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1.
Proc Natl Acad Sci U S A ; 121(41): e2407647121, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39361642

RESUMO

Memory effect refers to the phenomenon where past events influence a system's current and future states or behaviors. In biology, memory effects often arise from intra- or intermolecular interactions, leading to temporally correlated behaviors. Single-molecule studies have shown that enzymes and DNA-binding proteins can exhibit time-correlated behaviors of their activity. While memory effects are well documented and studied in vitro, no such examples exist in cells to our knowledge. Combining single-molecule tracking (SMT) and single-cell protein quantitation, we find in living Escherichia coli cells distinct temporal correlations in the binding/unbinding events on DNA by MerR- and Fur-family metalloregulators, manifesting as memory effects with timescales of ~1 s. These memory effects persist irrespective of the type of the metalloregulators or their metallation states. Moreover, these temporal correlations of metalloregulator-DNA interactions are associated with spatial confinements of the metalloregulators near their DNA binding sites, suggesting microdomains of ~100 nm in size that possibly result from the spatial organizations of the bacterial chromosome without the involvement of membranes. These microdomains likely facilitate repeated binding events, enhancing regulator-DNA contact frequency and potentially gene regulation efficiency. These findings provide unique insights into the spatiotemporal dynamics of protein-DNA interactions in bacterial cells, introducing the concept of microdomains as a crucial player in memory effect-driven gene regulation.


Assuntos
DNA Bacteriano , Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Escherichia coli/genética , DNA Bacteriano/metabolismo , DNA Bacteriano/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Regulação Bacteriana da Expressão Gênica , Ligação Proteica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Sítios de Ligação
2.
Nucleic Acids Res ; 52(15): 9303-9316, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39036959

RESUMO

Targeting inter-duplex junctions in catenated DNA with bidirectional bis-intercalators is a potential strategy for enhancing anticancer effects. In this study, we used d(CGTATACG)2, which forms a tetraplex base-pair junction that resembles the DNA-DNA contact structure, as a model target for two alkyl-linked diaminoacridine bis-intercalators, DA4 and DA5. Cross-linking of the junction site by the bis-intercalators induced substantial structural changes in the DNA, transforming it from a B-form helical end-to-end junction to an over-wounded side-by-side inter-duplex conformation with A-DNA characteristics and curvature. These structural perturbations facilitated the angled intercalation of DA4 and DA5 with propeller geometry into two adjacent duplexes. The addition of a single carbon to the DA5 linker caused a bend that aligned its chromophores with CpG sites, enabling continuous stacking and specific water-mediated interactions at the inter-duplex contacts. Furthermore, we have shown that the different topological changes induced by DA4 and DA5 lead to the inhibition of topoisomerase 2 activities, which may account for their antitumor effects. Thus, this study lays the foundations for bis-intercalators targeting biologically relevant DNA-DNA contact structures for anticancer drug development.


Assuntos
Antineoplásicos , DNA , Substâncias Intercalantes , Conformação de Ácido Nucleico , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Humanos , DNA/química , DNA/metabolismo , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo II/química , Linhagem Celular Tumoral , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia
3.
Proc Natl Acad Sci U S A ; 120(10): e2216722120, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36848556

RESUMO

Recent studies have uncovered the therapeutic potential of elesclomol (ES), a copper-ionophore, for copper deficiency disorders. However, we currently do not understand the mechanism by which copper brought into cells as ES-Cu(II) is released and delivered to cuproenzymes present in different subcellular compartments. Here, we have utilized a combination of genetic, biochemical, and cell-biological approaches to demonstrate that intracellular release of copper from ES occurs inside and outside of mitochondria. The mitochondrial matrix reductase, FDX1, catalyzes the reduction of ES-Cu(II) to Cu(I), releasing it into mitochondria where it is bioavailable for the metalation of mitochondrial cuproenzyme- cytochrome c oxidase. Consistently, ES fails to rescue cytochrome c oxidase abundance and activity in copper-deficient cells lacking FDX1. In the absence of FDX1, the ES-dependent increase in cellular copper is attenuated but not abolished. Thus, ES-mediated copper delivery to nonmitochondrial cuproproteins continues even in the absence of FDX1, suggesting alternate mechanism(s) of copper release. Importantly, we demonstrate that this mechanism of copper transport by ES is distinct from other clinically used copper-transporting drugs. Our study uncovers a unique mode of intracellular copper delivery by ES and may further aid in repurposing this anticancer drug for copper deficiency disorders.


Assuntos
Cobre , Complexo IV da Cadeia de Transporte de Elétrons , Hidrazinas , Ionóforos , Ferredoxinas/metabolismo
4.
Cell Mol Life Sci ; 81(1): 88, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349408

RESUMO

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.


Assuntos
Fibrilação Atrial , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas de Transporte/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , Espécies Reativas de Oxigênio , Tiorredoxinas/genética
5.
Anal Chem ; 96(2): 895-903, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38156958

RESUMO

Deciphering the oligomeric state of proteins within cells is pivotal to understanding their role in intricate cellular processes. With the recent advances in single-molecule localization microscopy, previous efforts have harnessed protein location density approaches, coupled with simulations, to extract membrane protein oligomeric states in cells, highlighting the value of such techniques. However, a comprehensive theoretical approach that can be universally applied across different proteins (e.g., membrane and cytosolic proteins) remains elusive. Here, we introduce the theoretical probability of neighbor density (PND) as a robust tool to discern protein oligomeric states in cellular environments. Utilizing our approach, the theoretical PND was validated against simulated data for both membrane and cytosolic proteins, consistently aligning with experimental baselines for membrane proteins. This congruence was maintained even when adjusting for protein concentrations or exploring proteins of various oligomeric states. The strength of our method lies not only in its precision but also in its adaptability, accommodating diverse cellular protein scenarios without compromising the accuracy. The development and validation of the theoretical PND facilitate accurate protein oligomeric state determination and bolster our understanding of protein-mediated cellular functions.


Assuntos
Proteínas de Membrana , Imagem Individual de Molécula , Proteínas de Membrana/metabolismo , Imagem Individual de Molécula/métodos , Citosol/metabolismo
6.
J Biomed Sci ; 31(1): 90, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261905

RESUMO

BACKGROUND: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. METHODS: Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. RESULTS: Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvß3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. CONCLUSIONS: Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Gelsolina , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Gelsolina/genética , Gelsolina/metabolismo , Camundongos , Neoplasias Esofágicas/metabolismo , Animais , Masculino , Feminino , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Fibrose
7.
MMWR Morb Mortal Wkly Rep ; 73(35): 758-762, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235998

RESUMO

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.


Assuntos
Viagem Aérea , Busca de Comunicante , Surtos de Doenças , Mpox , Humanos , Estados Unidos/epidemiologia , Viagem Aérea/estatística & dados numéricos , Mpox/epidemiologia , Feminino , Masculino , Adulto , Centers for Disease Control and Prevention, U.S. , Aeronaves
8.
Clin Transplant ; 38(6): e15335, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38804610

RESUMO

BACKGROUND: Antibody-mediated rejection (AMR) often leads to chronic kidney allograft damage and is a critical cause of allograft failure. The Banff classification, used to diagnose AMR, has become complex and challenging for clinicians. A Banff-based histologic chronicity index (CI) was recently proposed as a simplified prognostic indicator. Its reliability and reproducibility have not been externally validated. METHODS: This study investigated 71 kidney allograft biopsies diagnosed with AMR. Interobserver reproducibility of the recently proposed CI and its components (cg, cv, ct, and ci) were assessed. The association between CI and allograft failure was analyzed, and CI cut-off values were evaluated by Cox proportional hazards regression and Kaplan-Meier estimator with log-rank test. RESULTS: The study confirmed the association of CI with allograft failure, but also revealed that the assessment of CI varied between pathologists, impacting its reproducibility as a prognostic tool. Only 49 (69.0%) of the biopsies showed complete agreement on the proposed cut-off value of CI < 4 or CI ≥ 4. Furthermore, this cut-off did not reliably stratify allograft failure. Notably, the cg score, which carries significant weight in the CI calculation, had the lowest agreement between observers (kappa = .281). CONCLUSIONS: While a simplified prognostic indicator for AMR is needed, this study highlights the limitations of CI, particularly its poor interobserver reproducibility. Our findings suggest that clinicians should interpret CI cautiously and consider establishing their own cut-off values. This study underscores the need to address interobserver reproducibility before CI can be widely adopted for AMR management.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Variações Dependentes do Observador , Humanos , Rejeição de Enxerto/patologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/diagnóstico , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Seguimentos , Reprodutibilidade dos Testes , Adulto , Fatores de Risco , Estudos Retrospectivos , Taxa de Filtração Glomerular , Complicações Pós-Operatórias , Testes de Função Renal
9.
Artigo em Inglês | MEDLINE | ID: mdl-39307997

RESUMO

BACKGROUND AND AIM: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia. METHODS: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled. RESULTS: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases. CONCLUSIONS: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

10.
Dig Dis Sci ; 69(6): 2193-2203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653947

RESUMO

BACKGROUND: The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. METHODS: A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. RESULTS: From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). CONCLUSION: In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes.


Assuntos
Hepatite Autoimune , Cirrose Hepática , Neoplasias Hepáticas , Humanos , Hepatite Autoimune/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Taiwan/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Cirrose Hepática/epidemiologia , Cirrose Hepática/diagnóstico , Transplante de Fígado/estatística & dados numéricos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Idoso , Recidiva , Incidência , Estudos Retrospectivos , Fígado/patologia , Adulto Jovem , Imunossupressores/uso terapêutico
11.
Dermatology ; 240(1): 13-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37939694

RESUMO

BACKGROUND: Atopic dermatitis (AD) shares similarities with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) regarding pathogenesis involving neuroinflammation and genetics. Nevertheless, evidence on the associations of AD with ADHD and/or ASD is inconclusive. This study aimed to systematically examine the existing evidence on the associations between AD, ADHD, and ASD. METHODS: The Meta-Analysis of Observational Studies in Epidemiology guideline was followed. We searched MEDLINE, Embase, Cochrane Library, and Web of Science databases from their respective inceptions to March 4, 2022. Observational studies providing adjusted estimates and/or prevalences for ADHD and ASD in patients with AD were enrolled. A random-effects model meta-analysis was conducted to calculate pooled odds ratios (ORs) and confidence intervals (CIs). Subgroup analyses according to AD severity, age, geographic location, and study design were performed. RESULTS: Overall, a total of 24 studies with 71,373,639 subjects were enrolled. Our meta-analysis demonstrated significant associations of AD with ADHD (pooled OR: 1.28; 95% CI: 1.18-1.40) and ASD (pooled OR: 1.87; 95% CI: 1.30-2.68). Subgroup analyses revealed that the associations for ADHD were the most prominent in studies evaluating severe AD patients as well as in studies focusing on school-age children and adolescents. Among patients with AD, the pooled prevalence of ADHD was 6.6%, and the respective prevalence of ASD was 1.6%. CONCLUSION: The evidence to date suggests significant associations of AD with ADHD and ASD. Psychiatric consultation and an interdisciplinary approach would benefit patients with AD presented with behavioral symptoms suggestive of ADHD or ASD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Dermatite Atópica , Criança , Adolescente , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Dermatite Atópica/diagnóstico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/psicologia
12.
Am J Otolaryngol ; 45(6): 104455, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39106678

RESUMO

AIM: This study aims to investigate the key elements for successful operation and management of primary otolaryngologic clinics in Taiwan amidst a declining birth rate and increasing competition among clinics. It employs the Innovation Through Tradition (ITT) theory as a theoretical framework to develop an operational model for effective management strategies. METHODS: This research utilized the triangulation method to identify key elements crucial for the operation and management of primary otolaryngologic clinics. Five key elements were identified, namely service attitude, medication efficacy, diagnostic and treatment procedures, treatment costs, and operating hours. Outpatient satisfaction was analyzed using Donabedian's structure-process-outcomes model to assess the impact of these elements on patient experience. RESULTS: Analysis revealed that service attitude significantly influences outpatient visits, indicating its paramount importance in clinic management. Patient satisfaction was highest in the service outcome dimension, emphasizing the significance of effective treatment outcomes. However, satisfaction was lowest in the service structure dimension, indicating potential areas for improvement in clinic infrastructure and organization. CONCLUSION: Understanding these key elements and enhancing outpatient satisfaction can drive improvements in the quality of medical services, contributing to the overall success of primary otolaryngologic clinics.

13.
Eur Arch Otorhinolaryngol ; 281(3): 1473-1481, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38127096

RESUMO

PURPOSE: By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). METHODS: A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. RESULTS: There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. CONCLUSIONS: The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.


Assuntos
Neoplasias Hipofaríngeas , Neoplasias Bucais , Neoplasias Orofaríngeas , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagem , Neoplasias Hipofaríngeas/terapia , Radiômica , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/terapia , Fatores de Risco , Estudos Retrospectivos
14.
J Formos Med Assoc ; 123(4): 461-466, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37805306

RESUMO

BACKGROUND: The rating result reflects not only the performance of the candidate but some extent of the examiner's preference. Examiner bias could be objective, which means it can't be changed by the examiner like gender, age, race, educational level, or professional experience. No study about examiner bias was performed in the dental education realm, especially in the orthodontic field. Therefore, this study aimed to figure out possible influencing factors in examiners from examples of the Taiwan Board of Orthodontist examination. METHODS: The examiner groups comprised 29 males and 21 females selected from the certificated Taiwan Board of Orthodontists. Every examiner would receive a series of lectures about rating standards before the exam. The score data were collected from 2009 to 2019. RESULTS: As for the univariate regression model of the Taiwan Board of Orthodontist examination, the experienced examiner with a certification of more than 15 years tends to rate more leniently, but female examiners tend to rate harsher. The scores would increase with the examiner's age in both the univariate regression model of self-prepared and assigned cases. CONCLUSION: As for the multivariate model of self-prepared exams, the elder and the examiner who work in private practice clinics tend to rate more leniently. As for the multivariate model of the assigned case exam, the score would be only affected by age. However, further studies are necessary to determine the direct relation among these factors.


Assuntos
Certificação , Ortodontistas , Masculino , Humanos , Feminino , Taiwan , Competência Clínica
15.
J Environ Manage ; 368: 122118, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39191059

RESUMO

Environmental regulations such as the "dual carbon" target directly act on the restriction of the total amount of dirty capital to reduce carbon emissions. The change in factor endowment will have a range of effects on production and income distribution. To examine the effects of environmental regulations restricting dirty capital endowment on income distribution, this paper presents a general equilibrium model with two sectors and three factors. The unregulated clean capital-intensive sector is imperfectly competitive and features firm dynamics, using labor and clean capital as factors of production, while the regulated dirty capital-intensive sector is perfectly competitive using labor and dirty capital. We show that a decrease in the dirty capital endowment will reduce the output of the dirty capital-intensive sector and expand the clean capital-intensive sector in the long run, making society transition to green production. The tighter the restriction on the use of the dirty capital endowment is, the more firms will enter the clean capital-intensive sector, while the business-stealing effect will reduce the output of individual clean firms. We further show that the rents of both dirty and clean capital will rise while the wage of labor will fall due to the regulation. Changes in factor prices do not necessarily lead to inequality in income distributions. When the factor substitution effect in the regulated sector is large enough, clean production regulation will increase the share of labor income and decrease the share of capital income.


Assuntos
Renda , Humanos , Fatores Socioeconômicos
16.
J Chem Educ ; 101(2): 514-520, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-39070090

RESUMO

Single-molecule localization microscopy (SMLM) has revolutionized our ability to visualize cellular structures, offering unprecedented detail. However, the intricate biophysical principles that underlie SMLM can be daunting for newcomers, particularly undergraduate and graduate students. To address this challenge, we introduce the fundamental concepts of SMLM, providing a solid theoretical foundation. In addition, we have developed an intuitive graphical interface APP that simplifies these core concepts, making them more accessible for students. This APP clarifies how super-resolved images are fitted and highlights the crucial factors determining image quality. Our approach deepens students' understanding of SMLM by combining theoretical instruction with practical learning. This development equips them with the skills to carry out single-molecule super-resolved experiments and explore the microscopic world beyond the diffraction limit.

17.
Opt Express ; 31(23): 37452-37463, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017873

RESUMO

Surface plasmonic waves (SPWs) that propagate at meta-dielectric interface are a good source of information carrier waves for on-chip photonic devices, where SPW excitation is one key procedure. Recently, controlling SPW excitation using metasurface methods has drawn considerable attention owing to their design flexibility, wherein achieving dynamic control is of great importance. However, most studies in the terahertz regime so far are working in a passive way or only dynamically controllable at the propagation process. In this work, an active design for controlling terahertz SPWs at the excitation process is proposed using graphene metasurfaces based on the manipulation of the electromagnetically induced transparency (EIT) effect. Large modulation depth with controllable SPW excitations is demonstrated. Our method is flexible and promising in achieving more controlling degree of freedom, which can find broadband applications in future integrated devices and systems.

18.
Am J Public Health ; 113(8): 904-908, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37319391

RESUMO

Objectives. To describe trends in the number of air travelers categorized as infectious with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; the virus that causes COVID-19) in the context of total US COVID-19 vaccinations administered, and overall case counts of SARS-CoV-2 in the United States. Methods. We searched the Quarantine Activity Reporting System (QARS) database for travelers with inbound international or domestic air travel, a positive SARS-CoV-2 lab result, and a surveillance categorization of SARS-CoV-2 infection reported during January 2020 to December 2021. Travelers were categorized as infectious during travel if they had arrival dates from 2 days before to 10 days after symptom onset or a positive viral test. Results. We identified 80 715 persons meeting our inclusion criteria; 67 445 persons (83.6%) had at least 1 symptom reported. Of 67 445 symptomatic passengers, 43 884 (65.1%) reported an initial symptom onset date after their flight arrival date. The number of infectious travelers mirrored the overall number of US SARS-CoV-2 cases. Conclusions. Most travelers in the study were asymptomatic during travel, and therefore unknowingly traveled while infectious. During periods of high community transmission, it is important for travelers to stay up to date with COVID-19 vaccinations and consider wearing a high-quality mask to decrease the risk of transmission. (Am J Public Health. 2023;113(8):904-908. https://doi.org/10.2105/AJPH.2023.307325).


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , Estados Unidos/epidemiologia , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Viagem , Quarentena
19.
Int J Mol Sci ; 24(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37445793

RESUMO

This study undertakes a comprehensive exploration of the impact of slightly acidic electrolyzed water (SAEW) on Listeria monocytogenes, a common foodborne pathogen, with a particular focus on understanding the molecular mechanisms leading to the viable but nonculturable (VBNC) state. Given the widespread application of SAEW as an effective disinfectant in the food industry, uncovering these molecular pathways is crucial for improving food safety measures. We employed tandem mass tags (TMT), labeling proteomic techniques and LC-MS/MS to identify differentially expressed proteins under two doses of SAEW conditions. We indicated 203 differential expressed proteins (DEPs), including 78 up-regulated and 125 down-regulated DEPs. The functional enrichment analysis of these proteins indicated that ribosomes, biosynthesis of secondary metabolites, and aminoacyl-tRNA biosynthesis were enriched functions affected by SAEW. Further, we delved into the role of protein chlorination, a potential consequence of reactive chlorine species generated during the SAEW production process, by identifying 31 chlorinated peptides from 22 proteins, with a dominant sequence motif of Rxxxxx[cY] and functionally enriched in translation. Our findings suggest that SAEW might prompt alterations in the protein translation process and trigger compensatory ribosome biosynthesis. However, an imbalance in the levels of elongation factors and AARSs could hinder recovery, leading to the VBNC state. This research carries substantial implications for food safety and sanitation, as it adds to our understanding of the SAEW-induced VBNC state in L. monocytogenes and offers potential strategies for its control.


Assuntos
Listeria monocytogenes , Água , Água/química , Cromatografia Líquida , Proteômica , Espectrometria de Massas em Tandem , Ácidos/farmacologia , Eletrólise , Concentração de Íons de Hidrogênio
20.
Molecules ; 28(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298852

RESUMO

The aim of this study was to investigate the physicochemical characteristics and volatile flavor of fried tilapia skins under three frying methods. Conventional deep-fat frying usually increases the oil content of the fried fish skin and leads to lipid oxidation, which reduces the product quality. Alternative frying methods, such as air frying for 6 and 12 min under 180 °C (AF6, and AF12) and vacuum frying at 0.085 MPa for 8 and 24 min under 120 °C (VF8, and VF24) were compared to conventional frying for 2 and 8 min under 180 °C (CF2, and CF8) for tilapia skin. Physical properties of fried skin, such as the moisture content, water activity, L* values and breaking force decreased under all frying methods, while the lipid oxidation and a*, b* values increased with the increase in frying time. In general, VF offered higher hardness of product compared to AF which had a lower breaking force. Especially AF12 and CF8 had the lowest breaking force, which indicated higher crispness. For the oil quality inside the product, AF and VF reduced conjugated dienes formation and retarded oxidation compared to CF. The results of the flavor compositions of fish skin measured using gas chromatography mass spectrometry (GC/MS) with solid phase microextraction (SPME) showed that CF obtained higher unpleasant oily odor (nonanal, 2,4-decadienal, etc.), while AF presented greater grilling flavor (pyrazine derivatives). Because fish skin fried by AF only relied on hot air, Maillard reaction derived compounds, such as methylpyrazine, 2,5-dimethylpyrazine, and benzaldehyde were the leading flavors. This made the aroma profiles of AF very different from VF and CF. Among all the approaches, AF and VF developed lower oil content, mild fat oxidation and better flavor attributes, which proves their practical applications for frying tilapia fish skin.


Assuntos
Culinária , Reação de Maillard , Animais , Culinária/métodos , Vácuo , Oxirredução , Lipídeos
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