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1.
bioRxiv ; 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39282356

RESUMO

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4x mean depth) and deep whole exome (30-40x mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations. We evaluated the accuracy of BGE imputed genotypes against raw genotype calls from the Illumina Global Screening Array. All PUMAS cohorts had R 2 concordance ≥95% among SNPs with MAF≥1%, and never fell below ≥90% R 2 for SNPs with MAF<1%. Furthermore, concordance rates among local ancestries within two recently admixed cohorts were consistent among SNPs with MAF≥1%, with only minor deviations in SNPs with MAF<1%. We also benchmarked the discovery capacity of BGE to access protein-coding copy number variants (CNVs) against deep whole genome data, finding that deletions and duplications spanning at least 3 exons had a positive predicted value of ∼90%. Our results demonstrate BGE scalability and efficacy in capturing SNPs, indels, and CNVs in the human genome at 28% of the cost of deep whole-genome sequencing. BGE is poised to enhance access to genomic testing and empower genomic discoveries, particularly in underrepresented populations.

2.
Protein Sci ; 33(10): e5171, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39276020

RESUMO

Human epidermal growth factor receptors (HER)-also known as EGFR or ErbB receptors-are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time-resolved fluorescence technique called pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single-cell protein expression levels and diffusion coefficients. Our PIE-FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4-specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands.


Assuntos
Receptores ErbB , Multimerização Proteica , Receptor ErbB-4 , Receptor ErbB-4/metabolismo , Receptor ErbB-4/química , Receptor ErbB-4/genética , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/química , Receptores ErbB/genética , Espectrometria de Fluorescência
3.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39273565

RESUMO

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.


Assuntos
Biomarcadores , Exossomos , MicroRNAs , Humanos , Exossomos/metabolismo , Exossomos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Autopsia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Líquido Pericárdico/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala
4.
Nucleic Acids Res ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39217466

RESUMO

PARP inhibitors (PARPi) show selective efficacy in tumors with homologous recombination repair (HRR)-defects but the activation mechanism of HRR pathway in PARPi-treated cells remains enigmatic. To unveil it, we searched for the mediator bridging PARP1 to ATM pathways by screening 211 human ubiquitin-related proteins. We discovered TRIM44 as a crucial mediator that recruits the MRN complex to damaged chromatin, independent of PARP1 activity. TRIM44 binds PARP1 and regulates the ubiquitination-PARylation balance of PARP1, which facilitates timely recruitment of the MRN complex for DSB repair. Upon exposure to PARPi, TRIM44 shifts its binding from PARP1 to the MRN complex via its ZnF UBP domain. Knockdown of TRIM44 in cells significantly enhances the sensitivity to olaparib and overcomes the resistance to olaparib induced by 53BP1 deficiency. These observations emphasize the central role of TRIM44 in tethering PARP1 to the ATM-mediated repair pathway. Suppression of TRIM44 may enhance PARPi effectiveness and broaden their use even to HR-proficient tumors.

5.
Appl Ergon ; 121: 104369, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39182395

RESUMO

Mode awareness is important for the safe use of automated vehicles, yet drivers' understanding of mode transitions has not been sufficiently investigated. In this study, we administered an online survey to 838 respondents to examine their understanding of control responsibilities in partial and conditional driving automation with four types of interventions (brake pedal, steering wheel, gas pedal, and take-over request). Results show that most drivers understand that they are responsible for speed and distance control after brake pedal interventions and steering control after steering wheel interventions. However, drivers have mixed responses regarding the responsibility for speed and distance control after steering wheel interventions and the responsibility for steering control after gas pedal interventions. With a higher automation level (conditional driving automation), drivers expect automation to remain responsible more often compared to a lower automation level (partial driving automation). Regarding Hands-on requirements, more than 99% of respondents answered that drivers would keep their hands on the steering wheel after all intervention types in partial automation, while 60-95% would place their hands on the wheel after various intervention types in conditional automation. A misalignment between actual logic and drivers' expectations regarding control responsibilities is observed by comparing survey responses to the mode transition logic of commercial partially automated vehicles. To resolve confusion about control responsibilities and ensure consistent expectations, we propose implementing a consistent mode design and providing enhanced information to drivers.


Assuntos
Automação , Condução de Veículo , Humanos , Condução de Veículo/psicologia , Adulto , Masculino , Feminino , Inquéritos e Questionários , Pessoa de Meia-Idade , Automóveis , Análise e Desempenho de Tarefas , Adulto Jovem , Lógica , Sistemas Homem-Máquina , Compreensão
6.
Sensors (Basel) ; 24(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39204828

RESUMO

Wireless local area networks (WLANs) have recently evolved into technologies featuring extremely high throughput and ultra-high reliability. As WLANs are predominantly utilized in Internet of Things (IoT) and Wi-Fi-enabled sensor applications powered by coin cell batteries, these high-efficiency, high-performance technologies often cause significant battery depletion. The introduction of the trigger frame-based uplink transmission method, designed to enhance network throughput, lacks adequate security measures, enabling attackers to manipulate trigger frames. Devices receiving such frames must respond immediately; however, if a device receives a fake trigger frame, it fails to enter sleep mode, continuously sending response signals and thereby increasing power consumption. This problem is specifically acute in next-generation devices that support multi-link operation (MLO), capable of simultaneous transmission and reception across multiple links, rendering them more susceptible to battery draining attacks than conventional single-link devices. To address this, this paper introduces a Secure Triggering Frame-Based Dynamic Power Saving Mechanism (STF-DPSM) specifically designed for multi-link environments. Experimental results indicate that even in a multi-link environment with only two links, the STF-DPSM improves energy efficiency by an average of approximately 55.69% over conventional methods and reduces delay times by an average of approximately 44.7% compared with methods that consistently utilize encryption/decryption and integrity checks.

7.
Org Lett ; 26(35): 7352-7356, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39177181

RESUMO

A rapid Brønsted superbase catalysis for highly functionalized sulfur(VI)-fluoride exchange (SuFEx) hubs bearing all-carbon quaternary centers was developed. Remarkable functional group tolerance toward esters and nitriles was achieved by Michael addition of cyanoacetate derivatives to ethenesulfonyl fluoride with low catalyst loadings (∼0.5 mol %) within a short reaction time (0.5-30 min). Gram-scalability, water tolerance, and compatibility in polymeric catalysis showcase its unique practicability. SuFEx click conjugations were demonstrated using various amines, including DNA-tethered biomolecules.

8.
Am J Dent ; 37(4): 171-176, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39186595

RESUMO

PURPOSE: To evaluate the impact of coffee attributes on tooth discoloration, emphasizing the importance of potential factors such as serving temperature, bean variety, and chlorogenic acid (CGA) content. METHODS: Coffee preparation involved the extraction of espresso from four types of roasted beans (Vietnam Robusta, Uganda Robusta, Ethiopia Yirgacheffe Arabica, and Colombia Supremo Arabica), followed by chlorogenic content analysis using high-performance liquid chromatography. Bovine tooth enamel specimens were carefully prepared and stained with coffee (hot and iced), with a color assessment conducted at different time intervals (3, 9, 24, 48, and 72 hours). The Vickers hardness tester was employed to ensure specimen quality, while spectrophotometry aided in color analysis using the CIEDE2000 formula. RESULTS: The results revealed varying effects of serving temperature, bean type, and CGA content on tooth discoloration. It was demonstrated that perceptible color differences occur after a 3-hour immersion in coffee, with hot coffee showing higher staining potential compared to iced variations. Furthermore, chlorogenic acid content and bean type significantly affected tooth discoloration, with higher chlorogenic acid levels associated with increased staining. Notably, Robusta coffee showed less discoloration compared to Arabica, potentially due to differences in pH levels. CLINICAL SIGNIFICANCE: The findings provide valuable insights for both dental practitioners and coffee consumers, assisting in making informed decisions regarding coffee intake and oral hygiene.


Assuntos
Ácido Clorogênico , Café , Descoloração de Dente , Café/química , Descoloração de Dente/induzido quimicamente , Ácido Clorogênico/análise , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Cor , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/química , Espectrofotometria , Temperatura
9.
Environ Microbiome ; 19(1): 60, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39160591

RESUMO

BACKGROUND: Lake Bonney, which is divided into a west lobe (WLB) and an east lobe (ELB), is a perennially ice-covered lake located in the McMurdo Dry Valleys of Antarctica. Despite previous reports on the microbial community dynamics of ice-covered lakes in this region, there is a paucity of information on the relationship between microbial genomic diversity and associated nutrient cycling. Here, we applied gene- and genome-centric approaches to investigate the microbial ecology and reconstruct microbial metabolic potential along the depth gradient in Lake Bonney. RESULTS: Lake Bonney is strongly chemically stratified with three distinct redox zones, yielding different microbial niches. Our genome enabled approach revealed that in the sunlit and relatively freshwater epilimnion, oxygenic photosynthetic production by the cyanobacterium Pseudanabaena and a diversity of protists and microalgae may provide new organic carbon to the environment. CO-oxidizing bacteria, such as Acidimicrobiales, Nanopelagicales, and Burkholderiaceae were also prominent in the epilimnion and their ability to oxidize carbon monoxide to carbon dioxide may serve as a supplementary energy conservation strategy. In the more saline metalimnion of ELB, an accumulation of inorganic nitrogen and phosphorus supports photosynthesis despite relatively low light levels. Conversely, in WLB the release of organic rich subglacial discharge from Taylor Glacier into WLB would be implicated in the possible high abundance of heterotrophs supported by increased potential for glycolysis, beta-oxidation, and glycoside hydrolase and may contribute to the growth of iron reducers in the dark and extremely saline hypolimnion of WLB. The suboxic and subzero temperature zones beneath the metalimnia in both lobes supported microorganisms capable of utilizing reduced nitrogens and sulfurs as electron donors. Heterotrophs, including nitrate reducing sulfur oxidizing bacteria, such as Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), and denitrifying bacteria, such as Gracilimonas (MAG7), Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), dominated the hypolimnion of WLB, whereas the environmental harshness of the hypolimnion of ELB was supported by the relatively low in metabolic potential, as well as the abundance of halophile Halomonas and endospore-forming Virgibacillus. CONCLUSIONS: The vertical distribution of microbially driven C, N and S cycling genes/pathways in Lake Bonney reveals the importance of geochemical gradients to microbial diversity and biogeochemical cycles with the vertical water column.

10.
Clin Cancer Res ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150541

RESUMO

PURPOSE: Histological transformation from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a key mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs). However, transcriptomic changes between NSCLC and transformed SCLC (t-SCLC) remain unexplored. EXPERIMENTAL DESIGN: We conducted whole transcriptome analysis of 59 regions of interest (ROIs) through the spatial profiling of FFPE tissues obtained from ten patients (lung adenocarcinoma, 22; combined SCLC/NSCLC, 7; t-SCLC, 30 ROIs). Transcriptomic profiles and differentially expressed genes (DEGs) were compared between pre- and post-transformed tumors. RESULTS: Following EGFR-TKI treatment, 93.7% (15/16) of transformed-SCLC (t-SCLC) components evolved into neuroendocrine-high subtypes (SCLC-A or SCLC-N). The transition to t-SCLC occurred regardless of EGFR-TKI treatment and EGFR mutational status, with a notable decrease in EGFR expression (P < 0.001) at both mRNA and protein levels. Pathway analysis revealed that gene overexpression was related to epigenetic alterations in t-SCLC. Interestingly, Histone deacetylase (HDAC) inhibitors restored EGFR expression in SNU-2962A cells and their organoid model. The synergistic effects of third-generation EGFR-TKI osimertinib and the HDAC inhibitor fimepinostat were validated in both in vitro and in vivo models. CONCLUSIONS: Our study demonstrated most t-SCLC showed neuronal subtypes with low EGFR expression. DEGs analysis and t-SCLC preclinical models identified an epigenetic modifier as a promising treatment strategy for t-SCLC.

11.
J Prev Med Public Health ; 57(4): 327-338, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965927

RESUMO

OBJECTIVES: Estimating the number of deaths caused by smoking is crucial for developing and evaluating tobacco control and smoking cessation policies. This study aimed to determine smoking-attributable mortality (SAM) in Korea in 2020. METHODS: Four large-scale cohorts from Korea were analyzed. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) of smoking-related death. By conducting a meta-analysis of these HRs, the pooled HRs of smoking-related death for 41 diseases were estimated. Population-attributable fractions (PAFs) were calculated based on the smoking prevalence for 1995 in conjunction with the pooled HRs. Subsequently, SAM was derived using the PAF and the number of deaths recorded for each disease in 2020. RESULTS: The pooled HR for all-cause mortality attributable to smoking was 1.73 for current men smokers (95% confidence interval [CI], 1.53 to 1.95) and 1.63 for current women smokers (95% CI, 1.37 to 1.94). Smoking accounted for 33.2% of all-cause deaths in men and 4.6% in women. Additionally, it was a factor in 71.8% of men lung cancer deaths and 11.9% of women lung cancer deaths. In 2020, smoking was responsible for 53 930 men deaths and 6283 women deaths, totaling 60 213 deaths. CONCLUSIONS: Cigarette smoking was responsible for a significant number of deaths in Korea in 2020. Monitoring the impact and societal burden of smoking is essential for effective tobacco control and harm prevention policies.


Assuntos
Fumar , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Causas de Morte/tendências , Bases de Dados Factuais , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Prevalência , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia
12.
Lung Cancer ; 194: 107870, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38986212

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion-specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion. METHODS: In this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. RESULTS: Among 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7-5.5) months and 6.5 (95 % CI = 3.9-not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib. CONCLUSION: Osimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions. CLINICALTRIALS: govIdentifier: NCT03414814.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Éxons , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Mutagênese Insercional , Mutação , Resultado do Tratamento , República da Coreia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Indóis , Pirimidinas
13.
Eur J Cancer ; 208: 114206, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38981315

RESUMO

BACKGROUND: Mobocertinib, an EGFR exon 20 insertion (Ex20ins)-specific tyrosine kinase inhibitor has been used for treatment of advanced/metastatic EGFR Ex20ins-mutant non-small cell lung cancer (NSCLC). However, resistance mechanisms to EGFR Ex20ins-specific inhibitors and the efficacy of subsequent amivantamab treatment is unknown. METHODS: To investigate resistance mechanisms, tissue and cfDNA samples were collected before treatment initiation and upon development of resistance from NSCLC patients with EGFR Ex20ins mutations received mobocertinib, poziotinib, and amivantamab treatments. Genetic alterations were analyzed using whole-genome and targeted sequencing, and in vitro resistant cell lines were generated for validation. RESULTS: EGFR amplification (n = 6, including 2 broad copy number gain) and EGFR secondary mutation (n = 3) were observed at the resistance of mobocertinib. One patient had both EGFR secondary mutation and high EGFR focal amplification. In vitro models harboring EGFR alterations were constructed to validate resistance mechanisms and identify overcoming strategies to resistance. Acquired EGFR-dependent alterations were found to mediate resistance to mobocertinib in patients and in vitro models. Furthermore, two of six patients who received sequential amivantamab followed by an EGFR tyrosine kinase inhibitor had MET amplification and showed partial response. CONCLUSIONS: Our study revealed EGFR-dependent and -independent mechanisms of mobocertinib resistance in patients with advanced EGFR Ex20ins-mutant NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Éxons , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mutagênese Insercional , Mutação , /uso terapêutico
14.
Int Immunopharmacol ; 140: 112767, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39083922

RESUMO

The skin acts as a vital barrier, shielding the body from external threats that can trigger dryness, itching, and inflammation. Pilea mongolica, a traditional Chinese medicinal herb, holds promise for various ailments, yet its anti-inflammatory properties remain understudied. This study aimed to explore the potential anti-inflammatory effects of the methanol extract of P. mongolica (MEPM) and its underlying molecular mechanisms and active compounds in LPS-stimulated human keratinocytes. MEPM treatment, at concentrations without cytotoxicity, significantly decreased NO productions and the iNOS, IL-6, IL-1ß, and TNF-α levels in LPS-induced HaCaT cells. Moreover, MEPM suppressed IRAK4 expression and phosphorylation of JNK, ERK, p38, p65, and c-Jun, suggesting that the anti-inflammatory effects of MEPM result from the inhibition of IRAK4/MAPK/NF-κB/AP-1 signaling pathway. Through LC/MS/MS analysis, 30 compounds and 24 compounds were estimated in negative and positive modes, respectively, including various anti-inflammatory compounds, such as corilagin and geraniin. Through HPLC analysis, geraniin was found to be present in MEPM at a concentration of 18.87 mg/g. Similar to MEPM, geraniin reduced iNOS mRNA expression and inhibited NO synthesis. It also decreased mRNA and protein levels of inflammatory cytokines, including IL-6 and TNF-α, and inhibited IRAK4 expression and the phosphorylation of MAPKs, NF-κB, and AP-1 pathways. Therefore, it can be inferred that the anti-inflammatory effects of MEPM are attributable to geraniin. Thus, MEPM and its active compound geraniin are potential candidates for use in natural functional cosmetics.


Assuntos
Anti-Inflamatórios , Glucosídeos , Taninos Hidrolisáveis , Queratinócitos , Lipopolissacarídeos , Extratos Vegetais , Transdução de Sinais , Humanos , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Glucosídeos/farmacologia , Células HaCaT , Taninos Hidrolisáveis/farmacologia , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Metanol/química , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo
15.
J Clin Med ; 13(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39064246

RESUMO

Background/Objectives: While deficits in executive attention and alerting systems in children with attention deficit hyperactivity disorder (ADHD) are well-documented, findings regarding orienting attention in ADHD have been inconsistent. The current study investigated the mechanism of attentional orienting in children with ADHD by examining their attentional bias towards threatening stimuli. Furthermore, we explored the modulating role of anxiety levels in ADHD on this attentional bias. Methods: In Experiment 1, 20 children with ADHD and 26 typically developing children (TDC) performed a continuous performance task that included task-irrelevant distractions consisting of angry faces and neutral places. In Experiment 2, 21 children with ADHD and 25 TDC performed the same task, but with angry and neutral faces as distractors. To measure children's anxiety levels, the State-Trait Anxiety Inventory was administered before each experiment. Results: In Experiment 1, results revealed no attentional bias effects in children with ADHD, whereas TDC exhibited attentional capture effects by both types of distractors. However, in Experiment 2, ADHD children demonstrated an attentional bias towards angry faces, which revealed a significant positive correlation with their trait anxiety levels (r = 0.61, p < 0.05). Further analyses combining all ADHD children showed that trait anxiety levels in Experiment 2 were significantly higher than those in Experiment 1. Finally, a significant positive correlation was found between anxiety levels and attentional bias towards angry faces in all ADHD children (r = 0.36, p < 0.01). Conclusions: Children with ADHD exhibited atypical attentional-orienting effects to threats, and their levels of trait anxiety appeared to modulate such attentional-orienting mechanisms.

16.
Molecules ; 29(14)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39064903

RESUMO

For the purpose of predicting the state of health of already used lithium-ion batteries from 85 kWh electric vehicles, a simplified equivalent circuit model is utilized to estimate the electrochemical time constant from constant current discharge profiles. The grading process among as-obtained LIB cells is classified into three level types according to the remaining capacity and direct current resistance. Theoretically, the logarithmic equation describing cycling behavior is derived and utilized in the prediction of the state of health of the used cells. After the selection of the electrochemical time constant obtained from the best-fitting results in constant current discharge data, the suitable cycle number until the 20th cycle was selected for the prediction of the state of health after the 250th cycling data, which revealed that a narrow error range below 5% was for high and medium battery grades. Also, this error range became abruptly wider in lowest grade batteries, indicating that our proposed model for cycling behavior was highly useful in the prediction of the future state of health of the used batteries.

17.
PLoS One ; 19(7): e0304907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008453

RESUMO

The objective of the review is to identify factors related to how East and Southeast Asian immigrant youth aged 12-24 and their families access mental health and substance use (MHSU) services. To address how East and Southeast Asian youth and their families access mental health and substance use services, a scoping review was conducted to identify studies in these databases: PubMed, MEDLINE (Ovid), EMBASE (Ovid), PsychINFO, CINAHL, and Sociology Collection. Qualitative content analysis was used to deductively identify themes and was guided by Bronfenbrenner's Ecological Systems Theory, the process-person-context-time (PPCT) model, and the five dimensions of care accessibility (approachability, acceptability, availability and accommodation, appropriateness, affordability). Seventy-three studies met the inclusion criteria. The dimensions of healthcare accessibility shaped the following themes: 1) Acceptability; 2) Appropriateness; 3) Approachability; 4) Availability and Accommodation. Bronfenbrenner's Ecological Systems Theory and the PPCT model informed the development of the following themes: 1) Immediate Environment/Proximal Processes (Familial Factors, Relationships with Peers; 2) Context (School-Based Services/Community Resources, Discrimination, Prevention, Virtual Care); 3) Person (Engagement in Services/Treatment/Research, Self-management); 4) Time (Immigration Status). The study suggests that there is a growing body of research (21 studies) focused on identifying acceptability factors, including Asian cultural values and the model minority stereotype impacting how East and Southeast Asian immigrant youth access MHSU services. This review also highlighted familial factors (16 studies), including family conflict, lack of MHSU literacy, reliance on family as support, and family-based interventions, as factors affecting how East and Southeast Asian immigrant youth access MHSU care. However, the study also highlighted a dearth of research examining how East and Southeast Asian youth with diverse identities access MHSU services. This review emphasizes the factors related to the access to MHSU services by East and Southeast Asian immigrant youth and families while providing insights that will improve cultural safety.


Assuntos
Emigrantes e Imigrantes , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Mental , Transtornos Relacionados ao Uso de Substâncias , Humanos , Emigrantes e Imigrantes/psicologia , Adolescente , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Sudeste Asiático/etnologia , Criança , Adulto Jovem , Família , Ásia Oriental , População do Sudeste Asiático
18.
Inorg Chem ; 63(32): 15044-15052, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39074868

RESUMO

Two o-carboranes with (i) 9,9-dimethyl-9H-xanthene and (ii) spiro[fluorene-9,9'-xanthene] moieties (XTC and sXTC, respectively) were prepared and characterized. Single X-ray crystallography analysis revealed the presence of intermolecular hydrogen bonds in XTC crystals. Although both compounds did not exhibit emission in tetrahydrofuran solutions at 298 K, intense bluish emission was observed in the solid states and frozen tetrahydrofuran solutions at 77 K. According to the results of theoretical calculations, this emission originated from an intramolecular charge transfer (ICT) transition with the o-carborane moiety. The absolute quantum efficiency (Φem) of the ICT-based emission in the film state equaled 49% for XTC and 20% for sXTC but was as high as 90% for the crystals of both compounds. The crystal structures of XTC and sXTC revealed that the o-carboranyl-appended phenyl plane was orthogonal (85-89°) to the carbon-carbon bonding axis in the o-carborane, indicating the existence of a strong exo-π-interaction, which was identified as the structural basis for the ICT-based transition. These results implied that the intermolecular structural effect of XTC in the randomly aggregated solid state (film) helped maintain the above orthogonality and, hence, the high efficiency from the ICT radiative mechanism. Thus, we concluded that the ICT radiative efficiency of o-carboranyl luminophores in the aggregated solid state can be controlled by specific intermolecular interactions and that the molecular geometric design inducing this feature can be important for developing highly efficient carboranyl luminophores.

19.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38931394

RESUMO

Yeokwisan (YWS) is an herbal medicine prescription consisting of six oriental herbal medicines, developed to treat reflux esophagitis. We focused on developing an analytical method capable of simultaneously quantifying 13 compounds in YWS samples using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and exploring their antioxidant effects. All compounds examined in both analytical systems were chromatographically separated on a SunFireTM C18 (4.6 × 250 mm, 5 µm) column and an Acquity UPLC BEH C18 (2.1 × 100 mm, 1.7 µm) column using gradient elution of a water-acetonitrile mobile phase. Antioxidant effects were evaluated based on radical scavenging activity (DPPH and ABTS tests) and ferrous ion chelating activity. In two analytical methods, the coefficient of determination of the regression equation was ≥0.9965, the recovery range was 81.11-108.21% (relative standard deviation (RSD) ≤ 9.33%), and the precision was RSD ≤ 11.10%. Application of the optimized analysis conditions gave quantitative analysis results for YWS samples of 0.02-100.36 mg/g. Evaluation of the antioxidant effects revealed that baicalein and baicalin exhibit significant antioxidant activity, suggesting that they play an important role in the antioxidant effects of YWS.

20.
Insects ; 15(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38921093

RESUMO

High-risk termites in wood imported to the Republic of Korea are currently treated with methyl bromide (MB), which has ozone-depleting properties and is highly toxic. This study evaluated the effectiveness of sulfuryl fluoride (SF) as a quarantine treatment against Reticulitermes speratus Kolbe (Blattodea: Rhinotermitidae) in wood, along with its wood sorption and penetration capacity. The LCt50 and LCt99 values for SF were 30.87 and 42.53 mg h/L at 23 °C and 151.62 and 401.9 mg h/L at 5 °C, respectively. The SF Ct values did not significantly differ between dry and wet wood at loading ratios of 10%, 30%, and 50% at both 5 °C and 23 °C (p > 0.05). In a closed wooden cube, the LCt50 and LCt99 for SF for R. speratus were 31.59 and 53.34 mg h/L, respectively, indicating an excellent wood penetration ability. SF caused 100% termite mortality with a 90% loading ratio in the scale-up trials (500 L). The SF concentration during ventilation decreased below the threshold limit value (TLV) of 5 ppm within 30 min, confirming that the working conditions were safe. This study provides a basis for the use of SF as an alternative to MB for the treatment of termites in wood.

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