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- Huang, Yi Shu, et al.
(författare)
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Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 118:19
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.
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- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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- Lin, Ci, et al.
(författare)
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Direct Band Gap in Multilayer Transition Metal Dichalcogenide Nanoscrolls with Enhanced Photoluminescence
- 2022
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Ingår i: ACS Materials Letters. - : American Chemical Society (ACS). - 2639-4979. ; 4:8, s. 1547-1555
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Tidskriftsartikel (refereegranskat)abstract
- A direct band gap that solely exists in monolayer semiconducting transition metal dichalcogenides (TMDs) endows strong photoluminescence (PL) features, whereas multilayer TMD structures exhibit quenched PL due to the direct-to-indirect band gap transition. We demonstrate multi-layer TMD (such as MoS2 and WS2) nanoscrolls with a preserved direct band gap fabricated by an effective and facile method of solvent-driven self-assembly. The resultant multi-layer nanoscrolls, exhibiting up to 11 times higher PL intensity than the remanent monolayer, are carefully characterized using PL spectroscopy. Significantly enlarged interlayer distances and modulated interlayer coupling in the fabricated nanostructures are unveiled by cross-sectional scanning transmission electron microscopy, atomic force microscopy, and Raman spectroscopy. The preservation of direct band gap features is further evidenced by density functional theory calculations using the simplified bilayer model with an experimentally obtained 15 & ANGS; interlayer distance. The modulation of the PL intensity as an indicator of the band gap crossover in the TMD nanoscrolls is demonstrated by removing the acetone molecules trapped inside the interlayer space. The general applicability of the method presents an opportunity for large-scale fabrication of a plethora of multilayer TMD nanoscrolls with direct band gaps.
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