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Malignant pleural mesothelioma (MPM) is a rare but lethal pleural cancer with high intratumor heterogeneity (ITH). A recent study in lung adenocarcinoma has developed a clonal gene signature (ORACLE) from multiregional transcriptomic data and demonstrated high prognostic values and reproducibility. However, such a strategy has not been tested in other types of cancer with high ITH. We aimed to identify biomarkers from multi-regional data to prognostically stratify MPM patients. We generated a multiregional RNA-seq dataset for 78 tumor samples obtained from 26 MPM patients, each with one sample collected from a superior, lateral, and inferior region of the tumor. By integrating this dataset with the Cancer Genome Atlas MPM RNA-seq data, we selected 29 prognostic genes displaying high variability across different tumors but low ITH, which named PRACME (Prognostic Risk Associated Clonal Mesothelioma Expression). We evaluated PRACME in two independent MPM datasets and demonstrated its prognostic values. Patients with high signature scores are associated with poor prognosis after adjusting established clinical factors. Interestingly, the PRACME and the ORACLE signatures defined respectively from MPM and lung adenocarcinoma cross-predict prognosis between the two cancer types. Further investigation indicated that the cross-prediction ability might be explained by the high similarity between the two cancer types in their genomic regions with copy number variation, which host many clonal genes. Overall, our clonal signature PRACME provided prognostic stratification in MPM and this study emphasized the importance of multi-regional transcriptomic data for prognostic stratification based on clonal genes.
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OBJECTIVE: To explore the influence of classroom-based physical activity (CB-PA) on the teaching quality of systemic lupus erythematosus (SLE) for medical undergraduates. METHODS: Students from 8 classes participating in the clinical medicine program of the affiliated hospital of Zunyi Medical University were divided into two groups. Four classes received regular teaching on the SLE chapter as the control group, and the other four received CB-PA intervention as the experimental group. After class, the basic ability (diagnostics and pharmacology scores in sophomore year) and teaching quality scores were collected and compared using a questionnaire. The performance of the 2 groups to the SLE review questions was compared. RESULTS: The scores of learning interest, the degree of satisfaction with the courses, and the level of mastering the teaching contents in the experimental group were significantly higher than those in the control group. The evaluation of the teacher's teaching level increased considerably. The experimental group's performance was also better than the control group's (the assessment performance was adjusted with the basic ability). CONCLUSION: CB-PA in teaching SLE improves students' interest in learning, teaching satisfaction, and mastery of knowledge and may ultimately enhance their assessment results.
Subject(s)
Lupus Erythematosus, Systemic , Humans , Students , Surveys and QuestionnairesABSTRACT
Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points ⢠To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. ⢠In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). ⢠Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Humans , Methotrexate/therapeutic use , Rituximab/therapeutic use , Fourth Ventricle , Immunosuppressive Agents/therapeutic use , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Granuloma/drug therapy , Granuloma/complications , Mycophenolic Acid/therapeutic use , Injections, Spinal , Dexamethasone/therapeutic use , Granulomatosis with Polyangiitis/complicationsABSTRACT
BACKGROUND: Diabetes that develops in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral therapy (ART) is usually type 2 diabetes mellitus (T2DM); however, autoimmune diabetes, such as type 1 diabetes mellitus (T1DM) can also develop in this population. After treatment with ART, patients might experience clinical deterioration following an increase in the CD4 cell count, which is termed immune reconstitution inflammatory syndrome (IRIS). Here, we describe an HIV-infected patient on ART who developed T1DMat due to IRIS, highlighting the clinical complexity in diagnosis and treatment. CASE PRESENTATION: A 36-year-old man infected with HIV had a nadir CD4 cell count of 15.53/µL before medication, which increased to 429.09/µL after 9 months of regular ART. The fasting serum glucose at 9 months was between 96 mg/dL and 117 mg/dL. After 11 months of ART, the patient was admitted to hospital for diabetic ketoacidosis (DKA) and Graves' disease (GD). Noninsulin antidiabetics (NIADs) were prescribed following the resolution of DKA. However, poor glycemic control was noted despite well-titrated NIADs. Further investigation demonstrated poor pancreatic beta cell function and elevated anti-glutamic acid decarboxylase (anti-GAD) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) titers. According to the results, he was diagnosed with T1DM and received multiple daily injections(MDI) of insulin. The regimen of MDI was insulin degludec as basal insulin and insulin aspart as prandial insulin. After MDI therapy, his glycemic control was improved. CONCLUSION: In this case, T1DM was ascribed to IRIS. Although this phenomenon has been demonstrated in previous case reports, further study is necessary to realize the mechanism of this association. Therefore, we emphasize that when HIV-infected patients on ART experience an unstable blood glucose level and abnormal thyroid function, physicians should consider T1DM and GD associated with ART-induced IRIS to reduce the subsequent complications and more serious endocrine dysfunction.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , HIV Infections , Immune Reconstitution Inflammatory Syndrome , Male , Humans , Adult , HIV , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Immune Reconstitution Inflammatory Syndrome/diagnosis , Immune Reconstitution Inflammatory Syndrome/etiology , Hypoglycemic Agents , HIV Infections/complications , HIV Infections/drug therapyABSTRACT
Azathioprine is clinically used as an immunosuppressant for treating autoimmune diseases. However it has narrow therapeutic indices due to frequent myelosuppression. Polymorphic variants of genes coding for thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X motif 15 (NUDT15) are critical determinants of AZA intolerance, and the differences in frequencies of the two genetic variants exist among people of different ethnicities. Most reports regarding NUDT15 variant, AZA-induced myelosuppression occurred in patients with inflammatory bowel disease and acute lymphoblastic leukemia. Moreover, detailed clinical characteristics were not frequently reported. Here we present the case of a young Chinese female with the NUDT15 c.415C>T (rs116855232, TT) homozygous variant and wild-type TPMT*2 (rs1800462), TPMT*3B (rs1800460), and TPMT*3C (rs1142345) who received high doses of AZA (2.3 mg/kg/d) for systematic lupus erythematosus and had not been told to undergo routine blood cell counts during AZA ingestion. The patient had suffered from severe AZA-induced myelosuppression and alopecia. Moreover, dynamic changes in blood cell counts and responses to treatment were observed. We also conducted a systematic review of published case reports of patients exclusively with NUDT15 c.415C>T homozygous or heterozygous variants to review the characteristics of dynamic changes in blood cells so as to provide reference information for clinical treatment.
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Background: In this study, we aimed to compare the effects of metformin-based dual therapy versus triple therapy on glycemic control and lipid profile changes in Taiwanese patients with type 2 diabetes mellitus (T2DM). Methods: In total, 60 patients were eligible for participation in this study. Patients received at least 24 months of metformin monotherapy, dual therapy, or triple therapy with metformin plus linagliptin (a dipeptidyl peptidase 4 (DPP-4) inhibitor) or dapagliflozin (a sodium-glucose cotransporter-2 (SGLT2) inhibitor). Blood samples were collected from each patient, followed by evaluation of changes in their blood glucose control and lipid profile-related markers. Results: A combination of metformin and DPP4 and SGLT2 inhibitor therapy more effectively reduced low-density lipoprotein cholesterol (LDL-C) (p = 0.016) than metformin monotherapy. A combination of metformin and DPP4 and SGLT2 inhibitor therapy more effectively improved total cholesterol (Chol, p = 0.049) and high-density lipoprotein cholesterol (HDL-C) than metformin monotherapy (p = 0.037). Metformin plus linagliptin dual therapy was more effective than metformin monotherapy in reducing glycosylated hemoglobin (HbA1C, p = 0.011). Patients who received a combination of linagliptin and empagliflozin showed a significant reduction in their fasting blood glucose (p = 0.019), HbA1c (p = 0.036), and Chol (p = 0.010) compared with those who received linagliptin dual therapy. Furthermore, patients who received metformin plus dapagliflozin and saxagliptin showed significantly reduced Chol (p = 0.011) and LDL-C (p = 0.035) levels compared with those who received metformin plus dapagliflozin. Conclusion: In conclusion, dual therapy with metformin and linagliptin yields similar glycemic control ability to triple therapy. Among metformin combination triple therapy, triple therapy of empagliflozin and linagliptin might have a better glycemic control ability than dual therapy of linagliptin. Moreover, Triple therapy of dapagliflozin and saxagliptin might have a better lipid control ability than dual therapy of dapagliflozin.
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OBJECTIVES: This study aims to investigate the effects of Icariin (ICA) on interleukin-1ß (IL-1ß)-induced osteoarthritis (OA) and its potential mechanism of action. METHODS: SW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation with IL-1ß to mimic OA. Expression levels of matrix metalloproteinases (MMP-3) and collagen II were determined using real-time PCR and Western blot assays. Autophagy activation (by ICA) or inhibition (by shRNA) was determined based on the expression levels of ULK1, Beclin-1, LC3-II/I, and p62, using Western blot analysis. The phosphorylation levels of PI3K, Akt, mTOR, and ULK1 were also detected using Western blot analysis. RESULTS: IL-1ß increased MMP-3 overproduction, induced collagen II degradation, and reduced the level of autophagy-associated proteins, including ULK1, Beclin-1, and LC3-II/I. In contrast, ICA pretreatment attenuated IL-1ß-induced MMP-3 overproduction, increased collagen II expression, and induced expression of autophagy-related proteins. ICA also decreased PI3K, Akt, and mTOR phosphorylation, increased the production of ULK1, and induced autophagy. Short hairpin RNA-mediated knockdown of ULK1 led to activation of the PI3K/Akt/mTOR pathway, which reversed the protective effects of ICA. CONCLUSIONS: Our findings indicate that ICA can induce autophagy by regulating the PI3K/AKT/mTOR/ULK1 signaling pathway. This study suggests that ICA may be effective for treating OA.
Subject(s)
Osteoarthritis , Proto-Oncogene Proteins c-akt , Autophagy , Autophagy-Related Protein-1 Homolog , Beclin-1/genetics , Beclin-1/metabolism , Beclin-1/pharmacology , Chondrocytes , Collagen , Flavonoids , Humans , Interleukin-1beta , Intracellular Signaling Peptides and Proteins , Matrix Metalloproteinase 3 , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering , Signal Transduction , TOR Serine-Threonine KinasesABSTRACT
Detecting genetic variants associated with the variance of complex traits, that is, variance quantitative trait loci (vQTLs), can provide crucial insights into the interplay between genes and environments and how they jointly shape human phenotypes in the population. We propose a quantile integral linear model (QUAIL) to estimate genetic effects on trait variability. Through extensive simulations and analyses of real data, we demonstrate that QUAIL provides computationally efficient and statistically powerful vQTL mapping that is robust to non-Gaussian phenotypes and confounding effects on phenotypic variability. Applied to UK Biobank (n = 375,791), QUAIL identified 11 vQTLs for body mass index (BMI) that have not been previously reported. Top vQTL findings showed substantial enrichment for interactions with physical activities and sedentary behavior. Furthermore, variance polygenic scores (vPGSs) based on QUAIL effect estimates showed superior predictive performance on both population-level and within-individual BMI variability compared to existing approaches. Overall, QUAIL is a unified framework to quantify genetic effects on the phenotypic variability at both single-variant and vPGS levels. It addresses critical limitations in existing approaches and may have broad applications in future gene-environment interaction studies.
Subject(s)
Biological Variation, Population , Models, Biological , Phenotype , Biological Variation, Population/genetics , Computer Simulation , Gene-Environment Interaction , Humans , Linear Models , Quantitative Trait LociABSTRACT
CmnC is an α-ketoglutarate (α-KG)-dependent non-heme iron oxygenase involved in the formation of the l-capreomycidine (l-Cap) moiety in capreomycin (CMN) biosynthesis. CmnC and its homologues, VioC in viomycin (VIO) biosynthesis and OrfP in streptothricin (STT) biosynthesis, catalyze hydroxylation of l-Arg to form ß-hydroxy l-Arg (CmnC and VioC) or ß,γ-dihydroxy l-Arg (OrfP). In this study, a combination of biochemical characterization and structural determination was performed to understand the substrate binding environment and substrate specificity of CmnC. Interestingly, despite having a high conservation of the substrate binding environment among CmnC, VioC, and OrfP, only OrfP can hydroxylate the substrate enantiomer d-Arg. Superposition of the structures of CmnC, VioC, and OrfP revealed a similar folds and overall structures. The active site residues of CmnC, VioC, and OrfP are almost conserved; however Leu136, Ser138, and Asp249 around the substrate binding pocket in CmnC are replaced by Gln, Gly, and Tyr in OrfP, respectively. These residues may play important roles for the substrate binding. The mutagenesis analysis revealed that the triple mutant CmnCL136Q,S138G,D249Y switches the substrate stereoselectivity from l-Arg to d-Arg with â¼6% relative activity. The crystal structure of CmnCL136Q,S138G,D249Y in complex with d-Arg revealed that the substrate loses partial interactions and adopts a different orientation in the binding site. This study provides insights into the enzyme engineering to α-KG non-heme iron oxygenases for adjustment to the substrate stereoselectivity and development of biocatalysts.
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Graves disease (GD) and type 2 diabetes mellitus (T2DM) both impair liver function; we therefore explored the possibility of a relationship among diabetic control, thyroid function, and liver function. This retrospective, cross-sectional study compared serum liver function biomarkers of primary GD patients in a single center between 2016 and 2020, derived from clinical databases, and clarified the correlation of liver function in GD patients with or without T2DM. Furthermore, the diabetes mellitus group was divided into glycated hemoglobin A1C (HbA1C) <6.5% group and ≥6.5% group to further analyze the effect by disease control in patients. Statistical differences between groups were assessed using independent t tests to clarify the association of serum biomarkers between GD with T2DM. Pearson test was applied to assess within-group statistical correlation of serum biomarkers. The correlation of factors in each group was demonstrated by using the Kendall tau-b method and stepwise regression analysis. A total of 77 patients were included in the study. In the study population, glutamate pyruvate transaminase (GPT) was significantly correlated with thyroid-stimulating hormone, and HbA1C was significantly correlated with alkaline phosphatase (ALK-P), glutamate oxaloacetate transaminase (GOT), and GPT. An examination of GOT, GPT, free thyroxine (FT4), and HbA1C levels revealed a significant difference between the non-T2DM and T2DM groups. GPT also exhibited a significant correlation with triiodothyronine in the T2DM group. The T2DM group was further divided into groups: HbA1C <6.5% and ≥6.5%. The results demonstrated that ALK-P, GOT, GPT, and FT4 levels were significantly different between the groups. A significant correlation between ALK-P and thyroid-stimulating hormone and between GOT and FT4 was also identified in the HbA1C <6.5% group. Our single-center study revealed that diabetes affects liver function in patients with GD. For patients with T2DM, when liver function becomes impaired, thyroid function control deteriorates. GPT was correlated with triiodothyronine but not with FT4, which indicated the impairment of deiodination in the liver. This phenomenon was not observed in the non-T2DM population. The early detection of abnormal liver function in patients with GD and T2DM may help limit the development of comorbidities and improve disease management.
Subject(s)
Diabetes Mellitus, Type 2 , Graves Disease , Alanine Transaminase , Aspartate Aminotransferases , Biomarkers , Cross-Sectional Studies , Glutamates , Glycated Hemoglobin , Graves Disease/complications , Humans , Receptor Protein-Tyrosine Kinases , Retrospective Studies , Taiwan/epidemiology , Thyrotropin , Thyroxine , TriiodothyronineABSTRACT
Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder due to defects in insulin secretion or insulin resistance leading to the dysfunction and damage of various organs. To improve the clinical evaluation of short-term blood glycemic variability monitoring, it is critical to identify another blood cell status and nutritional status biomarker that is less susceptible to interference. This study identifies the significance of serum lactate dehydrogenase (LDH) level among T2DM patients treated in outpatient clinics and investigates the relationship of LDH level with other variables. Methods: This study comprised 72 outpatients with T2DM over 20 years of age. Blood samples were collected followed by a hematological analysis of serum glycated albumin (GA), LDH, fasting blood glucose, glycosylated hemoglobin, C-peptide, and insulin antibodies (insulin Ab). Results: Serum LDH level was significantly correlated with GA (p < 0.001), C-peptide (p = 0.04), insulin Ab (p = 0.03), and thyroid-stimulating hormone (TSH) levels (p = 0.04). Hence, we performed a linear regression analysis of hematological markers. GA (p < 0.001, r2 = 0.45) and insulin Ab (p < 0.001, r2 = 0.40) were significantly associated with LDH level. Then, we classified patients into low (<200 U/L) and high (≥200 U/L) serum LDH level groups, respectively. GA (p < 0.001), C-peptide (p = 0.001), and TSH (p = 0.03) showed significant differences in patients with high LDH levels compared with those in patients with low LDH levels. Conclusion: In conclusion, we suggested that LDH level was independent of long-term but associated with short-term blood glucose monitoring. The results indicated that changes in serum GA induced cell damage and the abnormal elevation of the serum level of LDH may occur simultaneously with glycemic variability. It has been reported that many biomarkers are being used to observe glucose variability in T2DM. However, LDH could provide a more convenient and faster evaluation of glycemic variability in T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Lactate Dehydrogenases , Adult , Humans , Biomarkers/blood , Biomarkers/metabolism , Blood Glucose/metabolism , Blood Glucose Self-Monitoring , C-Peptide/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Glycated Serum Albumin/analysis , Glycated Serum Albumin/metabolism , Glycation End Products, Advanced , Serum Albumin/analysis , Thyrotropin/blood , Lactate Dehydrogenases/blood , Lactate Dehydrogenases/metabolismABSTRACT
Polygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize in practice due to limited access to individual-level data. Here, we introduce PUMAS, a novel method to fine-tune PRS models using summary statistics from genome-wide association studies (GWASs). Through extensive simulations, external validations, and analysis of 65 traits, we demonstrate that PUMAS can perform various model-tuning procedures using GWAS summary statistics and effectively benchmark and optimize PRS models under diverse genetic architecture. Furthermore, we show that fine-tuned PRSs will significantly improve statistical power in downstream association analysis.
Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Multifactorial Inheritance/genetics , Software , Statistics as Topic , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Computer Simulation , Humans , Linkage Disequilibrium/genetics , Models, Genetic , Neuroimaging , Quantitative Trait, Heritable , Risk Factors , Sample SizeSubject(s)
Behcet Syndrome/diagnosis , Arthralgia/etiology , Female , Fever/etiology , Humans , Lower Extremity , Middle Aged , Skin Ulcer/etiologyABSTRACT
Balloon angioplasty-induced neointimal hyperplasia remains a clinical problem that must be resolved. The bioactivities of the Crossostephium chinense extract (CCE) have demonstrated potential in preventing the progression of restenosis. The present study evaluated whether CCE can suppress balloon angioplasty-induced neointima formation and elucidated its possible pharmacological mechanisms. A rat model of carotid arterial balloon angioplasty was established to evaluate the inhibitory effect of CCEs on neointimal hyperplasia. Two cell lines, A10 vascular smooth muscle cells (VSMCs) and RAW264.7 macrophages, were used to investigate the potential regulatory activities and pharmacological mechanisms of CCEs in cell proliferation and migration and in inflammation. Our in vitro results indicated that CCE3, the ethanolic extract of C. chinense, exerted the strongest growth inhibitory and antimigratory effects on VSMCs. CCE3 blocked the activation of focal adhesion kinase, platelet-derived growth factor receptor-ß (PDGFRB), and its downstream molecules (AKT and mTOR) and reduced the expression of matrix metalloproteinase-2. In addition, our findings revealed that CCE3 significantly increased the expression of miRNA-132, an inhibitory regulator of inflammation and restenosis, and suppressed the expression of inflammation-related molecules (inducible nitric oxide synthase, cyclooxygenase-2, interleukin- (IL-) 1ß, and IL-6). Our in vivo study results indicated that balloon injury-induced neointimal hyperplasia was inhibited by CCE3. CCE3 could reduce neointima formation in balloon-injured arteries, and this effect may be partially attributed to the CCE3-induced suppression of PDGFRB-mediated downstream pathways and inflammation-related molecules.
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Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p = 2.1E-7), a transcription factor mainly expressed in developmental brain. Gene targets regulated by POU3F2 showed a 2.7-fold enrichment for known ASD genes (p = 2.0E-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p = 7.1E-5). These results provide a novel connection between rare and common variants, whereby ASD genes affected by very rare mutations are regulated by an unlinked transcription factor affected by common genetic variations.
Subject(s)
Autism Spectrum Disorder/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Hippocampus/metabolism , Homeodomain Proteins/genetics , POU Domain Factors/genetics , Transcriptome/genetics , Alleles , Databases, Genetic , Gene Expression Profiling , Humans , Mutation , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Risk Factors , Spatio-Temporal AnalysisABSTRACT
We synthesized and characterized methylammonium (MA) mixed tri-halide tin perovskites (MASnIBr2-x Clx ) for carbon-based mesoscopic solar cells free of lead and hole-transporting layers. Varied SnCl2 /SnBr2 ratios yielded tin perovskites with three halides (I, Br, and Cl) co-crystallized inside the tin-perovskite. When the SnCl2 proportion was ≥50 % (x≥1), phase separation occurred to give MASnI3-y Bry and MASnCl3-z Brz in the stoichiometric proportions of their precursors, confirmed by XRD. A device with MASnIBr1.8 Cl0.2 (SnCl2 =10 %) showed the best photovoltaic performance: JSC =14.0â mA cm-2 , VOC =380â mV, FF=0.573, and PCE=3.1 %, and long-term stability. Electrochemical impedance spectra (EIS) show superior charge recombination and dielectric relaxation properties for the MASnIBr1.8 Cl0.2 cell. Transient PL decays showed the intrinsic problem of tin-based perovskites with average lifetimes less than 100â ps.
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BACKGROUND: Some of the thyroid disorders (TD) and Myasthenia gravis (MG) are autoimmune related disease. The purpose of the study to evaluate the relationship of MG with all morphological and functional thyroid disorders. METHODS: We constructed a population-based cohort study during the period from January 2000-December 2002 by using reimbursement data from the Bureau National Health Insurance (NHI) system in Taiwan. Patients with TD and MG were identified by referring to the ICD-9-CM codes. (ICD-10-CM as reference) .The association of TD with MG occurred only in the same person within the study period. The Q value was used to measure the strength of disease-disease associations. RESULTS: We obtained 520628 TD and 7965 MG records for analysis. Diffuse toxic goiter had highest association rate, followed by nontoxic nodular goiter, simple goiter, chronic lymphocytic thyroiditis, thyroid cancer, and toxic nodular goiter. Female and older patients had a higher rate than their male and younger counterparts, respectively. Functional abnormalities revealed higher incidence of thyrotoxicosis and hypothyroidism in both sexes. We also found the strongest association in men with chronic thyroiditis, diffuse toxic goiter, thyrotoxicosis, acquired hypothyroidism, thyroid cancer, and simple goiter. While an intermediate association was observed in female with diffuse toxic goiter, in a male with toxic and nontoxic nodular/multinodular goiters, in female with thyrotoxicosis, thyroid cancer and acquired hypothyroidism. CONCLUSION: This population based cohort study showed potential association of all types of TD with MG, and observed a higher association rate in female autoimmune TD whereas males showed a higher strength of association.
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Asthma, a complex pulmonary allergic disease, major therapy is applied of drugs to control the disease, but quickly recur after the drugs are stopped. In patients with severe asthma may show steroid resistance and would benefit from the development of novel therapeutic drugs. Ovatodiolide, a unique macrocyclic diterpenoid isolated from Anisomeles indica, showed therapeutic potential for the treatment of allergic asthma. As a model of allergic inflammation, we used ovalbumin (OVA)-immunized mice, which displayed T helper cell type 2 (TH2) cytokine expression in bronchoalveolar lavage fluid (BALF), as well as airway inflammation and hyperresponsiveness (AHR). The results showed that ovatodiolide suppressed TH2 activation, including cell proliferation and production of the TH2 related cytokines, interleukin (IL)-4, IL-5, IL-13, IL-33, eosinophil chemotactic protein (eotaxin), and also reduced airway hyperresponsiveness. In this study, ovatodiolide inhibited allergic asthma through downregulation of TH2 responses in a murine model of asthma.
Subject(s)
Asthma/drug therapy , Diterpenes/pharmacology , Animals , Asthma/immunology , Asthma/metabolism , Disease Models, Animal , Diterpenes/therapeutic use , Down-Regulation/drug effects , GATA3 Transcription Factor/metabolism , Immunoglobulin E/biosynthesis , Interleukin-33/metabolism , Lung/drug effects , Lung/metabolism , Mice , Th2 Cells/drug effects , Th2 Cells/metabolismABSTRACT
Reversible protein S-nitrosylation, defined as the covalent addition of a nitroso moiety to the reactive thiol group on a cysteine residue, has received increasing recognition as a critical post-translational modification that exerts ubiquitous influence in a wide range of cellular pathways and physiological processes. Due to the lability of the S-NO bond, which is a dynamic modification, and the low abundance of endogenously S-nitrosylated proteins in vivo, unambiguous identification of S-nitrosylated proteins and S-nitrosylation sites remains methodologically challenging. In this review, we summarize recent advancements and the use of state-of-art approaches for the enrichment, systematic identification and quantitation of S-nitrosylation protein targets and their modification sites at the S-nitrosoproteome scale. These advancements have facilitated the global identification of >3000 S-nitrosylated proteins that are associated with wide range of human diseases. These strategies hold promise to site-specifically unravel potential molecular targets and to change S-nitrosylation-based pathophysiology, which may further the understanding of the potential role of S-nitrosylation in diseases.
Subject(s)
Proteome/isolation & purification , S-Nitrosothiols/isolation & purification , Animals , Chromatography, Affinity , Humans , Protein Processing, Post-Translational , Proteome/chemistry , Proteome/metabolism , S-Nitrosothiols/chemistry , S-Nitrosothiols/metabolism , Staining and Labeling , Tandem Mass SpectrometryABSTRACT
OBJECTIVE: To examine whether trends in death rate from diabetes according to multiple-cause-of-death (MCOD) data differed from those according to underlying-cause-of-death (UCOD) data in Taiwan and the United States. STUDY DESIGN AND SETTING: We used multiple cause mortality files for the years 1987, 1992, 1997, 2002, and 2007 to calculate the age-adjusted death rates from diabetes according to MCOD and UCOD and the ratio between diabetes mortality according to UCOD and that according to MCOD (U/M ratio) in Taiwan and the United States. RESULTS: In Taiwan, diabetes mortality according to MCOD increased persistently from 1987 to 2007, but no prominent changes were found according to UCOD in men. For women, the death rates according to MCOD did not change significantly between 1987 and 2007 but decreased drastically from 1992 to 2007 according to UCOD. In the United States, the patterns of change in diabetes mortality according to MCOD were similar to those according to UCOD in both sexes. The U/M ratio of diabetes mortality declined persistently between 1987 and 2007 in Taiwan, but no prominent change was found in the United States. CONCLUSION: Trends in death rate from diabetes according to MCOD differed from that according to UCOD in Taiwan but not in the United States. To properly interpret cause-specific mortality trends, it is important to provide both MCOD and UCOD data.