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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. |
- Ding, Jiangwei, et al.
(författare)
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All Roads Lead to Rome? : Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Background: Dravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A, which encodes the voltage-gated sodium channel NaV1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner.Objective: The purpose of this study was to identify genes other than SCN1A that may also cause DS or DS-like phenotypes. Methods: A comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized.Results: A PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on PCDH19, three on SCN2A, two on SCN8A, five on SCN1B, two on GABRA1, three on GABRB3, three on GABRG2, and three on STXBP1 were included. Only one study was recorded for CHD2, CPLX1, HCN1 and KCNA2, respectively. It is worth noting that a few articles reported on more than one epilepsy gene.Conclusion: DS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.
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| 6. |
- Fei, Keke, et al.
(författare)
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LcrQ coordinates with the YopD-LcrH complex to repress lcrF expression and control type III secretion by Yersinia pseudotuberculosis
- 2021
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Ingår i: mBio. - : American Society for Microbiology (ASM). - 2161-2129 .- 2150-7511. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Human-pathogenic Yersinia species employ a plasmid-encoded type III secretion system (T3SS) to negate immune cell function during infection. A critical element in this process is the coordinated regulation of T3SS gene expression, which involves both transcriptional and posttranscriptional mechanisms. LcrQ is one of the earliest identified negative regulators of Yersinia T3SS, but its regulatory mechanism is still unclear. In a previous study, we showed that LcrQ antagonizes the activation role played by the master transcriptional regulator LcrF. In this study, we confirm that LcrQ directly interacts with LcrH, the chaperone of YopD, to facilitate the negative regulatory role of the YopD-LcrH complex in repressing lcrF expression at the posttranscriptional level. Negative regulation is strictly dependent on the YopD-LcrH complex, more so than on LcrQ. The YopD-LcrH complex helps to retain cytoplasmic levels of LcrQ to facilitate the negative regulatory effect. Interestingly, RNase E and its associated protein RhlB participate in this negative regulatory loop through a direct interaction with LcrH and LcrQ. Hence, we present a negative regulatory loop that physically connects LcrQ to the posttranscriptional regulation of LcrF, and this mechanism incorporates RNase E involved in mRNA decay.
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| 7. |
- Hao, Wende, et al.
(författare)
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Vitronectin : a promising breast cancer serum biomarker for early diagnosis of breast cancer in patients
- 2016
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Ingår i: Tumor Biology. - : Springer. - 1010-4283 .- 1423-0380. ; 37:7, s. 8909-8916
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cancer in women worldwide, identification of new biomarkers for early diagnosis and detection will improve the clinical outcome of breast cancer patients. In the present study, we determined serum levels of vitronectin (VN) in 93 breast cancer patients, 30 benign breast lesions, 9 precancerous lesions, and 30 healthy individuals by enzyme-linked immunosorbent assays. Serum VN level was significantly higher in patients with stage 0-I primary breast cancer than in healthy individuals, patients with benign breast lesion or precancerous lesions, as well as those with breast cancer of higher stages. Serum VN level was significantly and negatively correlated with tumor size, lymph node status, and clinical stage (p < 0.05 in all cases). In addition, VN displayed higher area under curve (AUC) value (0.73, 95 % confidence interval (CI) [0.62-0.84]) than carcinoembryonic antigen (CEA) (0.64, 95 % CI [0.52-0.77]) and cancer antigen 15-3 (CA 15-3) (0.69, 95 % CI [0.58-0.81]) when used to distinguish stage 0-I cancer and normal control. Importantly, the combined use of three biomarkers yielded an improvement in receiver operating characteristic curve with an AUC of 0.83, 95 % CI [0.74-0.92]. Taken together, our current study showed for the first time that serum VN is a promising biomarker for early diagnosis of breast cancer when combined with CEA and CA15-3.
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| 8. |
- Hu, Haiman, et al.
(författare)
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Confining Ionic Liquids in Developing Quasi‐Solid‐State Electrolytes for Lithium Metal Batteries
- 2024
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Ingår i: Chemistry - A European Journal. - : John Wiley & Sons. - 0947-6539 .- 1521-3765. ; 30:5
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Forskningsöversikt (refereegranskat)abstract
- The concept of confining ionic liquids (ILs) in developing quasi-solid-state electrolytes (QSSEs) has been proposed, where ILs are dispersed in polymer networks/backbones and/or filler/host pores, forming the so-called confinement, and great research progress and promising research results have been achieved. In this review, the progress and achievement in developing QSSEs using IL-confinement for lithium metal batteries (LMBs), together with advanced characterizations and simulations, were surveyed, summarized, and analyzed, where the influence of specific parameters, such as IL (type, content, etc.), substrate (type, structure, surface properties, etc.), confinement methods, and so on, was discussed. The confinement concept was further compared with the conventional one in other research areas. It indicates that the IL-confinement in QSSEs improves the performance of electrolytes, for example, increasing the ionic conductivity, widening the electrochemical window, and enhancing the cycle performance of the assembled cells, and being different from those in other areas, i.e., the IL-confinement concept in the battery area is in a broad extent. Finally, insights into developing QSSEs in LMBs with the confinement strategy were provided to promote the development and application of QSSE LMBs.
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| 9. |
- Hu, Haiman, et al.
(författare)
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Revealing the role and working mechanism of confined ionic liquids in solid polymer composite electrolytes
- 2024
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Ingår i: Journal of Energy Chemistry. - : Elsevier. - 2095-4956 .- 2096-885X. ; 99, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- The confined ionic liquid (IL) in solid polymer composite electrolytes (SCPEs) can improve the performance of lithium metal batteries. However, the impact/role and working mechanism of confined IL in SCPEs remain ambiguous. Herein, IL was immobilized on SiO2 (SiO2@IL-C) and then used to prepare the confined SCPEs together with LiTFSI and PEO to study the impacts of confined-IL on the properties and performance of electrolytes and reveal the Li+ transport mechanism. The results show that, compared to the IL-unconfined SCPE, the IL-confined ones exhibit better performance of electrolytes and cells, such as higher ionic conductivity, higher tLi+, and wider electrochemical windows, as well as more stable cycle performance, due to the increased dissociation degree of lithium salt and enlarged polymer amorphousness. The finite-element/molecular-dynamics simulations suggest that the IL confined on the SiO2 provided an additional Li+ transport pathway (Li+ → SiO2@IL-C) that can accelerate ion transfer and alleviate lithium dendrites, leading to ultrastable stripping/plating cycling over 1900 h for the Li/SCPEs/Li symmetric cells. This study demonstrates that IL-confinement is an effective strategy for the intelligent approach of high-performance lithium metal batteries.
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| 10. |
- Hu, Wei, et al.
(författare)
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Axisymmetric and Asymmetric Naphthalene-Bisthienothiophene Based Nonfullerene Acceptors: On Constitutional Isomerization and Photovoltaic Performance
- 2020
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 3:6, s. 5734-5744
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Tidskriftsartikel (refereegranskat)abstract
- Two pairs of constitutional isomers of fused-octacyclic nonfullerene acceptors (NFAs) based on a naphthalene-bisthienothiophene core with or without fluorination at the ending groups have been developed. Compared with the axisymmetric NFAs N66-IC and N66-2FIC with two six-member-ring bridges, their asymmetric constitutional isomers N65-IC and N65-2FIC both with one six-member-ring bridge and one five-member-ring bridge exhibit remarkable red-shifted absorption, higher crystallinity, and slightly down-shifted LUMO energy levels. Organic solar cells based on PBDB-T-2F:N65-2FIC achieved a promising power conversion efficiency of 10.19%, which is three times higher than that of its counterpart PBDB-T-2F:N66-2FIC cell (3.46%). While being blended with PBDB-T as the donor material, the asymmetric acceptor analogue N65-IC based solar cell pronounces a PCE of 9.03%, being significantly improved from that of 5.45% for the PBDB-T:N66-IC based cell, which is in consistency with the results from those cells from their both fluorinated donor and acceptor counterparts. Design rules on either both fluorinated, both nonfluorinated, or cross-combined donor/acceptors for device fabrication has been explored. In addition, PBDB-T-2F:N65-2FIC possesses very promising device stability with 85% of its initial PCE after an exposure time of 1500 h under one sun illumination, which is meaningful for their future commercial devices.
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