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1.
Diabetes ; 73(5): 728-742, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387030

RESUMEN

The ß-cell plays a crucial role in the pathogenesis of type 1 diabetes, in part through the posttranslational modification of self-proteins by biochemical processes such as deamidation. These neoantigens are potential triggers for breaking immune tolerance. We report the detection by LC-MS/MS of 16 novel Gln and 27 novel Asn deamidations in 14 disease-related proteins within inflammatory cytokine-stressed human islets of Langerhans. T-cell clones responsive against one Gln- and three Asn-deamidated peptides could be isolated from peripheral blood of individuals with type 1 diabetes. Ex vivo HLA class II tetramer staining detected higher T-cell frequencies in individuals with the disease compared with control individuals. Furthermore, there was a positive correlation between the frequencies of T cells specific for deamidated peptides, insulin antibody levels at diagnosis, and duration of disease. These results highlight that stressed human islets are prone to enzymatic and biochemical deamidation and suggest that both Gln- and Asn-deamidated peptides can promote the activation and expansion of autoreactive CD4+ T cells. These findings add to the growing evidence that posttranslational modifications undermine tolerance and may open the road for the development of new diagnostic and therapeutic applications for individuals living with type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Humanos , Linfocitos T CD4-Positivos , Diabetes Mellitus Tipo 1/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Islotes Pancreáticos/metabolismo , Péptidos
2.
Diabetologia ; 67(5): 908-927, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38409439

RESUMEN

AIMS/HYPOTHESIS: The proinflammatory cytokines IFN-α, IFN-γ, IL-1ß and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown. METHODS: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes. RESULTS: IFN-α and IFN-γ had a greater impact on the beta cell transcriptome when compared with IL-1ß and TNF-α. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from individuals with type 1 diabetes, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to 'danger signals' such as viral infections. Zinc finger NFX1-type containing 1 (ZNFX1), a double-stranded RNA sensor, was identified as highly induced by IFNs and shown to play a key role in the antiviral response in beta cells. CONCLUSIONS/INTERPRETATION: These data suggest that IFN-α and IFN-γ are key cytokines at the islet level in human type 1 diabetes, contributing to the triggering and amplification of autoimmunity.


Asunto(s)
Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Humanos , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Interferones/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interferón gamma/metabolismo , Islotes Pancreáticos/metabolismo
3.
Transplant Proc ; 56(3): 469-478, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38365513

RESUMEN

BACKGROUND: The lack of donor organs is a major barrier to the advancement of organ transplantation. This study aimed to understand the current status of knowledge, attitudes, and willingness to donate organs among intensive care unit (ICU) health care workers and analyzed the influencing factors to provide a scientific basis for improving the situation of a serious imbalance between the ratio of organ supply and demand. METHODS: From November 2021 to March 2022, 160 ICU health care workers from 3 level 3A hospitals in Huzhou City, Zhejiang Province, China were chosen as subjects by the cluster sampling method. A cross-sectional study of the participants was carried out using a general information questionnaire, Organ Donation Knowledge Scale, Organ Donation Attitude Scale, and Organ Donation Willingness Scale. The determinants of ICU health care workers' knowledge, attitudes, and willingness toward organ donation were examined using multiple linear regression analysis. RESULTS: A total of 150 ICU health care workers completed the survey within the prescribed time, and the recovery rate of this questionnaire was 93.75%. The score on the Organ Donation Knowledge Scale was 7 (5, 7) points, and the full score was 10 points. The score on the Organ Donation Attitude Scale was (3.87 ± 0.93), and the full score was 7. The Organ Donation Willingness Scale score was 2 (2, 3) out of 5. The results of the multiple linear regression analysis revealed that several factors significantly influenced the score of organ donation knowledge. These factors were identified as the professional title and persuasive experience related to organ donation. Additionally, the score of organ donation attitude was found to be influenced primarily by the persuasive experience of organ donation. Furthermore, the score of organ donation willingness was influenced by 3 main factors: marital status, professional title, and persuasive experience in the context of organ donation. CONCLUSIONS: Although the level of ICU health care workers' knowledge and attitudes toward organ donation was above the median level, they still needed to be improved. The current status of ICU health care workers' desire to donate organs is not optimistic; thus, relevant departments should take specific actions to improve the situation.


Asunto(s)
Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Unidades de Cuidados Intensivos , Obtención de Tejidos y Órganos , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Personal de Salud/psicología , China
4.
Int J Mol Sci ; 25(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38279284

RESUMEN

This study explores the impact of RNAi in terms of selectively inhibiting the expression of the OsBBTI5 gene, with the primary objective of uncovering its involvement in the molecular mechanisms associated with salt tolerance in rice. OsBBTI5, belonging to the Bowman-Birk inhibitor (BBI) family gene, is known for its involvement in plant stress responses. The gene was successfully cloned from rice, exhibiting transcriptional self-activation in yeast. A yeast two-hybrid assay confirmed its specific binding to OsAPX2 (an ascorbate peroxidase gene). Transgenic OsBBTI5-RNAi plants displayed insensitivity to varying concentrations of 24-epibrassinolide in the brassinosteroid sensitivity assay. However, they showed reduced root and plant height at high concentrations (10 and 100 µM) of GA3 immersion. Enzyme activity assays revealed increased peroxidase (POD) and superoxide dismutase (SOD) activities and decreased malondialdehyde (MDA) content under 40-60 mM NaCl. Transcriptomic analysis indicated a significant upregulation of photosynthesis-related genes in transgenic plants under salt stress compared to the wild type. Notably, this study provides novel insights, suggesting that the BBI gene is part of the BR signaling pathway, and that OsBBTI5 potentially enhances stress tolerance in transgenic plants through interaction with the salt stress-related gene OsAPX2.


Asunto(s)
Oryza , Tolerancia a la Sal , Tolerancia a la Sal/genética , Oryza/metabolismo , Interferencia de ARN , Estrés Salino/genética , Peroxidasas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Nano Lett ; 24(5): 1769-1775, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38251648

RESUMEN

Field-emission nanodiodes with air-gap channels based on single ß-Ga2O3 nanowires have been investigated in this work. With a gap of ∼50 nm and an asymmetric device structure, the proposed nanodiode achieves good diode characteristics through field emission in air at room temperature. Measurement results show that the nanodiode exhibits an ultrahigh emission current density, a high enhancement factor of >2300, and a low turn-on voltage of 0.46 V. More impressively, the emission current almost keeps constant over a wide range (8 orders of magnitude) of air pressures below 1 atm. Meanwhile, the fluctuation in field-emission current is below 8.7% during long-time monitoring, which is better than the best reported field-emission device based on ß-Ga2O3 nanostructures. All of these results indicate that ß-Ga2O3 air-gapped nanodiodes are promising candidates for vacuum electronics that can also operate in air.

6.
medRxiv ; 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38076918

RESUMEN

Aim/hypothesis: Growth/differentiation factor 15 (GDF15) is a therapeutic target for a variety of metabolic diseases, including type 1 diabetes (T1D). However, the nausea caused by GDF15 is a challenging point for therapeutic development. In addition, it is unknown why the endogenous GDF15 fails to protect from T1D development. Here, we investigate the GDF15 signaling in pancreatic islets towards opening possibilities for therapeutic targeting in ß cells and to understand why this protection fails to occur naturally. Methods: GDF15 signaling in islets was determined by proximity-ligation assay, untargeted proteomics, pathway analysis, and treatment of cells with specific inhibitors. To determine if GDF15 levels would increase prior to disease onset, plasma levels of GDF15 were measured in a longitudinal prospective study of children during T1D development (n=132 cases vs. n=40 controls) and in children with islet autoimmunity but normoglycemia (n=47 cases vs. n=40 controls) using targeted mass spectrometry. We also investigated the regulation of GDF15 production in islets by fluorescence microscopy and western blot analysis. Results: The proximity-ligation assay identified ERBB2 as the GDF15 receptor in islets, which was confirmed using its specific antagonist, tucatinib. The untargeted proteomics analysis and caspase assay showed that ERBB2 activation by GDF15 reduces ß cell apoptosis by downregulating caspase 8. In plasma, GDF15 levels were higher (p=0.0024) during T1D development compared to controls, but not in islet autoimmunity with normoglycemia. However, in the pancreatic islets GDF15 was depleted via sequestration of its mRNA into stress granules, resulting in translation halting. Conclusions/interpretation: GDF15 protects against T1D via ERBB2-mediated decrease of caspase 8 expression in pancreatic islets. Circulating levels of GDF15 increases pre-T1D onset, which is insufficient to promote protection due to its localized depletion in the islets. These findings open opportunities for targeting GDF15 downstream signaling for pancreatic ß cell protection in T1D and help to explain the lack of natural protection by the endogenous protein.

7.
Int J Mol Sci ; 24(21)2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37958684

RESUMEN

Utilizing carbon quantum dots (CQDs) as biomaterials for delivering small substances has gained significant attention in recent research. However, the interactions and mechanisms of action of CQDs on plants have received relatively little focus. Herein, we investigated the transportation of CQDs into various organs of Arabidopsis thaliana (L.) Heynh. via the vessel system, leading to the epigenetic inheritance of Argonaute family genes. Our findings reveal that CQDs may interact with microRNAs (miRNAs), leading to the repression of post-transcriptional regulation of target genes in the cytoplasm. Transcriptome and quantitative PCR analyses demonstrated consistent gene expression levels in offspring. Moreover, microscopic observations illustrated rapid CQD localization on cell membranes and nuclei, with increased nuclear entry at higher concentrations. Notably, our study identified an alternative regulatory microRNA, microRNA172D, for the Argonaute family genes through methylation analysis, shedding light on the connection between CQDs and microRNAs.


Asunto(s)
Arabidopsis , MicroARNs , Puntos Cuánticos , Carbono , Arabidopsis/genética , MicroARNs/genética , Expresión Génica
8.
Int J Mol Sci ; 24(19)2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37834456

RESUMEN

The color of the chili fruit is an important factor that determines the quality of the chili, as red chilies are more popular among consumers. The accumulation of capsanthin is the main cause of reddening of the chili fruit. Capsanthin is an important metabolite in carotenoid metabolism, and its production level is closely linked to the expression of the genes for capsanthin/capsorubin synthase (CCS) and carotenoid hydroxylase (CrtZ). We reported for the first time that the synthesis of capsanthin in chili was enhanced by using a geminivirus (Bean Yellow Dwarf Virus). By expressing heterologous ß-carotenoid hydroxylase (CrtZ) and ß-carotenoid ketolase (CrtW) using codon optimization, the transcription level of the CCS gene and endogenous CrtZ was directly increased. This leads to the accumulation of a huge amount of capsanthin in a very short period of time. Our results provide a platform for the rapid enhancement of endogenous CCS activity and capsanthin production using geminivirus in plants.


Asunto(s)
Capsicum , Geminiviridae , Proteínas de Plantas/genética , Capsicum/genética , Capsicum/metabolismo , Carotenoides/metabolismo , Oxigenasas de Función Mixta/metabolismo , Geminiviridae/genética , Geminiviridae/metabolismo
9.
Plants (Basel) ; 12(19)2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37836253

RESUMEN

The Chinese plum (Prunus salicina L.) is a fruit tree belonging to the Rosaceae family, native to south-eastern China and widely cultivated throughout the world. Fruit sugar metabolism and color change is an important physiological behavior that directly determines flavor and aroma. Our study analyzed six stages of fruit growth and development using RNA-seq, yielding a total of 14,973 DEGs, and further evaluation of key DEGs revealed a focus on sugar metabolism, flavonoid biosynthesis, carotenoid biosynthesis, and photosynthesis. Using GO and KEGG to enrich differential genes in the pathway, we selected 107 differential genes and obtained 49 significant differential genes related to glucose metabolism. The results of the correlation analyses indicated that two genes of the SWEET family, evm.TU.Chr1.3663 (PsSWEET9) and evm.TU.Chr4.676 (PsSWEET2), could be closely related to the composition of soluble sugars, which was also confirmed in the ethylene treatment experiments. In addition, analysis of the TOP 20 pathways between different growth stages and the green stage, as well as transient overexpression in chili, suggested that capsanthin/capsorubin synthase (PsCCS) of the carotenoid biosynthetic pathway contributed to the color change of plum fruit. These findings provide an insight into the molecular mechanisms involved in the ripening and color change of plum fruit.

10.
Nano Converg ; 10(1): 39, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626161

RESUMEN

As an emerging single crystals growth technique, the 2D-material-assisted epitaxy shows excellent advantages in flexible and transferable structure fabrication, dissimilar materials integration, and matter assembly, which offers opportunities for novel optoelectronics and electronics development and opens a pathway for the next-generation integrated system fabrication. Studying and understanding the lattice modulation mechanism in 2D-material-assisted epitaxy could greatly benefit its practical application and further development. In this review, we overview the tremendous experimental and theoretical findings in varied 2D-material-assisted epitaxy. The lattice guidance mechanism and corresponding epitaxial relationship construction strategy in remote epitaxy, van der Waals epitaxy, and quasi van der Waals epitaxy are discussed, respectively. Besides, the possible application scenarios and future development directions of 2D-material-assisted epitaxy are also given. We believe the discussions and perspectives exhibited here could help to provide insight into the essence of the 2D-material-assisted epitaxy and motivate novel structure design and offer solutions to heterogeneous integration via the 2D-material-assisted epitaxy method.

11.
NAR Genom Bioinform ; 5(3): lqad068, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37435358

RESUMEN

Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA-sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies regulators of cell identity and cell states in the human adult pancreas. We predict that HEYL, BHLHE41 and JUND are active in acinar, beta and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell (hiPSC)-derived islet cells. Using single-cell transcriptomics, we found that JUND represses beta cell genes in hiPSC-alpha cells. BHLHE41 depletion induced apoptosis in primary pancreatic islets. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity and cell states in the human adult pancreas.

12.
Diabetologia ; 66(7): 1273-1288, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37148359

RESUMEN

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).


Asunto(s)
Diabetes Mellitus Tipo 2 , Salud Poblacional , Humanos , Estudio de Asociación del Genoma Completo , Diabetes Mellitus Tipo 2/genética , Medicina de Precisión , Genotipo , Hispánicos o Latinos/genética , Polimorfismo de Nucleótido Simple/genética
13.
Genes (Basel) ; 14(3)2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36980831

RESUMEN

The bulb formation of Lilium is affected by many physiological and biochemical phenomena, including flower bud differentiation, starch and sucrose accumulation, photoperiod, carbon fixation, plant hormone transduction, etc. The transcriptome analysis of flower buds of Lilium hybrid 'Siberia' at different maturity stages showed that floral bud formation is associated with the accumulation of anthocyanins. The results of HPLC-MS showed that cyanidin is the major anthocyanin found in Lilium 'Siberia'. Transcriptome KEGG enrichment analysis and qRT-PCR validation showed that two genes related to flavonoid biosynthesis (LhANS-rr1 and LhDFR) were significantly up-regulated. The functional analysis of differential genes revealed that LhMYB114 was directly related to anthocyanin accumulation among 19 MYB transcription factors. Furthermore, the qRT-PCR results suggested that their expression patterns were very similar at different developmental stages of the lily bulbs. Virus-induced gene silencing (VIGS) revealed that down-regulation of LhANS-rr1, LhDFR, and LhMYB114 could directly lead to a decrease in anthocyanin accumulation, turning the purple phenotype into a white color. Moreover, this is the first report to reveal that LhMYB114 can regulate anthocyanin accumulation at the mature stage of lily bulbs. The accumulation of anthocyanins is an important sign of lily maturity. Therefore, these findings have laid a solid theoretical foundation for further discussion on lily bulb development in the future.


Asunto(s)
Flores , Lilium , Flores/genética , Flores/metabolismo , Lilium/genética , Lilium/metabolismo , Antocianinas , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica
14.
Adv Mater ; 35(18): e2211075, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36897809

RESUMEN

Beyond traditional heteroepitaxy, 2D-materials-assisted epitaxy opens opportunities to revolutionize future material integration methods. However, basic principles in 2D-material-assisted nitrides' epitaxy remain unclear, which impedes understanding the essence, thus hindering its progress. Here, the crystallographic information of nitrides/2D material interface is theoretically established, which is further confirmed experimentally. It is found that the atomic interaction at the nitrides/2D material interface is related to the nature of underlying substrates. For single-crystalline substrates, the heterointerface behaves like a covalent one and the epilayer inherits the substrate's lattice. Meanwhile, for amorphous substrates, the heterointerface tends to be a van der Waals one and strongly relies on the properties of 2D materials. Therefore, modulated by graphene, the nitrides' epilayer is polycrystalline. In contrast, single-crystalline GaN films are successfully achieved on WS2 . These results provide a suitable growth-front construction strategy for high-quality 2D-material-assisted nitrides' epitaxy. It also opens a pathway toward various semiconductors heterointegration.

15.
Artículo en Inglés | MEDLINE | ID: mdl-36673901

RESUMEN

This paper reports on a study of the determinants of the adoption behaviour related to Organic-Substitute-Chemical-Fertilizer (OSCF) against the background of Green and Low-carbon Circular Agriculture (GLCA) by analysing a survey of 318 greenhouse vegetable farmers in Shandong Province, China. We use regression analyses to identify policy measures and farmers' psychological cognition of the determinants of adoption behaviour on farmers' psychological cognition. We use three indices for farmers' cognition, including economic value, resource capacity, and ecosystem impact, to examine the differences between training and subsidy. Our findings showed that two policy measures (training and subsidy) had a significant positive impact on vegetable farmers' fertilizer application. Farmers' cognition played a mediating role. We identified and discussed the influence of policy measures on farmers' behaviour and the mediating role of farmers' cognition. Hence, we suggest that local governments should strengthen farmers' training in relation to fertilizer application techniques and enhance farmers' cognition of organic fertilizer as a substitute for chemical fertilizer in terms of economic, resource and environment aspects.


Asunto(s)
Agricultores , Fertilizantes , Humanos , Verduras , Ecosistema , Agricultura/métodos , China
16.
Nat Cell Biol ; 25(1): 20-29, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36543979

RESUMEN

Impaired proinsulin-to-insulin processing in pancreatic ß-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. 1,2), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. 3-8); nonetheless, the role of specific SL species in ß-cell function and demise is unclear. Here we define the lipid signature of T2D-associated ß-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. ß-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL-protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum-Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in ß-cell function and T2D-associated ß-cell failure.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Proinsulina/genética , Proinsulina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Esfingolípidos/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Insulina/metabolismo , Homeostasis , Proteínas Portadoras/metabolismo , Glucosa/metabolismo , Células Secretoras de Insulina/metabolismo
17.
iScience ; 25(11): 105376, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36345338

RESUMEN

Target tissues of autoimmune and degenerative diseases show signals of inflammation. We used publicly available RNA-seq data to study whether pancreatic ß-cells in type 1 and type 2 diabetes and neuronal tissue in multiple sclerosis and Alzheimer's disease share inflammatory gene signatures. We observed concordantly upregulated genes in pairwise diseases, many of them related to signaling by interleukins and interferons. We next mined these signatures to identify therapies that could be re-purposed/shared among the diseases and identified the bromodomain inhibitors as potential perturbagens to revert the transcriptional signatures. We experimentally confirmed in human ß-cells that bromodomain inhibitors I-BET151 and GSK046 prevent the deleterious effects of the pro-inflammatory cytokines interleukin-1ß and interferon-γ and at least some of the effects of the metabolic stressor palmitate. These results demonstrate that key inflammation-induced molecular mechanisms are shared between ß-cells and brain in autoimmune and degenerative diseases and that these signatures can be mined for drug discovery.

18.
Opt Express ; 30(15): 26676-26689, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-36236855

RESUMEN

Heterogeneous integration of nitrides on Si (100) is expected to open the door to the new possibilities for this material system in the fields of high-speed integrated photonics and information processing. In this work, GaN epitaxial layer grown on the patterned sapphire substrate is transferred onto Si (100) by a combination of wafer bonding, laser lift-off and chemical mechanical polishing (CMP) processes. The GaN epilayer transferred is uniformly thinned down to 800 nm with a root mean square surface roughness as low as 2.33 Å. The residual stress within the InGaN quantum wells transferred is mitigated by 79.4% after the CMP process. Accordingly, its emission wavelength exhibits a blue shift of 8.8 nm, revealing an alleviated quantum-confined Stark effect. Based on this platform, an array of microcavities with diverse geometrics and sizes are fabricated, by which optically-pumped green lasing at ∼505.8 nm is achieved with a linewidth of ∼0.48 nm from ∼12 µm microdisks. A spontaneous emission coupling factor of around 10-4 is roughly estimated based on the light output characteristics with increasing the pumping densities. Lasing behaviors beyond the threshold suggest that the microdisk suffers less thermal effects as compared to its undercut counterparts. The electrically-injected microdisks are also fabricated, with a turn-on voltage of ∼2.0 V and a leakage current as low as ∼2.4 pA at -5 V. Being compatible with traditional semiconductor processing techniques, this work provides a feasible solution to fabricate large-area heterogeneously integrated optoelectronic devices based on nitrides.

19.
Opt Express ; 30(12): 21349-21361, 2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-36224856

RESUMEN

Versatile applications have driven a desire for dual-band detection that enables seeing objects in multiple wavebands through a single photodetector. In this paper, a concept of using graphene/p-GaN Schottky heterojunction on top of a regular AlGaN-based p-i-n mesa photodiode is reported for achieving solar-/visible-blind dual-band (275 nm and 365 nm) ultraviolet photodetector with high performance. The highly transparent graphene in the front side and the polished sapphire substrate at the back side allows both top illumination and back illumination for the dual band detection. A system limit dark current of 1×10-9 A/cm2 at a negative bias voltage up to -10 V has been achieved, while the maximum detectivity obtained from the detection wavebands of interests at 275 nm and 365 nm are ∼ 9.0 ×1012 cm·Hz1/2/W at -7.5 V and ∼8.0 × 1011 cm·Hz1/2/W at +10 V, respectively. Interestingly, this new type of photodetector is dual-functional, capable of working as either photodiode or photoconductor, when switched by simply adjusting the regimes of bias voltage applied on the devices. By selecting proper bias, the device operation mode would switch between a high-speed photodiode and a high-gain photoconductor. The device exhibits a minimum rise time of ∼210 µs when working as a photodiode and a maximum responsivity of 300 A/W at 6 µW/cm2 when working as a photoconductor. This dual band and multi-functional design would greatly extend the utility of detectors based on nitrides.

20.
Small ; 18(41): e2202529, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35986697

RESUMEN

Use of 2D materials as buffer layers has prospects in nitride epitaxy on symmetry mismatched substrates. However, the control of lattice arrangement via 2D materials at the heterointerface presents certain challenges. In this study, the epitaxy of single-crystalline GaN film on WS2 -glass wafer is successfully performed by using the strong polarity of WS2 buffer layer and its perfectly matching lattice geometry with GaN. Furthermore, this study reveals that the first interfacial nitrogen layer plays a crucial role in the well-constructed interface by sharing electrons with both Ga and S atoms, enabling the single-crystalline stress-free GaN, as well as a violet light-emitting diode. This study paves a way for the heterogeneous integration of semiconductors and creates opportunities to break through the design and performance limitations, which are induced by substrate restriction, of the devices.

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