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Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Proteínas de Homeodominio , Neuronas , Factores del Dominio POU , Factores de Transcripción del Factor Regulador X , Humanos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Perfilación de la Expresión Génica , Regiones Promotoras Genéticas , RNA-Seq , Diferenciación Celular , Proteínas de Homeodominio/genética , Factores del Dominio POU/genética , Factores de Transcripción del Factor Regulador X/genéticaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The high human-to-human transmission and rapid evolution of SARS-CoV-2 have resulted in a worldwide pandemic. To contain SARS-CoV-2, it is essential to efficiently control the transmission of the virus through the early diagnosis of infected individuals, including asymptomatic people. Therefore, a rapid and accurate assay is vital for the early diagnosis of SARS-CoV-2 in suspected individuals. In this study, we developed a colorimetric lateral flow immunoassay (LFIA) in which a CBP31-BC linker was used to immobilize antibodies on a cellulose membrane in an oriented manner. The developed LFIA enabled sensitive detection of cultured SARS-CoV-2 in 15 min with a detection limit of 5 × 104 copies/mL. The clinical performance of the LFIA for detecting SARS-CoV-2 was evaluated using 19 clinical samples validated by reverse transcription-polymerase chain reaction (RT-PCR). The LFIA detected all the positive and negative samples accurately, corresponding to 100% accuracy. Importantly, patient samples with low viral loads were accurately identified. Thus, the proposed method can provide a useful platform for rapid and accurate point-of-care testing of SARS-CoV-2 in infected individuals to efficiently control the COVID-19 pandemic.
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BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles. MATERIALS AND METHODS: First, hyaluronic acid-loaded microneedle patches (HA-MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA-MNs. Lastly, proteins were isolated from the collected samples, and AD-related biomarkers were analyzed by enzyme-linked immunosorbent assay. RESULTS: Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA-MNs, except hollow microneedles. Interleukin (IL)-4, IL-13, and interferon-γ were detected in the HA-MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL-4 and IL-13 with an improvement in AD symptoms. CONCLUSION: Overall, our results verified that HA-MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/patología , Interleucina-13/metabolismo , Piel/patología , Citocinas/metabolismo , Biomarcadores/metabolismoRESUMEN
BACKGROUND: Though antenatal magnesium sulfate (MgSO4) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. METHODS: We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24-31 weeks. RESULTS: Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18-24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. CONCLUSION: Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.
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Fármacos Neuroprotectores , Nacimiento Prematuro , Lactante , Humanos , Embarazo , Femenino , Recién Nacido , Sulfato de Magnesio/uso terapéutico , Nacimiento Prematuro/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Atención Prenatal , Recién Nacido de muy Bajo PesoRESUMEN
Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.
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Glucosamina , Osteoartritis , Humanos , Glucosamina/farmacología , Sulfatos de Condroitina/uso terapéutico , Suplementos Dietéticos , Osteoartritis/tratamiento farmacológico , Interacciones Farmacológicas , Sistema Enzimático del Citocromo P-450RESUMEN
Poly(ADP-ribose) polymerase 1 (PARP1) facilitates DNA damage response (DDR). While the Ewing's sarcoma breakpoint region 1 (EWS) protein fused to FLI1 triggers sarcoma formation, the physiological function of EWS is largely unknown. Here, we investigate the physiological role of EWS in regulating PARP1. We show that EWS is required for PARP1 dissociation from damaged DNA. Abnormal PARP1 accumulation caused by EWS inactivation leads to excessive Poly(ADP-Ribosy)lation (PARylation) and triggers cell death in both in vitro and in vivo models. Consistent with previous work, the arginine-glycine-glycine (RGG) domain of EWS is essential for PAR chain interaction and PARP1 dissociation from damaged DNA. Ews and Parp1 double mutant mice do not show improved survival, but supplementation with nicotinamide mononucleotides extends Ews-mutant pups' survival, which might be due to compensatory activation of other PARP proteins. Consistently, PARP1 accumulates on chromatin in Ewing's sarcoma cells expressing an EWS fusion protein that cannot interact with PARP1, and tissues derived from Ewing's sarcoma patients show increased PARylation. Taken together, our data reveal that EWS is important for removing PARP1 from damaged chromatin.
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Sarcoma de Ewing , Animales , Cromatina/genética , Daño del ADN , Trastornos Disociativos , Humanos , Ratones , Poli(ADP-Ribosa) Polimerasa-1 , Proteína EWS de Unión a ARN/genética , Proteína EWS de Unión a ARN/metabolismo , Sarcoma de Ewing/genéticaRESUMEN
BACKGROUND AND OBJECTIVES: The treatment of Riehl's melanosis, also known as pigmented contact dermatitis, is highly challenging. Intense pulsed light (IPL) and 1064 nm Q-switched Nd:Yag (QS-Nd:YAG) laser are reported to have some efficacy. However, no single effective treatment has yet been identified. In this study, we demonstrated the efficacy and safety of the non-ablative 1927 nm fractional thulium fiber laser (TFL, LASEMD™; Lutronic Corp., Goyang, Korea) for patients with Riehl's melanosis. STUDY DESIGN/MATERIALS AND METHODS: A retrospective chart and photographic review of nine patients with Riehl's melanosis, who had received at least three sessions of TFL treatment, was performed. Before the start of TFL treatment, combination treatment with a topical cream containing hydroquinone, low-fluence QS-Nd:YAG laser, pulsed dye laser, and IPL was used with variable and discouraging effects. Seven patients were treated on the face and two patients on the neck with three to seven sessions at 1-month intervals. Clinical improvement was assessed using clinical photos taken before and after every treatment session according to dermal pigmentation area and severity index (DPASI) and a quartile grading scale by two blinded dermatologists. RESULTS: Patients underwent three to seven sessions of TFL treatment depending on severity of pigmentation. Of nine patients, six demonstrated a clinical improvement of 51%-75%, one demonstrated an improvement of 76%-100%, and two showed an improvement of 26%-50% after treatment. The DPASI was significantly decreased from 9.55 to 5.25 on average. Melanin index was decreased after treatment in two patients whose melanin index were measured at initial visits. Treatment-related adverse events, such as scarring or postinflammatory hyperpigmentation (PIH), were not observed in all patients except for transient erythema and swelling. CONCLUSIONS: This report suggests that TFL could be an alternative and/or additive treatment option for hyperpigmentation in intractable Riehl's melanosis and might be a promising treatment for PIH caused by any reason including Riehl's melanosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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Láseres de Estado Sólido , Melanosis , Eritema , Humanos , Láseres de Estado Sólido/uso terapéutico , Melanosis/terapia , Estudios Retrospectivos , Tulio , Resultado del TratamientoRESUMEN
BACKGROUND: Fractional microneedle radiofrequency (FMR) and nonablative 1927-nm fractional thulium fiber laser (TFL) are widely used for skin rejuvenation treatment. OBJECTIVES: To investigate the efficacy and safety of combined treatment with both devices for wrinkles. PATIENTS AND METHODS: Twenty-five patients with wrinkles were enrolled. One side of the face was treated with FMR alone, while the other side was treated with a combination of FMR and TFL. Each treatment consisted of 3 sessions at four-week intervals and patients were followed up 12 weeks after the last treatment. Overall improvement was assessed by patient global assessment (PGA) and investigator global assessment (IGA). Depression scores for the evaluation of wrinkles were objectively assessed by Antera 3D system. RESULTS: Both sides of the face led to clinical improvement in both mean PGA and IGA. Combination treatment demonstrated a greater improvement in both mean PGA and IGA compared with FMR alone. In addition, wrinkle grading scales and depression scores showed greater improvement in the combination group than in FMR alone. CONCLUSION: This study demonstrated that FMR and TFL comprise a good combination treatment for the treatment of wrinkles because both treatments have a synergistic effect on wrinkle improvement.
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Técnicas Cosméticas , Láseres de Estado Sólido/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Ablación por Radiofrecuencia/métodos , Envejecimiento de la Piel/efectos de la radiación , Terapia Combinada , Técnicas Cosméticas/efectos adversos , Femenino , Humanos , Láseres de Estado Sólido/efectos adversos , Terapia por Luz de Baja Intensidad/efectos adversos , Masculino , Persona de Mediana Edad , Agujas , Estudios Prospectivos , Ablación por Radiofrecuencia/efectos adversos , Rejuvenecimiento , TulioRESUMEN
The purpose of this study was to evaluate and compare the results of plate osteosynthesis, intramedullary nailing (IMN), and hybrid fixation for the treatment of both-forearm-bone shaft fractures in adults. One-hundred-one cases of both-forearm-bone shaft fractures were retrospectively reviewed. All fractures were divided into the following three groups, according to the method used for internal fixation : open reduction and internal fixation ORIF group (plate osteosynthesis), IMN group, and HYBRID group (plate osteosynthesis for the radius and intramedullary nail for the ulna). The results were assessed based on the time to union, functional recovery, restoration of the ulna and radial bow, operating time, complications, and patient satisfaction. In the ORIF, IMN, and HYBRID groups, the average union time was 10.8, 14.9, and 11.5 weeks, respectively. No intergroup differences were observed in the functional outcomes. The ORIF and HYBRID groups had a significantly better radial bow ratio compared to the IMN group. All patients in the three groups achieved union, with the exception of a single case of nonunion in the IMN group. ORIF and HYBRID fixation resulted in a more anatomical restoration of radial bow ratio, compared to the contralateral side. Such significant differences in the restoration of the radial bow had no effect on the final functional outcomes and minimal effect on forearm range of motion. Although there are statistically significant effects on the final forearm range of motion, the difference was only 5°. Thus, if the indication is properly selected, our results suggest that hybrid fixation would be acceptable and effective treatment options for both-forearm-bone fractures in adults.
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Fracturas del Radio/cirugía , Fracturas del Cúbito/cirugía , Adulto , Placas Óseas , Femenino , Fijación Interna de Fracturas/métodos , Fijación Intramedular de Fracturas/métodos , Humanos , Masculino , Reducción Abierta/métodos , Tempo Operativo , Satisfacción del Paciente , Radiografía , Fracturas del Radio/complicaciones , Fracturas del Radio/diagnóstico por imagen , Estudios Retrospectivos , Fracturas del Cúbito/complicaciones , Fracturas del Cúbito/diagnóstico por imagenRESUMEN
Strain M1-21T is a Gram-stain-negative, strictly aerobic and short-rod-shaped bacterium, motile by means of a single polar flagellum; it was isolated from freshwater sediment in Korea. It grew at 10-40 °C (optimum 25 °C), pH 6.0-8.0 (optimum pH 7.0) and with 0-0.75â% (w/v) NaCl (optimal growth occurred in the absence of NaCl) on R2A agar, and it accumulated poly-ß-hydroxybutyrate granules inside the cells. According to 16S rRNA gene sequence analysis, strain M1-21T showed highest sequence similarity with Uliginosibacterium gangwonense (94.7â%) and Uliginosibacterium paludis (94.4â%). Phylogenetic analysis of the 16S rRNA gene sequences revealed that strain M1-21T belongs to the genus Uliginosibacterium. The DNA G+C content of strain M1-21T was 61.9 mol%. The predominant respiratory quinone was ubiquinone-8. The major fatty acids (>10â% of the total) were C16â:â0 and summed feature 3 (C16â:â1ω6c and/or C16â:â1ω7c), and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain M1-21T showed distinct phenotypic characteristics that differentiated it from species of the genus Uliginosibacterium. Based on these results, strain M1-21T represents a novel species of the genus Uliginosibacterium, for which the name Uliginosibacterium sediminicola sp. nov. is proposed. The type strain is M1-21T (=KACC 19271T=JCM 32000T).
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Agua Dulce/microbiología , Sedimentos Geológicos/microbiología , Filogenia , Rhodocyclaceae/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hidroxibutiratos/química , Fosfolípidos/química , Poliésteres/química , ARN Ribosómico 16S/genética , República de Corea , Rhodocyclaceae/genética , Rhodocyclaceae/aislamiento & purificación , Análisis de Secuencia de ADN , Ubiquinona/químicaRESUMEN
Monitoring the health and condition of wetlands using biological assessments can serve as an effective tool for environmental managers to better evaluate and monitor the status and trends of their wetland ecosystems. Woody species can be used as conspicuous biological assessment tools due to their direct response to environmental change, such as hydrologic alteration. The purpose of this study is to use field-measured morphological measurement indices to develop and optimize tree growth parameters and growth curves using multi-model combination approach to improve tree biomass estimations. Field morphological investigations were conducted for two common wetland tree species in Texas. A range of morphological characteristics including leaf area index, height, and biomass was measured for black willow (Salix nigra Marsh) and green ash (Fraxinus pennsylvanica) sampled from 15 sites in a wetland near Cameron, Texas. The measured morphological parameters were used to optimize tree growth and development with the ALMANAC model. The developed tree growth parameters and growth curves were subsequently used in the APEX model to simulate tree biomass at the catchment scale. Both models accurately simulated biomass of trees growing in the wetland. This accurate biomass prediction will be useful to advance science to better monitor and assess wetland health on a large scale (e.g. national or global).
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Biomasa , Monitoreo del Ambiente , Árboles/crecimiento & desarrollo , Humedales , Ecosistema , Ambiente , Hidrología , Salix , TexasRESUMEN
A system for simultaneous detection of two orchid-infecting viruses was developed and applied to several orchid species. The detection system involved multiplex reverse transcription-polymerase chain reaction (RT-PCR) and could simultaneously identify Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) from the orchid species studied. Multiplex RT-PCR was conducted using two virus-specific primer pairs and an internal control pair of primers to amplify the CymMV and ORSV coat protein regions, and orchid 18S rDNA, respectively. For optimization of multiplex RT-PCR conditions, serial dilutions of total RNA and cDNA were performed and the detection limit of the system was evaluated. The optimized multiplex detection system for CymMV and ORSV was applied to various orchid species, including several cultivars of Doritaenopsis, Cymbidium, Dendrobium, and Phalaenopsis to test the efficacy of this method. Our results indicate that the multiplex RT-PCR detection system will be a rapid, simple, and precise diagnosis tool in a range of orchid species.
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Orchidaceae/virología , Enfermedades de las Plantas/virología , Potexvirus/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Tobamovirus/aislamiento & purificación , Proteínas de la Cápside/genética , Cartilla de ADN/genética , ADN Ribosómico/genética , Dendrobium/virología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Potexvirus/clasificación , Potexvirus/genética , ARN Viral/genética , Tobamovirus/clasificación , Tobamovirus/genética , Proteínas Virales/genéticaRESUMEN
OBJECTIVE: In this study, we aimed to evaluate the usability single nucleotide polymorphisms (SNPs) for parentage testing of horse breeds in Korea. METHODS: The genotypes of 93 horse samples (38 Thoroughbred horses, 17 Jeju horses, 20 Quarter horses, and 18 American miniature horses) were determined using 15 microsatellite (Ms) markers (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10, LEX3, and VHL20) and 101 SNP markers. RESULTS: Paternity tests were performed using 15 Ms markers and 101 SNP markers in Thoroughbred horses and Quarter horses. AHT5, ASB2, ASB17, ASB23, CA425, HMS7, HTG10, and LEX3 did not follow Mendelian inheritance in Thoroughbred horses, whereas in Quarter horses, only AHT4, ASB2, and HMS2 showed Mendelian inheritance, consequently, paternity was not established. Meanwhile, 31 markers, including MNEc_2_2_ 2_98568918_BIEC2_502451, in Thoroughbred horses, and 30 markers, including MNEc_ 2_30_7430735_BIEC2_816793, in Quarter horses did not conform with Mendelian inheritance and therefore, could not be used for establishing parentage. CONCLUSION: The possibility of replacing Ms markers with SNP markers for paternity testing in horses was confirmed. However, further research using more samples is necessary.
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Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as ß-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications.
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Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped together without considering their heterogeneity. This approach has resulted in a lack of phenotype- and endotype-adapted therapeutic strategies. Comprehensive insights into AD pathogenesis have enabled precise medicinal approach for AD. These efforts aimed to redefine the endophenotype of AD and develop various biomarkers for diverse purposes. Among these endeavours, efforts are underway to elucidate the mechanisms (and related biomarkers) that lead to the emergence and progression of atopic diseases originating from AD (e.g., atopic march). This review focuses on diverse AD phenotypes and calls for a definition of endophenotypes. While awaiting scientific validation, these biomarkers ensure predicting disease onset and trajectory and tailoring therapeutic strategies for the future.
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Biomarcadores , Dermatitis Atópica , Fenotipo , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/etiología , Humanos , Endofenotipos , AnimalesRESUMEN
BACKGROUND/AIMS: Epicardial adipose tissue (EAT) shares pathophysiological properties with other visceral fats and potentially triggers local inflammation. However, the association of EAT with cardiovascular disease (CVD) is still debatable. The study aimed to observe the changes and associations in EAT and risk factors over time, as well as to investigate whether EAT was associated with CVD. METHODS: A total of 762 participants from Seoul National University Hospital (SNUH) and SNUH Gangnam Center were included in this study. EAT was measured using coronary computed tomography angiography. RESULTS: Baseline EAT level was positively associated with body mass index (BMI), calcium score, atherosclerotic cardiovascular disease (ASCVD) 10-year risk score, glucose, triglycerides (TG)/high-density lipoprotein (HDL), but not with total cholesterol, low-density lipoprotein (LDL). At follow-up, EAT levels increased in all groups, with low EAT groups demonstrating a significant increase in EAT per year. Change in EAT was associated with a change in BMI, TG/HDL, and glucose, while changes in LDL, calcium score, and ASCVD 10-year risk score were not associated. Although calcium score and ASCVD 10-year risk score were associated with CVD events, baseline information of EAT, baseline EAT/body surface area, or EAT change was not available. CONCLUSION: Metabolic risks, e.g., BMI, TG/HDL, and glucose, were associated with EAT change per year, whereas classical CVD risks, e.g., LDL, calcium score, and ASCVD 10-year risk score, were not. The actual CVD event was not associated with EAT volume, warranting future studies combining qualitative assessments with quantitative ones.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Humanos , Angiografía por Tomografía Computarizada/efectos adversos , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Tejido Adiposo Epicárdico , Calcio , Pericardio/diagnóstico por imagen , Factores de Riesgo , Triglicéridos , Glucosa , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria/métodosRESUMEN
This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in serum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment significantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, enhanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This approach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
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To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.
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Highly ordered freestanding TiO(2) nanotube arrays with atomic layer control of wall thickness were fabricated using an organic-inorganic hybrid nanoporous template and atomic layer deposition (ALD). The hybrid nanoporous template with a high-aspect-ratio cylindrical nanopore array can be readily fabricated by pattern transfer from a thin silicon-containing block copolymer film into a thick cross-linked organic polymer layer. The template exhibited excellent thermal stability and thus allowed the high-temperature ALD process to conformally deposit TiO(2) thin films on the inner surface of cylindrical nanopores. The ultrafine thickness tunability of the ALD process made it possible to develop TiO(2) nanotubes with various wall thicknesses. After the template was removed using a dry etch followed by calcination, vertically aligned and highly crystalline anatase TiO(2) nanotube arrays were produced without collapse or bundling. We also fabricated the highly uniform freestanding arrays of multi-component nanotubes composed of TiO(2)/Al(2)O(3)/TiO(2) nanolaminate and Ti-Al-O mixed-phase films with precisely controlled thickness and composition.
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This study aimed to prove that deep learning can be effectively used for identifying various equine facial expressions as welfare indicators. In this study, a total of 749 horses (healthy: 586 and experiencing pain: 163) were investigated. Moreover, a model for recognizing facial expressions based on images and their classification into four categories, i.e., resting horses (RH), horses with pain (HP), horses immediately after exercise (HE), and horseshoeing horses (HH), was developed. The normalization of equine facial posture revealed that the profile (99.45%) had higher accuracy than the front (97.59%). The eyes-nose-ears detection model achieved an accuracy of 98.75% in training, 81.44% in validation, and 88.1% in testing, with an average accuracy of 89.43%. Overall, the average classification accuracy was high; however, the accuracy of pain classification was low. These results imply that various facial expressions in addition to pain may exist in horses depending on the situation, degree of pain, and type of pain experienced by horses. Furthermore, automatic pain and stress recognition would greatly enhance the identification of pain and other emotional states, thereby improving the quality of equine welfare.