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1.
Diabetologia ; 67(4): 623-640, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38349399

RESUMEN

AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by pancreatic beta cell destruction. In this study, we explored the pathogenic immune responses in initiation of type 1 diabetes and new immunological targets for type 1 diabetes prevention and treatment. METHODS: We obtained peripheral blood samples from four individuals with newly diagnosed latent autoimmune diabetes in adults (LADA) and from four healthy control participants. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells to uncover transcriptomic profiles of early LADA. Validation was performed through flow cytometry in a cohort comprising 54 LADA, 17 adult-onset type 2 diabetes, and 26 healthy adults, matched using propensity score matching (PSM) based on age and sex. A similar PSM method matched 15 paediatric type 1 diabetes patients with 15 healthy children. Further flow cytometry analysis was performed in both peripheral blood and pancreatic tissues of non-obese diabetic (NOD) mice. Additionally, cell adoptive transfer and clearance assays were performed in NOD mice to explore the role of this monocyte subset in islet inflammation and onset of type 1 diabetes. RESULTS: The scRNA-seq data showed that upregulated genes in peripheral T cells and monocytes from early-onset LADA patients were primarily enriched in the IFN signalling pathway. A new cluster of classical monocytes (cluster 4) was identified, and the proportion of this cluster was significantly increased in individuals with LADA compared with healthy control individuals (11.93% vs 5.93%, p=0.017) and that exhibited a strong IFN signature marked by SIGLEC-1 (encoding sialoadhesin). These SIGLEC-1+ monocytes expressed high levels of genes encoding C-C chemokine receptors 1 or 2, as well as genes for chemoattractants for T cells and natural killer cells. They also showed relatively low levels of genes for co-stimulatory and HLA molecules. Flow cytometry analysis verified the elevated levels of SIGLEC-1+ monocytes in the peripheral blood of participants with LADA and paediatric type 1 diabetes compared with healthy control participants and those with type 2 diabetes. Interestingly, the proportion of SIGLEC-1+ monocytes positively correlated with disease activity and negatively with disease duration in the LADA patients. In NOD mice, the proportion of SIGLEC-1+ monocytes in the peripheral blood was highest at the age of 6 weeks (16.88%), while the peak occurred at 12 weeks in pancreatic tissues (23.65%). Adoptive transfer experiments revealed a significant acceleration in diabetes onset in the SIGLEC-1+ group compared with the SIGLEC-1- or saline control group. CONCLUSIONS/INTERPRETATION: Our study identified a novel group of SIGLEC-1+ monocytes that may serve as an important indicator for early diagnosis, activity assessment and monitoring of therapeutic efficacy in type 1 diabetes, and may also be a novel target for preventing and treating type 1 diabetes. DATA AVAILABILITY: RNA-seq data have been deposited in the GSA human database ( https://ngdc.cncb.ac.cn/gsa-human/ ) under accession number HRA003649.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Animales , Niño , Humanos , Lactante , Ratones , Diabetes Mellitus Tipo 2/metabolismo , Interferones/metabolismo , Leucocitos Mononucleares/metabolismo , Ratones Endogámicos NOD , Monocitos/metabolismo , Lectina 1 Similar a Ig de Unión al Ácido Siálico/metabolismo
2.
Materials (Basel) ; 16(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37763588

RESUMEN

Zero-dimensional (0D) tin halide perovskites, characterized by their broadband and adjustable emissions, high photoluminescence quantum yield, and absence of self-absorption, are crucial for the fabrication of high-efficiency optoelectronic devices, such as LEDs, solar cells, and sensors. Despite these attributes, boosting their emission efficiency and stability poses a significant challenge. In this work, Cr3+-doped Cs4SnBr6-xFx perovskites were synthesized using a water-assisted wet ball-milling method. The effect of CrF3 addition on photoluminescence properties of Cs4SnBr6-xFx Perovskites was investigated. We found that Cr3+-doped Cs4SnBr6-xFx Perovskites exhibit a broad emission band, a substantial Stokes shift, and an efficient green light emission centered at about 525 nm at ambient temperature. The derived photoluminescence quantum yield amounted to as high as 56.3%. In addition, these Cr3+-doped Cs4SnBr6-xFx perovskites outperform their undoped counterparts in terms of thermal stability. Through a comprehensive analysis of photoluminescence measurements, our findings suggested that the elevated photoluminescence quantum yield can be attributed to the enhanced exciton binding energy of self-trapped excitons (STEs) and the suitable electron-phonon coupling resulting from the substantial distortion of [SnBr6]4- octahedra instigated by the addition of CrF3.

3.
Materials (Basel) ; 16(11)2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37297162

RESUMEN

We report a rapid synthesis method for producing CsSnCl3:Mn2+ perovskites, derived from SnF2, and investigate the effects of rapid thermal treatment on their photoluminescence properties. Our study shows that the initial CsSnCl3:Mn2+ samples exhibit a double luminescence peak structure with PL peaks at approximately 450 nm and 640 nm, respectively. These peaks originate from defect-related luminescent centers and the 4T1→6A1 transition of Mn2+. However, as a result of rapid thermal treatment, the blue emission is significantly reduced and the red emission intensity is increased nearly twofold compared to the pristine sample. Furthermore, the Mn2+-doped samples demonstrate excellent thermal stability after the rapid thermal treatment. We suggest that this improvement in photoluminescence results from enhanced excited-state density, energy transfer between defects and the Mn2+ state, as well as the reduction of nonradiative recombination centers. Our findings provide valuable insights into the luminescence dynamics of Mn2+-doped CsSnCl3 and open up new possibilities for controlling and optimizing the emission of rare-earth-doped CsSnCl3.

4.
Neural Netw ; 161: 359-370, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36780859

RESUMEN

Video summarization has long been used to ease video browsing and plays a more crucial role with the explosion of online videos. In the context of event-centric videos, we aim to extract the corresponding clips of more important events in the video. To tackle the dilemma between the detection precision and the clip completeness faced by previous methods, we present an efficient Boundary-Aware framework for Summary clip Extraction (BASE) to extract summary clips with more precise boundaries while maintaining their completeness. Specifically, we propose a new distance-based importance signal to reflect the progress information in each video. The signal can not only help us to detect boundaries with higher precision, but also make it possible to preserve the clip completeness. For the feature presentation part, we also explore new information types to facilitate video summarization. Our approach outperforms current state-of-the-art video summarization models in terms of more precise clip boundaries and more complete summary clips. Note that we even yield comparable results to manual annotations.


Asunto(s)
Grabación en Video , Grabación en Video/métodos
5.
Biomed Res Int ; 2022: 4625183, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060125

RESUMEN

Circular RNAs (circRNAs) participate in development of malignancies through its active role as a "miRNA sponge." Their roles in type 1 diabetes mellitus (T1DM) pathogenesis are elusive. Here, the important role of circRNAs in T1DM was explored. circRNA profiling was performed for isolated CD4+ T cells from blood of T1DM and healthy volunteers. There were 257 differentially expressed circRNAs. Only three upregulated DEcircRNAs (hsa_circ_0000324, hsa_circ_0001853, and hsa_circ_0068797) were consistent with the GEO database. Through KEGG analyses, it was found that the three DEcircRNAs were associated with 11 miRNAs and 8 immune-related target genes (mRNA). Further analysis found that four miRNAs, two circRNAs, and four mRNAs were associated with nine circRNA-miRNA-mRNA networks. This confirmed the requirements of sponge mechanisms. The qRT-PCR analysis revealed that circRNA000324/miRNA675-5p/MAPK14 and circRNA000324/miRNA-675-5p/SYK may be potential mechanisms in regulation of differentiation and proliferation of CD4+ T cell in patients with T1DM. Therefore, targeting circRNA to regulate cellular immune responses by regulating CD4+ T cell differentiation may be a new strategy for the treatment of T1DM.


Asunto(s)
Diabetes Mellitus Tipo 1 , MicroARNs , Linfocitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
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