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1.
Kidney Int ; 106(2): 226-240, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38789037

RESUMEN

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.


Asunto(s)
Modelos Animales de Enfermedad , Fibrosis , Glucólisis , Histonas , FN-kappa B , Fosfofructoquinasa-2 , Insuficiencia Renal Crónica , Daño por Reperfusión , Animales , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/metabolismo , Humanos , Ratones , Masculino , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , FN-kappa B/metabolismo , Histonas/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Transducción de Señal , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/metabolismo , Ácido Láctico/metabolismo , Riñón/patología , Riñón/metabolismo
2.
Small ; 20(37): e2403198, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38738744

RESUMEN

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.

3.
Cell Commun Signal ; 22(1): 308, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831451

RESUMEN

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.


Asunto(s)
Calcio , Nefritis Lúpica , Proteínas de Unión a Fosfato , Nefritis Lúpica/patología , Nefritis Lúpica/metabolismo , Nefritis Lúpica/genética , Animales , Humanos , Ratones , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Proteínas de Unión a Fosfato/deficiencia , Calcio/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Neutrófilos/metabolismo , Granulocitos/metabolismo , Células Mieloides/metabolismo , Ratones Endogámicos C57BL , Femenino , Trampas Extracelulares/metabolismo , Diferenciación Celular , Gasderminas
4.
Inorg Chem ; 63(34): 16095-16102, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39136321

RESUMEN

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.

5.
Blood Purif ; 50(6): 837-847, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33596582

RESUMEN

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.


Asunto(s)
Metilaminas/sangre , Diálisis Peritoneal/mortalidad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales
6.
Angew Chem Int Ed Engl ; 60(36): 20021-20026, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34223690

RESUMEN

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.

7.
J Hum Genet ; 65(3): 241-249, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31857673

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , Proteínas de Ciclo Celular/genética , Glomerulonefritis por IGA/genética , Enfermedades Inflamatorias del Intestino/genética , Adulto , Alelos , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Glomerulonefritis por IGA/patología , Humanos , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo
8.
Appl Opt ; 58(17): 4806-4811, 2019 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-31251304

RESUMEN

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.


Asunto(s)
Técnicas Biosensibles , Interferometría/instrumentación , Cristales Líquidos/química , Penicilinasa/metabolismo , Bacillus cereus/enzimología , Concentración de Iones de Hidrógeno , Fibras Ópticas , Penicilina G/metabolismo
9.
Perit Dial Int ; 44(3): 194-202, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38449341

RESUMEN

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.


Asunto(s)
Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Fallo Renal Crónico , Diálisis Peritoneal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Factores de Crecimiento de Fibroblastos/sangre , Estimación de Kaplan-Meier , Fallo Renal Crónico/terapia , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/sangre , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo
10.
Artículo en Inglés | MEDLINE | ID: mdl-39453825

RESUMEN

Pyro-phototronic effect (PPE) can significantly boost the performance of hybrid perovskite (HPs) photodetectors due to the effective modulation of photogenerated charge carrier separations, transportation, and extraction. However, there are few reports on the application of PPE in lead-free HPs. Herein, a polar lead-free HP (1,3-BMACH)BiBr5 [1,3-BMACH = 1,3-bis(aminomethyl)cyclohexane] is synthesized and realized broadband self-powered photoresponse from X-rays to near-infrared (NIR) through the PPE. Particularly, this light-induced PPE in lead-free HPs breaks the limitation of the optical band gap, making them suitable for broadband self-powered photodetection. Under 405 nm illumination, compared with a purely photovoltaic system, Iphoto+pyro is boosted by 3100%, and R and D* are both enhanced by 260% after coupled PPE. It is particularly interesting that an obvious X-ray-induced PPE phenomenon is also observed, which endows (1,3-BMACH)BiBr5 with a high sensitivity of 154 µC Gy-1 cm-2 and a low detection limit of 307 nGy s-1 under the self-powered mode. The implementation of light-induced PPE from X-rays to NIR in lead-free HPs provides a new approach for constructing environmentally friendly, broadband, and self-powered optoelectronic devices in the future.

11.
Biol Pharm Bull ; 36(5): 764-71, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23445942

RESUMEN

Alzheimer's disease (AD), one of the most common forms of dementia, is primarily ascribed to the cholinergic deficits and neuronal dysfunction. Magnolol (Mag), a bioactivator extracted from Magnolia officinalis, has protective effects on cholinergic neurons, but the specific mechanism remains unknown. To further evaluate the therapeutic effects of Mag on the learning and memory impairment in a scopolamine (Scop)-induced mouse model, the passive avoidance and the Morris water maze tests, the measurement of the ratio of brain/hippocampus to body weight, activities of acetyl cholinesterase (AChE), superoxide dismutase (SOD), total nitric oxide synthase (total NOS) and the content of methane dicarboxylic aldehyde (MDA) in hippocampus homogenate as well as the immunefluorescence staining of the AChE positive nerve fibers were performed. Therapeutically treated with Mag, the impaired abilities of learning and memory of the Scop-induced mice were almost restored to the native levels. The restored AChE, total NOS and SOD activities and the MDA level were observed, with a relatively normal density of AChE positive nerve fibers in hippocampus CA3 molecular layer. The improving efficacy of Mag on learning and memory impairment induced by Scop is dose-dependent, indicating that Mag has potential neuroprotective effects against neuronal impairment and memory dysfunction induced by Scop in mice. The underlying mechanisms may be associated with the anti-oxidative effects of Mag and its protective effects on hippocampus cholinergic neurons.


Asunto(s)
Reacción de Prevención/efectos de los fármacos , Compuestos de Bifenilo/uso terapéutico , Lignanos/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Acetilcolina/metabolismo , Animales , Compuestos de Bifenilo/farmacología , Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Neuronas Colinérgicas/efectos de los fármacos , Neuronas Colinérgicas/fisiología , Lignanos/farmacología , Masculino , Malondialdehído/metabolismo , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Ratones , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/fisiología , Fármacos Neuroprotectores/farmacología , Óxido Nítrico Sintasa/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Escopolamina , Superóxido Dismutasa/metabolismo
12.
J Phys Chem Lett ; 14(18): 4304-4312, 2023 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-37129553

RESUMEN

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 ∼70 nW/cm2. Moreover, the on/off ratios and detectivity of the devices can reach ∼103 and ∼1012 Jones at both 377 and 405 nm, respectively. This work highlights great potential of DJ hybrid perovskites toward weak light detection.

13.
Adv Sci (Weinh) ; 10(35): e2302804, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37915129

RESUMEN

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.


Asunto(s)
Nefritis Lúpica , Humanos , Animales , Ratones , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Inmunidad Innata , Linfocitos , Ratones Endogámicos MRL lpr , Riñón
15.
Front Immunol ; 13: 973169, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311737

RESUMEN

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.


Asunto(s)
Factor B del Complemento , Glomerulonefritis por IGA , Humanos , Factor B del Complemento/genética , Glomerulonefritis por IGA/metabolismo , Simulación del Acoplamiento Molecular , Pueblo Asiatico/genética , Proteínas , China
16.
ACS Appl Mater Interfaces ; 14(9): 11690-11698, 2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35213126

RESUMEN

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.

17.
Front Med (Lausanne) ; 8: 684548, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34222290

RESUMEN

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.

18.
Front Med (Lausanne) ; 8: 760394, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926505

RESUMEN

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.

19.
Hum Immunol ; 82(3): 186-192, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33597097

RESUMEN

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.


Asunto(s)
Glomerulonefritis por IGA/metabolismo , Leucocitos Mononucleares/metabolismo , Proteínas de la Membrana/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Adulto , Células Cultivadas , Regulación hacia Abajo , Femenino , Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Glomerulonefritis por IGA/genética , Humanos , Leucocitos Mononucleares/patología , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Receptores de Superficie Celular/genética , Receptores Inmunológicos/genética , Transcriptoma
20.
Chem Commun (Camb) ; 56(92): 14381-14384, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33140773

RESUMEN

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 (∼103), fast response time (∼200 µs) and high photodetectivity (∼109 Jones) for promising UV photodetection.

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