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  • Oxford University Press (OUP)  (66)
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  • Oxford University Press (OUP)  (66)
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  • 1
    In: Stem Cells, Oxford University Press (OUP), ( 2023-09-02)
    Abstract: Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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    detail.hit.zdb_id: 1143556-2
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  • 2
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 15, No. 7 ( 2021-07-05), p. 1161-1173
    Abstract: Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30] . The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC]  = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of & gt; 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000] . Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 3
    In: The Plant Cell, Oxford University Press (OUP), Vol. 35, No. 10 ( 2023-09-27), p. 3782-3808
    Abstract: Plant genomes encode many receptor-like kinases (RLKs) that localize to the cell surface and perceive a wide variety of environmental cues to initiate downstream signaling cascades. Whether these RLKs participate in dehydration stress signaling in plants is largely unknown. DROOPY LEAF1 (DPY1), a leucine-rich repeat (LRR)-RLK, was recently shown to regulate plant architecture by orchestrating early brassinosteroid signaling in foxtail millet (Setaria italica). Here, we show that DPY1 is essential for the acclimation of foxtail millet to drought stress. DPY1 can be phosphorylated and activated in response to osmotic stress and is required for more than half of osmotic stress–induced global phosphorylation events, including the phosphorylation of sucrose nonfermenting kinase 2s (SnRK2s), the central kinases involved in osmotic stress. DPY1 acts upstream of STRESS-ACTIVATED PROTEIN KINASE 6 (SAPK6, a subclass I SnRK2) and is required for full SAPK6 activation, thereby allowing regulation of downstream genes to mount a response against drought stress. These signaling events are largely independent of DPY1-mediated brassinosteroid signaling. The DPY1-SAPK6 module is specific to seed plants and is absent in ancestral nonseed plants. Our findings reveal a dehydration stress–activated RLK that plays an indispensable role in osmotic stress signaling and mediates SnRK2 activation at the cell surface.
    Type of Medium: Online Resource
    ISSN: 1040-4651 , 1532-298X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
    In: European Heart Journal, Oxford University Press (OUP), Vol. 44, No. 29 ( 2023-08-01), p. 2730-2742
    Abstract: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction–mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC–A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. Methods and results The expression of LEC–A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)–induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell–specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (−19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation–mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. Conclusion The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 5
    In: Sleep, Oxford University Press (OUP), Vol. 45, No. 12 ( 2022-12-12)
    Abstract: The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep–wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep–wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii152-ii152
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii152-ii152
    Abstract: A new imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons remove tumor mass completely. Transferrin receptors (TfR 1) have been widely investigated as a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT) can accumulate at high levels in GBM tissues. In our study, taking the advantage of CRT, we synthesized two molecular imaging probes for imaging GBM precisely. One is a PET/CT probe 18F-NOTA-CRT, and the other is a near-infrared fluorescent (NIFR) probe Cy5-CRT. METHODS We initially confirmed the overexpression of TfR 1 in most of GBM and the tumor-specific homing ability of 18F-NOTA-CRT and Cy5-CRT in orthotopic U87 GBM (TfR 1 overexpression) mouse models. We then examined the feasibility of Cy5-CRT for specially identifying the GBM tissue margin in the intracranial U87 xenografts in vivo and ex vivo. Next, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins. Finally, we used Cy5-CRT to carry out a fluorescence-guided operation on a orthotopic U87 mouse model. RESULTS Both 18F-NOTA-CRT and Cy5-CRT probes specifically accumulated in U87 GBM xenografts with TfR 1 overexpression, but not in U373 GBM xenografts with very low TfR 1 expression. Cy5-CRT detected the intracranial tumor burden with exceptional contrast, enabling fluorescence-guided GBM resection under NIFR live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium. CONCLUSIONS Our probes were capable of thoroughly detecting GBM tissue in vivo imaging. For translational applications, we may screen patients before surgery by PET/CT imaging with 18F-NOTA-CRT to identify gliomas with TfR 1 overexpression. As for fluorescence-guided surgery, the TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM. Keywords: Transferrin receptor 1; PET/CT; near-infrared fluorescence imaging; glioblastoma, fluorescence-guided surgery
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 7
    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
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 8
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 112, No. 2 ( 2020-02-01), p. 145-153
    Abstract: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 9
    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
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 10
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 65, No. 4 ( 2017-08-15), p. 588-594
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2002229-3
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