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Organic A'-site ligand structure plays a crucial role in the crystal growth of 2D perovskites, but the underlying mechanism has not been adequately understood. This problem is tackled by studying the influence of two isomeric A'-site ligands, linear-shaped n-butylammonium (n-BA+ ) and branched iso-butylammonium (iso-BA+ ), on 2D perovskites from precursor to device, with a combination of in situ grazing-incidence wide-angle X-ray scattering and density functional theory. It is found that branched iso-BA+ , due to the lower aggregation enthalpies, tends to form large-size clusters in the precursor solution, which can act as pre-nucleation sites to expedite the crystallization of vertically oriented 2D perovskites. Furthermore, iso-BA+ is less likely to be incorporated into the MAPbI3 lattice than n-BA+ , suppressing the formation of unwanted multi-oriented perovskites. These findings well explain the better device performance of 2D perovskite solar cells based on iso-BA+ and elucidate the fundamental mechanism of ligand structural impact on 2D perovskite crystallization.
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Purpose: To investigate whether the Notch signaling pathway participates in the occurrence and development of experimental autoimmune thyroiditis (EAT) by affecting the differentiation and function of Th17 cells. Materials and Methods: Experimental mice were randomly divided into a control group, an EAT-A group (porcine thyroid immunoglobulin- (pTg-) treated mice) and an EAT-B group (treated with the DAPT γ-secretase inhibitor before pTg). HE staining, IHC staining, flow cytometry, RT-qPCR, and ELISA were used to evaluate the degrees of thyroiditis, detect the percentage of Th17 cells and measure the expression of retinoic acid-related orphan receptor gamma t (RORγt), interleukin-17A (IL-17A), and the main components of the Notch signaling pathway. Results: The degrees of thyroiditis, the proportions of Th17 cells, and the expression of RORγt and IL-17A were significantly decreased in the EAT-B group after blocking the Notch signaling pathway by DAPT, and these parameters were significantly increased in the EAT-A group compared to the control group (all P < 0.05). Additionally, the Th17 cell percentages and IL-17A concentrations in spleen mononuclear cells (SMCs) from EAT-A mice decreased in a dose-dependent manner after DAPT treatment in vitro (all P < 0.01). Correlation analyses revealed that the Th17 cell percentages were positively correlated with the serum TgAb titers, Notch pathway-related mRNA expression levels, and IL-17A concentrations in EAT mice (all P < 0.05). Conclusions: The expression of Notch signaling pathway components was upregulated in EAT mice, but blockade of the Notch signaling pathway alleviated the degree of thyroiditis, decreased the Th17 cell proportions, and downregulated the IL-17A effector cytokine both in vivo and in vitro. These findings suggested that the Notch signaling pathway may be involved in the pathogenesis of thyroid autoimmune injury in EAT mice by promoting the differentiation of Th17 cells.
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Doença de Hashimoto , Tireoidite Autoimune , Camundongos , Animais , Tireoidite Autoimune/patologia , Interleucina-17/metabolismo , Células Th17/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Diferenciação Celular , Transdução de SinaisRESUMO
Some certain genetic polymorphisms have been considered to implicate in the pathogenesis and progression of autoimmune diseases and may predispose to an early stage of general autoimmune susceptibility. Recent studies have been conducted to investigate the association between macrophage migration inhibitory factor- (MIF-) 173G/C gene polymorphism and autoimmune diseases; however, the results were not exactly identical. In the present study, a systematic review and meta-analysis of case-control studies was performed to estimate the relationship. A comprehensive search of PubMed, Ebsco, EMbase, WanFang databases and CNKI was done. Odds ratio (ORs) and corresponding 95% confidence intervals (CIs) were combined to pool the effect size. The publication bias was examined by Begg's funnel plots and Egger's test. RevMan 5.3 and STATA 12.0 software were used for statistical processing. 23 papers were included, and the results revealed that MIF-173G/C was significantly associated with an increased risk of autoimmune diseases in five genetic models (recessive genetic model: OR = 1.95, 95% CI: 1.52-2.50; dominant genetic model: OR = 1.35, 95% CI: 1.24-1.46; allele model: OR = 1.32, 95% CI: 1.23-1.41; homozygote model: OR = 1.92, 95% CI: 1.57-2.35; heterozygote model: OR = 4.92, 95% CI: 4.03-6.02), whether in Asia, Europe, or North America. Furthermore, subgroup analysis showed an increasing risk in rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), atopic dermatitis (AD), Henoch-Schonlein purpura (HSP), and Henoch-Schonlein purpura nephritis (HSPN), but it was not related to the susceptibility of autoimmune hepatitis (AIH). Therefore, it could be considered that MIF-173G/C polymorphism could increase the susceptibility of autoimmune diseases, while there may be the discrepancy of disease entity.
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Asma/genética , Asma/fisiopatologia , Doenças Autoimunes/genética , Predisposição Genética para Doença , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo Genético , Linfócitos T CD8-Positivos/citologia , Humanos , Sistema Imunitário , Memória Imunológica , Inflamação , Interleucinas/metabolismo , Macrófagos/metabolismo , Células Th1/citologia , Células Th17/citologia , Células Th2/citologia , Interleucina 22RESUMO
PURPOSE: To evaluate the regulating effect of Notch-Hes1 signaling on IL-17A+ γδ +T cell expression and IL-17A secretion in mouse psoriasis-like skin inflammation. MATERIALS AND METHODS: Experimental mice were randomly divided into control group, model group (5% imiquimod- (IMQ-) treated mice), and intervention group (IMQ and γ-secretase inhibitor DAPT cotreated mice). The severity of psoriasis-like skin inflammation was evaluated by target lesion score based on the clinical psoriasis area and severity index (PASI). Flow cytometry detected IL-17A+ γδ +T cell percentage. Quantitative real-time RT-PCR detected Hes1 mRNA expression. Enzyme-linked immunosorbent assay and western blot measured IL-17A serum concentration and protein expression. Additionally, splenic single cells from model mice were treated by DAPT to further evaluate the inhibitory effect of blocking Notch-Hes1 signaling on IL-17A+ γδ +T cell differentiation and IL-17A secretion. RESULTS: The spleen index, IL-17A+ γδ +T cell percentage, Hes1 mRNA expression, IL-17A serum concentration, and protein expression were all significantly higher in model mice than control mice, while dramatically reduced in intervention mice by DAPT treatment, which also obviously alleviated the target lesion score, epidermal hyperplasia, and dermal inflammatory cell infiltration of intervention mice. In vitro study demonstrated that DAPT treatment could result in dose-dependent decrease of IL-17A+ γδ +T cell percentage and IL-17A secretion in splenic single cells of model mice.
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Interleucina-17/metabolismo , Psoríase/metabolismo , Receptores Notch/metabolismo , Linfócitos T/citologia , Fatores de Transcrição HES-1/metabolismo , Animais , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imiquimode/uso terapêutico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Pele/metabolismo , Baço/metabolismo , Linfócitos T/imunologia , Células Th17/metabolismoRESUMO
BACKGROUND: Many studies have aimed to clarify the relationship between Notch1 signaling and papillary thyroid carcinoma (PTC), but the results have been inconsistent to date. In the present study, a systematic review and meta-analysis were performed to analyze the relationship between Notch1 signaling and the clinical characteristics of PTC. METHODS: Literature databases, including PubMed (Medline), Embase and China National Knowledge Infrastructure, were searched for relevant studies from inception to April 2018. A total of five studies, including 421 patients with PTC from China and South Korea, were included in the meta-analysis. RESULTS: The results revealed that the upregulation of Notch1 signaling was positively correlated with lymph node metastasis in patients with PTC (OR = 3.25, 95% CI 1.14-9.23, P = 0.03). Additionally, positive correlations were found between Notch1 signaling and tumor size (OR = 4.34, 95% CI 1.66-11.38, P = 0.003), capsular invasion (OR = 3.49, 95% CI 1.90-6.41, P < 0.0001) and clinical stage of PTC (OR = 2.31, 95% CI 1.05-5.11, P = 0.04). CONCLUSIONS: The Notch1 signaling pathway may play a catalytic role in the progression of PTC, and upregulation of Notch1 signaling may have significant predictive value for the clinical prognosis of PTC.
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BACKGROUND/AIMS: Epithelial cells line the intestinal mucosa and form an important barrier for maintaining host health. This study aimed to explore the mechanism of the Sphingosine-1-phosphate (S1P)/Sphingosine-1-phosphate receptor 2 (S1PR2) pathway in intestinal epithelial cells (IECs) that participate in the intestinal barrier function. METHODS: In this study, we constructed a knockout of the S1PR2 gene in mice, and Dextra sulfate sodium (DSS) was used to induce colitis. We isolated IECs from wild type (WT) and S1PR2-/- mice, and the endogenous expression of S1PR2 and Zonula occludens 1 (ZO-1) in IEC were detected by Western blot. Next, the major histocompatibility complex II (MHC-II) expression was analyzed by reverse transcription quantitative real-time (RT-qPCR) and flow cytometry. The in vivo and in vitro intestinal permeability were evaluated by serum fluorescein isothiocyanate (FITC) concentration. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) levels in cell suspension were analyzed by enzyme-linked immuno sorbent assay (ELISA). A carboxyfluorescein diacetate succinimidyl ester (CFSE) assay was used to detect the T-cell proliferation in a co-culture system. RESULTS: The intestinal mucosal barrier damage in S1PR2-/- mice was more severe than in the WT mice, and there were more CD4+T-cells in the colon tissue of DSS-treated S1PR2-/- mice. Either the mouse colon carcinoma cell line (CT26. WT) or the IECs upregulated MHC-II expression, which then promoted CD4+T-cell proliferation. The S1P/S1PR2 pathway controlled MHC-II expression to regulate CD4+T-cell proliferation via the extracellular signal-regulated kinase (ERK) pathway. In addition, the IFN-γ that was secreted by CD4+T-cells increased DSS-induced damage of intestinal epithelial cell barrier function. ZO-1 expression was increased by S1P in CT26.WT cells, while S1PR2 antagonist JTE-013 expression was downregulated. However, in CT26.WTsi-S1PR2 cells, S1P had no effect on ZO-1 expression. CONCLUSIONS: The S1P/S1PR2 axis in IECs mediated CD4+T-cell activation via the ERK pathway and MHC-II expression to regulate intestinal barrier function.
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Linfócitos T CD4-Positivos/imunologia , Colite/imunologia , Mucosa Intestinal/imunologia , Lisofosfolipídeos/imunologia , Receptores de Lisoesfingolipídeo/imunologia , Transdução de Sinais , Esfingosina/análogos & derivados , Animais , Linfócitos T CD4-Positivos/patologia , Comunicação Celular , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células , Células Cultivadas , Colite/genética , Colite/patologia , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Absorção Intestinal , Mucosa Intestinal/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Lisoesfingolipídeo/genética , Esfingosina/imunologia , Receptores de Esfingosina-1-FosfatoRESUMO
BACKGROUND: Th17 cells and its effective cytokine IL-17A play an important role in the pathogenesis of abnormal immune responses in psoriasis. Notch1 signaling has been implicated in Th17 cell differentiation and function. In this study, our aim was to evaluate the possible inhibitory effect of Notch1 signaling inhibitor, γ-secretase inhibitor DAPT, on psoriatic Th17 cell differentiation and function in a mouse model of psoriasis-like skin inflammation. METHODS: Mouse psoriasis-like skin inflammation model was established by topical 5% imiquimod (IMQ) application, and experimental mice were divided into control group, IMQ-treated group and IM + DAPT-treated group. DAPT and the equivalent amount of Dimethyl sulfoxide was intraperitoneally injected in IMQ + DAPT-treated group and the other two experimental groups respectively. Skin tissues of the three experimental groups were acquired and stained with haematoxylin and eosin (HE). Splenic single-cells and serum were collected to detect the percentage of Th17 cells, the mRNA expression levels of Notch1 and its target gene Hes-1, Th17-specific transcription factor RORγt and its effective cytokines IL-17A, as well as IL-17A serum concentration. In addition, splenic CD4+ T cells from IMQ-treated mice were isolated and treated by DAPT to further measure the inhibitory effect of DAPT on the Th17 cell differentiation and IL-17A secretion in vitro. RESULTS: DAPT treatment alleviated the severity of IMQ-induced mouse psoriasis-like skin inflammation and decreased the scores of erythema, scaling and thickening. HE stain reveals obviously reduced epidermal hyperplasia and dermal inflammatory cells infiltration in IMQ + DAPT-treated mice. The increased expression of splenic Th17 cell percentage, along with Notch1, Hes-1, RORγt and IL-17A mRNA and IL-17A serum concentration in IMQ-treated mice were significantly decreased when experimental mice were treated by IMQ and DAPT combinedly. Data obtained from in vitro study in IMQ-treated mice also demonstrated that blocking Notch1 signaling by DAPT can result in a dose-dependent decrease of Th17 cell proportion, mRNA expression of Notch1, Hes-1, RORγt and IL-17A as well as IL-17A secretion in splenic CD4+ T cells. CONCLUSION: These data suggest that Notch1 inhibition by DAPT can effectively alleviate the severity of mouse psoriasis-like skin inflammation by regulating the differentiation and function of Th17 cells, indicating that DAPT might be a potential therapeutic candidate for the treatment of psoriatic inflammation.
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Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Diferenciação Celular , Dipeptídeos/farmacologia , Inflamação/patologia , Psoríase/imunologia , Psoríase/patologia , Pele/patologia , Células Th17/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Dipeptídeos/uso terapêutico , Regulação para Baixo , Imiquimode , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Psoríase/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Esplenomegalia/patologia , Células Th17/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). MATERIALS AND METHODS: Notch1, Hes-1, RORγt, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4+ T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4+ T cells from 12 PV patients were treated with γ-secretase inhibitor DAPT, and the above indexes were measured. RESULTS: PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and RORγt/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4+ T cells, RORγt and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4+ T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. CONCLUSION: Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.
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Psoríase/imunologia , Psoríase/metabolismo , Receptor Notch1/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Adolescente , Adulto , Polaridade Celular/efeitos dos fármacos , Diaminas/farmacologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Psoríase/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Tiazóis/farmacologia , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo , Adulto JovemRESUMO
BACKGROUND: Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD. METHODS: In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER. RESULTS: The expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002. CONCLUSION: MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.
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Absorção Intestinal/fisiologia , Mucosa Intestinal/fisiologia , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Células CACO-2 , Humanos , Permeabilidade , Transdução de Sinais/fisiologia , Receptores de Esfingosina-1-FosfatoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is originated from uncontrolled inflammation, and desired methods for IBD therapy remains the main difficult. The network comprised with miRNA and lncRNA has been verified to play an important role on diverse human diseases. In this study, we demonstrated the role of miR-34c and lncRNA PlncRNA1 on the function of intestinal barrier. METHODS: Intestinal epithelial barrier model was constructed based on normal intestinal epithelial cell line Caco-2. 2% DSS was supplemented in the Apical side of the model cells to induce the injury of intestinal epithelial barrier. Real-time PCR or western blot was used to determine mRNA or protein expression of miR-34c, PlncRNA1, Myc-associated zinc finger protein (MAZ), zonula occludens 1 (ZO-1) and occludin. RESULTS: DSS induced injury of intestinal epithelial barrier, while overexpression of PlncRNA1 seemed to protect intestinal epithelial barrier from injury. Tight junction (TJ) proteins ZO-1 and occludin were regulated by MAZ, while, miR-34c targeted MAZ to regulate its expression, in addition, PlncRNA1 and miR-34c bound together to regulate the expressions of MAZ, ZO-1 and occludin. The protect effects of PlncRNA1 overexpression on intestinal epithelial barrier function was reversed by overexpression of miR-34c. CONCLUSION: MAZ and TJ proteins were involved in the function of intestinal epithelial barrier, while miR-34c and PlncRNA1 regulated the intestinal dysfunction cooperatively.
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Mucosa Intestinal/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas de Junções Íntimas/genética , Regiões 3' não Traduzidas/genética , Sequência de Bases , Western Blotting , Células CACO-2 , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sulfato de Dextrana/farmacologia , Regulação da Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/fisiopatologia , MicroRNAs/metabolismo , Ocludina/genética , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Proteínas de Junções Íntimas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
PURPOSE: To explore the possible role of MIF and Th17 cells in the thyroid-specific autoimmune damage of Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: We enrolled 40 HT patients and 30 healthy controls and divided HT patients into euthyroid subset (n = 22) and subclinical or overt hypothyroidism subset (n = 18). The percentages of Th17 cells and expressions of MIF, interleukin 17A (IL-17A) mRNA in PBMCs, as well as serum concentrations of MIF, and IL-17A, and thyroid functions, and thyroid-specific autoantibodies (TPOAb, TgAb) were detected by flow cytometry, real-time RT-PCR, ELISA, and ECLIA in all subjects. RESULTS: MIF mRNA, IL-17A mRNA expressions and Th17 cells percentages, serum MIF, and IL-17A protein levels were all significantly higher in HT patients, even in euthyroid subgroup. Additionally, the differences became more obvious in dysfunction subgroup. Importantly, both MIF levels and Th17 cells percentage were positively correlated with serum TPOAb, TgAb, and thyrotropin (TSH) levels in HT patients. CONCLUSIONS: These data suggest that MIF and Th17 cells increased dynamically and positively correlated with the markers of thyroid autoimmune damage, which indicated that interaction between MIF and Th17 cells may participate in the pathogenesis and development of thyroid-specific autoimmunity in HT.
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Doença de Hashimoto/imunologia , Oxirredutases Intramoleculares/fisiologia , Fatores Inibidores da Migração de Macrófagos/fisiologia , Células Th17/imunologia , Adulto , Autoanticorpos/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Doença de Hashimoto/etiologia , Humanos , Interleucina-17/sangue , Interleucina-17/genética , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , RNA Mensageiro/análise , Glândula Tireoide/imunologiaRESUMO
BACKGROUND: It is uncertain whether the extra acquisition costs of atypical antipsychotics over typical antipsychotics are offset by their other reduced resource use especially in hospital services in China. This study compared the psychiatric-related health care resource utilization and direct medical costs for patients with schizophrenia initiating atypical or typical antipsychotics in Tianjin, China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008-2010). Adult patients with schizophrenia with ≥1 prescription for antipsychotics after ≥90-day washout and 12-month continuous enrollment after first prescription was included. Psychiatric-related resource utilization and direct medical costs of the atypical and typical cohorts were estimated during the 12-month follow-up period. Logistic regressions, ordinary least square (OLS), and generalized linear models (GLM) were employed to estimate differences of resource utilization and costs between the two cohorts. One-to-one propensity score matching was conducted as a sensitivity analysis. RESULTS: 1131 patients initiating either atypical (N = 648) or typical antipsychotics (N = 483) were identified. Compared with the typical cohort, the atypical cohort had a lower likelihood of hospitalization (45.8% vs. 56.7%, P < 0.001; adjusted OR: 0.58, P < 0.001) over the follow-up period. Medication costs for the atypical cohort were higher than the typical cohort ($438 vs. $187, P < 0.001); however, their non-medication medical costs were significantly lower ($1223 vs. $1704, P < 0.001). The total direct medical costs were similar between the atypical and typical cohorts before ($1661 vs. $1892, P = 0.100) and after matching ($1711 vs. 1868, P = 0.341), consistent with the results from OLS and GLM models for matched cohorts. CONCLUSIONS: The atypical cohort had similar total direct medical costs compared to the typical cohort. Higher medication costs associated with atypical antipsychotics were offset by a reduction in non-medication medical costs, driven by fewer hospitalizations.
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Antipsicóticos/economia , Antipsicóticos/uso terapêutico , Custos de Medicamentos/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Two-dimensional (2D) organic-inorganic hybrid iodide perovskites have been put forward in recent years as stable alternatives to their three-dimensional (3D) counterparts. Using first-principles calculations, we demonstrate that equilibrium concentrations of point defects in the 2D perovskites PEA2PbI4, BA2PbI4, and PEA2SnI4 (PEA, phenethylammonium; BA, butylammonium) are much lower than in comparable 3D perovskites. Bonding disruptions by defects are more destructive in 2D than in 3D networks, making defect formation energetically more costly. The stability of 2D Sn iodide perovskites can be further enhanced by alloying with Pb. Should, however, point defects emerge in sizable concentrations as a result of nonequilibrium growth conditions, for instance, then those defects likely hamper the optoelectronic performance of the 2D perovskites, as they introduce deep traps. We suggest that trap levels are responsible for the broad sub-bandgap emission in 2D perovskites observed in experiments.
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OBJECTIVES: The aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio, an indicator for liver fibrosis, could be easily detected in clinical practice. The aim of this study was to examine the association between the AST/ALT ratio and skeletal muscle mass among Chinese community adult residents. METHODS: We enrolled 2644 participants, age ≥18 y, undergoing bioelectrical impedance analysis and liver function test. Univariate and multivariate logistic regression models were used to analyze the effect of the AST/ALT ratio on the presence of low muscle mass (LMM). Multiple linear regression analysis was used to assess the factors associated with the skeletal muscle mass index (SMI) and to construct a formula to calculate the SMI. RESULTS: When the AST/ALT ratio was regarded as a categorical variable, AST/ALT quartiles 9-2.19) kept independent effects on the presence of LMM status. When it was regarded as a continuous variable, each unit of the AST/ALT ratio was significantly associated with a 49% (P < 0.01) augment of the prevalence of LMM. By multiple general linear regression analysis, the formula was constructed with an adjusted R2 of 0.72: SMI (kg/m2) = -0.14 AST/ALT ratio + 1.35 sex (male: 1; female: 0) + 0.72 overweight status (yes: 1; no: 0) - 0.14 age (≤65: 0; >65: 1) + 6.26. CONCLUSION: In general, the high AST/ALT ratio was an independent adverse indicator of the presence of LMM.
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População do Leste Asiático , Músculo Esquelético , Adulto , Humanos , Masculino , Feminino , Alanina Transaminase , Aspartato Aminotransferases , Testes de Função HepáticaRESUMO
As the most important cultural crustacean species worldwide, studies about Pacific white shrimp (Litopenaeus vannamei) have received more attention. It has been well-documented that various pathogens could infect L. vannamei, resulting in huge economic losses. The studies about the responding mechanism of L. vannamei to sole pathogens such as Vibrio parahaemolyticus and white spot virus (WSSV) have been extensively reported, while the studies about the differently responding mechanisms remain unclear. In the present study, we identified the differently expressed genes (DEGs) of L. vannamei hemocytes post V. parahaemolyticus and WSSV infection with RNA-seq technology and compared the DEGs between the two groups. The results showed 2672 DEGs post the V. parahaemolyticus challenge (1079 up-regulated and 1593 down-regulated genes), while 1146 DEGs post the WSSV challenge (1067 up-regulated and 513 down-regulated genes). In addition, we screened the genes that simultaneously respond to WSSV and V. parahaemolyticus (434), solely respond to WSSV (1146), and V. parahaemolyticus challenge (2238), respectively. Six DEGs involved in innate immunity were quantified to validate the RNA-seq results, and the results confirmed the high consistency of both methods. Furthermore, we found plenty of innate immunity-related genes that responded to V. parahaemolyticus and WSSV infection, including pattern recognition receptors (PRRs), the proPO activating system, antimicrobial peptides (AMPs), and other immunity-related proteins. The results revealed that they were differently expressed after different pathogen challenges, demonstrating the complex and specific recognition systems involved in defending against the invasion of different pathogens in the environment. The present study improved our understanding of the molecular response of hemocytes of L. vannamei to V. parahaemolyticus and WSSV stimulation.
Assuntos
Hemócitos , Penaeidae , Transcriptoma , Vibrio parahaemolyticus , Vírus da Síndrome da Mancha Branca 1 , Animais , Vírus da Síndrome da Mancha Branca 1/fisiologia , Penaeidae/genética , Penaeidae/virologia , Penaeidae/imunologia , Penaeidae/microbiologia , Perfilação da Expressão Gênica , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologiaRESUMO
Lattice defects affect the long-term stability of halide perovskite solar cells. Whereas simple point defects, i.e., atomic interstitials and vacancies, have been studied in great detail, here we focus on compound defects that are more likely to form under crystal growth conditions, such as compound vacancies or interstitials, and antisites. We identify the most prominent defects in the archetype inorganic perovskite CsPbI3, through first-principles density functional theory (DFT) calculations. We find that under equilibrium conditions at room temperature, the antisite of Pb substituting Cs forms in a concentration comparable to those of the most prominent point defects, whereas the other compound defects are negligible. However, under nonequilibrium thermal and operating conditions, other complexes also become as important as the point defects. Those are the Cs substituting Pb antisite, and, to a lesser extent, the compound vacancies of PbI2 or CsPbI3 units, and the I substituting Cs antisite. These compound defects only lead to shallow or inactive charge carrier traps, which testifies to the electronic stability of the halide perovskites. Under operating conditions with a quasi-Fermi level very close to the valence band, deeper traps can develop.
RESUMO
The two-dimensional (2D) mixed halide perovskite PEA2Pb(I1-x Br x )4 exhibits high phase stability under illumination as compared to the three-dimensional (3D) counterpart MAPb(I1-x Br x )3. We explain this difference using a thermodynamic theory that considers the sum of a compositional and a photocarrier free energy. Ab initio calculations show that the improved compositional phase stability of the 2D perovskite is caused by a preferred I-Br distribution, leading to a much lower critical temperature for halide segregation in the dark than for the 3D perovskite. Moreover, a smaller increase of the band gap with Br concentration x and a markedly shorter photocarrier lifetime in the 2D perovskite reduce the driving force for phase segregation under illumination, enhancing the photostability.
RESUMO
Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12 weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8 weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake.
Assuntos
Iodo , Tireoidite Autoimune , Feminino , Animais , Camundongos , Interleucina-9/efeitos adversos , Iodo/efeitos adversos , Camundongos Endogâmicos C57BL , Células Th17/metabolismoRESUMO
Liver fibrosis is a wound-healing response to chronic injury, which may result in cirrhosis and liver failure. Studies have been carried on the mechanisms and pathogenesis of liver fibrosis. However, the potential cell-specific expressed marker genes involved in fibrotic processes remain unknown. In this study, we combined a publicly accessible single-cell transcriptome of human liver with microarray datasets to evaluate the cell-specific expression patterns of differentially expressed genes in the liver. We noticed that EMP1 (epithelial membrane protein 1) is significantly active not only in CCl4 (carbon tetrachloride)-treated mouse liver fibrosis but also in BDL (bile duct ligation)-induced liver fibrosis and even in human fibrotic liver tissues such as alcoholic hepatitis, NASH (nonalcoholic steatohepatitis), and advanced stage liver fibrosis. Furthermore, we demonstrated that EMP1 is a specific fibrotic gene expressed in HSCs (hepatic stellate cells) and endothelial cells using the Protein Atlas single-cell transcriptome RNA-sequencing clustering. Its expression was significantly elevated in fibrotic HSCs or CCl4 and NASH-induced fibroblasts. Previous research revealed that EMP1 plays a role in proliferation, migration, metastasis, and tumorigeneses in different cancers via a variety of mechanisms. Because HSC activation and proliferation are two important steps following liver injury, it would be interesting to investigate the role of EMP1 in these processes. All of this information suggested that EMP1 could be used as a novel fibrotic liver marker and a possible target in the future.
RESUMO
Perovskite photovoltaics has achieved conversion efficiencies of 26.0% by optimizing the optoelectronic properties of the absorber and its interfaces with charge transport layers (CTLs). However, commonly adopted organic CTLs can lead to parasitic absorption and device instability. Therefore, metal oxides like atomic layer-deposited (ALD) SnO2 in combination with fullerene-based electron transport layers have been introduced to enhance mechanical and thermal stability. Instead, when ALD SnO2 is directly processed on the absorber, i.e., without the fullerene layer, chemical modifications of the inorganic fraction of the perovskite occur, compromising the device performance. This study focuses on the organic fraction, particularly the formamidinium cation (FA+), in a CsFAPb(I,Br)3 perovskite. By employing in situ infrared spectroscopy, we investigate the impact of ALD processing on the perovskite, such as vacuum level, temperature, and exposure to half and full ALD cycles using tetrakis(dimethylamido)-Sn(IV) (TDMA-Sn) and H2O. We observe that exposing the absorber to vacuum conditions or water half-cycles has a negligible effect on the chemistry of the perovskite. However, prolonged exposure at 100 °C for 90 min results in a loss of 0.7% of the total formamidinium-related vibrational features compared to the pristine perovskite. Supported by density functional theory calculations, we speculate that FA+ deprotonates and that formamidine desorbs from the perovskite surface. Furthermore, the interaction between TDMA-Sn and FA+ induces more decomposition of the perovskite surface compared to vacuum, temperature, or H2O exposure. During the exposure to 10 ALD half-cycles of TDMA-Sn, 4% of the total FA+-related infrared features are lost compared to the pristine perovskite. Additionally, IR spectroscopy suggests the formation and trapping of sym-triazine, i.e., a decomposition product of FA+. These studies enable to decouple the effects occurring during direct ALD processing on the perovskite and highlight the crucial role of the Sn precursor in affecting the perovskite surface chemistry and compromising the device performance.