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  • 1
    Online Resource
    Online Resource
    DataSheet1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 12 ( 2022-3-1)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2022-3-1)
    Abstract: Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.777395
    DOI: 10.3389/fphar.2021.777395.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-4)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein–protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.868724
    DOI: 10.3389/fimmu.2022.868724.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    The ATP-P2X7 Signaling Axis Is an Essential Sentinel for Intracellular Clostridium difficile Pathogen-Induced Inflammasome Activation
    Frontiers Media SA ; 2018
    In:  Frontiers in Cellular and Infection Microbiology Vol. 8 ( 2018-3-16)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 8 ( 2018-3-16)
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2018.00084
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2619676-1
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  • 4
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    Data_Sheet_3.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Public Health Vol. 9 ( 2021-12-10)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 9 ( 2021-12-10)
    Abstract: Background: Along with individual-level factors, vaccination-related characteristics are important in understanding COVID-19 vaccine hesitancy. This study aimed to determine the influence of these characteristics on vaccine acceptance to formulate promotion strategies after considering differences among respondents with different characteristics. Methods: An online discrete choice experiment was conducted among people aged 18–64 years in Hong Kong, China, from 26 to 28 February 2021. Respondents were asked to make choices regarding hypothetical vaccination programmes described by vaccination-related characteristics—the attributes derived from a prior individual interview. Subgroup analysis was performed to identify the differences in vaccination-related characteristics among respondents with different personal characteristics. Results: A total of 1,773 respondents provided valid responses. The vaccine efficacy and brand were the most important factors affecting acceptance, followed by the exemption of quarantine for vaccinated travelers, safety, venue for vaccination, vaccine uptake of people in their lives, and recommendations by general physicians or government. Frequent exposure to vaccination information on social media has been associated with increasing vaccine refusal. Substantial preference heterogeneity for the attributes was found among people of different ages, incomes, chronic conditions, and previous acceptance of influenza vaccines. Conclusion: The findings provided evidence to formulate interventions to promote vaccine uptake, including the provision of vaccination at housing estate or workplaces, involvement of general physicians and interpersonal communication in vaccine promotion and information dissemination, and exemption of quarantine for vaccinated people. Moreover, social media is a significant information channel that cannot be neglected in the dissemination of official information.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fpubh.2021.793533
    DOI: 10.3389/fpubh.2021.793533.s001
    DOI: 10.3389/fpubh.2021.793533.s002
    DOI: 10.3389/fpubh.2021.793533.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2711781-9
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  • 5
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    Online Resource
    Differentiation Between Malignant and Benign Pulmonary Nodules by Using Automated Three-Dimensional High-Resolution Representation Learning With Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-3-18)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-18)
    Abstract: The investigation of incidental pulmonary nodules has rapidly become one of the main indications for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), currently combined with computed tomography (PET-CT). There is also a growing trend to use artificial Intelligence for optimization and interpretation of PET-CT Images. Therefore, we proposed a novel deep learning model that aided in the automatic differentiation between malignant and benign pulmonary nodules on FDG PET-CT. Methods In total, 112 participants with pulmonary nodules who underwent FDG PET-CT before surgery were enrolled retrospectively. We designed a novel deep learning three-dimensional (3D) high-resolution representation learning (HRRL) model for the automated classification of pulmonary nodules based on FDG PET-CT images without manual annotation by experts. For the images to be localized more precisely, we defined the territories of the lungs through a novel artificial intelligence-driven image-processing algorithm, instead of the conventional segmentation method, without the aid of an expert; this algorithm is based on deep HRRL, which is used to perform high-resolution classification. In addition, the 2D model was converted to a 3D model. Results All pulmonary lesions were confirmed through pathological studies (79 malignant and 33 benign). We evaluated its diagnostic performance in the differentiation of malignant and benign nodules. The area under the receiver operating characteristic curve (AUC) of the deep learning model was used to indicate classification performance in an evaluation using fivefold cross-validation. The nodule-based prediction performance of the model had an AUC, sensitivity, specificity, and accuracy of 78.1, 89.9, 54.5, and 79.4%, respectively. Conclusion Our results suggest that a deep learning algorithm using HRRL without manual annotation from experts might aid in the classification of pulmonary nodules discovered through clinical FDG PET-CT images.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.773041
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 6
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    Corrigendum: The ATP-P2X7 Signaling Axis Is an Essential Sentinel for Intracellular Clostridium difficile Pathogen-Induced Inflammasome Activation
    Frontiers Media SA ; 2019
    In:  Frontiers in Cellular and Infection Microbiology Vol. 9 ( 2019-7-17)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 9 ( 2019-7-17)
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2019.00260
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2619676-1
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  • 7
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    Table_5.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Public Health Vol. 10 ( 2022-7-14)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-7-14)
    Abstract: Zero-time Exercise (ZTEx), a simple strength- and stamina-enhancing physical activity (PA) requiring no extra equipment, can potentially increase PA and fitness. This pilot trial examined the feasibility and potential effectiveness of a smartphone ZTEx intervention to promote PA and fitness in patients with coronary heart disease (CHD). Methods A parallel-group assessor-blinded pilot randomized controlled trial was conducted on Chinese patients with stable coronary heart disease (CHD) in three cardiology clinics. The experimental group received a 15-min brief individual face-to-face session and a 12-week ZTEx instant messaging with 28 picture e-messages and a smartphone ZTEx application (ZTExApp). The control group received the same duration of individual session and number and format of e-messages, but the content was healthy eating and breathing exercise. The feasibility was assessed based on: attrition rate, usage, response rate and perception of the intervention. The outcome evaluation included primary outcome (PA), fitness, exercise self-efficacy and intention, perceived happiness and health, and quality of life. A linear mixed model was used with intention-to-treat analysis adjusting for sex, age and baseline values. A semi-structured interview was conducted to collect feedback from the experiment group. Results One hundred thirty-nine patients (mean age 59.8 ± 6.6; 71.2% male) were randomized to the experimental group ( n = 70) or control group ( n = 69), and 80% (56/70) and 82% (57/69) of patients completed the 12-week follow-up assessment, respectively. The attrition rate was 18.7%. The experimental group reported that ZTEx was feasible to integrate PA into their daily life and appreciated the picture e-messages, and 95% of them sent feedback to us, but only 19.6% (13/70) of the participants entered their PA information into the e-diary of the ZTExApp. The experimental group had a significantly greater increase in time spent walking [mean difference (95% CI): 155.3 (10.1, 300.4), P = 0.04, Cohen's d = 0.34] than the control group. Conclusions This pilot study showed using a brief ZTEx face-to-face session with picture e-messages empowered patients with CHD to integrate PA into daily life. Future definitive trials with a longer follow-up and a more user-friendly ZTExApp interface are necessary to determine the effectiveness of the smartphone ZTEx intervention in enhancing PA and related outcomes. Trial Registration The research protocol was registered at the Hong Kong University Clinical Trials Registry (HKUCTR) on 22 Jul 2016 (Study identifier: HKUCTR-2165) and was also retrospectively registered at the National Institutes of Health (identifier number: NCT03464331) on 14 March 2018.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fpubh.2022.865712
    DOI: 10.3389/fpubh.2022.865712.s001
    DOI: 10.3389/fpubh.2022.865712.s002
    DOI: 10.3389/fpubh.2022.865712.s003
    DOI: 10.3389/fpubh.2022.865712.s004
    DOI: 10.3389/fpubh.2022.865712.s005
    DOI: 10.3389/fpubh.2022.865712.s006
    DOI: 10.3389/fpubh.2022.865712.s007
    DOI: 10.3389/fpubh.2022.865712.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 8
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    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-2-25)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-2-25)
    Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%–2% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response via their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-κB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation via decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.591706
    DOI: 10.3389/fimmu.2021.591706.s001
    DOI: 10.3389/fimmu.2021.591706.s002
    DOI: 10.3389/fimmu.2021.591706.s003
    DOI: 10.3389/fimmu.2021.591706.s004
    DOI: 10.3389/fimmu.2021.591706.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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