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  • 1
    In: Autophagy, Informa UK Limited, Vol. 17, No. 1 ( 2021-01-02), p. 1-382
    Type of Medium: Online Resource
    ISSN: 1554-8627 , 1554-8635
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2262043-6
    SSG: 12
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  • 2
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-10-23), p. 1-15
    Abstract: Nuclear receptor subfamily 4 group A member 3 (NR4A3) protects the vascular endothelial cell (VEC) against hypoxia stress, whose expression is primarily reported to be governed at a transcriptional level. However, the regulation of NR4A3 in the protein level is largely unknown. Here, we report that NR4A3 protein abundance is decreased immensely in VEC injury induced by reoxygenation after oxygen-glucose deprivation (OGD-R), which is significantly blocked by the administration of the antioxidative steroid TRIOL. Moreover, the notable improvement of NR4A3 and the alleviation of pulmonary endothelial barrier hyperpermeability induced by acute hypobaric hypoxia in cynomolgus monkeys are also observed after TRIOL administration. The overproduction of reactive oxygen species (ROS) decreases NR4A3 protein abundance in VEC under OGD-R condition, which is reversed by TRIOL and N-acetylcysteine (NAC). TRIOL dose-dependently increases the NR4A3 protein level by inhibiting ubiquitination and ubiquitin proteasome system- (UPS-) mediated degradation rather than promoting its transcription. Using yeast two-hybrid screening, we further identify the interaction between NR4A3 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and the DNA-binding domain of NR4A3 is required for this interaction. Knockdown of SMARCB1 reduces ubiquitination and degradation of NR4A3, suggesting the proubiquitylation effect of this interaction which is enhanced by ROS in VEC injury induced by OGD-R. In summary, our study here for the first time reveals a posttranslational regulation in SMARCB1-mediated NR4A3 protein degradation which is driven by ROS, providing further understanding of the impaired regulation of NR4A3-mediated prosurvival pathways under pathological condition in VEC.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2455981-7
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  • 3
    In: Journal of Neuroinflammation, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2022-12-28)
    Abstract: Dysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown. Methods Middle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS). Results Here, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization. Conclusions Taken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic.
    Type of Medium: Online Resource
    ISSN: 1742-2094
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2156455-3
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  • 4
    Online Resource
    Online Resource
    Institute of Electrical and Electronics Engineers (IEEE) ; 2018
    In:  IEEE Transactions on Dependable and Secure Computing Vol. 15, No. 6 ( 2018-11-1), p. 1016-1026
    In: IEEE Transactions on Dependable and Secure Computing, Institute of Electrical and Electronics Engineers (IEEE), Vol. 15, No. 6 ( 2018-11-1), p. 1016-1026
    Type of Medium: Online Resource
    ISSN: 1545-5971 , 1941-0018 , 2160-9209
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2018
    detail.hit.zdb_id: 2162420-3
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  • 5
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-5-20)
    Abstract: Retinal ischemia is a common pathological event that can result in retinal ganglion cell (RGC) death and irreversible vision loss. The pathogenic mechanisms linking retinal ischemia to RGC loss and visual deficits are uncertain, which has greatly hampered the development of effective treatments. It is increasingly recognized that pyroptosis of microglia contributes to the indirect inflammatory death of RGCs. In this study, we report a regulatory NOD-like receptor, NOD-, LRR- and CARD-containing 5 (NLRC5), as a key regulator on microglial pyroptosis and the retinal ischemia process. Through an in-depth analysis of our recently published transcriptome data, we found that NLRC5 was significantly up-regulated in retina during ischemia–reperfusion injury, which were further confirmed by subsequent detection of mRNA and protein level. We further found that NLRC5 was upregulated in retinal microglia during ischemia, while NLRC5 knockdown significantly ameliorated retinal ischemic damage and RGC death. Mechanistically, we revealed that knockdown of NLRC5 markedly suppressed gasdermin D (GSDMD) cleavage and activation of interleukin-1β (IL-1β) and caspase-3, indicating that NLRC5 promotes both microglial pyroptosis and apoptosis. Notably, we found that NLRC5 directly bound to NLRP3 and NLRC4 in inflammasomes to cooperatively drive microglial pyroptosis and apoptosis mediating retinal ischemic damage. Overall, these findings reveal a previously unidentified key contribution of NLRC5 signaling to microglial pyroptosis under ischemia or hypoxia conditions. This NLRC5-dependent pathway may be a novel therapeutic target for treatment of ischemic retinopathy.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  Sensors Vol. 18, No. 10 ( 2018-09-21), p. 3193-
    In: Sensors, MDPI AG, Vol. 18, No. 10 ( 2018-09-21), p. 3193-
    Abstract: Multitarget tracking algorithms based on sonar usually run into detection uncertainty, complex channel and more clutters, which cause lower detection probability, single sonar sensors failing to measure when the target is in an acoustic shadow zone, and computational bottlenecks. This paper proposes a novel tracking algorithm based on multisensor data fusion to solve the above problems. Firstly, under more clutters and lower detection probability condition, a Gaussian Mixture Probability Hypothesis Density (GMPHD) filter with computational advantages was used to get local estimations. Secondly, this paper provided a maximum-detection capability multitarget track fusion algorithm to deal with the problems caused by low detection probability and the target being in acoustic shadow zones. Lastly, a novel feedback algorithm was proposed to improve the GMPHD filter tracking performance, which fed the global estimations as a random finite set (RFS). In the end, the statistical characteristics of OSPA were used as evaluation criteria in Monte Carlo simulations, which showed this algorithm’s performance against those sonar tracking problems. When the detection probability is 0.7, compared with the GMPHD filter, the OSPA mean of two sensor and three sensor fusion was decrease almost by 40% and 55%, respectively. Moreover, this algorithm successfully tracks targets in acoustic shadow zones.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2052857-7
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  • 7
    In: Marine Drugs, MDPI AG, Vol. 17, No. 5 ( 2019-05-05), p. 267-
    Abstract: High intraocular pressure (IOP)-induced retinal ischemia leads to acute glaucoma, which is one of the leading causes of irreversible visual-field loss, characterized by loss of retinal ganglion cells (RGCs) and axonal injury in optic nerves (ONs). Oxidative stress and the inflammatory response play an important role in the ischemic injury of retinal and optic nerves. We focus on 5α-androst-3β, 5α, 6β-triol (TRIOL), a synthetic neuroactive derivative of natural marine steroids 24-methylene-cholest-3β, 5α, 6β, 19-tetrol and cholestane-3β, 5α, 6β-triol, which are two neuroactive polyhydroxysterols isolated from the soft coral Nephthea brassica and the gorgonian Menella kanisa, respectively. We previously demonstrated that TRIOL was a neuroprotective steroid with anti-inflammatory and antioxidative activities. However, the potential role of TRIOL on acute glaucoma and its underlying mechanisms remains unclear. Here, we report TRIOL as a promising neuroprotectant that can protect RGCs and their axons/dendrites from ischemic–reperfusion (I/R) injury in an acute intraocular hypertension (AIH) model. Intravitreal injection of TRIOL significantly alleviated the loss of RGCs and the damage of axons and dendrites in rats and mice with acute glaucoma. As NF-E2-related factor 2 (Nrf2) is one of the most critical regulators in oxidative and inflammatory injury, we further evaluated the effect of TRIOL on Nrf2 knockout mice, and the neuroprotective role of TRIOL on retinal ischemia was not observed in Nrf2 knockout mice, indicating that activation of Nrf2 is responsible for the neuroprotection of TRIOL. Further experiments demonstrated that TRIOL can activate and upregulate Nrf2, along with its downstream hemeoxygenase-1 (HO-1), by negative regulation of Kelch-like ECH (Enoyl-CoA Hydratase) associated Protein-1 (Keap1). In conclusion, our study shed new light on the neuroprotective therapy of retinal ischemia and proposed a promising marine drug candidate, TRIOL, for the therapeutics of acute glaucoma.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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  • 8
    In: Biomaterials Science, Royal Society of Chemistry (RSC), Vol. 10, No. 5 ( 2022), p. 1373-1383
    Abstract: Bacterial induced wound infection is very common in real life, but the abuse of antibiotics means that is poses a potential threat to human health. The development of non-antibiotic type antibacterial materials appears to be of importance. Herein, a microenvironment-responsive and biodegradable hydrogel complex, consisting of an acid-degradable antibacterial hydrogel and a hydrogen peroxide (H 2 O 2 )-responsive polymer/gold hybrid film with photothermal conversion ability was constructed based on polyethylenimine (PEI), polyethylene glycol (PEG), hexachlorocyclic triphosphonitrile (HCCP), and gold nanoparticles. The resultant hydrogel showed excellent adhesion to various surfaces, whether in air or underwater. However, a simple glycerine and water (v/v = 1/1) mixed solution could rapidly promote the detachment of the hydrogel from skin automatically, without any external force and no residue was left, exhibiting a manmade controllable flexible feature. Moreover, the in vitro antibacterial performance against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus ( S. aureus ), as well as wound healing investigations conducted in living mice confirmed that these hydrogels possessed excellent antibacterial, antioxidative, and wound healing abilities. We believe this proof of concept could create a novel pathway for the design and construction of highly efficient hydrogel dressings using readily available polymeric materials and that the resulting dressing have potential for clinical applications.
    Type of Medium: Online Resource
    ISSN: 2047-4830 , 2047-4849
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2022
    detail.hit.zdb_id: 2693928-9
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  • 9
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2016
    In:  Journal of the Acoustical Society of America Vol. 140, No. 4_Supplement ( 2016-10-01), p. 3231-3231
    In: Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 140, No. 4_Supplement ( 2016-10-01), p. 3231-3231
    Abstract: A kind of underwater communication receiver combined with Vector Time-Reversal algorithm and multichannel decision feedback equalizer (VTR-MDFE) is studied, which can address the problem of inter-symbol interference and waveform distortion, resulting from time-varying multipath channel. Impacts of environmental noise can be suppressed by use of vector sensor’s combined directivity and Corresponding vector signal processing technology. Meanwhile, error rate is reduced while system capacity is enhanced by time-reversal algorithm’s anti-multipath ability. The performance of VTR-MDFE are proved by simulated results in the communication channel provided by a ray-based acoustic model, for different ocean conditions and source-receiver geometries.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2016
    detail.hit.zdb_id: 1461063-2
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  • 10
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2017
    In:  The Journal of the Acoustical Society of America Vol. 142, No. 4_Supplement ( 2017-10-01), p. 2586-2587
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 142, No. 4_Supplement ( 2017-10-01), p. 2586-2587
    Abstract: In the field of multistatic remote detection for underwater target, as a time-variant and multi-path channel interfered by environmental noise, complex underwater acoustic environment limits the spatial share of channel and poses a great challenge against spatial-division-multiplexing (SDM) in multistatic detection. In this paper, a kind of method of spatial-division-multiplexing(SDM) based on vector adaptive time-reversal technique is proposed. By use of time-reversal technique, multi-path structure of channel is efficiently restrained; Meanwhile, with adaptive filtering applied, time-variant characteristic of channel is effectively suppressed. Moreover, with single vector hydrophone, spatial focus of target echoes and noise interference suppression is accomplished by spatial filtering. Finally, excellent results are performed in SDM of multistatic detection, supported by the experimental simulation.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2017
    detail.hit.zdb_id: 1461063-2
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