RESUMEN
Atrial myxoma is a rare primary tumour of the heart that typically arises from the left atrium. Patients typically present with obstructive symptoms such as dyspnoea, but constitutional and embolic symptoms can be seen as well. Gastrointestinal symptoms in the absence of embolisation are rarely reported in the literature. Our case presents a 55-year-old female who was found to have a large left atrial myxoma after presenting with gastrointestinal symptoms, which resolved upon resection of the tumour. This case illustrates that atrial myxomas can have an atypical presentation with gastrointestinal symptoms, which could be related to inflammation of gastric mucosa from interleukin-6 produced by the tumour cells. Careful history-taking followed by early detection and prompt treatment is important as atrial myxomas can lead to potentially devastating complications. LEARNING POINTS: Atrial myxomas are primary tumours of the heart that can present with a wide spectrum of symptoms.Early consideration and recognition of atypical presentations of atrial myxomas can be crucial in preventing serious consequences such as cardiac arrest.
RESUMEN
BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.
RESUMEN
Background: Evaluating left ventricular diastolic function (LVDF) is crucial in echocardiography; however, the complexity and time demands of current guidelines challenge clinical use. This study aimed to develop an artificial intelligence (AI)-based framework for automatic LVDF assessment to reduce subjectivity and improve accuracy and outcome prediction. Methods: We developed an AI-based LVDF assessment framework using a nationwide echocardiographic dataset from five tertiary hospitals. This framework automatically identifies views, calculates diastolic parameters, including mitral inflow and annular velocities (E/A ratio, e' velocity, and E/e' ratio), maximal tricuspid regurgitation velocity, left atrial (LA) volume index, and left atrial reservoir strain (LARS). Subsequently, it grades LVDF according to guidelines. The AI-framework was validated on an external dataset composed of randomly screened 173 outpatients who underwent transthoracic echocardiography with suspicion for diastolic dysfunction and 33 individuals from medical check-ups with normal echocardiograms at Seoul National University Bundang Hospital, tertiary medical center in Korea, between May 2012 and June 2022. Additionally, we assessed the predictive value of AI-derived diastolic parameters and LVDF grades for a clinical endpoint, defined as a composite of all-cause death and hospitalization for heart failure, using Cox-regression risk modelling. Results: In an evaluation with 200 echocardiographic examinations (167 suspected diastolic dysfunction patients, 33 controls), it achieves an overall accuracy of 99.1% in identifying necessary views. Strong correlations (Pearson coefficient 0.901-0.959) were observed between AI-derived and manually-derived measurements of diastolic parameters, including LARS as well as conventional parameters. When following the guidelines, whether utilizing AI-derived or manually-derived parameters, the evaluation of LVDF consistently showed high concordance rates (94%). However, both methods exhibited lower concordance rates with the clinician's prior assessments (77.5% and 78.5%, respectively). Importantly, both AI-derived and manually-derived LVDF grades independently demonstrated significant prognostic value [adjusted hazard ratio (HR) =3.03; P=0.03 and adjusted HR =2.75; P=0.04, respectively] for predicting clinical outcome. In contrast, the clinician's prior grading lost its significance as a prognostic indicator after adjusting for clinical risk factors (adjusted HR =1.63; P=0.36). AI-derived LARS values significantly decreased with worsening LVDF (P for trend <0.001), and low LARS (<17%) was associated with increased risk for the clinical outcome (Log-rank P=0.04) relative to that for preserved LARS (≥17%). Conclusions: Our AI-based approach for automatic LVDF assessment on echocardiography is feasible, potentially enhancing clinical diagnosis and outcome prediction.
RESUMEN
A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.
Asunto(s)
Antibacterianos , Compuestos de Azabiciclo , Bacteriemia , Ceftazidima , Combinación de Medicamentos , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Humanos , Ceftazidima/uso terapéutico , Ceftazidima/farmacología , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Masculino , Compuestos de Azabiciclo/uso terapéutico , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Secuenciación Completa del Genoma , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Meropenem/uso terapéutico , Meropenem/farmacología , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
CONTEXT.: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors. OBJECTIVE.: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs). DESIGN.: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden. RESULTS.: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs). CONCLUSIONS.: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.
RESUMEN
Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.
Asunto(s)
Asma , Factor 2 Relacionado con NF-E2 , Células Th2 , Animales , Femenino , Humanos , Ratones , Asma/inmunología , Asma/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinofilia/inmunología , Eosinofilia/metabolismo , Glucólisis , Interleucina-33/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/metabolismo , Fosforilación Oxidativa , PPAR gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.
RESUMEN
Purpose: The purpose of this study was to examine the level of evidence (LOE) characteristics and associated factors that change over time in three leading prosthodontics journals. Materials and methods: Articles published in The Journal of Prosthetic Dentistry (JPD), International Journal of Prosthodontics (IJP), and Journal of Prosthodontics (JP) in 2013 and 2020 were reviewed by eight independent reviewers. After applying exclusion and inclusion criteria, the number of authors, the corresponding author's educational degree, corresponding author's origin in each clinical research article were recorded. The included articles were rated by reviewers according to the level of evidence criteria and proposed level of evidence-associated factors. Descriptive statistics, univariable, and binary logistic regression analysis were performed to investigate dependent variables and potentially associated factors. All independent variables with a significant effect were analyzed by using a multivariable test. The entry and exit alpha level were set at αE = 0.15. The statistical significance was set at α = 0.05. Results: A total of 439 articles from 3 selected journals for the years studied met the inclusion criteria. The percentages of level 1, 2, 3, 4, and 5 articles were 2.7 %, 11.4 %, 9.6 %, 13.4 % and 62.9 %, respectively. Univariable analysis results demonstrated significant associations related to the number of authors (P = 0.005), the corresponding author's educational degree (P = 0.022), and the corresponding author's geographic origin (P = 0.042). Multivariable analysis results demonstrated significant associations related to the number of authors (P = 0.002), and the corresponding author's geographic origin (P = 0.014). Conclusions: The number of authors, CA degree, and CA origin had a significant association with the LOE of included prosthodontic studies. Although there was an increase in the number of publications from 2013 to 2020, the level of evidence trend shows no improvement over the years.
RESUMEN
PURPOSE: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 µm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.
RESUMEN
Non-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT). LKB1 loss, in collaboration with KEAP1 loss, activated SHMT through inactivation of the salt-induced kinase (SIK)-NRF2 axis and satisfied the increased demand for one-carbon units necessary for antioxidant defence. Chemical and genetic SHMT suppression increased cellular sensitivity to oxidative stress and cell death. Further, the SHMT inhibitor enhanced the in vivo therapeutic efficacy of paclitaxel (first-line NSCLC therapy inducing oxidative stress) in KEAP1-mutant KL tumours. The data reveal how this highly aggressive molecular subtype of NSCLC fulfills their metabolic requirements and provides insight into therapeutic strategies.
Asunto(s)
Quinasas de la Proteína-Quinasa Activada por el AMP , Antioxidantes , Carcinoma de Pulmón de Células no Pequeñas , Glicina Hidroximetiltransferasa , Proteína 1 Asociada A ECH Tipo Kelch , Neoplasias Pulmonares , Mutación , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas p21(ras) , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Glicina Hidroximetiltransferasa/genética , Glicina Hidroximetiltransferasa/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Antioxidantes/metabolismo , Animales , Estrés Oxidativo , Ratones , Línea Celular Tumoral , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.
Asunto(s)
Autoinmunidad , Receptores X del Hígado , PPAR gamma , Piel , Animales , Piel/inmunología , Piel/metabolismo , Piel/patología , Humanos , Receptores X del Hígado/metabolismo , Ratones , PPAR gamma/metabolismo , Psoriasis/inmunología , Psoriasis/patología , Psoriasis/metabolismo , Ratones Endogámicos C57BL , Interleucina-13/metabolismo , Factor de Transcripción STAT6/metabolismo , Inmunidad Innata , Masculino , Femenino , Linfocitos/inmunología , Linfocitos/metabolismoRESUMEN
The nuclear pore complex (NPC) is a proteinaceous nanopore that solely and selectively regulates the molecular transport between the cytoplasm and nucleus of a eukaryotic cell. The â¼50 nm-diameter pore of the NPC perforates the double-membrane nuclear envelope to mediate both passive and facilitated molecular transport, thereby playing paramount biological and biomedical roles. Herein, we visualize single NPCs by scanning electrochemical microscopy (SECM). The high spatial resolution is accomplished by employing â¼25 nm-diameter ion-selective nanopipets to monitor the passive transport of tetrabutylammonium at individual NPCs. SECM images are quantitatively analyzed by employing the finite element method to confirm that this work represents the highest-resolution nanoscale SECM imaging of biological samples. Significantly, we apply the powerful imaging technique to address the long-debated origin of the central plug of the NPC. Nanoscale SECM imaging demonstrates that unplugged NPCs are more permeable to the small probe ion than are plugged NPCs. This result supports the hypothesis that the central plug is not an intrinsic transporter, but is an impermeable macromolecule, e.g., a ribonucleoprotein, trapped in the nanopore. Moreover, this result also supports the transport mechanism where the NPC is divided into the central pathway for RNA export and the peripheral pathway for protein import to efficiently mediate the bidirectional traffic.
Asunto(s)
Microscopía Electroquímica de Rastreo , Poro Nuclear , Poro Nuclear/metabolismo , Poro Nuclear/química , Compuestos de Amonio Cuaternario/química , NanoporosRESUMEN
Colloidal quantum dots (QDs) are promising candidates for next-generation display technology because of their unique optical properties and have already appeared in the market as a high-end product. On the basis of their extraordinary properties, QD emissions with a given chemical composition can be tailored in a wide spectral window due to quantum size effects, which constitutes a key advantage of QDs in the display field. Specifically, investigations of structure-dependent and composition-dependent characterizations outside the quantum confinement effect have become an important part of practical applications. Therefore, from the perspective of designing nanostructures with well-defined heterointerfaces, strong quantum confinement effects with effective carrier confinement are desirable. Our results show that the photoluminescence (PL) intensity of CdSe/CdZnS core-shell QDs was enhanced 5.7 times compared with that of the CdSe core QDs. Supplementary analytical techniques involving transmission electron microscopy revealed the heterointerface configuration and composition distribution of the core and shell materials. The effects of the heterointerface on carrier dynamics in core-shell QDs were revealed by monitoring wavelength-dependent time-resolved PL. To further develop the QD light-emitting diodes (QD-LEDs), we produced an all-solution processed inverted QD-LEDs using CdSe/CdZnS core-shell QDs as the emitter. The electroluminescence spectrum of deep-red emissive QD-LEDs with CIE chromaticity coordinates of (0.68, 0.32) exhibited a peak at 638 nm.
RESUMEN
Plasmonic nanoparticles with an externally open nanogap can localize the electromagnetic (EM) field inside the gap and directly detect the target via the open nanogap with surface-enhanced Raman scattering (SERS). It would be beneficial to design and synthesize the open gap nanoprobes in a high yield for obtaining uniform and quantitative signals from randomly oriented nanoparticles and utilizing these particles for direct SERS analysis. Here, we report a facile strategy to synthesize open cross-gap (X-gap) nanocubes (OXNCs) with size- and EM field-tunable gaps in a high yield. The site-specific growth of Au budding structures at the corners of the AuNC using the principle that the Au deposition rate is faster than the surface diffusion rate of the adatoms allows for a uniform X-gap formation. The average SERS enhancement factor (EF) for the OXNCs with 2.6 nm X-gaps was 1.2 × 109, and the EFs were narrowly distributed within 1 order of magnitude for â¼93% of the measured OXNCs. OXNCs consistently displayed strong EM field enhancement on large particle surfaces for widely varying incident light polarization directions, and this can be attributed to the symmetric X-gap geometry and the availability of these gaps on all 6 faces of a cube. Finally, the OXNC probes with varying X-gap sizes have been utilized in directly detecting biomolecules with varying sizes without Raman dyes. The concept, synthetic method, and biosensing results shown here with OXNCs pave the way for designing, synthesizing, and utilizing plasmonic nanoparticles for selective, quantitative molecular-fingerprint Raman sensing and imaging applications.
RESUMEN
Recently, machine-learning approaches have accelerated computational materials design and the search for advanced solid electrolytes. However, the predictors are currently limited to static structural parameters, which may not fully account for the dynamic nature of ionic transport. In this study, we meticulously curated features considering dynamic properties and developed machine-learning models to predict the ionic conductivity, σ, of solid electrolytes. We compiled 14 phonon-related descriptors from first-principles phonon calculations along with 16 descriptors related to the structure and electronic properties. Our logistic regression classifiers exhibit an accuracy of 93%, while the random forest regression model yields a root-mean-square error for log(σ) of 1.179 S/cm and R2 of 0.710. Notably, phonon-related features are essential for estimating the ionic conductivities in both models. Furthermore, we applied our prediction model to screen 264 Li-containing materials and identified 11 promising candidates as potential superionic conductors.
RESUMEN
Laurus nobilis L. (LNL) belongs to the evergreen Lauraceae family. It is native to the Mediterranean and widely distributed in the southern United States, Europe, and the Middle East. LNL is rich in active ingredients of the sesquiterpene lactone series and has been reported to have antioxidant, anti-inflammatory, and anticancer effects. And parthenolide, known as a sesquiterpene lactone-based compound, inhibits the activation of lipopolysaccharide-binding protein (LBP), which is a major trigger for leaky gut syndrome. However, the effectiveness of LNL in improving the state of increased intestinal permeability has not yet been reported. Therefore, we demonstrated the efficacy of LNL, which is known to be rich in parthenolide, in improving intestinal permeability induced by IL-13. We investigated the improvement in permeability and analyzed major tight junction proteins (TJs), permeability-related mechanisms, weight and disease activity indices, and corresponding cytokine mechanisms. LNL maintained TJs homeostasis and clinical improvement by reducing increased claudin-2 through the inhibition of IL-13/STAT6 activation in TJ-damaged conditions. These results are expected to be effective in preventing leaky gut syndrome through the TJ balance and to further improve intestinal-related diseases, such as inflammatory bowel disease.
Asunto(s)
Laurus , Proteínas de Uniones Estrechas , Animales , Proteínas de Uniones Estrechas/metabolismo , Laurus/química , Permeabilidad , Extractos Vegetales/farmacología , Masculino , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Ratones , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Humanos , Citocinas/metabolismoRESUMEN
Numerous unique flora and fauna inhabit the Lower Florida Keys, including the endangered Florida Key deer, found nowhere else. In this vulnerable habitat of flat islands with low elevation, accelerated sea level rise poses a threat. Predicting the impact of sea level rise on vegetation and wildlife is crucial. This study used 5 Intergovernmental Panel on Climate Change (IPCC) sea level rise scenarios to assess their effects on No Name Key, Florida. The goal was to estimate changes in the Florida Key deer population relative to sea level rise using a lidar-derived elevation data and a vegetation map. The method used 2 cases to model the sea level rise impact. In Case 1, total non-submerged area at current sea level was determined. Using 5 IPCC scenarios, a new total non-submerged land area was estimated, and deer numbers were predicted for each scenario. In Case 2, upward migration of coastal vegetation combined with the coastal squeeze process was modeled. A distinct elevation range for each vegetation type at the current sea level was determined. Vegetation ranges were redistributed based on respective elevation ranges in the sea level rise scenarios. Areas for each vegetation type were recalculated, and Key deer numbers were estimated for each sea level rise scenario. Results under the worst emission scenario showed the following: (1) for case 1, the land area was reduced to 30 % of the current land area, corresponding to having about 27 deer, and (2) for case 2, the land area was reduced to 70 % of the current land area, having about 54 deer on No Name Key. The results indicated reduced non-submerged land area and less upland vegetation, particularly hardwoods/hammocks, by the year 2100. As less land area is available, a decline in Key deer population is expected as sea levels rise. Since Key deer favor upland vegetation, habitat affected by sea level rise will likely support a smaller deer population. The findings emphasize the need for precise, timely predictions of sea level rise impacts and long-term conservation strategies. Specifically designed measures are required to protect and maintain endangered wildlife, such as the Florida Key deer, residing on these vulnerable islands.
Asunto(s)
Ecosistema , Modelos Teóricos , Elevación del Nivel del Mar , Elevación del Nivel del Mar/estadística & datos numéricos , Florida , Dinámica Poblacional/estadística & datos numéricos , Distribución Animal , Simulación por Computador , Dispersión de las PlantasRESUMEN
Since 2011, South Korea has implemented biannual vaccinations against foot-and-mouth disease (FMD) and recently, lumpy skin disease (LSD), to mitigate the spread of transboundary animal diseases. However, due to past adverse reactions, potentially linked to acute phase responses from FMD vaccinations, there is hesitancy among Korean livestock farmers regarding new strategies for simultaneous vaccinations against both FMD and LSD. This study was conducted to assess possible adverse reactions to the LSD vaccination by analyzing acute phase proteins (APPs) in three groups: cows vaccinated against FMD (G1-FMDV), LSD (G2-LSDV), and both (G3-FMDV/LSDV). In G1-FMDV, APP levels peaked on day 3 post-vaccination (p < 0.001) and returned to baseline. In G2-LSDV, APP levels increased gradually, peaking on day 10 post-vaccination. In G3-FMDV/LSDV, APP levels peaked on day 3 post-vaccination and remained high until day 10 (p < 0.001). These results indicate that LSD vaccines trigger a later immune response compared to FMD vaccines, possibly due to different adjuvants. Therefore, a longer follow-up period for monitoring adverse reactions to LSD vaccinations may be required to understand and mitigate potential risks.
RESUMEN
With aging, men develop testosterone-deficiency syndrome (TDS). The development is closely associated with age-related mitochondrial dysfunction of Leydig cell and oxidative stress-induced reactive oxygen species (ROS). Testosterone-replacement therapy (TRT) is used to improve the symptoms of TDS. However, due to its various side effects, research on functional ingredients derived from natural products that do not have side effects is urgently needed. In this study, using the mitochondrial dysfunction TM3 (mouse Leydig) cells, in which testosterone biosynthesis is reduced by H2O2, we evaluated the effects of elderberry extract and monosaccharide-amino acid (fructose-leucine; FL) on mRNA and protein levels related to steroidogenesis-related enzymes steroidogenic acute regulatory protein (StAR), cytochrome P450 11A1(CYP11A1, cytochrome P450 17A1(CYP17A1), cytochrome P450 19A1(CYP19A1, aromatase), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and 17ß-hydroxysteroid dehydrogenase(17ß-HSD). We analyzed elderberry extract and extract-derived FL for changes in ROS scavenging activity and testosterone secretion. Elderberry extract and FL significantly reduced H2O2-induced intracellular ROS levels, improved testosterone secretion, and increased the mRNA and protein expression levels of steroidogenesis-related enzymes (StAR, 3b-HSD, 17b-HSD, CYP11A1, CYp17A1). However, the conversion of testosterone to estradiol was inhibited by elderberry extract and extract-derived FL, which reduced the mRNA and protein expression of CYP19A1. In conclusion, elderberry extract and FL are predicted to have value as novel functional ingredients that may contribute to the prevention of TDS by ameliorating reduced steroidogenesis.
Asunto(s)
Peróxido de Hidrógeno , Células Intersticiales del Testículo , Extractos Vegetales , Testosterona , Animales , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Ratones , Peróxido de Hidrógeno/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Línea Celular , Aminoácidos/metabolismo , Monosacáridos , Sambucus/química , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfoproteínas/metabolismo , Fosfoproteínas/genéticaRESUMEN
BACKGROUND AND OBJECTIVES: Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs. prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADS-P2A2RC, after percutaneous coronary intervention (PCI). METHODS: This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. RESULTS: Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358-6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868-3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). CONCLUSIONS: The CHADS-P2A2RC risk score is valuable in discriminating high-ischemic-risk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.