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Carbon allotropes have contributed to all aspects of people's lives throughout human history. As emerging carbon-based low-dimensional materials, graphyne family members (GYF), represented by graphdiyne, have a wide range potential applications due to their superior physical and chemical properties. In particular, graphdiyne (GDY), as the leader of the graphyne family, has been practically applied to various research fields since it was first successfully synthesized. GYF have a large surface area, both sp and sp2 hybridization, and a certain band gap, which was considered to originate from the overlap of carbon 2pz orbitals and the inhomogeneous π-bonds of carbon atoms in different hybridization forms. These properties mean GYF-based materials still have many potential applications to be developed, especially in energy storage and catalytic utilization. Since most of the GYF have yet to be synthesized and applications of successfully synthesized GYF have not been developed for a long time, theoretical results in various application fields should be shared to experimentalists to attract more intentions. In this Review, we summarized and discussed the synthesis, structural properties, and applications of GYF-based materials from the theoretical insights, hoping to provide different viewpoints and comments.
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Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O2-â¢) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.
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Celecoxib , Lutecio , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Animales , Humanos , Porfirinas/química , Porfirinas/farmacología , Ratones , Lutecio/química , Celecoxib/química , Celecoxib/farmacología , Inmunoterapia , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , FemeninoRESUMEN
A new carbon allotrope, cyclo[16]carbon (C16), has recently been successfully synthesized. It is hypothesized to exhibit double antiaromatic properties owing to the 4n π electrons. Theoretical calculations are a feasible method for systematically studying the structures and properties of unstable antiaromatic molecules. The results show that C16 has a planar structure characterized by alternating long and short bonds with D8h, and a strong antiaromatic characteristic originates from the two perpendicular π systems. We performed an extensive comparative analysis of C16 and the aromatic cyclo[18]carbon, C18. This study offers valuable insight into the structural and electronic characteristics of C16 and could inspire innovative applications and avenues for its utilization in various fields.
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BACKGROUND: We aimed to investigate mortality, severity, and risk of hospitalization in coronavirus disease 2019 (COVID-19) patients with cancer. METHODS: Data of all patients aged 40-79 years from the Korean Disease Control and Prevention Agency-COVID19-National Health Insurance Service who were diagnosed with COVID-19 between January 1, 2020 and March 31, 2022, in Korea were included. After 1:1 propensity score matching, 397,050 patients with cancer and 397,050 patients without cancer were enrolled in the main analysis. A cancer survivor was defined as a patient who had survived 5 or more years since the diagnosis of cancer. Multiple logistic regression analysis was performed to compare the risk of COVID-19 according to the diagnosis of cancer and time since diagnosis. RESULTS: Cancer, old age, male sex, incomplete vaccination against COVID-19, lower economic status, and a higher Charlson comorbidity index were associated with an increased risk of hospitalization, hospitalization with severe state, and death. Compared to patients without cancer, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization, hospitalization with severe state, and death in patients with cancer were 1.09 (1.08-1.11), 1.17 (1.11-1.24), and 1.94 (1.84-2.05), respectively. Compared to patients without cancer, the ORs (95% CIs) for hospitalization in cancer survivors, patients with cancer diagnosed 2-5 years, 1-2 years, and < 1 year ago were 0.96 (0.94-0.98), 1.10 (1.07-1.13), 1.30 (1.25-1.34), and 1.82 (1.77-1.87), respectively; the ORs (95% CIs) for hospitalization for severe disease among these patients were 0.90 (0.85-0.97), 1.22 (1.12-1.32), 1.60 (1.43-1.79), and 2.29 (2.09-2.50), respectively. CONCLUSION: The risks of death, severe state, and hospitalization due to COVID-19 were higher in patients with cancer than in those without; the more recent the diagnosis, the higher the aforementioned risks. Cancer survivors had a lower risk of hospitalization and hospitalization with severe disease than those without cancer.
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COVID-19 , Supervivientes de Cáncer , Neoplasias , Humanos , Masculino , COVID-19/epidemiología , SARS-CoV-2 , Comorbilidad , Hospitalización , Neoplasias/complicaciones , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Individuals with autism spectrum disorders (ASD) have difficulty accessing dental care. We aim to verify whether individuals with ASD are properly managed by checking the frequency of dental visits, cost and severity of dental treatment compared with those without ASD. This cross-sectional study used the Korean Health Insurance Database to analyze the frequency, cost and severity of dental treatment in 209,780 people under the age of 19 with or without ASD in 2020. The average frequency of dental visits for individuals without ASD was 2.98 times, which was significantly higher (p < 0.001) than the 2.89 times for those with ASD. However, the average dental cost for individuals with ASD was USD 132.63, which was significantly higher (p < 0.001) than USD 116.57 for those without ASD. Additionally, the average number of times that individuals without ASD received severe dental treatment was 1.23 times, significantly higher than the 1.15 times for those with ASD. Further, per 10,000 people, we found that trauma treatment was recorded for an average of 21.90 individuals with ASD, significantly higher than the 7.75 recorded for those without ASD (p < 0.001). Individuals with ASD encounter significant disparities in accessing dental care, as evidenced by their relatively infrequent dental visits. This discrepancy can be attributed to various barriers including the financial burden compared with those without ASD.
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Trastorno del Espectro Autista , Niño , Humanos , Adolescente , Trastorno del Espectro Autista/terapia , Estudios Transversales , Atención Odontológica , República de Corea/epidemiologíaRESUMEN
Recent studies on plasmon-assisted chemical reactions postulate that the hot electrons of plasmon-excited nanostructures may induce a non-thermal vibrational activation of metal-bound reactants. However, the postulate has not been fully validated at the level of molecular quantum states. We directly and quantitatively prove that such activation occurs on plasmon-excited nanostructures: The anti-Stokes Raman spectra of reactants undergoing a plasmon-assisted reaction reveal that a particular vibrational mode of the reactant is selectively excited, such that the reactants possess >10 times more energy in the mode than is expected from the fully thermalized molecules at the given local temperature. Furthermore, a significant portion (â¼20%) of the excited reactant is in vibrational overtone states with energies exceeding 0.5 eV. Such mode-selective multi-quantum excitation could be fully modeled by the resonant electron-molecule scattering theory. Such observations suggest that the vibrationally hot reactants are created by non-thermal hot electrons, not by thermally heated electrons or phonons of metals. The result validates the mechanism of plasmon-assisted chemical reactions and further offers a new method to explore the vibrational reaction control on metal surfaces.
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Characterization of the conformational alterations involved in monomer misfolding is essential for elucidating the molecular basis of the initial stage of protein accumulation. Here, we report the first structural analyses of transthyretin (TTR) (26-57) fragments with two histidine tautomeric states (δ; Nδ1H and ε; Nε2H) using replica-exchange molecular dynamics (REMD) simulations. Explaining the organizational properties and misfolding procedure is challenging because the δ and ε configurations can occur in the free neutral state. REMD revealed that ß-sheet generation is favored for the δδ (16.8%) and εδ (6.7%) tautomeric isomers, showing frequent main-chain contacts between the stable regions near the head (N-terminus) and central (middle) part compared to the εε (4.8%) and δε (2.8%) isomers. The presence of smaller and wider local energy minima may be related to the structural stability and toxicity of δδ/εδ and εε/δε. Histidines31 and 56 were the parts of regular (such as ß-strand) and nonregular (such as coil) secondary structures within the highly toxic TTR isomer. For TTR amyloidosis, focusing on hazardous isomeric forms with high sheet contents may be a potent treatment strategy. Overall, our findings support the tautomerism concept and aid in our comprehension of the basic tautomeric actions of neutral histidine throughout the misfolding process.
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Amiloidosis , Histidina , Humanos , Histidina/química , Prealbúmina , Simulación de Dinámica Molecular , Amiloidosis/metabolismo , Estructura Secundaria de ProteínaRESUMEN
Molecular diameter is an essential molecule-size descriptor that is widely used to understand, e.g., the gas separation preference of a permeable membrane. In this contribution, we have proposed two new molecular diameters calculated respectively by the circumscribed-cylinder method (Dn') and the group-separated method (Dn), and compared them with the already known kinetic diameter (Dk), averaged diameters (Dpa), and maximum diameters (Dpm and Dmm) in correlating with the penetration barriers of small gas molecules on a total of 14 porous carbon-based monolayer membranes (PCMMs). D1' and D2' give the best barrier-diameter correlations with average Pearson's correlation coefficients of 0.91 and 0.90, which are markedly larger than those (0.77, 0.76, 0.60, 0.48, 0.33, and 0.32) for D1, D2, Dk, Dpa, Dpm, and Dmm. Our results manifest that the choice of vdW radii set does not drastically change the barrier-diameter correlation. Our newly defined D1', D2', D1, and D2, especially D1' and D2', show universal applicability in predicting the relative permeability of small gas molecules on different PCMMs. The circumscribed-cylinder method proposed here is a facile approach that considers the molecule's directionality and can be applicable to larger molecules. The excellent linear correlation between Dn' and gas penetration barrier implies that the computationally less demanding molecular diameter Dn' can be an alternative to the penetration barrier in diagnosing the gas separation preference of the PCMMs.
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Microplastic (MPs) contamination in groundwater has received massive attention since plastic waste has been released directly into the environment. This study investigates MPs contamination in groundwater on the Jeju volcanic Island, Korea. To the best of our knowledge, this is the first study to identify MPs in groundwater from volcanic islands. A total of 21 sites were sampled for groundwater wells and springs in July and September (2021). Sampling was performed without cross-contamination through quality assurance and quality control. The results showed that MPs abundance ranged from 0.006 to 0.192 particles/L in groundwater samples. Additionally, MPs were detected in deep groundwater wells where the groundwater level was 143 m below ground surface. Eight MPs polymer types, including polypropylene, polyethylene, polyethylene terephthalate, polyvinyl chloride, polystyrene, polyamide, acrylonitrile butadiene styrene, and polyurethane, were detected using Micro-Fourier Transform Infrared Spectroscopy (µ-FT-IR). Most of the detected MPs size ranged from 20 to 100 µm, accounting for 95% of the total. Fragments and fiber shaped MPs were detected, with the majority of them being fragmented in groundwater samples. The concentrations of MPs and major ions in groundwater showed a positive correlation. A negative correlation was observed between MPs concentration and topographic elevation (r = -0.59, p = 0.01). The source of MPs contamination is most likely attributed to agricultural activities, such as plastic mulching and greenhouses, which account for most of the land use in the study area. In this study, MPs entered the aquifer through the soil at the surface and seeped through cracks in fractured rock on basalt with sealed groundwater wells. This study takes 500 L of samples to prevent sample bias, reveal plastic contamination in groundwater, and indicating the characteristics and sources of contaminated plastics.
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Agua Subterránea , Contaminantes Químicos del Agua , Microplásticos , Plásticos , Espectroscopía Infrarroja por Transformada de Fourier , República de Corea , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisisRESUMEN
Microplastics (MP) and nanoplastics (NP) contamination of the terrestrial environment is a growing concern worldwide and is thought to impact soil biota, particularly the micro and mesofauna community, by various processes that may contribute to global change in terrestrial systems. Soils act as a long-term sink for MP, accumulating these contaminants and increasing their adverse impacts on soil ecosystems. Consequently, the whole terrestrial ecosystem is impacted by microplastic pollution, which also threatens human health by their potential transfer to the soil food web. In general, the ingestion of MP in different concentrations by soil micro and mesofauna can adversely affect their development and reproduction, impacting terrestrial ecosystems. MP in soil moves horizontally and vertically because of the movement of soil organisms and the disturbance caused by plants. However, the effects of MP on terrestrial micro-and mesofauna are largely overlooked. Here, we give the most recent information on the forgotten impacts of MP contamination of soil on microfauna and mesofauna communities (protists, tardigrades, soil rotifers, nematodes, collembola and mites). More than 50 studies focused on the impact of MP on these organisms between 1990 and 2022 have been reviewed. In general, plastic pollution does not directly affect the survival of organisms, except under co-contaminated plastics that can increase adverse effects (e.g. tire-tread particles on springtails). Besides, they can have adverse effects at oxidative stress and reduced reproduction (protists, nematodes, potworms, springtails or mites). It was observed that micro and mesofauna could act as passive plastic transporters, as shown for springtails or mites. Finally, this review discusses how soil micro- and mesofauna play a key role in facilitating the (bio-)degradation and movement of MP and NP through soil systems and, therefore, the potential transfer to soil depths. More research should be focused on plastic mixtures, community level and long-term experiments.
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Ecosistema , Plásticos , Humanos , Plásticos/toxicidad , Suelo , Microplásticos , Cadena AlimentariaRESUMEN
We previously found that methylmercury induces expression of oncostatin M (OSM), which is released extracellularly and binds to tumor necrosis factor receptor 3 (TNFR3), possibly enhancing its own toxicity. However, the mechanism by which methylmercury causes OSM to bind to TNFR3 rather than to its known receptors, OSM receptor and LIFR, is unknown. In this study, we aimed to elucidate the effect of methylmercury modification of cysteine residues in OSM on binding to TNFR3. Immunostaining of TNFR3-V5-expressing cells suggested that methylmercury promoted binding of OSM to TNFR3 on the cell membrane. In an in vitro binding assay, OSM directly bound to the extracellular domain of TNFR3, and this binding was promoted by methylmercury. Additionally, the formation of a disulfide bond in the OSM molecule was essential for the binding of both proteins, and LC/MS analysis revealed that methylmercury directly modified the 105th cysteine residue (Cys105) in OSM. Next, mutant OSM, in which Cys105 was replaced by serine or methionine, increased the binding to TNFR3, and a similar effect was observed in immunoprecipitation using cultured cells. Furthermore, cell proliferation was inhibited by treatment with Cys105 mutant OSMs compared with wildtype OSM, and this effect was cancelled by TNFR3 knockdown. In conclusion, we revealed a novel mechanism of methylmercury toxicity, in which methylmercury directly modifies Cys105 in OSM, thereby inhibiting cell proliferation via promoting binding to TNFR3. This indicates a chemical disruption in the interaction between the ligand and the receptor is a part of methylmercury toxicity.
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Cisteína , Compuestos de Metilmercurio , Oncostatina M/química , Oncostatina M/metabolismo , Compuestos de Metilmercurio/toxicidad , Receptores del Factor de Necrosis Tumoral , Proliferación CelularRESUMEN
BACKGROUND: The epidemiology of influenza is commonly used to understand and establish relevant health policies for emerging respiratory infections, including coronavirus disease 2019 (COVID-19). However, Korea has no confirmed nationwide data on influenza incidence, severity, and mortality rate. METHODS: We conducted a cross-sectional study to obtain epidemic data on influenza at the national level using National Health Insurance claims data during 2010 to 2020. Influenza cases were defined as 90-day timeframe episodes based on all inpatient and outpatient claims data with disease code J09, J10, and J11. Influenza incidence, severity, and mortality rate were calculated, and logistic regressions were performed to assess the associations of demographic characteristics and comorbidity with influenza-related hospitalization, severe illness, and death. RESULTS: There were 0.4-5.9% influenza cases in the population from 2010 to 2020, with 9.7-18.9%, 0.2-0.9%, and 0.03-0.08% hospitalized, used in the intensive care unit, and dead, respectively. Age-standardized incidence and mortality rates were 424.3-6847.4 and 0.2-1.9 per 100,000 population, respectively. While more than half of the influenza cases occurred in populations aged younger than 20 years, deaths in older than 60 years accounted for more than two-thirds of all deaths. CONCLUSION: This study provided the simplest but most important statistics regarding Korean influenza epidemics as a reference. These can be used to understand and manage other new acute respiratory diseases, including COVID-19, and establish influenza-related policies.
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COVID-19 , Gripe Humana , Humanos , Anciano , Gripe Humana/epidemiología , COVID-19/epidemiología , Estudios Transversales , Incidencia , Programas Nacionales de Salud , Política de Salud , República de Corea/epidemiologíaRESUMEN
Land subsidence is the gradual or sudden dropping of the ground surface developed by increasing the total stress. Most studies have discussed the relationship between land subsidence with groundwater level. However, there is a lack of discussion on groundwater environmental changes after occurring land subsidence. This study aimed to evaluate the hydrogeological and water chemistry characteristics of construction sites with land subsidence. Land subsidence in the Yangyang coastal area occurred suddenly on August 3, 2022, when the retaining wall of the construction collapsed. The groundwater level was measured three times, and water samples were collected twice between August 5, 2022, and September 5, 2022, for laboratory analysis. After land subsidence occurred, the average groundwater level was - 19.91 m ground level (GL) on August 9, 2022, and finally decreased to - 19.21 m GL on September 05, 2022. The groundwater levels surrounding the construction site gradually increased for a month. The electrical conductivity value measured at the monitoring wells ranged from 89 to 7800 µS/cm, and four wells exceeded the measurement limit near the groundwater leaked points. The highest mixing ratio of leaked water samples, collected on August 9, 2022, was 27.6%. Furthermore, the fresh groundwater-saltwater interface depth was estimated to be above the construction bottom. Although groundwater levels recovered, the groundwater quality continuously is affected by saltwater. This finding could contribute to understanding the hydrogeological characteristics surrounding construction sites with land subsidence and provide insight into the hydrochemical evolution process during declined groundwater levels in coastal aquifers.
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Agua Subterránea , Agua , Agua/análisis , Monitoreo del Ambiente , Agua Subterránea/análisis , Agua Dulce , República de CoreaRESUMEN
We conducted a retrospective cohort study using claims data to determine the number and types of complications from coronavirus disease (COVID-19) that patients experience and which patients are more vulnerable to those complications compared with complications in patients with influenza. Among the cohort, 19.6% of COVID-19 patients and 28.5% of influenza patients had >1 new complication. In most complications, COVID-19 patients had lower or similar relative risk compared with influenza patients; exceptions were hair loss, heart failure, mood disorder, and dementia. Young to middle-aged adult COVID-19 patients and patients in COVID-19 hotspots had a higher risk for complications. Overall, COVID-19 patients had fewer complications than influenza patients, but caution is necessary in high-risk groups. If the fatality rate for COVID-19 is reduced through vaccination, management strategies for this disease could be adapted, similar to those for influenza management, such as easing restrictions on economic activity or requirements for close-contact isolation.
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COVID-19 , Gripe Humana , Adulto , Humanos , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , Estaciones del AñoRESUMEN
Cadmium (Cd) is an environmental contaminant that causes renal toxicity. We have previously demonstrated that Cd induces renal toxicity by altering transcriptional activities. In this study, we show that Cd markedly inhibited the activity of transcription factor MEF2A in HK-2 human proximal tubule cells, which generated significant cytotoxicity in the cells. This reduction in the nuclear levels of MEF2A protein may be involved in the Cd-induced inhibition of MEF2A activity. We also demonstrate that one of the glucose transporters, GLUT4, was downregulated not only by Cd treatment but also by MEF2A knockdown. Knockdown of SLC2A4, encoding GLUT4, eliminated both cell viability and Cd toxicity. Cd treatment or SLC2A4 deficiency reduced the cellular concentration of glucose. Therefore, the suppression of SLC2A4 expression, which mediates the reduction in cellular glucose, is involved in Cd toxicity. The Cd toxicity induced by the reduction in GLUT4 may be associated with a reduction of cellular ATP levels in HK-2 cells. The levels of Slc2a4 mRNA in the kidney of mice exposed to Cd for 6 or 12 months were significantly lower than those in the control group. These results demonstrate that Cd exerts its cytotoxicity through the suppression in SLC2A4 expression and the subsequent inhibition of MEF2A transcriptional activity. Cd-induced suppression of SLC2A4 expression also reduces cellular ATP levels, partly by reducing glucose levels. This study suggests that the glucose transporter plays an important role in the renal toxicity of Cd, and provides a crucial breakthrough in our understanding of the mechanism of Cd toxicity.
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Cadmio/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 4/biosíntesis , Túbulos Renales Proximales/metabolismo , Animales , Línea Celular , Técnicas de Silenciamiento del Gen , Transportador de Glucosa de Tipo 4/genética , Humanos , Túbulos Renales Proximales/patología , Factores de Transcripción MEF2/genética , Factores de Transcripción MEF2/metabolismo , RatonesRESUMEN
Compared to the p-n junction photovoltaic effect, the bulk photovoltaic effect is a potential way to overcome the external limitations of solar energy conversion. It is challenging to find new materials with a bulk photovoltaic effect. In this article, using first-principles calculations and the maximum local Wannier function, we investigated the bulk photovoltaic effect in GaNGeC quaternary compound semiconductors with six different crystal structures (S-1, S-2, S-3, S-4, S-5, and S-6 for short). These semiconductors showed a large effective three-dimensional shift current conductivity, where the maximum absolute value of the shift current conductivity ranges from 10 µA V-2 to 425 µA V-2, indicating that they are promising candidates for photoelectric conversion applications. Furthermore, the electron localization function, difference charge density, and atomic configurations as well as Löwdin population analysis revealed that dimerization of the GaN layer and the GeC layer in S-5 and S-6 induces delocalization of electrons. This delocalization of electrons enhances their shift current conductivities, which provides valuable insight for further design and development of new photovoltaic materials.
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Monitoring early-stage ß-amyloid (Aß) dimerization is a formidable challenge for understanding neurological diseases. We compared ß-sheet formation and histidine site-specific two-dimensional infrared (2D IR) spectroscopic signatures of Aß dimers with different histidine states (δ; Nδ1-H, ε; Nε2-H, or π; both protonated). Molecular dynamics (MD) simulations revealed that ß-sheet formation is favored for the δδδ:δδδ and πππ:πππ tautomeric isomers showing strong couplings and frequent contacts between the central hydrophobic core and C-terminus compared with the εεε:εεε isomer. Characteristic blue-shifts in the 2D IR central bands were observed upon monomer-dimer transformation. The εεε:εεε dimer exhibited larger frequency shifts than δδδ:δδδ and πππ:πππ implying that the red-shift may have a correlation with Nδ1-H(δ) protonation. Our results support the tautomerization/protonation hypothesis that attributes Aß misfolding to histidine tautomers as a possible primary initiator for Aß aggregation and facilitates the application of histidine site-specific 2D IR spectroscopy for studying early-stage Aß self-assembly.
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Péptidos beta-Amiloides , Histidina , Péptidos beta-Amiloides/química , Histidina/química , Simulación de Dinámica Molecular , Fragmentos de Péptidos/química , Conformación Proteica en Lámina betaRESUMEN
BACKGROUND: The aim of this study was to estimate the 8-year prevalence and mortality statistics of autism spectrum disorder (ASD) according to birth year (2002-2012). METHODS: We used the National Health Insurance Service database with 4,989,351 children born from 2002 to 2012 including 35,529 children diagnosed with ASD until 8 years of age. The 8-year cumulative prevalence of ASD was calculated annually (2010-2020) with 8 years of follow-up. The 8-year mortality was estimated using Cox models adjusted for sex, household income, area of residence, and year of birth. RESULTS: Of the 473,494 children born in 2002, 2,467 (5.2 per 1,000 births) were diagnosed with ASD until 2010. The ASD prevalence was 2.6 times higher among boys (1,839; 7.4 per 1,000 boy births) than girls (628; 2.8 per 1,000 girl births). Of the 467,360 children born in 2012, 4,378 (9.4 per 1,000 births) were diagnosed with ASD until 2020. The ASD prevalence was 2.7 times higher among boys (3,246; 13.5 per 1,000 boy births) than girls (1,132; 5.0 per 1,000 girl births). The risk of all-cause mortality was higher among children with ASD than those without (hazard ratio [HR], 2.340; 95% confidence interval [CI], 2.063-2.654), which is substantially higher among girls (HR, 4.223; 95% CI, 3.472-5.135) than boys (HR, 1.774; 95% CI, 1.505-2.090). CONCLUSION: The present study demonstrated that national-level prevalence and mortality statistics of ASD can be estimated effectively using claims data comprising newborns born each year and followed up for to the age of interest. Because this information is essential to establish evidence-based policies, health authorities need to consider producing epidemiological information of ASD continuously using the same methodology.
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Trastorno del Espectro Autista/epidemiología , Mortalidad Prematura , Adolescente , Trastorno del Espectro Autista/mortalidad , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Prevalencia , República de Corea/epidemiología , Adulto JovenRESUMEN
Hundreds of millions of people around the world have been affected by Type 2 diabetes (T2D) which is a metabolic disorder. Clinical research has revealed T2D as a possible risk factor for Alzheimer's disease (AD) development (and vice versa). Amyloid-ß (Aß) and human islet amyloid polypeptide are the main pathological species in AD and T2D, respectively. However, the mechanisms by which these two amyloidogenic peptides co-aggregate are largely uninvestigated. Herein, for the first time, we present the cross-seeding between Amylin1-37 and Aß40 considering the particular effect of the histidine tautomerism at atomic resolution applying the all-atom molecular dynamics (MD) simulations for heterodimeric complexes. The results via random seed MD simulations indicated that the Aß40(δδδ) isomer in cross-talking with Islet(ε) and Islet(δ) isomers could retain or increase the ß-sheet content in its structure that may make it more prone to further aggregation and exhibit higher toxicity. The other tautomeric isomers which initially did not have a ß-sheet structure in their monomeric forms did not show any generated ß-sheet, except for one seed of the Islet(ε) and Aß40(εεε) heterodimers complex that displayed a small amount of formed ß-sheet. This computational research may provide a different point of view to examine all possible parameters that may contribute to the development of AD and T2D and provide a better understanding of the pathological link between these two severe diseases.
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Péptidos beta-Amiloides/metabolismo , Histidina/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Humanos , Simulación de Dinámica Molecular , Fragmentos de Péptidos/metabolismo , Conformación Proteica en Lámina beta/fisiologíaRESUMEN
Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. Renal proximal tubule disorder is the main symptom of Cd chronic poisoning. Our previous study demonstrated that Cd inhibits the total activities of peroxisome proliferator-activated receptor (PPAR) transcription factors in human and rat proximal tubular cells. In this study, we investigated the involvement of PPAR in Cd renal toxicity using the HK-2 human proximal tubular cell line. Among PPAR isoform genes, only PPARD knockdown significantly showed resistance to Cd toxicity in HK-2 cells. The transcriptional activity of PPARδ was decreased not only by PPARD knockdown but also by Cd treatment. DNA microarray analysis showed that PPARD knockdown changed the expression of apoptosis-related genes in HK-2 cells. PPARD knockdown decreased apoptosis signals and caspase-3 activity induced by Cd treatment. PPARD knockdown did not affect the intracellular Cd level after Cd treatment. These results suggest that PPARδ plays a critical role in the modification of susceptibility to Cd renal toxicity and that the apoptosis pathway may be involved in PPARδ-related Cd toxicity.