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  • Oxford University Press (OUP)  (236)
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  • Oxford University Press (OUP)  (236)
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  • 1
    Online Resource
    Online Resource
    Chronic Blockade of NMDAR Subunit 2A in the Hypothalamic Paraventricular Nucleus Alleviates Hypertension Through Suppression of MEK/ERK/CREB Pathway
    Oxford University Press (OUP) ; 2021
    In:  American Journal of Hypertension Vol. 34, No. 8 ( 2021-08-09), p. 840-850
    Details
    In: American Journal of Hypertension, Oxford University Press (OUP), Vol. 34, No. 8 ( 2021-08-09), p. 840-850
    Abstract: N-Methyl-d-aspartate receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) plays critical roles in regulating sympathetic outflow. Studies showed that acute application of the antagonists of NMDAR or its subunits would reduce sympathetic nerve discharges. However, little is known about the effect of long-term management of NMDAR in hypertensive animals. METHODS PEAQX, the specific antagonist of NMDAR subunit 2A (GluN2A) was injected into both sides of the PVN of two-kidney, one-clip (2K1C) renal hypertensive rats and control (normotensive rats) for 3 weeks. RESULTS Three weeks of PEAQX infusion significantly reduced the blood pressure of the 2K1C rats. It managed to resume the balance between excitatory and inhibitory neural transmitters, reduce the level of proinflammatory cytokines and reactive oxygen species in the PVN, and reduce the level of norepinephrine in plasma of the 2K1C rats. PEAQX administration also largely reduced the transcription and translation levels of GluN2A and changed the expression levels of NMDAR subunits 1 and 2B (GluN1 and GluN2B). In addition, NMDAR was known to function through activating the extracellular regulated protein kinases (ERK) or phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways. In our study, we found that in the PVN of 2K1C rats treated with PEAQX, the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), ERK1/2, and cAMP-response element-binding protein (CREB) significantly reduced, while the phosphorylation level of PI3K did not change significantly. CONCLUSIONS Chronic blockade of GluN2A alleviates hypertension through suppression of MEK/ERK/CREB pathway.
    Type of Medium: Online Resource
    ISSN: 0895-7061 , 1941-7225
    URL: Article
    DOI: 10.1093/ajh/hpab047
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1479505-X
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  • 2
    Online Resource
    Online Resource
    A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223
    Oxford University Press (OUP) ; 2016
    In:  European Heart Journal Vol. 37, No. 33 ( 2016-09-01), p. 2602-2611
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 37, No. 33 ( 2016-09-01), p. 2602-2611
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/eurheartj/ehv713
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2001908-7
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  • 3
    Online Resource
    Online Resource
    IMB-BZ as an Inhibitor Targeting ESX-1 Secretion System to Control Mycobacterial Infection
    Oxford University Press (OUP) ; 2022
    In:  The Journal of Infectious Diseases Vol. 225, No. 4 ( 2022-02-15), p. 608-616
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 225, No. 4 ( 2022-02-15), p. 608-616
    Abstract: Resistance to anti-tuberculosis (TB) drugs is a major issue in TB control, and demands the discovery of new drugs targeting the virulence factor ESX-1. Methods We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacteria and reducing bacterial virulence. We further investigated the probability of inducing drug resistance and the underlying mechanism using mycobacterial protein fragment complementation. Results A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1–dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10–EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drugs, and exhibit high potency against chronic mycobacterial infection. Conclusions Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiab486
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1473843-0
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  • 4
    Online Resource
    Online Resource
    Acidic open-cage solution containing basic cage-confined nanospaces for multipurpose catalysis
    Oxford University Press (OUP) ; 2022
    In:  National Science Review Vol. 9, No. 5 ( 2022-05-30)
    Details
    In: National Science Review, Oxford University Press (OUP), Vol. 9, No. 5 ( 2022-05-30)
    Abstract: The nanoscale chemical spaces inherent in porous organic/coordination cages or solid/liquid materials have been continuously explored for their nanoconfinement effect on selective adsorption and reaction of small gas or organic molecules. Herein, we aim to rationalize the unconventional chemical reactivities motivated by the cage-confined nanospaces in aqueous solutions, where the robust yet permeable nanospaces defined by the open cages facilitate dynamic guest exchange and unusual chemical reactions. The high positive charges on [(Pd/Pt)6(RuL3)8]28+ nanocages drive imidazole–proton equilibrium to display a significantly perturbed pKa shift, creating cage-defined nanospaces in solution with distinct intrinsic basicity and extrinsic acidity. The supramolecular cage effect plays pivotal roles in elaborating robust solution nanospaces, controlling ingress-and-egress molecular processes through open-cage portals and endowing nanocages with transition-state stabilization, amphoteric reactivities and the phase transfer of insoluble molecules, thus promoting chemical transformations in unconventional ways. Consequently, a wide range of application of cage-confined catalysis with anomalous reactivities may be expected based on this kind of open-cage solution medium, which combines cage nanocavity, solution heterogeneity and liquid-phase fluidity to benefit various potential mass transfer and molecular process options.
    Type of Medium: Online Resource
    ISSN: 2095-5138 , 2053-714X
    URL: Article
    DOI: 10.1093/nsr/nwab155
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2745465-4
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  • 5
    Online Resource
    Online Resource
    Excess palmitate induces decidual stromal cell apoptosis via the TLR4/JNK/NF-kB pathways and possibly through glutamine oxidation
    Oxford University Press (OUP) ; 2020
    In:  Molecular Human Reproduction Vol. 26, No. 2 ( 2020-02-29), p. 88-100
    Details
    In: Molecular Human Reproduction, Oxford University Press (OUP), Vol. 26, No. 2 ( 2020-02-29), p. 88-100
    Abstract: During gestation, excess palmitate (PA) is enriched in decidua. Both excess PA and decidual dysfunctions are associated with numerous adverse pregnancy outcomes such as gestational diabetes, preeclampsia and preterm birth and intrauterine growth restriction. Here, mRNA data about the effects of PA were collected from multiple databases and analyzed. Human decidual tissues were obtained from clinically normal pregnancies, terminated for non-medical reasons, during the first trimester, and decidual stromal cells (DSCs) were isolated and exposed to PA, alone or together with the inhibitors of Toll-like receptor 4 (TLR4), Jun N-terminal kinase (JNK), nuclear factor-kappa-gene binding (NF-kB) or glutamine (GLN) oxidation. Furthermore, DSCs were transfected with lentiviral particles overexpressing human TLR4. We demonstrate that excess PA interacting with its receptor TLR4 disturbs DSC hemostasis during the first trimester. Specifically, high PA signal induced DSC apoptosis and formed an inflammatory program (elevated interleukin-1 beta and decreased interleukin-10) via the activation of TLR4/JNK/NF-kB pathways. A complexed cross-talk was found between TLR4/JNK/NF-kB signals and PA deposition in DSCs. Besides, under an excess PA environment, GLN oxidation was significantly enhanced in DSCs and the suppression of GLN oxidation further augmented PA-mediated DSC apoptosis and inflammatory responses. In conclusion, excess PA induces apoptosis and inflammation in DSCs via the TLR4/JNK/NF-kB pathways, which can be augmented by the suppression of GLN oxidation.
    Type of Medium: Online Resource
    ISSN: 1460-2407
    URL: Article
    DOI: 10.1093/molehr/gaaa004
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1497467-8
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  • 6
    Online Resource
    Online Resource
    Type 1 active galactic nucleus fraction in the SDSS/FIRST survey : Type 1 AGN fraction in SDSS/FIRST
    Oxford University Press (OUP) ; 2010
    In:  Monthly Notices of the Royal Astronomical Society ( 2010-04), p. no-no
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), ( 2010-04), p. no-no
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1111/j.1365-2966.2010.16434.x
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 7
    Online Resource
    Online Resource
    The 2009 outburst from the new X-ray transient and black-hole candidate XTE J1652-453 : 2009 outburst from XTE J1652-453
    Oxford University Press (OUP) ; 2011
    In:  Monthly Notices of the Royal Astronomical Society Vol. 413, No. 2 ( 2011-05-11), p. 1072-1078
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 413, No. 2 ( 2011-05-11), p. 1072-1078
    Type of Medium: Online Resource
    ISSN: 0035-8711
    URL: Issue
    URL: Article
    DOI: 10.1111/mnr.2011.413.issue-2
    DOI: 10.1111/j.1365-2966.2011.18197.x
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 8
    Online Resource
    Online Resource
    Prospective observational cohort study on grading the severity of postoperative complications in global surgery research
    Oxford University Press (OUP) ; 2019
    In:  British Journal of Surgery Vol. 106, No. 2 ( 2019-01-08), p. e73-e80
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 106, No. 2 ( 2019-01-08), p. e73-e80
    Abstract: The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1002/bjs.11025
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2006309-X
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  • 9
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    Online Resource
    The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder
    Oxford University Press (OUP) ; 2022
    In:  Psychoradiology Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Details
    In: Psychoradiology, Oxford University Press (OUP), Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Abstract: Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.
    Type of Medium: Online Resource
    ISSN: 2634-4416
    URL: Article
    DOI: 10.1093/psyrad/kkac005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3076092-6
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  • 10
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    Large expert-curated database for benchmarking document similarity detection in biomedical literature search
    Oxford University Press (OUP) ; 2019
    In:  Database Vol. 2019 ( 2019-01-01)
    Details
    In: Database, Oxford University Press (OUP), Vol. 2019 ( 2019-01-01)
    Abstract: Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
    Type of Medium: Online Resource
    ISSN: 1758-0463
    URL: Article
    DOI: 10.1093/database/baz085
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2496706-3
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