factors associated with time to first intervention and preoperative mortality are poorly understood. METHODS: Individuals with RHD who met indications for valve surgery were identified using the Uganda National RHD Registry (January 2010-August 2022). Kaplan-Meier estimates and multivariable Cox proportional hazard models were used. RESULTS: Of the cohort with clinical RHD, 64% (1452 of 2269) met criteria for an index operation. Of those, 13.5% obtained a surgical intervention, whereas 30.6% died before the operation. The estimated likelihood of first operation was 50% at 9.3 years of follow-up (95% CI, 8.1-upper limit not reached). Intervention was more likely in men vs women (hazard ratio [HR], 1.78; 95% CI, 1.21-2.64), those with postsecondary education vs primary school or less (HR, 3.60; 95% CI, 1.88-6.89), and those with a history of atrial fibrillation (HR, 2.78; 95% CI, 1.63-4.76). Surgical intervention was less likely for adults vs those aged <18 years (HR, 0.49; 95% CI, 0.32-0.77) and those with New York Heart Association Functional Class III/IV vs I/II (HR, 0.51; 95% CI, 0.32-0.83). The median preoperative survival time among those awaiting first operation was 4.6 years (95% CI, 3.9-5.7 years). History of infective endocarditis, right ventricular dysfunction, pericardial effusion, atrial fibrillation, and having surgical indications for multiple valves were associated with increased probability of death. CONCLUSIONS: Our analysis revealed a prolonged time to first surgical intervention and high preintervention death for RHD in Uganda, with factors such as age, sex, and education level remaining barriers to obtaining surgery.
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BACKGROUND: Stair-climbing (SC) is an essential daily life skill, and stair-climbing exercise (SCE) serves as a valuable method for promoting physical activity in older adults. This study aimed to compare the impact of SCEs with heel contact (HC) and heel off (HO) during SC on functional mobility and trunk muscle (TM) activation amplitudes in community-dwelling older adults. METHODS: In the pilot randomized controlled trial, participants were randomly allocated to either the HC group (n = 17; mean age 75.9 ± 6.3 years) or the HO group (n = 17; mean age 76.5 ± 4.6 years). The HC participants performed SCE with the heel of the ankle in contact with the ground, while the HO participants performed SCE with the heel of the ankle off the ground during SC. Both groups participated in progressive SCE for one hour per day, three days per week, over four consecutive weeks (totaling 12 sessions) at the community center. We measured timed stair-climbing (TSC), timed up and go (TUG), and electromyography (EMG) amplitudes of the TMs including rectus abdominis (RA), external oblique (EO), transverse abdominus and internal oblique abdominals (TrA-IO), and erector spinae (ES) during SC before and after the intervention. RESULTS: Both groups showed a significant improvement in TSC and TUG after the intervention (P < .01, respectively), with no significant difference between the groups. There was no significant difference in the EMG activity of the TMs between the groups after the intervention. The amplitude of TMs significantly decreased after the intervention in both groups (P < .01, respectively). CONCLUSION: Both SCE methods could improve balance and SC ability in older adults while reducing the recruitment of TMs during SC. Both SCE strategies are effective in improving functional mobility and promoting appropriate posture control during SC in older adults.
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Eletromiografia , Vida Independente , Subida de Escada , Humanos , Idoso , Masculino , Projetos Piloto , Feminino , Subida de Escada/fisiologia , Idoso de 80 Anos ou mais , Tronco/fisiologia , Músculo Esquelético/fisiologiaRESUMO
PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.
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Xanthine oxidoreductase (XOR) contributes to reactive oxygen species production. We investigated the cytoprotective mechanisms of XOR inhibition against high glucose (HG)-induced glomerular endothelial injury, which involves activation of the AMP-activated protein kinase (AMPK). Human glomerular endothelial cells (GECs) exposed to HG were subjected to febuxostat treatment for 48 h and the expressions of AMPK and its associated signaling pathways were evaluated. HG-treated GECs were increased xanthine oxidase/xanthine dehydrogenase levels and decreased intracellular AMP/ATP ratio, and these effects were reversed by febuxostat treatment. Febuxostat enhanced the phosphorylation of AMPK, the activation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1α and PPAR-α and suppressed the phosphorylation of forkhead box O (FoxO)3a in HG-treated GECs. Febuxostat also decreased nicotinamide adenine dinucleotide phosphate oxidase (Nox)1, Nox2, and Nox4 expressions; enhanced superoxide dismutase activity; and decreased malondialdehyde levels in HG-treated GECs. The knockdown of AMPK inhibited PGC-1α-FoxO3a signaling and negated the antioxidant effects of febuxostat in HG-treated GECs. Despite febuxostat administration, the knockdown of hypoxanthine phosphoribosyl transferase 1 (HPRT1) also inhibited AMPK-PGC-1α-FoxO3a in HG-treated GECs. XOR inhibition alleviates oxidative stress by activating AMPK-PGC-1α-FoxO3a signaling through the HPRT1-dependent purine salvage pathway in GECs exposed to HG conditions.
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Proteínas Quinases Ativadas por AMP , Injúria Renal Aguda , Células Endoteliais , Glucose , Purinas , Xantina Desidrogenase , Humanos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Febuxostat/farmacologia , Glucose/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Purinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantina Desidrogenase/antagonistas & inibidores , Xantina Desidrogenase/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismoRESUMO
Importance: Many epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood. Objective: To examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aß) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults. Design, Setting, and Participants: This was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aß deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aß deposition were included. Exposure: Plasma leptin levels as assessed by enzyme-linked immunosorbent assay. Main Outcomes and Measures: Baseline levels and longitudinal changes of global Aß and AD-signature region tau deposition measured by PET scans. Results: Among the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aß deposition (ß = -0.04; 95% CI, -0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (ß = -0.02; 95% CI, -0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (ß = -0.06; 95% CI, -0.11 to -0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aß deposition (ß = 0.006; 95% CI, 0.00-0.02; P = .27). Conclusions and Relevance: The present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aß and tau deposition.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Leptina , Proteínas tau , Humanos , Leptina/sangue , Feminino , Masculino , Idoso , Doença de Alzheimer/sangue , Estudos Longitudinais , Estudos Transversais , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Tomografia por Emissão de Pósitrons , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , República da Coreia/epidemiologia , Idoso de 80 Anos ou mais , Disfunção Cognitiva/sangue , Biomarcadores/sangue , Pessoa de Meia-IdadeRESUMO
Concerns about dioxin-like compounds have increased; however, the monitoring of polychlorinated naphthalenes (PCNs) in food and the assessment of dietary intake remain limited. In this study, various foods were collected from Korean markets and analyzed for PCNs. Fishery products exhibited the highest mean concentration (48.0 pg/g ww) and toxic equivalent (TEQ) (0.0185 pg-TEQ/g ww). Agricultural products were the largest contributors (35.7%) to the total dietary intake of PCNTEQ, followed by livestock products (33.6%), fishery products (20.2%), and processed foods (10.5%). The mean intake of PCNTEQ for the Korean population was 0.901 pg-TEQ/day for males and 0.601 pg-TEQ/day for females. Generally, males and younger groups had higher daily intakes of PCNTEQ, but they did not exceed the tolerable weekly intakes. Nonetheless, it is important to manage potential health risks associated with PCNs and other dioxin-like compounds by identifying major food items contributing to PCN exposure and considering age and gender differences.
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Contaminação de Alimentos , Naftalenos , República da Coreia , Humanos , Contaminação de Alimentos/análise , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Naftalenos/análise , Adolescente , Criança , Poluentes Ambientais/análise , Idoso , Pré-Escolar , Exposição Dietética/análise , AnimaisRESUMO
The present study aimed to investigate the structural and physicochemical characteristics of alkali-extracted pectic polysaccharide (AkPP) and to evaluate its prebiotic effects. AkPP was obtained from pumpkin pulp using an alkaline extraction method. AkPP, which had a molecular weight (Mw) of mainly 13.67 kDa and an esterification degree of 9.60%, was composed mainly of galacturonic acid (GalA), rhamnose (Rha), galactose, and arabinose. The ratio of the homogalacturonan (HG) region to the rhamnogalacturonan-I (RG-I) region in AkPP was 48.74:43.62. In the nuclear magnetic resonance spectrum, the signals indicating α-1,4-linked D-GalA, α-1,2-linked L-Rha, α-1,2,4-linked L-Rha residues were well resolved, demonstrating the presence of the HG and RG-I regions in its molecular structure. Collectively, AkPP was low methoxyl pectin rich in the RG-I region with short side chains and had a low Mw. Thermal analysis revealed that AkPP had good thermal stability. Compared to inulin, AkPP more effectively promoted the proliferation of Lactobacillus acidophilus, Lacticaseibacillus rhamnosus GG, Lacticaseibacillus casei, and Lacticaseibacillus paracasei and the production of lactic, acetic, and propionic acids. This study presents the unique structural features of AkPP and provides a scientific basis for further investigation of the potential of AkPP as a promising prebiotic.
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Cucurbita , Peso Molecular , Pectinas , Prebióticos , Pectinas/química , Cucurbita/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Ramnose/química , Álcalis/química , Soluções , Ácidos HexurônicosRESUMO
BACKGROUND: The purpose of this study was to determine the staining conditions and appropriate fan1 start time (FAN1ST) for Sysmex SP-50 to produce blood smears (BS) that reflect the true lymphocyte morphology of patient samples. METHODS: Using different start times of fan1, we obtained a set of 84 blood smear slides from 21 blood samples and measured 10,920 lymphocyte areas, which were then converted to compare lymphocyte sizes. We also performed a leukocyte differential count using Sysmex DI-60 on 202 blood smear slides prepared before and after the change in staining conditions and compared the results. RESULTS: The mean lymphocyte sizes at FAN1ST 0 second, 5 seconds, 10 seconds, and 30 seconds were 12.55 µm, 12.14 µm, 11.27 µm, and 10.50 µm, respectively. The mean differences in the preclassification of neutrophils, lymphocytes, monocytes, eosinophils, and basophils in DI-60, according to the SP-50 staining conditions, were 0.88, -1.58, -0.24, 0.37, and 0.07, respectively. CONCLUSIONS: Wright-Giemsa staining of blood smears prepared on the SP-50 showed that changing the pH of the concentrated phosphate buffer to 6.6 and adjusting the staining time did not affect the results of the leukocyte differential count. However, since fan1 was used to dry the blood smear on the SP-50 and the lymphocyte size gradually decreased as the start time was delayed, it was necessary to set a start time for fan1 that did not affect the lymphocyte size.
Assuntos
Monócitos , Neutrófilos , Humanos , Contagem de Leucócitos , Eosinófilos , Coloração e RotulagemRESUMO
Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.
RESUMO
The present study aimed to investigate the structural and physicochemical characteristics of acid-extracted pumpkin pectic polysaccharide (AcPP) and to evaluate their flow rheological properties. AcPP was extracted from pumpkin pulp using the citric acid extraction method. The physicochemical and structural properties were analyzed by chemical methods and instrumental analyses. The obtained results showed that AcPP consisted predominantly of GalA (85.99 %) and small amounts of Rha, Gal, and Ara, with the ratio of HG/RG-I being 81.39/16.75. In addition, AcPP had medium DE (45.34 %) and contained four macromolecular populations with different Mw of 106.03 (main), 10.15, 4.99, and 2.90 kDa. The NMR analysis further confirmed that AcPP contained a linear backbone consisting of α-1,4-linked GalA residues, some of which were partially methyl-esterified. Furthermore, AcPP was amorphous in nature and had favorable thermal stability. The effects of extrinsic factors on the flow rheological properties of AcPP were evaluated. In particular, the high concentrations of CaCl2 (8 mM) and MgCl2 (10 mM) were effective in enhancing the viscosity and non-Newtonian shear-thinning behavior of the AcPP solution. This study elucidates the unique molecular structure of AcPP and suggests the potential of AcPP as a rheology modifier in low-viscous and mineral-reinforced beverages.