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Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.
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Artrite Reumatoide , COVID-19 , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2/genética , Leucócitos Mononucleares , Receptores de Antígenos de Linfócitos T , Anticorpos Antivirais , VacinaçãoRESUMO
Purpose: To characterize features of central retinal artery occlusion (CRAO) using multicolor (MC) imaging and to assess the differences in CRAO grading between color fundus photography (CFP) and MC image qualitatively and quantitatively. Methods: We conducted a prospective, cross-sectional study in the Department of Ophthalmology of Renmin Hospital of Wuhan University. In total, 86 acute CRAO patients were included. Spectral-domain optical coherence tomography (SD-OCT), CFP, and MC examinations were taken at baseline. Based on the findings of these three examinations, CRAO was divided into three grades (incomplete, subtotal, and total). Based on OCT grading criteria, we qualitatively compared the ability of grading CRAO by CFP and MC. CRAO patient's visual acuity (VA) was obtained from the initial visit. The retinal thickness was measured by SD-OCT. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained from optical coherence tomography angiography (OCTA) examinations. Quantitative data were compared across the three acute CRAO subgroups and against three examination findings. Results: MC image had significantly higher power of acute CRAO detection than CFP (P = 0.03). In the same group of CRAO patients, there was no significant difference in VA when comparing OCT with the MC grading system or with the CFP grading system (all P > 0.05). Significant differences in VA were found between the three CRAO subgroups only under MC grading (P = 0.016). In incomplete CRAO patients, significant differences were found in central fovea thickness (CFT) when comparing OCT with the CFP grading system (P = 0.019). In the same group of CRAO patients, there was no significant difference in retinal thickness when comparing OCT with the MC grading system (All P > 0.05). Significance differences in CFT (P < 0.001), innermost retinal layer (IMRL; P < 0.01), middle retinal layer (MRL; P < 0.001), and outer retinal layer (ORL; P = 0.021) were found between the three CRAO subgroups by MC grading. Vessel density of SCP showed a statistically increased as the severity of three CRAO subgroups (P = 0.03), whereas DCP did not have significant differences (P = 0.745). Comparisons were made between the OCT grading method and the MC and CFP grading methods; there is no significant difference in vessel density of SCP and DCP (All P > 0.05). Conclusion: The images obtained by MC are superior to those obtained by CFP in CRAO grading, retinal thickness, and vessel density measurement. MC imaging may be more capable of CRAO grading than OCT. We recommend MC imaging to determine CRAO severity to guide disease treatment and predict visual prognosis.
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Central retinal artery occlusion (CRAO) is an acute retinal ischaemic disease, but early diagnosis is challenging due to a lack of biomarkers. Blood samples were collected from CRAO patients and cataract patients. Gene expression profiles were distinct between arterial/venous CRAO blood (A-V group) and venous CRAO/control blood (V-C group) samples. Differentially expressed genes (DEGs) were subjected to GO and KEGG enrichment analyses. Hub genes were identified by Cytoscape and used to predict gene interactions via GeneMANIA. Immune cell infiltration was analysed by CIBERSORT. More than 1400 DEGs were identified in the A-V group and 112 DEGs in the V-C group compared to controls. The DEGs in both groups were enriched in the ribosome pathway, and those in the V-C group were also enriched in antigen processing/MHC pathways. Network analysis identified ribosomal proteins (RPS2 and RPS5) as the core genes of the A-V group and MHC genes (HLA-F) as the core genes of the V-C group. Coexpression networks showed ribosomal involvement in both groups, with additional immune responses in the V-C group. Immune cell analysis indicated increased numbers of neutrophils and T cells. Ribosomal and MHC-related genes were identified as potential CRAO biomarkers, providing research directions for prevention, diagnosis, treatment and prognosis.
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Oclusão da Artéria Retiniana , Transcriptoma , Humanos , Perfilação da Expressão Gênica , Inflamação/genética , Biomarcadores , Biologia ComputacionalRESUMO
Central retinal artery occlusion (CRAO) is a kind of ophthalmic emergency which may cause loss of functional visual acuity. However, the limited treatment options emphasize the significance of early disease prevention. Metabolomics has the potential to be a powerful tool for early identification of individuals at risk of CRAO. The aim of the study was to identify potential biomarkers for CRAO through a comprehensive analysis. We employed metabolomics analysis to compare venous blood samples from CRAO patients with cataract patients for the venous difference, as well as arterial and venous blood from CRAO patients for the arteriovenous difference. The analysis of metabolites showed that PC(P-18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PC(P-18:0/20:4(5Z,8Z,11Z,14Z)) and octanoylcarnitine were strongly correlated with CRAO. We also used univariate logistic regression, random forest (RF), and support vector machine (SVM) to screen clinical parameters of patients and found that HDL-C and ApoA1 showed significant predictive efficacy in CRAO patients. We compared the predictive performance of the clinical parameter model with combined model. The prediction efficiency of the combined model was significantly better with area under the receiver operating characteristic curve (AUROC) of 0.815. Decision curve analysis (DCA) also exhibited a notably higher net benefit rate. These results underscored the potency of these three substances as robust predictors of CRAO occurrence.
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INTRODUCTION: Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis. METHODS: Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition. RESULTS: Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP+ osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix. CONCLUSIONS: These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.
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Dermatite Atópica , Periodontite , Humanos , Animais , Camundongos , Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/metabolismo , Dinitroclorobenzeno/farmacologia , Dinitroclorobenzeno/uso terapêutico , RNA Ribossômico 16S , Imunoglobulina E/metabolismo , Anti-Inflamatórios/farmacologia , Pele , Inflamação/metabolismo , Periodontite/complicações , Periodontite/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismoRESUMO
Local intra-arterial fibrinolysis (LIF) is a promising therapeutic option for CRAO. However, the narrow time window of 6 h has greatly limited the application of LIF. In this study, we explored the efficacy of LIF beyond the conventional time windows and compared the result with conservative therapy. This prospective study included 179 CRAO patients with baseline visual acuity (VA) ≤ 20/400 treated at Renmin Hospital of Wuhan University. The mean time from vision loss to presentation was 5.5 days. 58 patients received conventional standard therapy (CST) alone.121 patients underwent LIF. Main outcome was VA improvement ≥ 0.3 logMAR. Secondary outcome was a favorable VA outcome of 20/200 or better. Logistic regressions were performed to identify predictors of visual improvement. 43% patients in the LIF group experienced VA improvement versus 19% with CST (P = 0.002). LIF was associated with 4.0-fold higher likelihood of visual improvement compared to CST (P = 0.001). Poor baseline VA (light perception or no light perception) and shortened prothrombin time (PT) were associated with greater chance of visual improvement with LIF. However, LIF showed no significant advantage over CST for favorable VA outcomes. No major complications occurred. LIF beyond the therapeutic time window improved vision in functionally blind CRAO patients and showed better efficacy when compared with CST. PT may be a potential predictor of visual outcome after LIF. Our findings could complement existing time-based treatment guidelines and potentially allow for personalized decisions on the use of LIF beyond time windows.
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Fibrinolíticos , Oclusão da Artéria Retiniana , Humanos , Fibrinolíticos/uso terapêutico , Fibrinólise , Ativador de Plasminogênio Tecidual/uso terapêutico , Terapia Trombolítica/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Oclusão da Artéria Retiniana/tratamento farmacológicoRESUMO
BACKGROUND: Interprofessional education (IPE) aims to educate healthcare students to improve collaboration and the quality of care. The delivery of IPE through a problem-based learning (PBL) setting appears to hold good validity. However, there are few studies that show the value of combining these two teaching modes. MATERIALS AND METHODS: The research was a longitudinal intervention study. A total of 360 students were randomly divided into three interprofessional PBL (IPBL) groups that mixed nursing, pharmacy, and clinical medical students and three uniprofessional PBL (UPBL) groups that consisted of a single profession. An improved Attitude and Learning Ability Questionnaire (ALAQ) was used to measure the improvement in attitudes toward interprofessional cooperation and learning outcomes. The tutorial session and final examination grades were compared between IPBL and UPBL by Chi-square tests and Cochran-Mantel-Haenszel tests. Cronbach's α analysis was calculated to assess the validity and reliability. Cronbach's alpha coefficient of the questionnaire was 0.887, demonstrating high levels of reliability (95% confidence interval [CI]: 0.842 0.916). RESULTS: According to Chi-square tests and Cochran-Mantel-Haenszel tests, we observed the student's positive attitudes toward interprofessional collaboration and the student's role awareness in the IPBL students was increased compared with UPBL students. In addition, a great majority of IPBL students felt that they had improved their self-learning ability and maintained a high enthusiasm for learning during the course. CONCLUSION: Our study found that the IPBL teaching model was more effective than the UPBL teaching model in healthcare student's positive attitudes toward interprofessional collaboration and learning outcomes.
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To estimate the association between central retinal artery occlusion (CRAO) and major adverse cardiovascular and cerebrovascular events (MACCE), including their clinical characteristics, blood markers, and the contribution of CRAO to MACCE, as well as to assess any sex differences. This retrospective cohort study included continuous new-onset CRAO patients and 1:4 controls during the same period. Correlations of CRAO with the incidence of MACCE during follow-up and the sex-related differences were studied. One hundred and twenty-four CRAO patients and four hundred and ninety-six controls were enrolled. Neutrophil-to-lymphocyte ratio (NLR, P = 0.014) and high-sensitivity C-reactive protein (hs-CRP, P = 0.038) were tended to be higher in CRAO patients. After the follow-up period, 78 patients experienced MACCE. Multivariate Cox regression analysis showed that CRAO was a predictor of the occurrence of MACCE (HR 2.321, 95% CI 1.439-3.744, P = 0.001). Sex subgroups indicated that age, diabetes, current smoking, CRAO, NLR and hs-CRP increased the risk factor of MACCE in males (All P < 0.05) and CRAO, NLR, low-density lipoprotein cholesterol (LDL-C) and hs-CRP were independent influencing factors for females (All P < 0.05). New-onset CRAO significantly increases the probability of MACCE and is associated with a poor prognosis. The sex-related differences suggested that effective prevention of the occurrence of MACCE in high-risk patients requires that attention be given to individualized risk factors corresponding to sexes.
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Sistema Cardiovascular , Oclusão da Artéria Retiniana , Humanos , Feminino , Masculino , Caracteres Sexuais , Proteína C-Reativa , Estudos Retrospectivos , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/epidemiologiaRESUMO
Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.
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COVID-19 , Humanos , SARS-CoV-2 , Linfócitos T , Receptores de Antígenos de Linfócitos T/genética , Gravidade do PacienteRESUMO
BACKGROUND: Ulcerative colitis (UC) is an idiopathic inflammatory disease with an increasing incidence. This study aimed to identify potential UC biomarkers and associated immune infiltration characteristics. METHODS: Two datasets (GSE87473 and GSE92415) were merged to obtain 193 UC samples and 42 normal samples. Using R, differentially expressed genes (DEGs) between UC and normal samples were filtered out, and their biological functions were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Promising biomarkers were identified using least absolute shrinkage selector operator regression and support vector machine recursive feature elimination, and their diagnostic efficacy was evaluated through receiver operating characteristic (ROC) curves. Finally, CIBERSORT was used to investigate the immune infiltration characteristics in UC, and the relationship between the identified biomarkers and various immune cells was examined. RESULTS: We found 102 DEGs, of which 64 were significantly upregulated, and 38 were significantly downregulated. The DEGs were enriched in pathways associated with interleukin-17, cytokine-cytokine receptor interaction and viral protein interactions with cytokines and cytokine receptors, among others. Using machine learning methods and ROC tests, we confirmed DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 to be essential diagnostic genes for UC. Immune cell infiltration analysis revealed that all five diagnostic genes were correlated with regulatory T cells, CD8 T cells, activated and resting memory CD4 T cells, activated natural killer cells, neutrophils, activated and resting mast cells, activated and resting dendritic cells and M0, M1 and M2 macrophages. CONCLUSIONS: DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 were identified as prospective biomarkers for UC. A new perspective on understanding the progression of UC may be provided by these biomarkers and their relationship with immune cell infiltration.
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Colite Ulcerativa , beta-Defensinas , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Oxidases Duais , Biologia Computacional , Biomarcadores , Citocinas , Aprendizado de Máquina , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Proteínas Supressoras de TumorRESUMO
Novel enhancement-mode organic electrochemical transistors (OECTs) have been prepared by poly(3, 4-ethylenedioxythiophene)-poly(styrenesulfonate) de-doped polyethylenimine on the multi-walled carbon nanotube-modified viscose yarn. The fabricated devices exhibit low power consumption with a high transconductance of 6.7 mS, rapid response time < 2 s, and excellent cyclic stability. In addition, the device has washing durability and bending and long-term stability suitable for wearable applications. Biosensors based on enhancement-mode OECTs for the selective detection of adrenaline and uric acid (UA) are developed by using molecularly imprinted polymer (MIP)-functionalized gate electrodes. The detection limits of adrenaline and UA analysis are as low as 1 pM, with the linear ranges of 0.5 pM to 10 µM and 1 pM to 1 mM, respectively. Moreover, the sensor based on enhancement-mode transistors can efficiently amplify the current signals according to the modulation of the gate voltage. The MIP-modified biosensor has high selectivity in the presence of interferents and desirable reproducibility. Additionally, due to the wearable nature of the developed biosensor, this sensing tool has the capability of being integrated with fabrics. Therefore, it has successfully been applied in textiles for the determination of adrenaline and UA in artificial urine samples. The excellent recoveries and rsds are 90.22-109.05% and 3.97-6.94%, respectively. Ultimately, these sensitive, low-power, wearable, and dual-analyte sensors help to develop non-laboratory tools for early disease diagnosis and clinical research.
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Técnicas Biossensoriais , Impressão Molecular , Polímeros Molecularmente Impressos , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Eletrodos , Limite de DetecçãoRESUMO
PURPOSE: To evaluate and compare the blood lipid profile in retinal artery occlusion (RAO) and retinal vein occlusion (RVO). METHODS: We included 82 RAO patients and 95 RVO patients in this retrospective case-control study. Controls were matched to RAO or RVO patients at a 1:1 ratio, respectively. Associated lipid variates were analyzed in multivariable logistic regression models. RESULTS: LDL-C (OR = 1.69), non-HDL-C (OR = 1.87), and ApoB (OR = 11.72) individually significantly increased the risk of RAO. ApoA1 was associated with RVO (OR = 0.02), and with 75.8% sensitivity and 67.4% specificity. TG (OR = 1.61), LDL-C (OR = 1.69), non-HDL-C (OR = 1.91), and ApoB (OR = 12.12) each significantly increased the risk of RAO when compared with RVO. CONCLUSIONS: ApoB, non-HDL-C, and LDL-C may be potential biomarkers in RAO patients. Low ApoA1 is an independent risk factor for the development of RVO.
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The pandemic of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still underway. Due to the growing development of severe symptoms, it is necessary to promote effective therapies. Ambroxol [2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine] has long been used as one of the over-the-counter mucolytic agents to treat various respiratory diseases. Therefore, we focused on the mechanism of action of ambroxol in COVID-19 treatment. In vitro and in silico screening revealed that ambroxol may impede cell entry of SARS-CoV-2 by binding to neuropilin-1. Ambroxol could also interact with multiple inflammatory factors and signaling pathways, especially nuclear factor kappa B (NF-κB), to interfere cytokines cascade activated by SARS-CoV-2 internalization. Furthermore, multipathways and proteins, such as the cell cycle and matrix metalloproteinases (MMPs), were identified as significant ambroxol-targeting pathways or molecules in PBMC and lung of severe COVID-19 patients by bioinformatics analysis. Collectively, these results suggested that ambroxol may serve as a promising therapeutic candidate for the treatment of severe SARS-CoV-2 infection.
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Ambroxol , COVID-19 , Humanos , SARS-CoV-2 , Ambroxol/uso terapêutico , Ambroxol/farmacologia , Polifarmacologia , Tratamento Farmacológico da COVID-19 , Leucócitos MononuclearesRESUMO
Microwave and infrared-thermal radiation-compatible shielding fabrics represent an important direction in the development of wearable protective fabrics. Nevertheless, effectively and conveniently integrating compatible shielding functions into fabrics while maintaining breathability and moisture permeability remains a significant challenge. Here, we take hydrophilic PVA-co-PE nanofibrous film-coated PET fabric (NFs/PET) as a flexible substrate and deposit a dielectric/conductive (SiO2/Al) bilayer film via magnetron sputtering. This strategy endows the fabric surface with high electrical conductivity, nanoscale roughness comparable to visible and infrared waves, and a dielectric-metal contact interface possessing localized plasmon resonance and Mie scattering effects. The results demonstrate that the optimized SiO2/Al/NFs/PET composite conductive fabric (referred to as S4-1) possesses favorable X-band electromagnetic interference (EMI) shielding effectiveness (50 dB) as well as excellent long-wave infrared (LWIR) shielding or IR stealth performance (IR emissivity of 0.60). Notably, the S4-1 fabric has a cooling effect of about 12.4 °C for a heat source (80 °C) and an insulating effect of about 17.2 °C for a cold source (-20 °C), showing excellent shielding capability for heat conduction and heat radiations. Moreover, the moisture permeability of the S4-1 fabric is about 300 g/(m2·h), which is better than the requirement concerning moisture permeability for wearable fabrics (≥2500-5000 g/(m2·24 h)), indicating excellent heat and moisture comfort. In short, our fabrics have lightweight, thin, moisture-permeable and excellent shielding performance, which provides novel ideas for the development of wearable multi-band shielding fabrics applied to complex electromagnetic environments.
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Proallergic type 2 helper T (Th2A) cells are a subset of memory Th2 cells confined to atopic individuals, and they include all the allergen-specific Th2 cells. Recently, many studies have shown that Th2A cells characterized by CD3+ CD4+ HPGDS+ CRTH2+ CD161high ST2high CD49dhigh CD27low play a crucial role in allergic diseases, such as atopic dermatitis (AD), food allergy (FA), allergic rhinitis (AR), asthma, and eosinophilic esophagitis (EoE). In this review, we summarize the discovery, biomarkers, and biological properties of Th2A cells to gain new insights into the pathogenesis of allergic diseases.
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Dermatite Atópica , Esofagite Eosinofílica , Hipersensibilidade Alimentar , Rinite Alérgica , Alérgenos , HumanosRESUMO
Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.
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[This corrects the article DOI: 10.1155/2015/263630.].
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Coronavirus disease 2019 (COVID-19) continuously progresses despite the application of a variety of vaccines. Therefore, it is still imperative to find effective ways for treating COVID-19. Recent studies indicate that NRP1, an important receptor of the natural peptide tuftsin (released from IgG), facilitates SARS-CoV-2 infection. Here, we found 91 overlapping genes between tuftsin targets and COVID-19-associated genes. We have demonstrated that tuftsin could also target ACE2 and exert some immune-related functions. Molecular docking results revealed that tustin could combine with ACE2 and NRP1 in stable structures, and their interacted regions cover the binding surfaces of S1-protein with the two receptors. Using surface plasmon resonance (SPR) analysis, we confirmed that tuftsin can bind ACE2 and NRP1 directly. Importantly, using SPR-based competition assay we have shown here that tuftsin effectively prevented the binding of SARS-CoV-2 S1-protein to ACE2. Collectively, these data suggest that tuftsin is an attractive therapeutic candidate against COVID-19 and can be considered for translational as well as clinical studies.
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In this study, poly(3, 4-ethylenedioxythiophene) (PEDOT) nanocluster structure was synthesized on the reduced graphene oxide (rGO) modified cotton fibers. The organic electrochemical transistors based on the modified fiber have been assembled and their performance of different gate electrode transistors has been investigated. The transistor exhibits an excellent transconductance of up to 15.5 mS and a high on-off ratio close to 2*102. The bending angle and bending times have little effect on the device performance. The uric acid (UA) sensor based transistor has been fabricated for the first time. Flexible sensors based on molecularly imprinted polymer (MIP) membrane with different fiber gate electrodes have been investigated. The UA sensor with MIP/PEDOT/carbon fiber as the gate electrode has a sensitivity of 100 µA per decade from 1 nM to 500 µM, a linear coefficient of 0.97143, excellent selectivity, and good reproducibility. In addition, fiber based organic electrochemical transistors (FECTs) can be sewn into the fabric for monitoring and have successfully evaluated the detection of UA in artificial urine sample, with data consistent well with the UA concentration obtained from single fiber. Therefore, the sensor based FECTs can be used for low cost, accurate, non-enzymatic detection of UA in clinical diagnostics and bioanalytical applications.
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Técnicas Eletroquímicas , Ácido Úrico , Eletrodos , Polímeros , Reprodutibilidade dos TestesRESUMO
Transcription factor DP family member 3 (TFDP3) is a cancer-testis antigen, mainly expressed in normal testis and multiple cancers. TFDP3 gene (Gene ID: 51270) is located on the chromosome X and shares a high degree of sequence homology with TFDP1 and TFDP2, which can form heterodimers with E2F family members and enhance DNA-binding activity of E2Fs. In contrast to TFDP1 and TFDP2, TFDP3 downregulates E2F-mediated transcriptional activation. During DNA damage response in cancer cells, TFDP3 is induced and can inhibit E2F1-mediated apoptosis. Moreover, TFDP3 is involved in cell autophagy and epithelial-mesenchymal transition. Regarding cancer therapy opportunity, the transduction of dendritic cells with recombinant adenovirus-encoding TFDP3 can activate autologous cytotoxic T lymphocytes to target hepatoma cells. Here, we review the characterization of TFDP3, with an emphasis on the biological function and molecular mechanism. A better understanding of TFDP3 will provide new insights into the pathological mechanisms and therapeutic strategies for cancers.