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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Chen, Jian, et al.
(författare)
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AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling
- 2018
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 3:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barre syndrome(1,2). While progress has been made in understanding the causal link between ZIKV infection and microcephaly(3-9), the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV(10-22). Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor alpha chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.
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| 4. |
- Chen, Jian, et al.
(författare)
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Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects
- 2017
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Ingår i: Emerging Microbes & Infections. - : NATURE PUBLISHING GROUP. - 2222-1751. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barre syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.
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| 5. |
- Dong, Mei, et al.
(författare)
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Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis
- 2013
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Ingår i: Cell Metabolism. - : Elsevier (Cell Press). - 1550-4131 .- 1932-7420. ; 18:1, s. 118-129
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
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- Galetin, Aleksandra, et al.
(författare)
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Membrane transporters in drug development and as determinants of precision medicine
- 2024
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Ingår i: NATURE REVIEWS DRUG DISCOVERY. - 1474-1776 .- 1474-1784.
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Forskningsöversikt (refereegranskat)abstract
- The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.
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| 8. |
- Tong, Yang, et al.
(författare)
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Progress of the key materials for organic solar cells
- 2020
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Ingår i: Science in China Series B. - Beijing, China : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 63:6, s. 758-765
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Forskningsöversikt (refereegranskat)abstract
- Organic solar cells have attracted academic and industrial interests due to the advantages like lightweight, flexibility and roll-to-roll fabrication. Nowadays, 18% power conversion efficiency has been achieved in the state-of-the-art organic solar cells. The recent rapid progress in organic solar cells relies on the continuously emerging new materials and device fabrication technologies, and the deep understanding on film morphology, molecular packing and device physics. Donor and acceptor materials are the key materials for organic solar cells since they determine the device performance. The past 25 years have witnessed an odyssey in developing high-performance donors and acceptors. In this review, we focus on those star materials and milestone work, and introduce the molecular structure evolution of key materials. These key materials include homopolymer donors, D-A copolymer donors, A-D-A small molecular donors, fullerene acceptors and nonfullerene acceptors. At last, we outlook the challenges and very important directions in key materials development.
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| 9. |
- Yang, Fuliu, et al.
(författare)
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Efficient SO2 capture at ultra-low concentration using a hybrid absorbent of deep eutectic solvent and ethylene glycol
- 2023
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Ingår i: Journal of Molecular Liquids. - : Elsevier. - 0167-7322 .- 1873-3166. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Deep eutectic solvents (DESs) are considered as the highly effective absorbents for sulfur dioxide (SO2) capture. However, the high viscosity of DESs and the resulting slow absorption rate as well as low absorption capacity at low SO2 concentration seriously hinder their industrial application. In this study, DES of N-methyldiethanolamine (MDEA) and imidazole (Im) is simply blended with ethylene glycol (EG) forming a hybrid absorbent, namely MDEA/Im-EG, which exhibits extremely high SO2 capture capacity at low concentration. In particular, SO2 capture capacity in MDEA/Im-EG (molar ratio = 1:1) reaches 0.446 g SO2/g absorbent at 293.2 K with SO2 concentration of 2000 ppm. Moreover, the corresponding desorption enthalpy is only −40.67 kJ/mol. To well understand the results, thermodynamic analysis of SO2 capture is performed and the SO2 capture mechanism is speculated by nuclear magnetic resonance and Fourier transform infrared spectroscopy.
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