ABSTRACT
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.
Subject(s)
Asthma , NF-E2-Related Factor 2 , Th2 Cells , Animals , Female , Humans , Mice , Asthma/immunology , Asthma/metabolism , Cytokines/metabolism , Disease Models, Animal , Eosinophilia/immunology , Eosinophilia/metabolism , Glycolysis , Interleukin-33/metabolism , Lung/immunology , Lung/metabolism , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/metabolism , Oxidative Phosphorylation , PPAR gamma/metabolism , Reactive Oxygen Species/metabolism , Th2 Cells/immunology , Th2 Cells/metabolismABSTRACT
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.
ABSTRACT
BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
Subject(s)
Breast Neoplasms , Cell-Free Nucleic Acids , Neoplastic Cells, Circulating , Humans , Female , Breast Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Cell-Free Nucleic Acids/therapeutic use , Prognosis , Epithelial Cell Adhesion Molecule/genetics , Biomarkers, Tumor/genetics , Disease Progression , Class I Phosphatidylinositol 3-Kinases/genetics , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
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.
Subject(s)
Microscopy, Electrochemical, Scanning , Nuclear Pore , Nuclear Pore/metabolism , Nuclear Pore/chemistry , Quaternary Ammonium Compounds/chemistry , NanoporesABSTRACT
Unequivocally, Pb2+ as a harmful substance damaging children's brain and nerve systems, thereby causing behavior and learning disabilities, should be detected much lower than the elevated blood lead for children, 240 nM, endorsed by US CDC considering the unknown neurotoxic effects, yet the ultralow detection limit up to sub-ppb level remains a challenge due to the intrinsically insufficient sensitivity in the current analytical techniques. Here, we present nanoemulsion (NE)-integrated single-entity electrochemistry (NI-SEE) toward ultrasensitive sensing of blood lead using Pb-ion-selective ionophores inside a NE, i.e., Pb2+-selective NE. Through the high thermodynamic selectivity between Pb2+ and Pb-ionophore IV, and the extremely large partition coefficient for the Pb2+-Pb-ionophore complex inside NEs, we modulate the selectivity and sensitivity of NI-SEE for Pb2+ sensing up to an unprecedentedly low detection limit, 20 ppt in aqueous solutions, and lower limit of quantitation, 40 ppb in blood serums. This observation is supported by molecular dynamics simulations, which clearly corroborate intermolecular interactions, e.g., H-bonding and π*-n, between the aromatic rings of Pb-ionophore and lone pair electrons of oxygen in dioctyl sebacate (DOS), plasticizers of NEs, subsequently enhancing the current intensity in NI-SEE. Moreover, the highly sensitive sensing of Pb2+ is enabled by the appropriate suppression of hydroxyl radical formation during NI-SEE under a cathodic potential applied to a Pt electrode. Overall, the experimentally demonstrated NI-SEE approach and the results position our new sensing technology as potential sensors for practical environmental and biomedical applications as well as a platform to interrogate the stoichiometry of target ion-ionophore recognition inside a NE as nanoreactors.
Subject(s)
Lead , Water , Child , Humans , Electrochemistry/methods , Ionophores/chemistry , ElectrodesABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Bacteremia , Ceftazidime , Drug Combinations , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , beta-Lactamases , Humans , Ceftazidime/therapeutic use , Ceftazidime/pharmacology , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Male , Azabicyclo Compounds/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Bacteremia/drug therapy , Bacteremia/microbiology , Carbapenems/therapeutic use , Carbapenems/pharmacology , Whole Genome Sequencing , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Meropenem/therapeutic use , Meropenem/pharmacology , Drug Resistance, Multiple, Bacterial/geneticsABSTRACT
Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase ß and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.
Subject(s)
Neoplasms , Transcriptome , Humans , Gallic Acid/pharmacology , Gallic Acid/metabolism , Gene Expression ProfilingABSTRACT
Neutrophilic inflammation is a prominent feature of chronic obstructive pulmonary disease (COPD). Developmental endothelial locus-1 (Del-1) has been reported to limit excessive neutrophilic inflammation by inhibiting neutrophil adhesion to the vascular endothelial cells. However, the effects of Del-1 in COPD are not known. We investigated the role of Del-1 in the pathogenesis of COPD. Del-1 protein expression was decreased in the lungs of COPD patients, especially in epithelial cells and alveolar macrophages. In contrast to human lung tissue, Del-1 expression was upregulated in lung tissue from mice treated with cigarette smoke extracts (CSE). Overexpression of Del-1 significantly suppressed IL-8 release and apoptosis in CSE-treated epithelial cells. In contrast, knockdown of Del-1 enhanced IL-8 release and apoptosis. In macrophages, overexpression of Del-1 significantly suppressed inflammatory cytokine release, and knockdown of Del-1 enhanced it. This anti-inflammatory effect was mediated by inhibiting the phosphorylation and acetylation of NF-κB p65. Nuclear factor erythroid 2-related factor 2 (Nrf2) activators, such as quercetin, resveratrol, and sulforaphane, increased Del-1 in both cell types. These results suggest that Del-1, mediated by Nrf2, plays a protective role against the pathogenesis of COPD, at least in part through anti-inflammatory and anti-apoptotic effects.
Subject(s)
Interleukin-8 , Pulmonary Disease, Chronic Obstructive , Animals , Humans , Mice , Anti-Inflammatory Agents/pharmacology , Apoptosis/genetics , Endothelial Cells/metabolism , Inflammation/metabolism , Inflammation/pathology , Interleukin-8/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/metabolism , Tobacco Smoking/adverse effects , Calcium-Binding Proteins/metabolism , Cell Adhesion Molecules/metabolismABSTRACT
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.
Subject(s)
Ecosystem , Models, Theoretical , Sea Level Rise , Sea Level Rise/statistics & numerical data , Florida , Population Dynamics/statistics & numerical data , Animal Distribution , Computer Simulation , Plant DispersalABSTRACT
This study aims to develop a virtual reality-based education program for managing behavioral and psychological symptoms of dementia for family carers of persons living with dementia and investigate the feasibility for users. The program was developed through literature review, interviews with family carers, surveys, and expert content validity assessment. User feasibility was evaluated quantitatively through a questionnaire on usefulness, ease of use, and satisfaction, and qualitatively through participant interviews. The program was produced in two parts, Type 1 and Type 2, consisting of three and six episodes, respectively. Participants showed a high level of satisfaction with overall program scores of 4.28 ± 0.66 and 4.34 ± 0.41 for the two evaluations. Participants also expressed that both programs were helpful, Type 1 for achieving changes in attitude associated with more understanding of persons living with dementia and Type 2 for acquiring coping methods through communication training. Use of the virtual reality device was not inconvenient and was identified as helpful due to the high immersion experience. Results of this study confirmed that family carers had no resistance to education using new technologies such as virtual reality devices and that virtual reality-based education could be effective for training family carers.
Subject(s)
Dementia , Virtual Reality , Humans , Feasibility Studies , Caregivers/psychology , Communication , Dementia/therapy , Dementia/psychologyABSTRACT
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.
Subject(s)
Hydrogen Peroxide , Leydig Cells , Plant Extracts , Testosterone , Animals , Leydig Cells/metabolism , Leydig Cells/drug effects , Mice , Hydrogen Peroxide/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Male , Cell Line , Amino Acids/metabolism , Monosaccharides , Sambucus/chemistry , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Phosphoproteins/metabolism , Phosphoproteins/geneticsABSTRACT
The slogan "Breast is Best" has been popularized by medical organizations and parenting networks to extoll the benefits of breastfeeding, yet the causal effects are widely debated. Our study contributes to the debate by examining whether breastfeeding has differential effects based on the propensity to breastfeed, which is also known as causal effect heterogeneity. Prior studies attempt to isolate the causal effect of breastfeeding by netting out confounding characteristics, but we argue that the effects of breastmilk are unlikely to operate in a vacuum. The social forces that promote or constrain breastfeeding among different populations in American society can also shape its effects. Using rich intergenerational panel data from the NLSY79 Child and Young Adult cohort (n = 7902), we evaluate heterogeneous treatment effects in the relationship between breastfeeding and child development from ages 4 to 14 using stratification-multilevel propensity score models. We find that breastfeeding is associated with small benefits for behavioral development, math scores, and academic ability among those with the highest propensities to breastfeed. By contrast, its small benefits for reading comprehension and vocabulary are concentrated among children with the lowest propensities to breastfeed. Our findings suggest that the social process of selection into breastfeeding cannot be fully disentangled from its estimated effects. The social context not only shapes who breastfeeds in American society, but also who benefits most.
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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.
ABSTRACT
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.
Subject(s)
Laurus , Tight Junction Proteins , Animals , Tight Junction Proteins/metabolism , Laurus/chemistry , Permeability , Plant Extracts/pharmacology , Male , Tight Junctions/drug effects , Tight Junctions/metabolism , Mice , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Humans , Cytokines/metabolismABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
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Electrolyte-gated transistors (EGTs) are promising candidates as artificial synapses owing to their precise conductance controllability, quick response times, and especially their low operating voltages resulting from ion-assisted signal transmission. However, it is still vague how ion-related physiochemical elements and working mechanisms impact synaptic performance. Here, to address the unclear correlations, we suggest a methodical approach based on electrochemical analysis using poly(ethylene oxide) EGTs with three alkali ions: Li+, Na+, and K+. Cyclic voltammetry is employed to identify the kind of electrochemical reactions taking place at the channel/electrolyte interface, which determines the nonvolatile memory functionality of the EGTs. Additionally, using electrochemical impedance spectroscopy and qualitative analysis of electrolytes, we confirm that the intrinsic properties of electrolytes (such as crystallinity, solubility, and ion conductivity) and ion dynamics ultimately define the linearity/symmetricity of conductance modulation. Through simple but systematic electrochemical analysis, these results offer useful insights for the selection of components for high-performing artificial synapses.
ABSTRACT
BACKGROUND: Persicaria maackiana (Regel) is a potential medicinal plant that exerts anti-diabetic effects. However, the lack of genomic information on P. maackiana hinders research at the molecular level. OBJECTIVE: Herein, we aimed to construct a draft genome assembly and obtain comprehensive genomic information on P. maackiana using high-throughput sequencing tools PacBio Sequel II and Illumina. METHODS: Persicaria maackiana samples from three natural populations in Gaecheon, Gichi, and Uiryeong reservoirs in South Korea were used to generate genomic DNA libraries, perform genome de novo assembly, gene ontology analysis, phylogenetic tree analysis, genotyping, and identify microsatellite markers. RESULTS: The assembled P. maackiana genome yielded 32,179 contigs. Assessment of assembly integrity revealed 1503 (93.12%) complete Benchmarking Universal Single-Copy Orthologs. A total of 64,712 protein-coding genes were predicted and annotated successfully in the protein database. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs, 13,778 genes were annotated into 18 categories. Genes that activated AMPK were identified in the KEGG pathway. A total of 316,992 microsatellite loci were identified, and primers targeting the flanking regions were developed for 292,059 microsatellite loci. Of these, 150 primer sets were randomly selected for amplification, and 30 of these primer sets were identified as polymorphic. These primers amplified 3-9 alleles. The mean observed and expected heterozygosity were 0.189 and 0.593, respectively. Polymorphism information content values of the markers were 0.361-0.754. CONCLUSION: Collectively, our study provides a valuable resource for future comparative genomics, phylogeny, and population studies of P. maackiana.
Subject(s)
Polygonaceae , Molecular Sequence Annotation , Phylogeny , Polygonaceae/genetics , Genomics , Microsatellite Repeats/geneticsABSTRACT
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.