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A solid-state electrochemiluminescence (ECL) sensor was fabricated by immobilizing luminol, a classical luminescent reagent, on a Zn-Co-ZIF carbon fiber-modified electrode for the rapid and sensitive detection of procymidone (PCM) in vegetable samples. The sensor was created by sequentially modifying the glassy carbon electrode with Zn-Co-ZIF carbon fiber (Zn-Co-ZIF CNFs), Pt@Au NPs, and luminol. Zn-Co-ZIF CNFs, prepared through electrospinning and high-temperature pyrolysis, possessed a large specific surface area and porosity, making it suitable as carrier and electron transfer accelerator in the system. Pt@Au NPs demonstrated excellent catalytic activity, effectively enhancing the generation of active substances. The ECL signal was significantly amplified by the combination of Zn-Co-ZIF CNFs and Pt@Au NPs, which can subsequently be diminished by procymidone. The ECL intensity decreased proportionally with the addition of procymidone, displaying a linear relationship within the concentration range 1.0 × 10-13 to 1.0 × 10-6 mol L-1 (R2 = 0.993). The sensor exhibited a detection limit of 3.3 × 10-14 mol L-1 (S/N = 3) and demonstrated outstanding reproducibility and stability, making it well-suited for the detection of procymidone in vegetable samples.
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Cobalto , Técnicas Eletroquímicas , Ouro , Limite de Detecção , Medições Luminescentes , Luminol , Verduras , Zinco , Luminol/química , Verduras/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Medições Luminescentes/métodos , Zinco/química , Ouro/química , Cobalto/química , Nanopartículas Metálicas/química , Platina/química , Carbono/química , Eletrodos , Substâncias Luminescentes/química , Contaminação de Alimentos/análise , Reprodutibilidade dos TestesRESUMO
Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80loCD11bhiMHCIIhi MoMF-1 and decreased the abundance of pro-inflammatory F4/80loCD11bhiiNOShi MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.
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BACKGROUND: The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS: Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS: Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION: Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.
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Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Lateralidade Funcional/fisiologia , Cognição/fisiologia , Idoso , Testes de Estado Mental e DemênciaRESUMO
Developing novel drugs from natural products has proven to be a very effective strategy. Neocryptolepine was isolated from Cryptolepis sanguinolenta, a traditional endemic African herb, which exerts a wide range of biological activities such as antimalaria, antibacterial, and antitumor. 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] quinoline (compound 49) was synthesized, and its cytotoxicity was assessed on pancreatic cancer PANC-1 cells, colorectal cancer HCT116 cells, liver cancer SMMC-7721 cells, and gastric cancer AGS cells in vitro. The results of the in vitro assay showed that compound 49 exerted remarkable cytotoxicity on colorectal cancer HCT116 and Caco-2 cells. The cytotoxicity of compound 49 to colorectal cancer HCT116 cells was 17 times higher than that of neocryptolepine and to human normal intestinal epithelial HIEC cells was significantly reduced. Compound 49 exhibited significant cytotoxicity against the colorectal cancer HCT116 and Caco-2 cells, with IC50 of 0.35 and 0.54 µM, respectively. The mechanism of cytotoxicity of compound 49 to colorectal cancer HCT116 and Caco-2 cells was further investigated. The results showed that compound 49 could inhibit colony formation and cell migration. Moreover, compound 49 could arrest the cell cycle at the G2/M phase, promote the production of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The results of Western blot indicated that compound 49 showed cytotoxicity on HCT116 and Caco-2 cells by modulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these results suggested that compound 49 may be a potentially promising lead compound for the treatment of colorectal cancer.
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BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide that frequently presents with concomitant cardiovascular diseases. Despite the pathological distinction between individual COPD phenotypes such as emphysema and chronic bronchitis, there is a lack of knowledge about the impact of COPD phenotype on cardiovascular disease risk. Thus, this study aimed to utilize a nationally representative sample to investigate cardiovascular disease prevalence in patients with COPD with emphysema and chronic bronchitis phenotypes. METHODS: Data from 31,560 adults including 2504 individuals with COPD, collected as part of the National Health and Nutrition Examination Survey (1999-2018), were examined. RESULTS: A significantly increased cardiovascular disease risk, including coronary heart disease, heart failure, myocardial infarction and stroke, was identified in patients with COPD among all disease phenotypes. Particularly, compared to those without COPD, individuals with chronic bronchitis presented with 1.76 (95% CI: 1.41-2.20) times greater odds, individuals with emphysema with 2.31 (95% CI: 1.80-2.96) times greater odds, while those with a concurrent phenotype (combined chronic bronchitis and emphysema) exhibited 2.98 (95% CI: 2.11-4.21) times greater odds of reporting cardiovascular diseases. CONCLUSION: Our data confirms that patients with COPD present an elevated risk of developing cardiovascular disease among all phenotypes, with the most marked increase being in those with concurrent chronic bronchitis and emphysema phenotypes. These findings emphasize the need for awareness and appropriate cardiovascular screening in COPD.
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OBJECTIVE: To observe the therapeutic effect of gentiopicroside, as the main component of Gentianaceae, on wounds in pressure injury (PI) model rats and explore its mechanism. METHOD: Male Sprague Dawley rats were randomly divided into control group, model group and gentiopicroside groups (50, 100 and 200 mg·kg-1·d-1 for 9 consecutive days). The mice's skeletal muscle fibroblast line NOR-10 cells were collected after being treated with gentiopicroside (0.2~5.0 M) and basic fibroblast growth factor receptor 1 (bFGFR1) inhibitor (5.0 M SU5402) for 7 days. RESULTS: Compared to the model group, the gentiopicroside groups showed significantly increased wound healing rates, reduced inflammatory cells in the wound tissues, and significantly increased expression levels of proliferating cell nuclear antigen (PCNA) and bFGFR1, accompanied by increased proliferation of new myofibroblasts. Gentiopicroside upregulated the mRNA expression of bFGFR1 and PCNA in NOR-10 cells in a dose-dependent manner; however, SU5402 reversed the effect of gentiopicroside. CONCLUSION: Gentiopicroside may promote myofibroblast proliferation by upregulating the expression of bFGFR1 and PCNA and ultimately accelerating the healing of PI wounds.
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Glucosídeos Iridoides , Úlcera por Pressão , Ratos Sprague-Dawley , Regulação para Cima , Cicatrização , Animais , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/administração & dosagem , Cicatrização/efeitos dos fármacos , Masculino , Ratos , Úlcera por Pressão/tratamento farmacológico , Camundongos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Antígeno Nuclear de Célula em Proliferação/metabolismo , Distribuição Aleatória , Proliferação de Células/efeitos dos fármacosRESUMO
Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.
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Aeromonas hydrophila , Gema de Ovo , Doenças dos Peixes , Imunoglobulinas , Vibrioses , Vibrio , Animais , Imunoglobulinas/imunologia , Imunoglobulinas/sangue , Vibrioses/veterinária , Vibrioses/imunologia , Vibrioses/prevenção & controle , Vibrio/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Gema de Ovo/imunologia , Aeromonas hydrophila/imunologia , Carpa Dourada/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/prevenção & controle , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Imunização Passiva/veterinária , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagemRESUMO
The rising prevalence of cardiovascular disease presents an escalating challenge for current health services, which are grappling with increasing demands. Innovative changes are imperative to sustain the delivery of high-quality patient care. Recent technologic advances have resulted in the emergence of artificial intelligence as a viable solution. Advanced algorithms are now capable of performing complex analysis of large volumes of data rapidly and with exceptional accuracy. Multimodality artificial intelligence systems handle a diverse range of data including images, text, video, and audio. Compared with single-modality systems, multimodal artificial intelligence systems appear to hold promise for enhancing overall performance and enabling smoother integration into existing workflows. Such systems can empower physicians with clinical decision support and enhanced efficiency. Owing to the complexity of the field, however, truly multimodal artificial intelligence is still scarce in the management of cardiovascular disease. This article aims to cover current research, emerging trends, and the future utilisation of artificial intelligence in the management of cardiovascular disease, with a focus on multimodality systems.
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Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI.
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Disfunção Cognitiva , Imageamento por Ressonância Magnética , Lobo Temporal , Língua , Humanos , Disfunção Cognitiva/fisiopatologia , Masculino , Feminino , Idoso , Lobo Temporal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Língua/fisiopatologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Testes Neuropsicológicos , Amnésia/fisiopatologia , Amnésia/diagnóstico por imagem , Rememoração Mental/fisiologiaRESUMO
P4B (2-phenyl-1-[4-(6-(piperidin-1-yl) pyridazin-3-yl) piperazin-1-yl] butan-1-one) is a novel cellulose biosynthesis inhibitor (CBI) discovered in a screen for molecules to identify inhibitors of Arabidopsis (Arabidopsis thaliana) seedling growth. Growth and cellulose synthesis inhibition by P4B were greatly reduced in a novel mutant for the cellulose synthase catalytic subunit gene CESA3 (cesa3pbr1). Cross-tolerance to P4B was also observed for isoxaben-resistant (ixr) cesa3 mutants ixr1-1 and ixr1-2. P4B has an original mode of action as compared with most other CBIs. Indeed, short-term treatments with P4B did not affect the velocity of cellulose synthase complexes (CSCs) but led to a decrease in CSC density in the plasma membrane without affecting their accumulation in microtubule-associated compartments. This was observed in the wild type but not in a cesa3pbr1 background. This reduced density correlated with a reduced delivery rate of CSCs to the plasma membrane but also with changes in cortical microtubule dynamics and orientation. At longer timescales, however, the responses to P4B treatments resembled those to other CBIs, including the inhibition of CSC motility, reduced growth anisotropy, interference with the assembly of an extensible wall, pectin demethylesterification, and ectopic lignin and callose accumulation. Together, the data suggest that P4B either directly targets CESA3 or affects another cellular function related to CSC plasma membrane delivery and/or microtubule dynamics that is bypassed specifically by mutations in CESA3.
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OBJECTIVE: To describe the needs for subacute inpatient rehabilitation and community-based healthcare services, rehabilitation, and social support in patients with moderate-to-severe traumatic injury in the first 6 months post-injury. Further, to explore associations between sociodemographic and clinical characteristics and unmet needs. DESIGN: Multicentre prospective cohort study. SUBJECTS: Of 601 persons (75% males), mean (standard deviation) age 47 (21) years, admitted to trauma centres in 2020 with moderate-to-severe injury, 501 patients responded at the 6-month follow-up and thus were included in the analyses. METHODS: Sociodemographic and injury-related characteristics were recorded at inclusion. Estimation of needs was assessed with the Rehabilitation Complexity Scale Extended-Trauma and the Needs and Provision Complexity Scale on hospital discharge. Provision of services was recorded 6 months post-injury. Multivariable logistic regressions explored associations between baseline variables and unmet inpatient rehabilitation and community-based service needs. RESULTS: In total, 20% exhibited unmet needs for subacute inpatient rehabilitation, compared with 60% for community-based services. Predictors for unmet community-based service needs included residing in less central areas, profound injury severity, severe head injury, and rehabilitation referral before returning home. CONCLUSION: Inadequate provision of healthcare and rehabilitation services, particularly in the municipalities, resulted in substantial unmet needs in the first 6 months following injury.
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Centros de Traumatologia , Ferimentos e Lesões , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Ferimentos e Lesões/reabilitação , Necessidades e Demandas de Serviços de Saúde , Apoio Social , Avaliação das Necessidades , IdosoRESUMO
Aims: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke and death. While anticoagulants are effective at reducing these risks, they increase the risk of bleeding. Current clinical risk scores only perform modestly in predicting adverse outcomes, especially for the outcome of death. We aimed to test the multi-label gradient boosting decision tree (ML-GBDT) model in predicting risks for adverse outcomes in a prospective global AF registry. Methods and results: We studied patients from phase II/III of the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation registry between 2011 and 2020. The outcomes were all-cause death, ischaemic stroke, and major bleeding within 1 year following the AF. We trained the ML-GBDT model and compared its discrimination with the clinical scores in predicting patient outcomes. A total of 25 656 patients were included [mean age 70.3 years (SD 10.3); 44.8% female]. Within 1 year after AF, ischaemic stroke occurred in 215 (0.8%), major bleeding in 405 (1.6%), and death in 897 (3.5%) patients. Our model achieved an optimized area under the curve in predicting death (0.785, 95% CI: 0.757-0.813) compared with the Charlson Comorbidity Index (0.747, P = 0.007), ischaemic stroke (0.691, 0.626-0.756) compared with CHA2DS2-VASc (0.613, P = 0.028), and major bleeding (0.698, 0.651-0.745) as opposed to HAS-BLED (0.607, P = 0.002), with improvement in net reclassification index (10.0, 12.5, and 23.6%, respectively). Conclusion: The ML-GBDT model outperformed clinical risk scores in predicting the risks in patients with AF. This approach could be used as a single multifaceted holistic tool to optimize patient risk assessment and mitigate adverse outcomes when managing AF.
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Recent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly understood. We analyzed immune multiomics datasets to perform a consensus cluster analysis and validate the clustering results across multiple internal and external ccRCC datasets; and identified two distinctive immune phenotypes of ccRCC, which we named multiomics immune-based cancer subtype 1 (MOICS1) and subtype 2 (MOICS2). The former, MOICS1, is characterized by an immune-hot phenotype with poor clinical outcomes, marked by significant proliferation of CD4+ and CD8+ T cells, fibroblasts, and high levels of immune inhibitory signatures; the latter, MOICS2, exhibits an immune-cold phenotype with favorable clinical characteristics, characterized by robust immune activity and high infiltration of endothelial cells and immune stimulatory signatures. Besides, a significant negative correlation between immune infiltration and angiogenesis were identified. We further explored the mechanisms underlying these differences, revealing that negatively regulated endopeptidase activity, activated cornification, and neutrophil degranulation may promote an immune-deficient phenotype, whereas enhanced monocyte recruitment could ameliorate this deficiency. Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-ß pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.
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Carcinoma de Células Renais , Neoplasias Renais , Microambiente Tumoral , Humanos , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/imunologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , MultiômicaRESUMO
A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition. With increasing amount of FPT the ECL signal decreased. Under the optimum conditions, the ECL response was linearly related to the logarithm of FPT concentration. The developed ECL sensor allowed for sensitive determination of FPT and exhibited a wide linear range from 1.0 × 10- 10 mol L- 1 to 1.0 × 10- 6 mol L- 1. The limit of detection was 3.3 × 10- 11 mol L- 1 (S/N = 3). It can be used for the detection of FPT in vegetable samples.
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Luminescência , Impressão Molecular , Piretrinas , Luminol , Polímeros Molecularmente ImpressosRESUMO
Acute alcoholic liver disease (ALD) resulting from short-term heavy alcohol consumption has become a global health concern. Moreover, anthocyanins have attracted much attention for their ability to prevent oxidation and inflammation. The present work evaluates the protective effects of Lycium ruthenicum Murray (LRM) against ALD and explores the possible underlying mechanism involved. The total anthocyanin content in LRM was 43.64 ± 9.28 Pt g/100 g dry weight. Mice were orally administered 50, 125, or 375 mg LRM/kg body weight (BW) for 21 days. On days 18-21, mice were orally administered 15 mL of ethanol/kg BW. Markers of liver damage, oxidative stress, and inflammation were examined. Furthermore, the modulatory effect of LRM on Nrf2/HO-1/NF-κB pathway molecules was evaluated through quantitative reverse transcription polymerase chain reaction (RTâqPCR) and immunohistochemistry analyses. The difference between the groups indicated that LRM improved liver histopathology and the liver index, decreased aspartate transaminase, alanine transaminase, malondialdehyde, reactive oxygen species, IL-6, TNF-α, and IL-1ß expression, but elevated superoxide dismutase, catalase, and glutathione-s-transferase levels. Moreover, LRM upregulated Nrf2 and Ho-1 but downregulated Nf-κb and Tnf-α genes at the transcript level. In summary, LRM alleviated ethanol-induced ALD in mice by reducing oxidative damage and associated inflammatory responses. LRM protects against ALD by reducing damage factors and enhancing defense factors, especially via the Nrf2/HO-1/NF-κB pathway. Thus, LRM has application potential in ALD prophylaxis and treatment.
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Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Metilação de RNA , Relevância Clínica , Biomarcadores/metabolismo , RNA/metabolismo , Metilação de DNA/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Intratumoral bacteria might play essential roles in tumorigenesis in different cancer types. However, its features and potential roles in hepatocellular carcinoma (HCC) are largely unknown. METHODS: In this study, we assessed bacterial RNA by 16S rRNA fluorescence in situ hybridization and detected bacterial lipopolysaccharide (LPS) via immunohistochemistry. Hepa1-6 cells were used to establish orthotopic HCC models in mice. 2bRAD sequencing for microbiome was performed to determine the intratumoral bacterial characteristics, and liquid chromatography-mass spectrometry was conducted to explore the metabolic profile. The potential association between different intratumoral microbiota and metabolites were evaluated. RESULTS: We detected bacterial 16S rRNA and LPS in HCC tissues from the patients with HCC. In HCC mouse model, we found that the intratumor bacteria in HCC tissues were significantly different to adjacent nontumor tissues. Furthermore, we observed different metabolites in HCC tissues and adjacent nontumor tissues, such as N-acetyl-D-glucosamine and a-lactose. Our results showed that several bacteria were significantly associated with metabolites, such as Pseudomonas koreensis, which was positively correlated with N-acetyl-D-glucosamine and negatively correlated with citrulline. CONCLUSIONS: This study confirmed the close association between different bacteria and metabolites, which might provide novel opportunities for developing new biomarkers and therapeutic targets for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/genética , RNA Ribossômico 16S/genética , Acetilglucosamina , Hibridização in Situ Fluorescente , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos , BactériasRESUMO
Olfactory dysfunction (OD) is one of the important and difficult-to-treat symptoms of eosinophilic chronic rhinosinusitis (CRS), which is typically associated with type 2 inflammation where eosinophils (EOSs) function as both effectors and initiators. Eosinophilic infiltration in the olfactory mucosa (OM) is associated with severe OD, mucosal erosion, and more loss of olfactory sensory neurons (OSNs). Active EOS-derived cytokines, chemokines, and eosinophil granule proteins may lead to aggravation of inflammation, tissue damage, and impairment of the survival and regeneration of OSNs. Recent studies show that EOSs can lead to apoptosis of OSNs through axonal and neural body damage, turnover disorder of OSNs through the loss of immature OSNs and globose basal cells (GBCs), changed proliferative activity of horizontal basal cells (HBCs), and dysfunction of OSNs through the breakdown of neuroepithelial integrity and alteration of ion concentration in OSNs and mucin. In this review, we outline the current progress on the role of EOSs on OD in patients with eosinophilic CRS and the mechanism of EOS-associated injury of the OM and OSNs in experimental animal models with sinonasal inflammation. Further investigations on the molecular mechanisms of tissue eosinophilia-induced injury of OSNs are warranted to obtain new therapeutic targets and achieve better restoration of olfactory function.
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An efficient and innovative electrochemiluminescence (ECL) sensor was developed for trace detection of cyfluthrin. The sensor utilized materials such as lotus root shaped carbon fiber (Co CNFs), cadmium selenide quantum dots (CdSe QDs), and Fe3O4 to amplify Ru(bpy)32+ signals. Co CNFs, with its large specific surface area and porosity, served the purpose of not only enhancing the stability of the sensor by fixing CdSe QDs and Ru(bpy)32+ on the Co CNFs/GCE, but also facilitating electron transfer. CdSe QDs was involved in the luminescence reaction and collaborated with Ru(bpy)32+ to enhance the sensor's sensitivity, while Fe3O4 promoted electron transfer in the system due to its large surface area. The solid-state ECL sensor achieved satisfactory signal under the synergistic action of these components. The ECL signal of the sensor was quenched by cyfluthrin, and a favorable linear relationship was observed between the sensor and cyfluthrin in the concentration range 1 × 10-12 to 1 × 10-6 M. The detection limit of the sensor was 3.3 × 10-13 M (S/N = 3). The utilization of lotus root shaped carbon fiber, CdSe QDs, and Fe3O4 in the Ru(bpy)32+ system demonstrated a synergistic effect for cyfluthrin detection, presenting a new approach for the rapid determination analysis of pesticide residues in foods.
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BACKGROUND: Medication self-management capacity (MMC) is essential to safe and independent living. There is a need to understand the challenges low-income older adults face during the routine use of medications to promote safe medication use and healthy aging in place. OBJECTIVE: To assess the cognitive and physical deficiencies in MMC and the impact of using pharmaceutical aids/services on MMC among low-income older adults. METHODS: This was a cross-sectional study of 107 older residents of 5 low-income housing buildings in Richmond, VA. The Medication Management Instrument for Deficiencies in the Elderly was used to measure MMC during individual in-person interviews. Participants were asked whether they used any medication aids, including medication lists, organizers, or reminders, or pharmacy services such as specialized medication packaging, medication synchronization, prescription home delivery, or mail order services. Multiple regression modeling was used to assess the relationship between MMC and the use of pharmaceutical aids/services. RESULTS: Eighty-nine percent of participants were African American with a mean (standard deviation [±SD]) age of 68.5 (7.2) years. The mean deficit in MMC was 3 (±2.0). The most challenging skill was naming all the medications (69.2%), followed by stating their indications (46.7%) and knowing how or when all of the medications should be taken (38.3%). Seventy-nine percent used at least 1 pharmaceutical aid/service; using 1 pharmaceutical aid/service was significantly associated with better MMC (P = .0285). Low educational level and health literacy were associated with deficits in MMC (P < .05). CONCLUSION: Many older adults residing in low-income housing had impaired capacity to manage their medications independently. Inadequate medication knowledge affected their cognitive ability to manage medications. Using a pharmaceutical aid/service was associated with better MMC. Greater attention to developing medication self-management skills for older adults with low health literacy and adverse social determinants of health is needed.