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The integration of chirality, specifically through the chirality-induced spin selectivity (CISS) effect, into electrocatalytic processes represents a pioneering approach for enhancing the efficiency of energy conversion and storage systems. This review delves into the burgeoning field of chiral electrocatalysis, elucidating the fundamental principles, historical development, theoretical underpinnings, and practical applications of the CISS effect across a spectrum of electrocatalytic reactions, including the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and hydrogen evolution reaction (HER). We explore the methodological advancements in inducing the CISS effect through structural and surface engineering and discuss various techniques for its measurement, from magnetic conductive atomic force microscopy (mc-AFM) to hydrogen peroxide titration. Furthermore, this review highlights the transformative potential of the CISS effect in addressing the key challenges of the NRR and CO2RR processes and in mitigating singlet oxygen formation in metal-air batteries, thereby improving their performance and durability. Through this comprehensive overview, we aim to underscore the significant role of incorporating chirality and spin polarization in advancing electrocatalytic technologies for sustainable energy applications.
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BACKGROUND: In lymphocyte crossmatch using flow cytometry (flow cytometric crossmatch, FCXM), the conventional tricolor FCXM protocol requires a mononuclear cell isolation step. To develop a new, more streamlined protocol, we introduced whole blood lysis (WBL) and CD45 fluorescence-triggered acquisition using 4-color flow cytometry. METHODS: A total of 186 donor/recipient pairs for transplantation were classified into donor-specific human leukocyte antigen (HLA) alloantibody-positive (DSA+, n = 78) and DSA-negative (DSA-, n = 108) groups. The latter group was reclassified into blood group ABO-incompatible (ABOi, n = 56) and ABO-compatible (n = 52) subgroups. The WBL FCXM protocol with CD45 V500-C was optimized using a FACSLyric cytometer (BD Biosciences) with 3 lasers. Measurements for T cells or B cells were calculated as a mean fluorescence intensity (MFI) ratio (test divided by control). WBL FCXM was compared with conventional FCXM in each group. RESULTS: WBL FCXM showed no difference quantitatively compared with conventional FCXM, except for the B cell FCXM in the DSA- group (B cell MFI ratio: 1.06 ± 0.44 and 0.92 ± 0.41, respectively [P = .0001]). There was no ABO antibody interference in the ABOi subgroup. Similar results were observed in the qualitative determinations of FCXM as follows: 1) In the DSA+ group, the sensitivity of B cell WBL FCXM (96.2%) showed no difference compared with that of conventional FCXM (91.0%, P = .2188) and 2) In the DSA- group, the specificity of T cell WBL FCXM (96.3%) showed no difference compared with that of conventional FCXM (98.1%, P = .6250). WBL FCXM reduced the turnaround time by 50 min compared with that by conventional FCXM. CONCLUSIONS: WBL FCXM demonstrated comparable assay performance to that of conventional FCXM. Because this new FCXM protocol is simple and does not compromise assay sensitivity, it has the potential to replace the conventional method in histocompatibility laboratory settings.
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HLA-DPA1*02:124 differs from HLA-DRB1*02:02:02:01 by one nucleotide substitution in codon 5 in exon 2.
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Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas alfa de HLA-DP/genética , República de CoreaRESUMEN
Coupling post-combustion CO2 capture with electrochemical utilization (CCU) is a quantum leap in renewable energy science since it eliminates the cost and energy involved in the transport and storage of CO2. However, the major challenges involved in industrial scale implementation are selecting an appropriate solvent/electrolyte for CO2 capture, modeling an appropriate infrastructure by coupling an electrolyser with a CO2 point source and a separator to isolate CO2 reduction reaction (CO2RR) products, and finally selection of an appropriate electrocatalyst. In this review, we highlight the major difficulties with detailed mechanistic interpretation in each step, to find out the underpinning mechanism involved in the integration of electrochemical CCU to achieve higher-value products. In the past decades, most of the studies dealt with individual parts of the integration process, i.e., either selecting a solvent for CO2 capture, designing an electrocatalyst, or choosing an ideal electrolyte. In this context, it is important to note that solvents such as monoethanolamine, bicarbonate, and ionic liquids are often used as electrolytes in CO2 capture media. Therefore, it is essential to fabricate a cost-effective electrolyser that should function as a reversible binder with CO2 and an electron pool capable of recovering the solvent to electrolyte reversibly. For example, reversible ionic liquids, which are non-ionic in their normal forms, but produce ionic forms after CO2 capture, can be further reverted back to their original non-ionic forms after CO2 release with almost 100% efficiency through the chemical or thermal modulations. This review also sheds light on a focused techno-economic evolution for converting the electrochemically integrated CCU process from a pilot-scale project to industrial-scale implementation. In brief, this review article will summarize a state-of-the-art argumentation of challenges and outcomes over the different segments involved in electrochemically integrated CCU to stimulate urgent progress in the field.
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Hemagglutination assay has been used for blood typing and detecting viruses, thus applicable for the diagnosis of infectious diseases, including COVID-19. Therefore, the development of microfluidic devices for fast detection of hemagglutination is on-demand for point-of-care diagnosis. Here, we present a way to detect hemagglutination in 3D microfluidic devices via optical absorbance (optical density, OD) characterization. 3D printing is a powerful way to build microfluidic structures for diagnostic devices. However, mixing liquid in microfluidic chips is difficult due to laminar flow, which hampers practical applications such as antigen-antibody mixing. To overcome the issue, we fabricated 3D microfluidic chips with embedded microchannel and microwell structures to induce hemagglutination between red blood cells (RBCs) and antibodies. We named it a 3D microtrap chip. We also established an automated measurement system which is an integral part of diagnostic devices. To do this, we developed a novel way to identify RBC agglutination and non-agglutination via the OD difference. By adapting a 3D-printed aperture to the microtrap chip, we obtained a pure absorbance signal from the microchannels by eliminating the background brightness of the microtrap chip. By investigating the underlying optical physics, we provide a 3D device platform for detecting hemagglutination.
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COVID-19 , Hemaglutinación , Humanos , Microfluídica , Eritrocitos , Dispositivos Laboratorio en un ChipRESUMEN
C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Trasplante de Riñón , Nefritis Intersticial , Masculino , Humanos , Adulto , Trasplante de Riñón/efectos adversos , Glomerulonefritis/etiología , Inmunosupresores/efectos adversos , Glomerulonefritis Membranoproliferativa/complicacionesRESUMEN
Background: The C-reactive protein (CRP)-to-albumin ratio (CAR) is a more effective prognostic indicator than CRP or albumin alone in various diseases. This study aimed to evaluate the predictive value of the CAR for mortality in kidney transplant recipients (KTRs). Methods: A total of 924 patients who underwent their first kidney transplantation at Kyungpook National University Hospital during 2006-2020 were enrolled and classified into quartile (Q) groups according to their pretransplant CAR values. A Cox regression analysis was conducted to analyze the hazard ratios (HRs) of mortality. Results: Fifty-nine patients died during the posttransplant period (mean, 85.2±44.2 months). All-cause mortality (Q1, 3.0%; Q2, 4.8%; Q3, 7.8%; Q4, 10.0%; P for trend <0.001) and infection-related mortality increased linearly with an increase in CAR (P for trend=0.004). The Q3 and Q4 had higher risks of all-cause mortality than Q1 after adjusting for confounding factors (Q3 adjusted HR [aHR] 2.49, 95% confidence interval [CI] 1.04-5.99, P=0.041; Q4 aHR 3.09, 95% CI 1.31-7.27, P=0.010). Q4 was also independently associated with infection-related mortality (aHR 5.83, 95% CI 1.27-26.8, P=0.023). The area under the curve of the CAR for all-cause and infection-related mortality was higher than that of CRP or albumin alone. There was no association between CAR and death-censored graft failure or acute rejection. Conclusions: A higher pretransplant CAR increases the risk of posttransplant mortality, particularly infection-related, in KTRs. Pretransplant CAR can be an effective and easily accessible predictor of posttransplant mortality.
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HLA-DRB1*14:252 differs from HLA-DRB1*14:03:01 by one nucleotide substitution in codon 9 in exon 2.
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Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cadenas HLA-DRB1/genética , Alelos , Exones/genética , República de CoreaRESUMEN
This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.
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Anticuerpos Antinucleares , Enfermedades Autoinmunes , Humanos , Niño , Enfermedades Autoinmunes/diagnóstico , Relevancia Clínica , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. METHODS: This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. RESULTS: The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). CONCLUSIONS: The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.
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COVID-19 , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Virus , Niño , Humanos , Lactante , Preescolar , Anciano , Estudios Retrospectivos , Pandemias , COVID-19/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Hospitales , República de Corea/epidemiologíaRESUMEN
BACKGROUND: The interferon-γ (IFN-γ) release assay (IGRA) is widely used to diagnose tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb). However, indeterminate IGRA results due to "high Nil" or "low PHA" responses limit its clinical utility. We developed a novel assay using CD69 flow cytometry (FC) to complement IGRA. METHODS: CD69 FC measures the surface CD69 expression on T cells prior to centrifugation to harvest the plasma for IGRA. T cell responses against Mtb antigen 1 (Ag1) or Ag2 were measured using three-color FC (CD3, CD4, and CD69) in TB (n = 140) and non-TB groups (n = 117). The cutoff values of Δ%CD69bright cells (stimulated minus unstimulated) for CD4+ and CD4- T cells were established based on healthy individuals (n = 63). The assay performances of CD69 FC and IGRA were compared. RESULTS: In subjects with determinate IGRA results ("positive" or "negative"; n = 216), the diagnostic accuracies of CD69 FC (90.3%) and IGRA (87.0%) were not significantly different (p = 0.31). For indeterminate IGRA results (n = 40), CD69 FC attained a diagnostic accuracy of 92.5%. The CD4+ /CD4- ratio within CD69bright T cells measured by CD69 FC was significantly higher (p < 0.05) in the active TB group (6.39 ± 132.05; n = 72) than in other CD69 FC-positive subjects (2.84 ± 15.36; n = 63) (p < 0.05), whereas CD8 responses expected by IGRA (difference of IFN-γ levels between Mtb Ag tubes) did not differ significantly (0.00 ± 9.18 and 0.00 ± 4.25, respectively, IU/ml; p = 0.58). CONCLUSIONS: We demonstrated the potential of CD69 FC as a simple, rapid assay for clarifying indeterminate IGRA results and identifying active TB. With further improvements, CD69 FC may complement the IGRA to enhance TB risk stratification in the routine diagnostic workup.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Citometría de Flujo , Antígenos Bacterianos , Tuberculosis/diagnósticoRESUMEN
BACKGROUND: To assess protective immunity among a general population against severe acute respiratory syndrome coronavirus 2, the correlation of the commercially available solid-phase assay (SPA) for SARS-CoV-2 IgG with a neutralization assay must be investigated. METHODS: Both the neutralization assay and SPA were performed on samples of 143 recovered coronavirus disease 2019 (COVID-19) patients. SARS-CoV-2 IgG was measured using two SPAs for the chemiluminescence immunoassay principle with different target proteins: nucleocapsid and spike protein (Architect i2000SR [Abbott] and Liaison XL [DiaSorin], respectively). The plaque reduction neutralization test (PRNT) was conducted to obtain titers for the neutralizing antibody. RESULTS: All patients had PRNT titers ranging from 10 to 2,560. Spike Ab SPA had greater sensitivity than nucleocapsid Ab SPA (81.1% [116/143] and 70.6% [101/143], respectively, p = 0.003). The values measured for both SPAs had a positive correlation with the PRNT titers (both R = 0.77, p < 0.001). To predict a high PRNT titer (≥ 160), cutoff values of two SPAs were adjusted based on receiver-operating characteristics curve analysis. The nucleocapsid Ab SPA (cutoff index of 4.17) attained 90.3% sensitivity and 75.9% specificity, whereas the spike Ab SPA (cutoff value of 109 unit/mL) attained 87.1% sensitivity and 89.3% specificity. Therefore, the spike Ab SPA had greater specificity than the nucleocapsid Ab SPA (p = 0.003). CONCLUSIONS: The qualitative SPA for nucleocapsid Ab, as well as the quantitative SPA for spike Ab, had a modest positive correlation with the neutralization assay. However, spike Ab SPA was more suitable for neutralizing capacity.
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Anticuerpos Neutralizantes , COVID-19 , Anticuerpos Antivirales , COVID-19/diagnóstico , Humanos , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del CoronavirusRESUMEN
BACKGROUND: The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. METHODS: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. RESULTS: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14- 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51-6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. CONCLUSION: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.
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HLA-DRB1*13:320 differs from HLA-DRB1*13:02:01:02 by one nucleotide substitution in codon 22 in exon 2.
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Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Codón , Exones/genética , Cadenas HLA-DRB1/genética , HumanosRESUMEN
BACKGROUND: Saliva contains various cells, proteins, and molecules, and it is emerging as a material for diagnosing various diseases. Syndecan-1 (SDC-1) is a member of cell surface heparan sulfate proteoglycans and is mainly expressed in epithelial cells and plasma cells. SDC-1 is known to be associated with various cancers and inflammatory response, but there are few studies related to the change of SDC-1 levels in the saliva and plasma of healthy individuals due to aging process. METHODS: The study was conducted on 61 females who were healthy without any metabolic diseases, systemic infection, and oral cavity lesions. The subjects were divided into two groups based on age. Those below 40 years were placed in Group I and those who were 40 years and above were placed in Group II. Saliva was collected according to the guideline and the salivary flow rate (SFR) was determined. SDC-1 levels in the plasma and saliva were measured using a commercially available sandwich ELISA method. RESULTS: Age was significantly different between Group I and II (28.0 ± 2.5 vs. 47.4 ± 5.5, p < 0.001). SFR also showed a significant difference between Group I and II [0.32 (0.13 - 0.39) vs. 0.25 (0.16 - 0.35) ng/mL, p = 0.003]. Salivary SDC-1 level in Group I was significantly higher than that in Group II (p < 0.001). In addition, plasma SDC-1 level in Group I was also higher than that in Group II (p < 0.001). SFR was not significantly correlated as age increased, but it showed a significant negative correlation with salivary SDC-1 (r = -0.607, p < 0.001) and plasma SDC-1 levels (r = -0.373, p = 0.003). Salivary SDC-1 level was significantly correlated with plasma SDC-1 level (r = 0.331, p = 0.012). CONCLUSIONS: In the younger group, the SFR, salivary, and plasma SDC-1 levels were significantly higher than in the older group. Salivary and plasma SDC-1 showed significant negative correlation as age increased. Although this study was not conducted on a large scale, it might be thought to provide information on the age-related variation for salivary and plasma SDC-1 levels in the aging process.
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Saliva , Sindecano-1 , Ensayo de Inmunoadsorción Enzimática , Femenino , Estado de Salud , Humanos , PlasmaRESUMEN
HLA-DQA1*01:01:09 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon-12 in exon 1.
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Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Codón , Exones/genética , Cadenas alfa de HLA-DQ/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
Antinuclear antibody (ANA) testing is used to diagnose systemic autoimmune rheumatic disease (SARD). Nuclear homogeneous patterns on ANA-HEp-2 cells can result from anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-histone, anti-Scl-70, or anti-dense fine speckles 70 (DFS70) antibodies (Abs). This study aimed to find a way to discriminate DFS70 Abs from others by way of assessing neutrophil nuclear staining on anti-neutrophil cytoplasmic antibody (ANCA) testing. Nuclear staining on ANCA-neutrophils was assessed to stratify nuclear homogeneous patterns on ANA-HEp-2 cells. Enrolled subjects included (1) young individuals with a dense fine speckled pattern on ANA testing (young non-SARD group, n=71) and patients with (2) systemic lupus erythematosus (SLE group, n=35); (3) rheumatoid arthritis possibly with histone, nucleosome Abs, and others (RA group, n=51); and (4) diffuse systemic sclerosis with Scl-70 Abs (diffuse SSc group, n=19). Negative rates (95% confidence interval) of neutrophil nuclear staining were 97.2% (90.2%-99.7%) in the young non-SARD group, 2.9% (0.1%-14.9%) in the SLE group, 3.9% (0.5%-13.5%) in the RA group, and 47.4% (24.5%-71.1%) in the diffuse SSc group. The negative rate of the young non-SARD group was significantly higher than those of the other groups (all p<0.05). In conclusion, this study suggests that the assessment of nuclear staining on ANCA-neutrophils can help to stratify nuclear homogeneous patterns on ANA-HEp-2 cells and thus to determine whether the ANA pattern is attributed to DFS70 Abs, which can be found in healthy individuals, especially in young individuals.
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Sn0.9Sb0.1O2/TiO2 (ATO/TiO2) heterostructure is a potential visible light photocatalysts that function via an inter-semiconductor hole-transport mechanism. Herein we selectively deposited Au, Ag, or Pt onto the ATO surface of ATO/TiO2 to investigate charge-trapping behaviors of the noble metals and their effects on photocatalytic performance. We observed that Pt deposition greatly enhanced the photocatalytic activity whereas effects of Au or Ag depositions were not significant. The result of spectroscopic analysis also indicates that Pt is the most effective in scavenging the electrons from the ATO CB. Particularly, Pt/ATO/TiO2 (ATO:TiO2 = 15:85 in weight) produced CO2 of 42 ppmv in 2 h, which is 16 times and 4.8 times that of bare ATO/TiO2 and nitrogen-doped TiO2, respectively. Pt deposition on the ATO seems to suppress two independent charge recombination pathways, that is, recombination of electron-hole pairs in ATO and electron transport from the ATO CB to TiO2 VB.
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Plata , Titanio , Catálisis , LuzRESUMEN
BACKGROUND: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. METHODS: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. RESULTS: No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 µg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR. CONCLUSION: Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.
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Rechazo de Injerto/prevención & control , Enfermedades Hematológicas/etiología , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Ácido Micofenólico/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Anemia/etiología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/uso terapéutico , Leucopenia/etiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Oportunidad Relativa , Factores de Riesgo , Tacrolimus/uso terapéutico , Trombocitopenia/etiologíaRESUMEN
BACKGROUND: Human leukocyte antigen (HLA) molecules are cell-bound but can be identified in a soluble form. These soluble HLA (sHLA) molecules have an immunomodulatory function. We investigated whether natural sHLA in donor serum can neutralize donor-specific HLA alloantibodies (DSAs) in recipient serum. METHODS: Neutralizing effects of donor serum on DSAs in recipient serum were measured using inhibition assay principle of flow cytometric crossmatch (FCXM), performed using sera from 143 kidney transplant recipients and their donors. The adding of donor serum to recipient serum yielded lower mean fluorescence intensity (MFI) ratios (test/control) than when diluent was added [Roswell Park Memorial Institute (RPMI) or third-party serum], which was presumed to be caused by the neutralizing effects of sHLA. RESULTS: In the recipient group with class I DSAs alone (N=14), donor serum addition to recipient serum resulted in lower T cell MFI ratios [2.25 (1.31â32.51)] than those observed on RPMI addition [3.04 (1.33â125.39), P <0.05]. In the recipient group with class II DSAs alone (N=27), donor serum addition showed no significant difference in B cell MFI ratios [5.03 (1.41â103.53)] compared to diluent addition: RPMI [4.50 (1.34â145.98)] or third-party serum [5.08 (1.44â138.47)], P >0.05 for both. CONCLUSION: Using inhibition FCXM, we verified that natural sHLA class I in donor serum neutralizes DSAs in recipient serum. However, no neutralizing effects of sHLA class II were revealed in this study. These potentially beneficial effects of sHLA infused via blood-derived products should be considered when desensitizing highly HLA-sensitized patients.