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Ferroelectric materials with Curie temperature (Tc) below room temperature severely limit their practical applications. Although research on hybrid perovskite photoferroelectrics is ongoing, effective regulation of Tc still poses significant challenges. Herein, we utilized the cationic size effect to successfully regulate the Tc of hybrid perovskite photoferroelectric semiconductors. As the perovskitizer was replaced by a smaller-sized MA+ (methylammonium) with a larger-sized EA+ (ethylammonium), not only was the ferroelectricity of the hybrid perovskite well maintained but the Tc of (PA)2(MA)2Pb3Br10 (315 K) to (PA)2(EA)2Pb3Br10 (385 K) (PA is n-propylaminium) increased by 70 K, which was mainly due to the significant increase in the energy barriers that the system needed to overcome during the phase transition. Subsequently, we achieved efficient self-powered X-ray detection through the ferroelectric-induced bulk photovoltaic effect (BPVE) in (PA)2(EA)2Pb3Br10. The devices based on (PA)2(EA)2Pb3Br10 single crystals exhibit an outstanding sensitivity of 95 µC Gy-1 cm-2 and a low detection limit of 239 nGy s-1 at 0 V bias under X-ray radiation. This study provides an effective approach for designing and constructing high-temperature multilayer photoferroelectric semiconductors in the future.
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Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.
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Cálcio , Nefrite Lúpica , Proteínas de Ligação a Fosfato , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/genética , Animais , Humanos , Camundongos , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/deficiência , Cálcio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Neutrófilos/metabolismo , Granulócitos/metabolismo , Células Mieloides/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Armadilhas Extracelulares/metabolismo , Diferenciação Celular , GasderminasRESUMO
Hydrogen bonding as a multifunctional tool has always influenced the structure of hybrid perovskites. Compared with the research on hydrogen bonding, the study of halogen-halogen interactions on the structure and properties of hybrid perovskites is still in its early stages. Herein, a polar bilayered hybrid perovskite (IEA)2FAPb2I7 (IEA+ is 2-iodoethyl-1-ammonium, FA is formamidinium) with iodine-substituted spacer is successfully constructed by changing the configuration of interlayer cations and regulating non-covalent interactions at the organic-inorganic interface, which shows a shorter interlayer spacing and higher density (ρ = 3.862 g cm-3). The generation of structure polarity in (IEA)2FAPb2I7 is caused by the synergistic effect of hydrogen bonding and halogen-halogen interactions. Especially, as the length of the carbon chain in organic cations decreases, the I---I interaction in the system gradually strengthens, which may be the main reason for the symmetry-breaking. Polarity-induced bulk photovoltaics (Voc = 1.0 V) and higher density endow the device based on (I-EA)2FAPb2I7 exhibit a high sensitivity of 175.6 µC Gy-1 cm-2 and an ultralow detection limit of 60.4 nGy s-1 at 0 V bias under X-ray irradiation. The results present a facile approach for designing polar multifunctional hybrid perovskites, also providing useful assistance for future research on halogen-halogen interactions.
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Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.
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Modelos Animais de Doenças , Fibrose , Glicólise , Histonas , NF-kappa B , Fosfofrutoquinase-2 , Insuficiência Renal Crônica , Traumatismo por Reperfusão , Animais , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Humanos , Camundongos , Masculino , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/metabolismo , NF-kappa B/metabolismo , Histonas/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , Transdução de Sinais , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/metabolismo , Ácido Láctico/metabolismo , Rim/patologia , Rim/metabolismoRESUMO
BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD). METHODS: Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality. RESULTS: A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively. CONCLUSION: High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.
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Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Falência Renal Crônica , Diálise Peritoneal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Fatores de Crescimento de Fibroblastos/sangue , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de RiscoRESUMO
Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.
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Nefrite Lúpica , Humanos , Animais , Camundongos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Imunidade Inata , Linfócitos , Camundongos Endogâmicos MRL lpr , RimRESUMO
Two-dimensional (2D) Dion-Jacobson (DJ) hybrid perovskites with exceptional stability and enhanced out-of-plane carrier transport are regarded as one of the competive candidates for constructing next-generation photodetectors. However, the studies of DJ hybrid perovskites on weak light detection remain scarce, and the devices based on them usually show relatively poor weak light detection ability, with a detection limit of around µW/cm2. Herein, a new DJ hybrid perovskite (3AMPY)(MA)Pb2Br7 [3AMPY is 3-(aminomethyl)pyridinium, and MA is methylammonium] with short interlayer spacing and more lattice rigidity is obtained. The devices based on (3AMPY)(MA)Pb2Br7 crystals exhibit an ultrahigh sensibility to weak light at 377 and 405 nm, with an extremely low detection limit of â¼70 nW/cm2. Moreover, the on/off ratios and detectivity of the devices can reach â¼103 and â¼1012 Jones at both 377 and 405 nm, respectively. This work highlights great potential of DJ hybrid perovskites toward weak light detection.
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[This corrects the article DOI: 10.3389/fimmu.2022.973169.].
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Activation of the alternative pathway (AP) of complement is thought to play an important role in Immunoglobin A nephropathy (IgAN). Our previous study showed that rs4151657 within the complement factor B (CFB) gene increased the risk of IgAN. The protein encoded by the CFB gene is an initial factor that promotes AP activation. The aim of this study was to investigate whether other variants of CFB confer susceptibility to IgAN and elucidate their potential roles in AP activation. A total of 1,350 patients with IgAN and 1,420 healthy controls were enrolled and five tag single-nucleotide polymorphisms were selected for genotyping. The levels of key AP components, such as CFB, complement factor H and complement split product C3a, were measured by enzyme-linked immunosorbent assay. Molecular docking and molecular dynamic simulation were carried out to characterize the mutation of residues in the protein structure and the dynamic properties of wide type and mutation models of CFB protein. The allele-specific effect on CFB expression and its binding affinity to C3b were investigated through cell transfection and surface plasmon resonance analysis, respectively. We found that rs12614 significantly reduced the risk of IgAN (OR = 0.69, 95% CI = 0.52-0.91, P = 0.009), and the rs12614-T (R32W mutation) was correlated with lower CFB levels, higher serum C3 level, and less mesangial C3 deposition in patients with IgAN. The structural model showed that the R32W mutation reduced the structural stability of CFB protein. Furthermore, in vitro study revealed that rs12614-T decreased the expression of CFB and reduced its binding affinity to C3b by four-fold compared with rs12614-C. In conclusion, the rs12614-T in CFB was associated with low risk of IgAN probably by attenuating AP activation.
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Fator B do Complemento , Glomerulonefrite por IGA , Humanos , Fator B do Complemento/genética , Glomerulonefrite por IGA/metabolismo , Simulação de Acoplamento Molecular , Povo Asiático/genética , Proteínas , ChinaRESUMO
Two-dimensional (2D) multilayer Dion-Jacobson (DJ) phase organic inorganic hybrid perovskites (OIHPs) have attracted extensive research attention due to the high stability and excellent charge-transport properties in the optoelectronic field. However, the synthesis of 2D multilayer DJ OIHPs is still very challenging. Until now, only few multilayer DJ perovskites have been reported and most of them are based on volatile methylamine (MA) cations. Compared with MA-based OIHPs, the OIHPs constructed with formamidinium (FA) as perovskitizers not only improve the stability but also extend the light absorption range. Meanwhile, the introducing aromatic diamines as spacers could promote the electron-hole separation in such DJ hybrids. However, the DJ OIHP bulk single crystal constructed by using the advantages of FA as perovskitizers and aromatic diamines as spacers is still blank. Herein, we integrate the properties of organic cations and inorganic skeletons at a molecular-scale to construct a broadband-responsive 2D bilayer DJ perovskite (3AMPY)(FA)Pb2I7 [3AMPY = 3-(aminomethyl)pyridinium], which shows a fascinating detectivity from X-ray (5.23 × 104 µC Gyair-1 cm-2 at 200 V bias) and visible light (6 × 1012 jones at 637 nm) to the near-infrared region (2.6 × 109 jones at 780 nm). After an in-depth analysis of structure and optical properties, we found that the distortion degree of Pb-I-Pb bond angles between adjacent PbI6 octahedra plays a crucial role on optical properties; on the other hand, the interlayer spacer cations (3AMPY) and intralayer perovskitizers (FA) mutual participate in the contribution of the conduction band, making (3AMPY)(FA)Pb2I7 have a narrow optical band gap of 1.54 eV. Such a 2D perovskite material with a wide spectra response will be the preferred choice for photodetection under complex conditions.
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Hyperphosphatemia and hypoalbuminemia confer worse clinical outcomes, whether these risk factors interact to predispose to mortality is unclear. In this prospective cohort study, 2,118 patients undergoing incident continuous ambulatory peritoneal dialysis (CAPD) were enrolled and categorized into four groups based on the changing point regarding mortality at 1.5 mmol/L for serum phosphorus and 35 g/L for serum albumin. Risks of all-cause and cardiovascular mortality were examined independently and interactively in overall and subgroups. There was no association between serum phosphorus with all-cause and cardiovascular mortality, but significant interactions (p = 0.02) between phosphorus and albumin existed in overall population. Patients in subgroup with high phosphorus and low albumin were at greater risk of all-cause (HR 1.95, 95%CI 1.27-2.98, p = 0.002) but not cardiovascular mortality (HR 0.37, 95%CI 0.10-1.33, p = 0.13), as compared to those with low phosphorus and high albumin. In contrast, patients with both low parameters had a higher risk of all-cause (HR 1.75, 95%CI 1.22-2.50, p = 0.002) and cardiovascular mortality (HR 1.92, 95%CI 1.07-3.45, p = 0.03). Notably, an elevated risk of both all-cause and cardiovascular mortality was observed in those with low serum albumin, irrespective of phosphorus levels, suggesting low albumin may be useful to identify a higher-risk subgroup of patients undergoing CAPD with different serum phosphorus levels.
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Background: Increased serum hepcidin-25 level is associated with excess mortality in hemodialysis patients. However, there is a dearth of published information about its predictive effect for survival in patients on peritoneal dialysis (PD). The purpose of this study is to evaluate the association of serum hepcidin-25 with the risk of mortality in PD patients. Methods: Serum hepcidin-25 level was measured using an enzyme-linked immunosorbent assay in a prospective cohort study of PD patients with stored serum samples at baseline. Multivariate linear regression model was used to determine clinical characteristics associated with serum hepcidin-25 concentration. We evaluated the relationship between serum hepcidin-25 and all-cause mortality using a Cox proportional hazards model and the relationship between hepcidin-25 and cardiovascular (CV) and infection-related deaths using competing-risks regression models. Results: In total, 513 PD patients were included in this study. The median serum hepcidin-25 level was 40.9 (17.9-85.9) ng/mL. Body mass index and serum ferritin were positively correlated with serum hepcidin-25 levels. During a median follow-up period of 64.1 months, 122 (24%) patients died, including 61 (50%) CV deaths and 32 (26%) infection-related deaths. In multivariable analysis, patients with the highest tertile of serum hepcidin-25 had a greater risk of all-cause [adjusted hazard ratio (aHR) 1.85, 95% confidence interval (95%CI), 1.14 to 3.00, P = 0.013] and infection-related mortality (adjusted subdistribution hazard ratio [aSHR], 2.61; 95%CI, 1.01 to 6.76, P = 0.049) when compared with those in the second tertile. However, no significant relationship was observed between serum hepcidin-25 and CV mortality. Conclusions: Higher baseline serum hepcidin-25 level was associated with increased risk for all-cause and infection-related mortality in PD patients.
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The introduction of chirality into organic-inorganic hybrid perovskites (OIHPs) is expected to achieve excellent photoelectric and nonlinear materials related to circular dichroism. Owing to the existence of asymmetric center and intrinsic chirality in the chiral OIHPs, the different efficiencies of second harmonic generation (SHG) signal occurs when the circularly polarized light (CPL) with different phases passes through the chiral crystal, which is defined as second harmonic generation circular dichroism (SHG-CD). Here, the SHG-CD effect is developed in bulk single crystals of chiral one-dimensional (1D) [(R/S)-3-aminopiperidine]PbI4 . It is the first time that CPL is distinguished using chirality-dependent SHG-CD effect in OIHPs bulk single crystals. Such SHG-CD technology extends the detection range to near infrared region (NIR). In this way, the anisotropy factor (gSHG-CD ) through SHG-CD signal is as high as 0.21.
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BACKGROUND: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. METHODS: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. RESULTS: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8-61.0) µM. During a median follow-up of 63.7 months (IQR, 43.9-87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01-1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07-1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02-1.94; p = 0.038) in men but not in women. CONCLUSIONS: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.
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Metilaminas/sangue , Diálise Peritoneal/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Fc receptor-like (FCRL) molecules were considered to play a role in the pathogenesis of certain autoimmune diseases. Nonetheless, the clinical significance of FCRLs in IgA nephropathy (IgAN) remains unclear. OBJECTIVE: This study is aimed at investigating the expression levels of FCRLs molecules in IgAN patients and determining its relevance to disease activity. METHODS: The mRNA expression levels of FCRLs were determined in peripheral blood mononuclear cells (PBMCs) of 42 IgAN patients and 48 healthy controls by quantitative real-time PCR (qRT-PCR). FCRLs proteins expression in B cells of 25 IgAN patients, 14 patients with non-IgAN glomerulonephritis, and 29 healthy controls were detected by Flow cytometry. The Spearman correlation test was used to assess the correlation of FCRLs expression with clinical parameters of IgAN patients. RESULTS: Our results indicated significant down-regulation of FCRL2 and FCRL3 mRNA levels in IgAN patients compared to healthy subjects. Surface protein expression of FCRLs molecules confirmed the qRT-PCR results. But FCRL2 and FCRL3 protein levels did not correlate with clinicopathologic phenotypes of IgAN patients. However, we found a significant positively correlation of FCRL2 and FCRL3 mRNA expression with the core 1 ß1,3-galactosyltransferase (C1GALT1) and its molecular chaperone (Cosmc) mRNA levels in IgAN patients. CONCLUSIONS: FCRL2 and FCRL3 expression levels in IgAN patients are significantly decreased and correlated with CIGALT1 and Cosmc mRNA expression.
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Glomerulonefrite por IGA/metabolismo , Leucócitos Mononucleares/metabolismo , Proteínas de Membrana/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Células Cultivadas , Regulação para Baixo , Feminino , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Glomerulonefrite por IGA/genética , Humanos , Leucócitos Mononucleares/patologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Receptores de Superfície Celular/genética , Receptores Imunológicos/genética , TranscriptomaRESUMO
An unprecedented CsPbBr3-based polar Dion-Jacobson type bilayered hybrid, (2meptH2)CsPb2Br7 (1, where 2mept = 2-methyl-1,5-diaminopentane), has been reported. Polarization could benefit the charge transport to induce low Ntrap. 1 exhibits a large on/off ratio (â¼103), fast response time (â¼200 µs) and high photodetectivity (â¼109 Jones) for promising UV photodetection.
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BACKGROUND: ST6GAL1 has been identified as a novel susceptibility gene for IgA nephropathy (IgAN) in a previous genome-wide association study. The present study is aimed at exploring whether the genetic polymorphisms of ST6GAL1 gene correlate with IgAN susceptibility, clinical phenotypes and progression in a Chinese Han population. METHODS: Twenty-six single nucleotide polymorphisms (SNPs) of ST6GAL1 were genotyped in 1000 biopsy-proven IgAN patients and 1000 control subjects of Chinese Han population using Sequenom MassARRAY iPLEX. A logistic regression analysis with age and sex as covariates was performed to evaluate the effects of ST6GAL1 gene polymorphisms on IgAN susceptibility. Kaplan-Meier method and Cox proportional hazard models were applied to analyze the associations between genetic variants and renal survival. RESULTS: We found that rs7634389 (ORâ¯=â¯1.24, 95 % CIâ¯=â¯1.02-1.50, pdominant = 0.034) and rs6784233 (ORâ¯=â¯1.23, 95 % CIâ¯=â¯1.05-1.45, padditive = 0.013; ORâ¯=â¯1.28, 95 % CIâ¯=â¯1.05-1.55, pdominant = 0.014) were associated with susceptibility of IgAN. In addition, rs7634389 was correlated with hyperuricemia (ORâ¯=â¯1.27, pâ¯=⯠0.012) and segmental glomerulosclerosis (OR = 1.21, p = 0.047) in IgAN patients. Furthermore, rs7634389 was independently associated with renal survival after adjustments for multiple confounders (hazard ratio [HR]â¯=â¯0.51, 95 % CIâ¯=â¯0.33-0.78, pâ¯=⯠0.002). Haplotype analysis for ST6GAL1 polymorphisms confirmed their associations with the susceptibility to IgAN. CONCLUSIONS: Our research suggested that ST6GAL1 gene polymorphisms were implicated in IgAN susceptibility and clinical outcome in a Chinese Han population.
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Antígenos CD/genética , Predisposição Genética para Doença , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/etiologia , Polimorfismo de Nucleotídeo Único , Sialiltransferases/genética , Estudos de Casos e Controles , Progressão da Doença , Estudos de Associação Genética , Glomerulonefrite por IGA/metabolismo , Humanos , Estimativa de Kaplan-Meier , Razão de Chances , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13-1.45, P = 1.42 × 10-4) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus (CFB) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.
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Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas de Ciclo Celular/genética , Glomerulonefrite por IGA/genética , Doenças Inflamatórias Intestinais/genética , Adulto , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Glomerulonefrite por IGA/patologia , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
A novel, to the best of our knowledge, liquid crystal (LC) biosensor, based on an optical fiber Mach-Zehnder interferometer (MZI), is proposed. The proposed optical fiber MZI consists of two single-mode fibers and a tapered photonic crystal fiber (PCF). The PCF is coated with 4'-pentyl-biphenyl-4-carboxylic acid (PBA)-doped 4-cyano-4'-pentylbiphenyl (5CB). Being a pH-sensitive material, PBA can manipulate LC molecules to different orientations according to their pH values. When the orientation of LC molecules changes with varying pH, the effective refractive index of the cladding modes also is accordingly affected. Enzymatic reactions of penicillinase can release H+, which causes the decrease of the pH. Therefore, the enzymatic reactions of penicillinase can be sensed by monitoring the peak shift in the interference spectrum. The effects of the tapered diameter on the sensitivity of the sensor were experimentally investigated as well.
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Técnicas Biossensoriais , Interferometria/instrumentação , Cristais Líquidos/química , Penicilinase/metabolismo , Bacillus cereus/enzimologia , Concentração de Íons de Hidrogênio , Fibras Ópticas , Penicilina G/metabolismoRESUMO
In this article, we have synthesized a series of nitrogen-doped nanoporous carbon (NPC) from metal organic framework of UiO-66 with different ratios of adenine and 1,4-benzendicarboxylate (H2BDC) coated on carbon nanotube film (CNTF) to obtain a flexible porous electrode (NPC/CNTF). It is worth noting that the introduction of adenine at different ratios did not change the structure of UiO-66. We also investigated the effect of carbonization temperature from 800 to 1000°C on the electrochemical properties of the NPC. The ratio (H2BDC:adenine) 9 : 1 and the NPC carbonized at 900°C (denoted as NPC-1-900) exhibits better electrochemical properties. The results show that NPC-1-900/CNTF electrode exhibits an exceptional areal capacitance of 121.5 mF cm-2 compared to that of PC-900/CNTF electrode (22.8 mF cm-2) at 5 mV s-1 in a three-electrode system, indicating that the incorporation of nitrogen is beneficial to the electrochemical properties of nanoporous carbon. A symmetric flexible solid-state supercapacitor of NPC-1-900/CNTF has also been assembled and tested. Electrochemical data show that the device exhibited superior areal capacitance (43.2 mF cm-2) at the scan rate of 5 mV s-1; the volumetric energy density is 57.3 µWh cm-3 and the volumetric power density is 2.4 mW cm-3 at the current density of 0.5 mA cm-2 based on poly(vinyl alcohol)/H3PO4 gel electrolyte. For practical application, we have also studied the bending tests of the device, which show that the device exhibits outstanding mechanical stability under different bending angles. Furthermore, the flexible device shows excellent cyclic stability, which can retain 91.5% of the initial capacitance after 2000 cycles.