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1.
Nano Lett ; 22(23): 9500-9506, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36459088

RESUMO

Despite recent rapid advances in improving quantum dot light-emitting diodes, many fundamental aspects of the device operating mechanism remain unresolved. Through transient electroluminescence and time-resolved photoluminescence measurements, the effects of offset voltage on charging and charge transport are examined. First, capacitive charging occurs with a time constant of ∼500 ns, followed by electron transport through quantum dots with a mobility of ∼10-5 cm2 V-1 s-1. Hole injection then initiates an electroluminescence rise that is independent of offset voltage. The photoluminescence lifetime is also unaffected by the offset voltage, indicating no injection of charges into the quantum dots or on their surfaces prior to the voltage pulse. A slower equilibration to steady-state electroluminescence is dependent on the offset voltage, indicative of another charging process. Elemental mapping shows that ZnO deposition from solution can lead to the diffusion of charged species into the quantum dot layer, which may cause the slower process.

2.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446100

RESUMO

Fibroblast-to-myofibroblast transition (FMT) leads to excessive extracellular matrix (ECM) deposition-a well-known hallmark of fibrotic disease. Transforming growth factor-ß (TGF-ß) is the primary cytokine driving FMT, and this phenotypic conversion is associated with mitochondrial dysfunction, notably a metabolic reprogramming towards enhanced glycolysis. The objective of this study was to examine whether the establishment of favorable metabolic phenotypes in TGF-ß-stimulated fibroblasts could attenuate FMT. The hypothesis was that mitochondrial replenishment of TGF-ß-stimulated fibroblasts would counteract a shift towards glycolytic metabolism, consequently offsetting pro-fibrotic processes. Isolated mitochondria, functionalized with a dextran and triphenylphosphonium (TPP) (Dex-TPP) polymer conjugate, were administered to fibroblasts (MRC-5 cells) stimulated with TGF-ß, and effects on bioenergetics and fibrotic programming were subsequently examined. Results demonstrate that TGF-ß stimulation of fibroblasts led to FMT, which was associated with enhanced glycolysis. Dex-TPP-coated mitochondria (Dex-TPP/Mt) delivery to TGF-ß-stimulated fibroblasts abrogated a metabolic shift towards glycolysis and led to a reduction in reactive oxygen species (ROS) generation. Importantly, TGF-ß-stimulated fibroblasts treated with Dex-TPP/Mt had lessened expression of FMT markers and ECM proteins, as well as reduced migration and proliferation. Findings highlight the potential of mitochondrial transfer, as well as other strategies involving functional reinforcement of mitochondria, as viable therapeutic modalities in fibrosis.


Assuntos
Fibroblastos , Transdução de Sinais , Humanos , Fibroblastos/metabolismo , Fibrose , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fenótipo , Mitocôndrias/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas
3.
Small ; 18(29): e2202290, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35754301

RESUMO

Wide interest in quantum dot (QD) light-emitting diodes (QLEDs) for potential application to display devices and light sources has led to their rapid advancement in device performance. Despite such progress, detailed operation mechanisms of QLEDs, which are necessary for the fundamental understanding and further improvements, have been still uncertain because of the intricate interaction between charges and excitons in electrical operation. In this work, the transient electroluminescence (TREL) signals of dichromatic QLEDs which are purposely designed to consist of two different color-emitting QD layers are analyzed. As a result, not only can the charge injection and exciton recombination processes be visualized but the electron mobility of the QD layer can also be estimated. Furthermore, the effects of Förster resonant energy transfer between two QDs and exciton quenching near the QD layer are quantitatively measured in QLED operation. The authors believe that their results based on TREL analyses will contribute to the understanding and development of high-performance QLEDs.

4.
Opt Express ; 30(17): 31367-31380, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36242220

RESUMO

The stability of methylammonium (MA)-based perovskite solar cells (PSCs) remains one of the most urgent issues that need to be addressed. Inherent weak binding forces between MAs and halides cause the perovskite structure to become unstable under exposure to various external environmental factors such as moisture, oxygen, ultraviolet radiation, and heat. In particular, the degradation of perovskite films under light exposure accelerates the deterioration of the device, mainly due to the migration of halide ions. In this study, we investigated the effect of light energy on the degradation of inverted PSCs by introducing red ( = 610-800 nm), green (500-590 nm), and blue (300-500 nm) light-pass filters. After 30 h, the inverted PSCs of blue-light-induced devices retained a power conversion efficiency (PCE) of 70%, while those of the green and red light-induced devices retained PCEs of 85% and 90%, respectively. Direct evidence of light-induced degradation was obtained by investigating morphological changes in the perovskite films and the amount of ion accumulation on the Ag electrode. This evidence highlights the varying effect of light with different energies on device degradation. Furthermore, to minimize light-induced device degradation, we designed two types of blue cut-off filters that can selectively block light ranging from = 400 to 500 nm, comprising a multilayered inorganic metasurface. An optical simulation was used to optimize the performance of the designed filters. By investigating the changes in the photovoltaic parameters and the amount of ion accumulation on the Ag electrode, we confirmed that integrating blue cut-off filters into PSCs greatly improved the operational lifetime of the devices.

5.
BMC Musculoskelet Disord ; 22(1): 346, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845795

RESUMO

BACKGROUND: Tibial rotational alignment in total knee arthroplasty (TKA) is generally determined based on intra-articular structure, and can be difficult to ascertain in some cases. The aim of this study was to investigate whether the medial tangent angle of the tibia (MTAT) could be useful in determining the anteroposterior axis of the tibia. METHODS: This study was performed on 103 lower limbs in 53 patients who underwent primary total hip arthroplasty. The selection criteria for our study were based on the assumption that knees in patients undergoing THA exhibit fewer degenerative changes than knees in patients undergoing TKA. Using computed tomography images, the MTAT, comprising the medial tangent of the proximal tibia and the anteroposterior (AP) axis of the tibia, was measured on three horizontal planes: at the distal edge of the tibial tubercle (A), at 5 cm distally (B), and at 10 cm further distally (C). The tibial medial surface was grouped into three classes according to shape: valley type, flat type, and hill type. The percentage at which these shapes were observed in each group was also calculated. Measurement reliability was calculated using the intraclass correlation coefficient. RESULTS: The angles were 45.2° (interquartile range: IR 43.0-47.7) at A, 42.7° (IR 38.7-45.9) at B, and 42.4° (IR 38.2-45.9) at C. Intra-rater reliability and inter-rater reliability was 0.982 and 0.974 at A, 0.810 and 0.411 at B, and 0.940 and 0.811 at C, respectively. Regarding the tibial medial surface, the valley type was observed in all cases at A, and the hill type was observed in the highest percentage of cases at B and C. CONCLUSIONS: The MTAT was approximately 45° at level A, and reproducibility was the highest among the three groups. The two points forming the valley on the tibial medial surface were bony ridges. Therefore, the medial tangent of the tibia at level A could be easily determined. Because the distal edge of the tibial tubercle exists at the surgical area and the extra-articular area, it can be a suitable intraoperative, extra-articular landmark in determining the tibial AP axis, even for revision TKA.


Assuntos
Osteoartrite do Joelho , Tíbia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Reprodutibilidade dos Testes , Rotação , Tíbia/diagnóstico por imagem , Tíbia/cirurgia
6.
Cardiovasc Diabetol ; 19(1): 19, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070346

RESUMO

BACKGROUND: Empagliflozin (empa), a selective sodium-glucose cotransporter (SGLT)2 inhibitor, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk independent of glycemic control. The cardiovascular protective effect of empa was evaluated in an experimental model of metabolic syndrome, the obese ZSF1 rat, and its' lean control. METHODS: Lean and obese ZSF1 rats were either non-treated or treated with empa (30 mg/kg/day) for 6 weeks. Vascular reactivity was assessed using mesenteric artery rings, systolic blood pressure by tail-cuff sphygmomanometry, heart function and structural changes by echocardiography, and protein expression levels by Western blot analysis. RESULTS: Empa treatment reduced blood glucose levels from 275 to 196 mg/dl in obese ZSF1 rats whereas normoglycemia (134 mg/dl) was present in control lean ZSF1 rats and was unaffected by empa. Obese ZSF1 rats showed increased systolic blood pressure, and blunted endothelium-dependent relaxations associated with the appearance of endothelium-dependent contractile responses (EDCFs) compared to control lean rats. These effects were prevented by the empa treatment. Obese ZSF1 rats showed increased weight of the heart and of the left ventricle volume without the presence of diastolic or systolic dysfunction, which were improved by the empa treatment. An increased expression level of senescence markers (p53, p21, p16), tissue factor, VCAM-1, SGLT1 and SGLT2 and a down-regulation of eNOS were observed in the aortic inner curvature compared to the outer one in the control lean rats, which were prevented by the empa treatment. In the obese ZSF1 rats, no such effects were observed. The empa treatment reduced the increased body weight and weight of lungs, spleen, liver and perirenal fat, hyperglycemia and the increased levels of total cholesterol and triglycerides in obese ZSF1 rats, and increased blood ketone levels and urinary glucose excretion in control lean and obese ZSF1 rats. CONCLUSION: Empa reduced glucose levels by 28% and improved both endothelial function and cardiac remodeling in the obese ZSF1 rat. Empa also reduced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.


Assuntos
Compostos Benzidrílicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Glucosídeos/farmacologia , Síndrome Metabólica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Senescência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Obesidade/complicações , Ratos Zucker , Sístole
7.
J Prosthodont ; 29(1): 12-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31660673

RESUMO

PURPOSE: To compare abutment displacement between the virtual, customized abutment that was designed on a cast and the customized abutment prepared in the oral cavity. MATERIALS AND METHODS: Eleven patients were selected for a single posterior implant prosthetic treatment. The impression was obtained using the closed tray impression method with a vinyl polysiloxane material using a custom tray. The standard tessellation language files of the customized abutment that was designed using the computer-aided design system and acquired with an intraoral scanner in the oral cavity were superimposed and analyzed for distance and angle displacement using the three-dimensional inspection analysis program (Geomagic Control X). In the statistical analysis, distance and angle displacement values were analyzed with the Kruskal-Wallis H test (α = 0.05), and a post hoc comparison was performed using the Mann-Whitney U-test and Bonferroni correction method. RESULTS: The mean distance and angle displacement of the 15 customized abutments were 89.52 ± 66.86 µm and 0.83 ± 1.21°, respectively. There were significant differences in distance displacement (p < 0.001), and angle displacement (p < 0.001) among the 15 customized abutments, and there were no significant differences in angle displacement along the 4 directions (p = 0.735). CONCLUSIONS: The displacement values of the customized abutments evaluated in the oral cavity differed significantly from patient to patient.


Assuntos
Desenho Assistido por Computador , Dente Suporte , Humanos , Boca
8.
Mod Rheumatol ; 30(6): 967-974, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612762

RESUMO

Objectives: To evaluate changes in radiographic findings and plantar pressure distribution after rheumatoid forefoot surgery.Methods: This study was performed on patients with rheumatoid arthritis (RA) who underwent Swanson implant arthroplasty for the 1st metatarsophalangeal (MTP) joint combined with shortening oblique osteotomy at the 2nd through 5th metatarsal necks (group Sw, 55 feet). The following two groups were used as controls: group NS, consisting of 75 feet in RA patients without scheduled forefoot surgery, and group HC, consisting of 24 feet in healthy female subjects. Plantar pressure distribution, and radiographic findings of hallux valgus angle, the angle between the metatarsal bones, talocalcaneal angle, calcaneal pitch angle and calcaneo-first metatarsal angle (CFMA) were measured pre- and one year postoperatively. Peak pressure was measured in nine sections.Results: Calcaneal pitch angle decreased and CFMA increased in group Sw. Peak pressure at the 1st interphalangeal joint (IP) and the 2nd and 3rd MTPs in group Sw decreased, while that at midfoot increased.Conclusion: While the clinical outcome in group Sw was favorable, postoperative longitudinal arch decreased. Postoperative peak pressure at the 2nd through 5th MTPs was comparable with that in group NS; however, it was significantly lower than that in group HC.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia/efeitos adversos , Hallux Valgus/diagnóstico por imagem , Osteotomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Artroplastia/métodos , Feminino , Hallux Valgus/epidemiologia , Humanos , Masculino , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/cirurgia , Pessoa de Meia-Idade , Osteotomia/métodos , Complicações Pós-Operatórias/epidemiologia
9.
Nanotechnology ; 30(6): 065401, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30524088

RESUMO

We demonstrate the improvement in the efficiency of planar heterojunction perovskite solar cells by employing cadmium selenide tetrapods (CdSe TPs) as an electron extraction layer. The insertion of the CdSe TP layer between the titanium oxide (TiO2) and perovskite film facilitates electron transfer at the TiO2/perovskite interface, as indicated by the significantly quenched steady-state photoluminescence of the perovskite film. Furthermore, we observed a conductivity enhancement of the perovskite film by introducing the CdSe TP layer. The combination of both effects induced by the TPs leads to enhancement in the carrier extraction as well as decreased recombination losses in the perovskite solar cells. As a result, an efficiency of 13.5% (1 sun condition) is achieved in the perovskite solar cells that incorporate the CdSe TP layer, which is 10% higher than that of the device without the CdSe TP layer.

10.
Sensors (Basel) ; 19(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669651

RESUMO

The main focus of the paper is to propose a smart recommender system based on the methods of hybrid learning for personal well-being services, called a smart recommender system of hybrid learning (SRHL). The essential health factor is considered to be personal lifestyle, with the help of a critical examination of various disciplines. Integrating the recommender system effectively contributes to the prevention of disease, and it also leads to a reduction in treatment cost, which contributes to an improvement in the quality of life. At the same time, there exist various challenges within the recommender system, mainly cold start and scalability. To effectively address the inefficiencies, we propose combined hybrid methods in regard to machine learning. The primary aim of this learning method is to integrate the most effective and efficient learning algorithms to examine how combined hybrid filtering can help to improve the cold star problem efficiently in the provision of personalized well-being in regard to health food service. These methods include: (1) switching among content-based and collaborative filtering; (2) identifying the user context with the integration of dynamic filtering; and (3) learning the profiles with the help of processing and screening of reflecting feedback loops. The experimental results were evaluated by using three absolute error measures, providing comparable results with other studies relative to machine learning domains. The effects of using the hybrid learning method are gathered with the help of the experimental results. Our experiments also show that the hybrid method improves accuracy by 14.61% of the average error predicted in the recommender systems in comparison to the collaborative methods, which mainly focus on the computation of similar entities.

11.
Int J Mol Sci ; 20(2)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669409

RESUMO

: YYB-101 is a humanized rabbit anti-human hepatocyte growth factor (HGF)-neutralizing antibody currently in clinical trial. To test the effect of HGF neutralization with antibody on anti-cancer T cell immunity, we generated surrogate antibodies that are reactive to the mouse homologue of the epitope targeted by YYB-101. First, we immunized a chicken with human HGF and monitored changes in the B cell repertoire by next-generation sequencing (NGS). We then extracted the VH gene repertoire from the NGS data, clustered it into components by sequence homology, and classified the components by the change in the number of unique VH sequences and the frequencies of the VH sequences within each component following immunization. Those changes should accompany the preferential proliferation and somatic hypermutation or gene conversion of B cells encoding HGF-reactive antibodies. One component showed significant increases in the number and frequencies of unique VH sequences and harbored genes encoding antibodies that were reactive to human HGF and competitive with YYB-101 for HGF binding. Some of the antibodies also reacted to mouse HGF. The selected VH sequences shared 98.3% identity and 98.9% amino acid similarity. It is therefore likely that the antibodies encoded by them all react to the epitope targeted by YYB-101.


Assuntos
Anticorpos/genética , Anticorpos/imunologia , Mapeamento de Epitopos , Epitopos de Linfócito B/imunologia , Fator de Crescimento de Hepatócito/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Sequência de Aminoácidos , Animais , Anticorpos/química , Linfócitos B/imunologia , Linfócitos B/metabolismo , Galinhas , Mapeamento de Epitopos/métodos , Biblioteca Gênica , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Camundongos
12.
J Med Primatol ; 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29726008

RESUMO

We describe the first case of biliary cirrhosis in Japanese macaque. Clinical signs had not been detected. The liver was nodular. Histopathologically, portal-to-portal pattern of fibrosis might have indicated chronic cholestasis. Fibrotic septa were infiltrated with inflammatory cells. Therefore, this case could be diagnosed as active incomplete biliary cirrhosis.

13.
J Med Primatol ; 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29708278

RESUMO

BACKGROUND: Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that can infect warm-blooded animals including humans. New World monkeys, such as squirrel monkeys, are more susceptible to T. gondii than Old World monkeys, often developing fatal disease. METHODS: In this study, seven of thirteen dead squirrel monkeys at Seoul Grand Park were tested to find the cause of sudden death. RESULTS: The main histopathological findings included interstitial pneumonia, necrotizing hepatitis, and splenitis. Periodic acid-Schiff staining of liver, spleen, and lung revealed cyst structures consistent with bradyzoites. Amplification of the B1 gene was detected in the liver or spleen of all monkeys. Additionally, a restriction fragment length polymorphism assay and phylogenetic analysis of the GRA6 amplicon revealed a consistent clustering with the type II strain of T. gondii. CONCLUSIONS: This study is the first report of T. gondii infection of squirrel monkeys in Korea, and the first report of type II T. gondii based on GRA6 analysis in Korea.

14.
Mod Rheumatol ; 27(6): 990-994, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28333570

RESUMO

OBJECTIVES: The objective of this study is to clarify the surgical indication for rheumatoid forefoot deformity according to background characteristics and plantar pressure. METHODS: Patients with rheumatoid arthritis were divided into a non-surgical group (group N) and a surgical group (group S). The former consisted of 225 ft, and the latter consisted of 88 ft. DAS28, Japanese Society for Surgery of the Foot rheumatoid arthritis foot and ankle scale (JSSF scale) and hallux valgus angle (HVA) were evaluated as background characteristics. Distribution of peak pressure as plantar pressure was measured in nine sections. RESULTS: In groups N and S, the mean DAS28 was 3.6 and 3.0, the mean JSSF scale was 81.1 and 63.0, and the mean HVA was 19.9° and 35.3°, respectively. The mean peak pressure of group S at the first and third metatarsophalangeal joints was significantly higher compared with group N. Significant differences between the two groups were also seen in Δ pressure (the difference between the maximum and minimum peak pressure values). The cut-off values were 75.0 for JSSF scale, 24.9° for HVA and 3.94 kg/cm2 for Δ pressure. CONCLUSIONS: The combined assessment of HVA and Δ pressure was found to be useful as an indication for surgical treatment of the forefoot.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia/efeitos adversos , Deformidades Adquiridas do Pé/cirurgia , Hallux Valgus/cirurgia , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Artroplastia/métodos , Feminino , Deformidades Adquiridas do Pé/etiologia , Deformidades Adquiridas do Pé/patologia , Humanos , Masculino , Articulação Metatarsofalângica/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Pressão
15.
Eur Spine J ; 25 Suppl 1: 107-12, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26281982

RESUMO

BACKGROUND: It is known that sagittal compensating mechanisms are created for counteracting sagittal imbalance problems; however, they can sometimes be associated with incidents which affect the plan of management. PURPOSE: The purpose of this study was to report a case of the occurrence of common iliac vessel displacement into the intervertebral disc space following one of the spinal compensatory mechanisms. MATERIAL AND METHODS: The authors demonstrated this case by showing the patient history, physical examination, imaging studies, and treatment strategy as well as by reviewing some related literature. RESULTS: An 81-year-old woman presented with a long history of low back pain with claudication. An upright plain radiograph and flexion-extension study demonstrated a progressive local thoracolumbar kyphosis and losing of lumbar lordosis with significant widening of the intervertebral disc space of L4-L5. An MRI scan and 3D volume rendering spiral computed tomography (3D-CT) revealed an abnormal content which was depicted as common iliac vessels inside the disc space of L4-L5. Consequently, a rare case of the occurrence of common iliac vessel displacement into the intervertebral disc space following one of the spinal compensatory mechanisms was reported. CONCLUSION: The occurrence of vascular displacement into the intervertebral disc space related to lumbar hyperextension, as a compensating mechanism, is a rare incident but can occur. Consequently, when this mechanism presents with abnormal widening of the intervertebral disc space, especially at the low lumbar level, it should raise surgeon's concern about the probability of vascular injury when performing a disc procedure. Thorough investigation with imaging studies and selecting the optimum surgical treatment are warranted.


Assuntos
Veia Ilíaca/lesões , Deslocamento do Disco Intervertebral/complicações , Disco Intervertebral/irrigação sanguínea , Cifose/complicações , Idoso de 80 Anos ou mais , Feminino , Humanos , Vértebras Lombares , Vértebras Torácicas/patologia
16.
Arthritis Rheum ; 65(1): 109-19, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23055095

RESUMO

OBJECTIVE: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). A plausible pathway for the activation of synovial MCs is through IgG receptors, given the prevalence of circulating IgG isotype autoantibodies and synovial immune complexes in patients with RA. However, IgG receptor expression on human synovial MCs remains uncharacterized. The aim of this study was to identify which IgG receptor(s) on synovial MCs are responsible for MC activation in immune complexes. METHODS: Synovial tissue specimens were obtained from patients with RA or patients with osteoarthritis (OA) who were undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting. Mediators released from MCs were measured using enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS: Primary synovial MCs and cultured synovium-derived MCs obtained from both patients with RA and patients with OA expressed Fcε receptor I (FcεRI), FcγRI, and FcγRII but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNFα) through FcγRI. The aggregation of FcγRII caused histamine release from cultured MCs but not from primary MCs. Histamine release induced by aggregated IgG was significantly inhibited by neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody. CONCLUSION: With regard to the FcR expression profile, synovial MCs from patients with RA and patients with OA were similar. FcγRI was responsible for producing abundant TNFα from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII.


Assuntos
Artrite Reumatoide/imunologia , Imunoglobulina G/imunologia , Mastócitos/imunologia , Osteoartrite/imunologia , Receptores de IgG/imunologia , Membrana Sinovial/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Células Cultivadas , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Mastócitos/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Receptores de IgG/metabolismo , Membrana Sinovial/metabolismo
17.
Elife ; 122024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847802

RESUMO

CRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here, we show that sequence complementarity between the 5' and the 3' regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as sixfold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , RNA Guia de Sistemas CRISPR-Cas , Peixe-Zebra , Peixe-Zebra/genética , Animais , Edição de Genes/métodos , RNA Guia de Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , Embrião não Mamífero/metabolismo , Dobramento de RNA
18.
Front Immunol ; 15: 1342285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576618

RESUMO

B cell receptors (BCRs) denote antigen specificity, while corresponding cell subsets indicate B cell functionality. Since each B cell uniquely encodes this combination, physical isolation and subsequent processing of individual B cells become indispensable to identify both attributes. However, this approach accompanies high costs and inevitable information loss, hindering high-throughput investigation of B cell populations. Here, we present BCR-SORT, a deep learning model that predicts cell subsets from their corresponding BCR sequences by leveraging B cell activation and maturation signatures encoded within BCR sequences. Subsequently, BCR-SORT is demonstrated to improve reconstruction of BCR phylogenetic trees, and reproduce results consistent with those verified using physical isolation-based methods or prior knowledge. Notably, when applied to BCR sequences from COVID-19 vaccine recipients, it revealed inter-individual heterogeneity of evolutionary trajectories towards Omicron-binding memory B cells. Overall, BCR-SORT offers great potential to improve our understanding of B cell responses.


Assuntos
Subpopulações de Linfócitos B , Aprendizado Profundo , Humanos , Filogenia , Vacinas contra COVID-19 , Receptores de Antígenos de Linfócitos B/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-38285587

RESUMO

Work-related musculoskeletal disorders represent a major occupational disability issue, and 53.4% of these disorders occur in the back or shoulders. Various types of passive shoulder exoskeletons have been introduced to support the weight of the upper arm and work tools during overhead work, thereby preventing injuries and improving the work environment. The general passive shoulder exoskeleton is constructed with rigid links and joints to implement shoulder rotation, but there exists a challenge to align with the flexible joint movements of the human shoulder. Also, a force-generating part using mechanical springs require additional mechanical components to generate torque similar to the shoulder joint, resulting in increased overall volume and inertia to the upper arm. In this study, we propose a new type of passive shoulder exoskeleton that uses magnetic spring joint and link chain. The redundant degrees of freedom in the link chains enables to follow the shoulder joint movement in the horizontal direction, and the magnetic spring joint generates torque without additional parts in a compact form. Conventional exoskeletons experience a loss in the assisting torque when the center of shoulder rotation changed during arm elevation. Our exoskeleton minimizes the torque loss by customizing the installation height and initial angle of the magnetic spring joint. The performances of the proposed exoskeleton were verified by an electromyographic evaluation of shoulder-related muscles in overhead work and box lifting task.


Assuntos
Exoesqueleto Energizado , Ombro , Humanos , Ombro/fisiologia , Fenômenos Biomecânicos , Extremidade Superior , Fenômenos Magnéticos , Eletromiografia
20.
Int Arch Allergy Immunol ; 161 Suppl 2: 32-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23711851

RESUMO

BACKGROUND: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-33 is believed to play an important role in the pathogenesis of RA. We recently reported that FcγRI is responsible for producing abundant tumor necrosis factor alpha (TNF-α) from cultured synovium-derived MCs (SyMCs) in response to aggregated immunoglobulin G (IgG). However, whether or not IL-33 affects immune complex (IC)-induced synovial MC activation remains unknown. This study sought to evaluate the effect of IL-33 on IC-induced synovial MC activation. METHODS: Cultured SyMCs were generated by culturing synovial cells with stem cell factor. ST2 expression was analyzed using FACS and immunohistochemical techniques. Mediators released from the MCs were measured using EIAs or ELISAs. RESULTS: SyMCs obtained from patients with RA or osteoarthritis (OA) expressed ST2 on their surfaces. We confirmed the expression of ST2 in MCs using immunofluorescence staining in joint tissue obtained from RA patients. IC-triggered histamine release was not enhanced by IL-33. However, IL-33 synergistically enhanced IC-induced IL-8 and TNF-α production in SyMCs. CONCLUSIONS: ICs and IL-33 may exacerbate inflammation associated with RA by abundantly producing TNF-α and IL-8 from SyMCs.


Assuntos
Complexo Antígeno-Anticorpo/imunologia , Interleucina-8/biossíntese , Interleucinas/farmacologia , Mastócitos/imunologia , Mastócitos/metabolismo , Membrana Sinovial/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Células Cultivadas , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo
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