Publications by authors named "Yujia Zhou"

49 Publications

Selective laser trabeculoplasty in steroid-induced and uveitic glaucoma.

Can J Ophthalmol 2021 Jun 10. Epub 2021 Jun 10.

Department of Ophthalmology, Mayo Clinic, Rochester, Minn.. Electronic address:

Objective: To compare primary selective laser trabeculoplasty (SLT) response in uveitic, steroid-induced, primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX).

Design: Single-centre retrospective case-control study.

Participants: Patients with uveitic glaucoma, steroid-induced glaucoma, POAG, or PEX who had their first SLT.

Methods: Eyes with POAG or PEX were in control groups. Eyes with steroid-induced or uveitic glaucoma were in experimental groups. Change in intraocular pressure from baseline, treatment failure, complication rates, and medication use were compared using rank-sum and log-rank tests.

Results: Six-hundred and eight eyes of 433 patients were enrolled. Steroid-induced glaucoma eyes had higher mean baseline pressure and a decrease in pressure at 3-8 weeks (27.6-17.4 mm Hg) than those with PEX (21.7-16.5 mm Hg; p < 0.001) or POAG (18.6-14.9 mm Hg; p ≤ 0.025). Failure rates after 2 years were lower in steroid-induced glaucoma (54%) than in PEX (84%; p = 0.01) or POAG (84%; p = 0.005). This survival benefit persisted when excluding patients with changes to their steroid dosing (p ≤ 0.03) but showed mixed results when compared with patients with a baseline pressure of 25mm Hg or greater (p = 0.020 vs PEX; p = 0.67 vs POAG). At 18 months, the steroid-induced group decreased ocular hypotensive medication use (3.5-1.9; p = 0.005); the uveitic group increased medication use (2.7-3.5; p = 0.02).

Conclusions: SLT is an effective treatment for steroid-induced glaucoma, with greater response and a lower failure rate than in PEX and primary POAG, although high baseline intraocular pressure may be a confounder. Judicious use of SLT can be considered in uveitic glaucoma.
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http://dx.doi.org/10.1016/j.jcjo.2021.05.006DOI Listing
June 2021

Normalizing Clinical Document Titles to LOINC Document Ontology: an Initial Study.

AMIA Annu Symp Proc 2020 25;2020:1441-1450. Epub 2021 Jan 25.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.

The normalization of clinical documents is essential for health information management with the enormous amount of clinical documentation generated each year. The LOINC Document Ontology (DO) is a universal clinical document standard in a hierarchical structure. The objective of this study is to investigate the feasibility and generalizability of LOINC DO by mapping from clinical note titles across five institutions to five DO axes. We first developed an annotation framework based on the definition of LOINC DO axes and manually mapped 4,000 titles. Then we introduced a pre-trained deep learning model named Bidirectional Encoder Representations from Transformers (BERT) to enable automatic mapping from titles to LOINC DO axes. The results showed that the BERT-based automatic mapping achieved improved performance compared with the baseline model. By analyzing both manual annotations and predicted results, ambiguities in LOINC DO axes definition were discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075502PMC
January 2021

Dendrobium officinale polysaccharide triggers mitochondrial disorder to induce colon cancer cell death via ROS-AMPK-autophagy pathway.

Carbohydr Polym 2021 Jul 2;264:118018. Epub 2021 Apr 2.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, Jiangxi, 330047, China. Electronic address:

The homeostasis between mitochondrial function and autophagy is crucial to the physiological activity of cancer cells, and its mechanism is conducive to the development of anti-tumor drugs. Here, we aimed to explore the effect and mechanism of Dendrobium officinale polysaccharide (DOP) on colon cancer cell line CT26. Our data showed that DOP significantly inhibited the proliferation of CT26 cells and elevated autophagy level. Moreover, DOP disrupted mitochondrial function through increasing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP), thereby impairing ATP biosynthesis, which activated AMPK/mTOR autophagy signaling. Intriguingly, the further experiments demonstrated that DOP-induced cytotoxicity, excessive autophagy and mitochondrial dysfunction were reversed after CT26 cells pretreated with antioxidant (N-acetyl-l-cysteine). Herein, these findings implied that DOP-induced mitochondrial dysfunction and cytotoxic autophagy repressed the propagation of CT26 cells via ROS-ATP-AMPK signaling, providing a new opinion for the study of antineoplastic drugs.
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http://dx.doi.org/10.1016/j.carbpol.2021.118018DOI Listing
July 2021

Asymmetric Bubble Formation at Rectangular Orifices.

Langmuir 2021 Apr 2;37(14):4302-4307. Epub 2021 Apr 2.

Mechanical Science and Engineering, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, United States.

Bubble formation in liquids is frequently observed in nature and applied in various industrial processes. These include pool and flow boiling for thermal management systems, where bubbles may form asymmetrically at narrow slits and in convective flows. While previous studies have focused on symmetric bubble formation at circular orifices, the dynamics of asymmetric bubble formation remains poorly understood. Here, we experimentally investigate bubble formation at rectangular orifices and examine the effects of the orifice size and aspect ratio and the gas flow rate on the bubble size. The asymmetric bubble shape evolution at the rectangular orifice is analyzed, and we find that the size of the bubble neck is controlled either by the orifice size or by the capillary length. Based on these findings, we develop a static force balance model to predict the bubble size in the quasi-static regime, where the roles of Bond number and aspect ratio are identified. The bubble size evolution in the dynamic regime is further understood by introducing a Weber number that evaluates the effect of the virtual mass force induced by gas flow. Our study provides physical understanding of the dynamics of asymmetric bubble formation and guidance to predict the bubble size at asymmetric orifices.
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http://dx.doi.org/10.1021/acs.langmuir.1c00287DOI Listing
April 2021

COVID-19 SignSym: a fast adaptation of a general clinical NLP tool to identify and normalize COVID-19 signs and symptoms to OMOP common data model.

J Am Med Inform Assoc 2021 06;28(6):1275-1283

Melax Technologies, Inc, Houston, Texas, USA.

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 SignSym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.
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http://dx.doi.org/10.1093/jamia/ocab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989301PMC
June 2021

Short term visual and structural outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment delay during the first COVID-19 wave: A pilot study.

PLoS One 2021 17;16(2):e0247161. Epub 2021 Feb 17.

Department of Ophthalmology and Visual Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States of America.

Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The 'COVID-19 lockdown' was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247161PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888661PMC
March 2021

Whole-brain functional MRI registration based on a semi-supervised deep learning model.

Med Phys 2021 Feb 14. Epub 2021 Feb 14.

School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, China.

Purpose: Traditional registration of functional magnetic resonance images (fMRI) is typically achieved through registering their coregistered structural MRI. However, it cannot achieve accurate performance in that functional units which are not necessarily located relative to anatomical structures. In addition, registration methods based on functional information focus on gray matter (GM) information but ignore the importance of white matter (WM). To overcome the limitations of exiting techniques, in this paper, we aim to register resting-state fMRI (rs-fMRI) based directly on rs-fMRI data and make full use of GM and WM information to improve the registration performance.

Methods: We provide a robust representation of WM functional connectivity features using tissue-specific patch-based functional correlation tensors (ts-PFCTs) as auxiliary information to assist registration. Furthermore, we propose a semi-supervised deep learning model that uses GM and WM information (GM ts-PFCTs and WM ts-PFCTs) during training as a fine tweak to improve registration accuracy when such information is not provided in new test image pairs. We implement our method on the 1000 Functional Connectomes Project dataset. To evaluate our method, a group-level analysis was implemented in resting-state brain functional networks after registration, resulting in t maps.

Results: Our method increases the peak t values of the t maps of default mode network, visual network, central executive network, and sensorimotor network to 21.4, 20.0, 18.4, and 19.0, respectively. Through comparison with traditional methods (FMRIB Software Library(FSL), Statistical Parametric Mapping _ Echo Planar Image(SPM_EPI), and SPM_T1), our method achieves an average improvement of 67.39%, 12.96%, and 25.14%.

Conclusion: We propose a semi-supervised deep learning network by adding GM and WM information as auxiliary information for resting-state fMRI registration. GM and WM information is extracted and described as GM ts-PFCTs and WM ts-PFCTs. Experimental results show that our method achieves superior registration performance.
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http://dx.doi.org/10.1002/mp.14777DOI Listing
February 2021

Causal Discovery in Radiographic Markers of Knee Osteoarthritis and Prediction for Knee Osteoarthritis Severity With Attention-Long Short-Term Memory.

Front Public Health 2020 18;8:604654. Epub 2020 Dec 18.

School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, United States.

The goal of this study is to build a prognostic model to predict the severity of radiographic knee osteoarthritis (KOA) and to identify long-term disease progression risk factors for early intervention and treatment. We designed a long short-term memory (LSTM) model with an attention mechanism to predict Kellgren/Lawrence (KL) grade for knee osteoarthritis patients. The attention scores reveal a time-associated impact of different variables on KL grades. We also employed a fast causal inference (FCI) algorithm to estimate the causal relation of key variables, which will aid in clinical interpretability. Based on the clinical information of current visits, we accurately predicted the KL grade of the patient's next visits with 90% accuracy. We found that joint space narrowing was a major contributor to KOA progression. Furthermore, our causal structure model indicated that knee alignments may lead to joint space narrowing, while symptoms (swelling, grinding, catching, and limited mobility) have little impact on KOA progression. This study evaluated a broad spectrum of potential risk factors from clinical data, questionnaires, and radiographic markers that are rarely considered in previous studies. Using our statistical model, providers are able to predict the risk of the future progression of KOA, which will provide a basis for selecting proper interventions, such as proceeding to joint arthroplasty for patients. Our causal model suggests that knee alignment should be considered in the primary treatment and KOA progression was independent of clinical symptoms.
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http://dx.doi.org/10.3389/fpubh.2020.604654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779681PMC
May 2021

Lysosome-Mediated Cytotoxic Autophagy Contributes to Tea Polysaccharide-Induced Colon Cancer Cell Death via mTOR-TFEB Signaling.

J Agric Food Chem 2021 Jan 28;69(2):686-697. Epub 2020 Dec 28.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, Jiangxi 330047, China.

Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.
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http://dx.doi.org/10.1021/acs.jafc.0c07166DOI Listing
January 2021

Functional Dependency Analysis Identifies Potential Druggable Targets in Acute Myeloid Leukemia.

Cancers (Basel) 2020 Dec 10;12(12). Epub 2020 Dec 10.

Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610-0278, USA.

Refractory disease is a major challenge in treating patients with acute myeloid leukemia (AML). Whereas the armamentarium has expanded in the past few years for treating AML, long-term survival outcomes have yet to be proven. To further expand the arsenal for treating AML, we searched for druggable gene targets in AML by analyzing screening data from a lentiviral-based genome-wide pooled CRISPR-Cas9 library and gene knockout (KO) dependency scores in 15 AML cell lines (HEL, MV411, OCIAML2, THP1, NOMO1, EOL1, KASUMI1, NB4, OCIAML3, MOLM13, TF1, U937, F36P, AML193, P31FUJ). Ninety-four gene KOs met the criteria of (A) specifically essential to AML cell survival, (B) non-essential in non-AML cells, and (C) druggable according to three-dimensional (3D) modeling or ligand-based druggability scoring. Forty-four of 94 gene-KOs (47%) had an already-approved drug match and comprised a drug development list termed "deKO." Fifty of 94 gene-KOs (53%) had no drug in development and comprised a drug discovery list termed "disKO." STRING analysis and gene ontology categorization of the disKO targets preferentially cluster in the metabolic processes of UMP biosynthesis, IMP biosynthesis, dihydrofolate metabolism, pyrimidine nucleobase biosynthesis, vitellogenesis, and regulation of T cell differentiation and hematopoiesis. Results from this study serve as a testable compendium of AML drug targets that, after validation, may be translated into new therapeutics.
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http://dx.doi.org/10.3390/cancers12123710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764352PMC
December 2020

SpineParseNet: Spine Parsing for Volumetric MR Image by a Two-Stage Segmentation Framework With Semantic Image Representation.

IEEE Trans Med Imaging 2021 01 29;40(1):262-273. Epub 2020 Dec 29.

Spine parsing (i.e., multi-class segmentation of vertebrae and intervertebral discs (IVDs)) for volumetric magnetic resonance (MR) image plays a significant role in various spinal disease diagnoses and treatments of spine disorders, yet is still a challenge due to the inter-class similarity and intra-class variation of spine images. Existing fully convolutional network based methods failed to explicitly exploit the dependencies between different spinal structures. In this article, we propose a novel two-stage framework named SpineParseNet to achieve automated spine parsing for volumetric MR images. The SpineParseNet consists of a 3D graph convolutional segmentation network (GCSN) for 3D coarse segmentation and a 2D residual U-Net (ResUNet) for 2D segmentation refinement. In 3D GCSN, region pooling is employed to project the image representation to graph representation, in which each node representation denotes a specific spinal structure. The adjacency matrix of the graph is designed according to the connection of spinal structures. The graph representation is evolved by graph convolutions. Subsequently, the proposed region unpooling module re-projects the evolved graph representation to a semantic image representation, which facilitates the 3D GCSN to generate reliable coarse segmentation. Finally, the 2D ResUNet refines the segmentation. Experiments on T2-weighted volumetric MR images of 215 subjects show that SpineParseNet achieves impressive performance with mean Dice similarity coefficients of 87.32 ± 4.75%, 87.78 ± 4.64%, and 87.49 ± 3.81% for the segmentations of 10 vertebrae, 9 IVDs, and all 19 spinal structures respectively. The proposed method has great potential in clinical spinal disease diagnoses and treatments.
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http://dx.doi.org/10.1109/TMI.2020.3025087DOI Listing
January 2021

Representation of EHR data for predictive modeling: a comparison between UMLS and other terminologies.

J Am Med Inform Assoc 2020 10;27(10):1593-1599

School of Biomedical Informatics University of Texas Health Science Center, Houston, Texas, USA.

Objective: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

Materials And Methods: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, ICD-9, ICD-10, and PheWAS, and evaluated the prediction performances of these terminologies on 2 different tasks: the risk prediction of heart failure in diabetes patients and the risk prediction of pancreatic cancer. Two popular models were evaluated: logistic regression and a recurrent neural network.

Results: For logistic regression, using UMLS delivered the optimal area under the receiver operating characteristics (AUROC) results in both dengue hemorrhagic fever (81.15%) and pancreatic cancer (80.53%) tasks. For recurrent neural network, UMLS worked best for pancreatic cancer prediction (AUROC 82.24%), second only (AUROC 85.55%) to PheWAS (AUROC 85.87%) for dengue hemorrhagic fever prediction.

Discussion/conclusion: In our experiments, terminologies with larger vocabularies and finer-grained representations were associated with better prediction performances. In particular, UMLS is consistently 1 of the best-performing ones. We believe that our work may help to inform better designs of predictive models, although further investigation is warranted.
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http://dx.doi.org/10.1093/jamia/ocaa180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647355PMC
October 2020

Principles of RNA methylation and their implications for biology and medicine.

Biomed Pharmacother 2020 Nov 10;131:110731. Epub 2020 Sep 10.

Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China; The Key Lab of Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Guangdong Medical University, Zhanjiang, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang, China. Electronic address:

RNA methylation is a post-transcriptional level of regulation. At present, more than 150 kinds of RNA modifications have been identified. They are widely distributed in messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), noncoding small RNA (sncRNA) and long-chain non-coding RNA (lncRNA). In recent years, with the discovery of RNA methylation related proteins and the development of high-throughput sequencing technology, the mystery of RNA methylation has been gradually revealed, and its biological function and application value have gradually emerged. In this review, a large number of research results of RNA methylation in recent years are collected. Through systematic summary and refinement, this review introduced RNA methylation modification-related proteins and RNA methylation sequencing technologies, as well as the biological functions of RNA methylation, expressions and applications of RNA methylation-related genes in physiological or pathological states such as cancer, immunity and virus infection, and discussed the potential therapeutic strategies.
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http://dx.doi.org/10.1016/j.biopha.2020.110731DOI Listing
November 2020

Increased Intracranial Pressure Without Hydrocephalus Associated With Spinal Cord Tumor: Literature Review.

J Neuroophthalmol 2021 03;41(1):13-18

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota.

Abstract: Spinal cord tumors (SCTs) may rarely cause increased intracranial pressure without hydrocephalus (IICPWH). A review of the English literature published after 1970 revealed 29 cases of IICPWH secondary to SCT. The following data were acquired: demographics, tumor characteristics, ophthalmic and neurological manifestations, and cerebral spinal fluid (CSF) features. We summarize the existing literature regarding various theories of pathophysiology, spinal imaging recommendations, and treatment modalities used in managing such patients. Patients with papilledema who also have neurological signs or symptoms of myelopathy or elevated CSF protein particularly in the setting of an atypical demographic for pseudotumor cerebri should raise a suspicion for a spinal tumor and prompt further investigation with a spinal MRI.
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http://dx.doi.org/10.1097/WNO.0000000000001026DOI Listing
March 2021

Cyanidin-3-O-β-glucoside inactivates NLRP3 inflammasome and alleviates alcoholic steatohepatitis via SirT1/NF-κB signaling pathway.

Free Radic Biol Med 2020 11 14;160:334-341. Epub 2020 Aug 14.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Alcoholic liver disease (ALD) is a major cause of liver disease worldwide. In patients with ALD, an increased level of hepatic inflammasome components was observed, together with an increased circulating pro-inflammatory cytokines. Cyanidin-3-O-β-glucoside (Cy-3-G) is a bioactive compound belonging to the anthocyanin group, which widely exists in deep-colored fruits and vegetables. Consumption of Cy-3-G is associated with lower risks of non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, atherosclerosis, and inflammation. However, whether Cy-3-G has effects on inflammasome formation and activation thereby protects against alcohol-induced liver damage remain elusive. In this study, we identified that dietary provision of Cy-3-G remarkably attenuated liver damage caused by excess energy intake and alcohol consumption. Supplement with Cy-3-G mediated NAD homeostasis, which stimulated SirT1 activity, resulting in suppressed NF-κB acetylation. Interestingly, Cy-3-G treatment suppressed NF-κB acetylation when SirT1 action was blunted by selective antagonist, and subsequently suppressed NLRP3 inflammasome activation and proinflammatory cytokines release in hepatic cell lines. Our findings first demonstrate that Cy-3-G at a physiologically achievable dosage alleviates alcohol-induced hepatic inflammation via inactivation of NLRP3 inflammasome and deacetylation of NF-κB, suggesting a promising therapeutic approach to alleviate alcohol-induced liver damage.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.006DOI Listing
November 2020

Asthma Exacerbation Prediction and Risk Factor Analysis Based on a Time-Sensitive, Attentive Neural Network: Retrospective Cohort Study.

J Med Internet Res 2020 07 31;22(7):e16981. Epub 2020 Jul 31.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, United States.

Background: Asthma exacerbation is an acute or subacute episode of progressive worsening of asthma symptoms and can have a significant impact on patients' quality of life. However, efficient methods that can help identify personalized risk factors and make early predictions are lacking.

Objective: This study aims to use advanced deep learning models to better predict the risk of asthma exacerbations and to explore potential risk factors involved in progressive asthma.

Methods: We proposed a novel time-sensitive, attentive neural network to predict asthma exacerbation using clinical variables from large electronic health records. The clinical variables were collected from the Cerner Health Facts database between 1992 and 2015, including 31,433 adult patients with asthma. Interpretations on both patient and cohort levels were investigated based on the model parameters.

Results: The proposed model obtained an area under the curve value of 0.7003 through a five-fold cross-validation, which outperformed the baseline methods. The results also demonstrated that the addition of elapsed time embeddings considerably improved the prediction performance. Further analysis observed diverse distributions of contributing factors across patients as well as some possible cohort-level risk factors, which could be found supporting evidence from peer-reviewed literature such as respiratory diseases and esophageal reflux.

Conclusions: The proposed neural network model performed better than previous methods for the prediction of asthma exacerbation. We believe that personalized risk scores and analyses of contributing factors can help clinicians better assess the individual's level of disease progression and afford the opportunity to adjust treatment, prevent exacerbation, and improve outcomes.
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http://dx.doi.org/10.2196/16981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428917PMC
July 2020

Deep Learning Approach for Anterior Cruciate Ligament Lesion Detection: Evaluation of Diagnostic Performance Using Arthroscopy as the Reference Standard.

J Magn Reson Imaging 2020 12 26;52(6):1745-1752. Epub 2020 Jul 26.

Department of Medical Imaging, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

Background: MRI is the most commonly used imaging method for diagnosing anterior cruciate ligament (ACL) injuries. However, the interpretation of knee MRI is time-intensive and depends on the clinical experience of the reader. An automated detection system based on a deep-learning algorithm may improve interpretation time and reliability.

Purpose: To determine the feasibility of using a deep learning approach to detect ACL injuries within the knee joint on MRI.

Study Type: Retrospective.

Population: In all, 163 subjects with an ACL tear and 245 subjects with an intact ACL. There were 285, 81, and 42 volumes for training, validation, and test sets, respectively.

Field Strength/sequence: 2D sagittal proton density-weighted spectral attenuated inversion recovery sequences at 1.5T and 3.0T.

Assessment: Based on the architecture of 3D DenseNet, we constructed a classification convolutional neural network. We tested this deep learning approach with different inputs and two other algorithms, including VGG16 and ResNet. Then we had both inexperienced radiologists and senior radiologists read the MR images.

Statistical Tests: Using arthroscopic results as the reference standard, the performance of three different inputs and three different algorithms, the residents and senior radiologists assessed the classification accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC).

Results: The accuracy, sensitivity, specificity, PPV, and NPV of our customized 3D deep learning architecture was 0.957, 0.976, 0.944, 0.940, and 0.976, respectively. The average AUCs were 0.946, 0.859, 0.960 for ResNet, VGG16, and our proposed network, respectively. The diagnostic accuracy of our model, residents, and senior radiologists was 0.957, 0.814, and 0.899, respectively.

Data Conclusion: Our study demonstrated the feasibility of using an automated deep-learning-based detection system to evaluate ACL injury.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1745-1752.
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http://dx.doi.org/10.1002/jmri.27266DOI Listing
December 2020

Computational investigation of geometrical effects in 2D boron nitride nanopores for DNA detection.

Nanoscale 2020 May;12(18):10026-10034

School of Materials and Energy, Guangdong University of Technology, Guangzhou 510006, China.

Nanopore-based DNA detection and analysis have been intensively pursued theoretically and experimentally over the past decade. Owing to their nanometer thickness, 2D nanopores, such as boron nitride nanopores, show great potential for achieving DNA detection at base resolution. Although 2D nanopore devices hold great promise for next-generation DNA detection, efficiently and reliably detecting different DNA sequences is still a challenging problem. To date, most of the investigated nanopores adopt circular shapes. Because of the successful fabrication of triangular nanopores, investigating the shape effect of nanopores for DNA detection has become more and more important. In this study, boron nitride nanopores with circular, hexagonal, quadrangular and triangular shapes were modeled at various sizes. The translocation of homogeneous dsDNA through these nanopores was investigated by all-atom molecular dynamic simulations. The ionic conductivity of these nanopores was characterized and formulas for the total resistance based on the pore and access resistance were derived. The ionic current, dwell time and conductance blockade of homogeneous dsDNA were compared for nanopores with different shapes. We demonstrate that the charge distribution at the pore mouth plays an important role in the transportation of ions and DNA molecules. Our findings may shed light on the design of 2D nanopores and can facilitate the development of fast, low-cost and reliable nanopore-based DNA detection.
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http://dx.doi.org/10.1039/c9nr10172aDOI Listing
May 2020

Promotes the Degradation of Hypoxia-Inducible Factor 1 and Antiangiogenesis and Anti-Inflammation in Chronic Subdural Hematoma Rat Model.

Evid Based Complement Alternat Med 2020 6;2020:2305017. Epub 2020 Apr 6.

Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, China.

(XYK) is a Chinese patent medicine approved by the National Medical Product Administration which is used to treat intracranial hematoma in China. In this study, we observed the molecular mechanism of XYK in hypoxia-inducible factor 1 (HIF-1), inflammation and angiogenesis of chronic subdural hematoma (CSDH). The CSDH model was made by using internal iliac vein blood of Wister rats, and rats were divided into sham group, CSDH group and XYK group. The rats in the XYK group were gavaged with (185 mg/kg) for 7 days, and rats in the CSDH group and sham group were gavaged with the same amount of physiological saline for 7 days. In the CSHD rat model, active inflammation and angiogenesis were observed around the hematoma. XYK promoted the ubiquitination and degradation of HIF-1, and reduced the concentration of VEGF and the ratio of angiopoietin-1/angiopoietin-2. XYK reduced proinflammatory cytokines and increased anti-inflammatory cytokine. In tissue section, XYK reduced the size of the hematoma and membrane, and reduced vWF positive cells in membrane. Furthermore, the endothelial progenitor cells in blood decreased as well. Overall, XYK shows anti-inflammatory and antiangiogenesis effects which may relate to the degradation of HIF-1.
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http://dx.doi.org/10.1155/2020/2305017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165346PMC
April 2020

Cordyceps sinensis polysaccharide inhibits colon cancer cells growth by inducing apoptosis and autophagy flux blockage via mTOR signaling.

Carbohydr Polym 2020 Jun 4;237:116113. Epub 2020 Mar 4.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, Jiangxi, 330047, China; National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi, 330022, China. Electronic address:

Cordyceps sinensis is thought to have anti-cancer effects, but its mechanisms remain elusive. In this study, we aimed to investigate the anti-cancer effect of Cordyceps sinensis polysaccharide (CSP) on human colon cancer cell line (HCT116) and its mechanism. Results indicated that CSP significantly inhibited the proliferation of HCT116 cells, increased autophagy and apoptosis, while blocked autophagy flux and lysosome formation. Further experiments showed that CSP decreased the expression of PI3K and phosphorylation level of AKT and mTOR, increased the expression of AMPKa and phosphorylation level of ULK1. In addition, repression of CSP-induced autophagy by bafilomycin (autophagy inhibitor) enhanced apoptosis and cell death of HCT116 cells. Hence, our findings suggested that CSP inhibited the proliferation of HCT116 cells by inducing apoptosis and autophagy flux blockage, which might be achieved through PI3K-AKT-mTOR and AMPK-mTOR-ULK1 signaling. CSP may be a potential therapeutic agent for colon cancer.
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http://dx.doi.org/10.1016/j.carbpol.2020.116113DOI Listing
June 2020

Mucosal .

J Agric Food Chem 2019 Sep 23;67(35):9831-9839. Epub 2019 Aug 23.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang) , Nanchang University , 235 Nanjing East Road , Nanchang , Jiangxi 330047 , China.

Probiotic lactobacilli and their exopolysaccharides (EPS) are thought to modulate mucosal homeostasis; however, their mechanisms remain elusive. Thus, we tried to clarify the role of exopolysaccharides from NCU116 (EPS116) in the intestinal mucosal homeostasis. Our results indicated that EPS116 regulated the colon mucosal healing and homeostasis, enhanced the goblet cell differentiation, and promoted the expression of Muc2 gene in vivo and in vitro. Further experiments showed that EPS116 promoted the expression and phosphorylation of transcription factor c-Jun and facilitated its binding to the promoter of Muc2. Moreover, knocking down c-Jun or inhibiting its function in LS 174T cells treated with EPS116 led to decreased expression of Muc2, implying that EPS116 promoted the colonic mucosal homeostasis and Muc2 expression via c-Jun. Therefore, our study uncovered a novel model where EPS116 enhanced colon mucosal homeostasis by controlling the epithelial cell differentiation and c-Jun/Muc2 signaling.
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http://dx.doi.org/10.1021/acs.jafc.9b03939DOI Listing
September 2019

Aplasia of the Optic Nerve: A Report of Seven Cases.

Neuroophthalmology 2019 Jul 12;44(5):332-338. Epub 2019 Jul 12.

Division of Ophthalmology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Optic nerve aplasia (ONA) is a rare congenital anomaly with a limited number of published reports. A retrospective review was performed on seven patients with ONA seen during 2004-2017. Patient's ocular and extraocular manifestations, imaging findings, and clinical course were described. Magnetic resonance imaging (MRI) showed anomalies of the optic chiasm and tracts and other central nervous system involvement. In conclusion, in addition to thorough ophthalmic examinations, MRI is important in evaluating and diagnosing ONA. The patients need to be monitored for both ocular and extraocular concerns.
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http://dx.doi.org/10.1080/01658107.2019.1617320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518328PMC
July 2019

Cannabidiol protects livers against nonalcoholic steatohepatitis induced by high-fat high cholesterol diet via regulating NF-κB and NLRP3 inflammasome pathway.

J Cell Physiol 2019 11 29;234(11):21224-21234. Epub 2019 Apr 29.

Guangdong Provincial Key Laboratory of Food, Department of Nutrition, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.

Cannabidiol (CBD), an abundant nonpsychoactive constituent of marijuana, has been reported previously to protect against hepatic steatosis. In this study, we studied further the functions and mechanisms of CBD on liver inflammation induced by HFC diet. Mice feeding an HFC diet for 8 weeks were applied to test the protective effect of CBD on livers. RAW264.7 cells were incubated with LPS + ATP ± CBD to study the mechanisms of the effect of CBD against inflammasome activation. We found that CBD alleviated liver inflammation induced by HFC diet. CBD significantly inhibited the nuclear factor-κappa B (NF-κB) p65 nuclear translocation and the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome both in vivo and in vitro studies, which lead to the reduction of the expression of inflammation-related factors in our studies. In addition, Inhibitor of activation of NF-κB partly suppressed the NLRP3 inflammasome activation, while adding CBD further inhibited NF-κB activation and correspondingly suppressed the NLRP3 inflammasome activation in macrophages. In conclusion, the suppression of the activation of NLRP3 inflammasome through deactivation of NF-κB in macrophages by CBD might be one mechanism of its anti-inflammatory function in the liver.
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http://dx.doi.org/10.1002/jcp.28728DOI Listing
November 2019

Time-sensitive clinical concept embeddings learned from large electronic health records.

BMC Med Inform Decis Mak 2019 04 9;19(Suppl 2):58. Epub 2019 Apr 9.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Learning distributional representation of clinical concepts (e.g., diseases, drugs, and labs) is an important research area of deep learning in the medical domain. However, many existing relevant methods do not consider temporal dependencies along the longitudinal sequence of a patient's records, which may lead to incorrect selection of contexts.

Methods: To address this issue, we extended three popular concept embedding learning methods: word2vec, positive pointwise mutual information (PPMI) and FastText, to consider time-sensitive information. We then trained them on a large electronic health records (EHR) database containing about 50 million patients to generate concept embeddings and evaluated them for both intrinsic evaluations focusing on concept similarity measure and an extrinsic evaluation to assess the use of generated concept embeddings in the task of predicting disease onset.

Results: Our experiments show that embeddings learned from information within one visit (time window zero) improve performance on the concept similarity measure and the FastText algorithm usually had better performance than the other two algorithms. For the predictive modeling task, the optimal result was achieved by word2vec embeddings with a 30-day sliding window.

Conclusions: Considering time constraints are important in training clinical concept embeddings. We expect they can benefit a series of downstream applications.
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http://dx.doi.org/10.1186/s12911-019-0766-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454598PMC
April 2019

Nicotinamide riboside protects against liver fibrosis induced by CCl via regulating the acetylation of Smads signaling pathway.

Life Sci 2019 May 27;225:20-28. Epub 2019 Mar 27.

Department of Nutrition, Guangdong Provincial Key Laboratory of Food, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, People's Republic of China. Electronic address:

Aims: Increasing nicotinamide adenine dinucleotide (NAD) by Nicotinamide riboside (NR) provides protective benefits in multiple disorders. However, the role of NR on liver fibrosis is unclear. We performed in vivo and in vitro experiments to test the hepatic protective effects of NR against liver fibrosis and the underlying mechanisms.

Materials And Methods: Mice were injected with CCl to establish liver fibrosis model. NR was given by gavage to explore the hepatic protection of NR. LX-2 cells were given a TGF-β stimulation ± NR, the activation of LX-2 cells and the acetylation of Smads were analyzed. To further confirm the role of Sirt1 on the protective pathway of NR, we knockdown Sirt1 in LX-2 cells.

Key Findings: We found NR could prevent liver fibrosis and reverse the existing liver fibrosis. NR inhibited the activation of LX-2 cells induced by TGF-β, activated Sirt1 and deacetylated Smad2/3. Sirt1 knockdown diminished the inhibiting effect of NR on LX-2 cells activation, and increased expressions of acetylated Smads. In conclusion, NR could prevent liver fibrosis via suppressing activation of hepatic stellate cells (HSCs). This protective effect was mediated by regulating the acetylation of Smads signaling pathway.

Significance: NR protected mice against liver fibrosis induced by CCl. NR suppressed activation of hepatic stellate cells induced by TGF-β. NR protects liver fibrosis via increasing the activity of Sirt1 and decreasing the expression of P300, resulting in the deacetylation of Smads in stellate cells.
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http://dx.doi.org/10.1016/j.lfs.2019.03.064DOI Listing
May 2019

Correlation-Weighted Sparse Representation for Robust Liver DCE-MRI Decomposition Registration.

IEEE Trans Med Imaging 2019 10 20;38(10):2352-2363. Epub 2019 Mar 20.

Conducting an accurate motion correction of liver dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging remains challenging because of intensity variations caused by contrast agents. Such variations lead to the failure of the traditional intensity-based registration method. To address this problem, we propose a correlation-weighted sparse representation framework to separate the contrast agent from original liver DCE-MR images. This framework allows the robust registration of motion components over time without intensity variances. Existing sparse coding techniques recover a 3D image containing only contrast agents (named contrast enhancement component) from a manually labeled dictionary, whose column has the same size with the original 3D volume (3D-t mode). The high dimension of the recovery target (3D volume) and the indistinguishability between the unenhanced and enhanced images make accurate coding difficult. In this paper, we predefine an ideal time-intensity curve containing only contrast agents (named contrast agent curve) and recover it from the transpose dictionary (t-3D mode), whose column has been updated into the original time-intensity curves. The low dimension of the target (1D curve) and the significant intergroup difference between contrast agent curves and non-contrast agent curves can estimate a series of pure contrast agent curves. A "correlation-weighted" constraint is introduced for the selection of a coding subset with more contrast agent curves, leading to an efficient and accurate sparse recovery process. Then, the contrast enhancement component can be estimated by the solved sparse coefficients' map and the ideal curve and subtracted from the original DCE-MRI. Finally, we register the de-enhanced images and apply the obtained deformation fields for the original DCE-MRI to achieve the goal of motion correction. We conduct the experiments on both simulated and real liver DCE-MRI data. Compared with other state-of-the-art DCE-MRI registration methods, the experimental results show that our method achieves a better registration performance with less computational efficiency.
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http://dx.doi.org/10.1109/TMI.2019.2906493DOI Listing
October 2019

Automatic Nasopharyngeal Carcinoma Segmentation Using Fully Convolutional Networks with Auxiliary Paths on Dual-Modality PET-CT Images.

J Digit Imaging 2019 06;32(3):462-470

School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, China.

Nasopharyngeal carcinoma (NPC) is prevalent in certain areas, such as South China, Southeast Asia, and the Middle East. Radiation therapy is the most efficient means to treat this malignant tumor. Positron emission tomography-computed tomography (PET-CT) is a suitable imaging technique to assess this disease. However, the large amount of data produced by numerous patients causes traditional manual delineation of tumor contour, a basic step for radiotherapy, to become time-consuming and labor-intensive. Thus, the demand for automatic and credible segmentation methods to alleviate the workload of radiologists is increasing. This paper presents a method that uses fully convolutional networks with auxiliary paths to achieve automatic segmentation of NPC on PET-CT images. This work is the first to segment NPC using dual-modality PET-CT images. This technique is identical to what is used in clinical practice and offers considerable convenience for subsequent radiotherapy. The deep supervision introduced by auxiliary paths can explicitly guide the training of lower layers, thus enabling these layers to learn more representative features and improve the discriminative capability of the model. Results of threefold cross-validation with a mean dice score of 87.47% demonstrate the efficiency and robustness of the proposed method. The method remarkably outperforms state-of-the-art methods in NPC segmentation. We also validated by experiments that the registration process among different subjects and the auxiliary paths strategy are considerably useful techniques for learning discriminative features and improving segmentation performance.
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http://dx.doi.org/10.1007/s10278-018-00173-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499852PMC
June 2019

Oxidized Vitamin C (DHA) Overcomes Resistance to EGFR-targeted Therapy of Lung Cancer through Disturbing Energy Homeostasis.

J Cancer 2019 1;10(3):757-764. Epub 2019 Jan 1.

Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.

Switching aerobic respiration to anaerobic glycolysis of cancer cells plays an important role in development and progression of acquired resistance. Since vitamin C enabled the inhibition of glycolysis of cancer cells, and erlotinib-resistant sub-line of HCC827 (ER6 cells) switched its metabolic features to higher glycolysis for survival, we hypothesize that vitamin C is able to inhibit glycolysis of ER6 cells. In this study, we found that both reduced vitamin C and oxidized vitamin C (DHA) could selectively suppress the viability of ER6 cells. DHA was efficient in inhibiting glycolysis and leading to energy crisis, which could be one mechanism for overcoming drug resistance to erlotinib of ER6 cells. Our data suggest that applying DHA could be a novel treatment strategy for NSCLC with acquired resistance to targeted therapy.
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http://dx.doi.org/10.7150/jca.28087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360421PMC
January 2019

M-Current Expands the Range of Gamma Frequency Inputs to Which a Neuronal Target Entrains.

J Math Neurosci 2018 Dec 5;8(1):13. Epub 2018 Dec 5.

Department of Mathematics and Statistics, Boston University, Boston, USA.

Theta (4-8 Hz) and gamma (30-80 Hz) rhythms in the brain are commonly associated with memory and learning (Kahana in J Neurosci 26:1669-1672, 2006; Quilichini et al. in J Neurosci 30:11128-11142, 2010). The precision of co-firing between neurons and incoming inputs is critical in these cognitive functions. We consider an inhibitory neuron model with M-current under forcing from gamma pulses and a sinusoidal current of theta frequency. The M-current has a long time constant (∼90 ms) and it has been shown to generate resonance at theta frequencies (Hutcheon and Yarom in Trends Neurosci 23:216-222, 2000; Hu et al. in J Physiol 545:783-805, 2002). We have found that this slow M-current contributes to the precise co-firing between the network and fast gamma pulses in the presence of a slow sinusoidal forcing. The M-current expands the phase-locking frequency range of the network, counteracts the slow theta forcing, and admits bistability in some parameter range. The effects of the M-current balancing the theta forcing are reduced if the sinusoidal current is faster than the theta frequency band. We characterize the dynamical mechanisms underlying the role of the M-current in enabling a network to be entrained to gamma frequency inputs using averaging methods, geometric singular perturbation theory, and bifurcation analysis.
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http://dx.doi.org/10.1186/s13408-018-0068-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281550PMC
December 2018

Cyanidin-3-O-β-glucoside regulates the activation and the secretion of adipokines from brown adipose tissue and alleviates diet induced fatty liver.

Biomed Pharmacother 2018 Sep 10;105:625-632. Epub 2018 Jun 10.

Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510080, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, 510080, PR China. Electronic address:

Aim: Cyanidin-3-O-β-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT.

Methods: Male C57BL/6 J mice were fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks. In in vitro experiments, the differentiated brown adipocytes (BAC) and C3H10T1/2 clone8 cells were treated with 0.2 mM palmitate with or without Cy-3-G for 72 or 96 h. Then the culture media of C3H10T1/2 clone8 cells were collected for measuring the adipokines secretion by immunoblot assay and were applied to culture HepG2 cells or LO2 cells for 24 h. Lipid accumulation in HepG2 cells or LO2 cells were evaluated by oil red O staining.

Results: Here we found that Cy-3-G regulated the activation of BAT and the expression of adipokines in BAT which were disrupted by HFC diet and alleviated diet induced fatty liver in mice. In in vitro experiments, Cy-3-G inhibited the release of adipokines including extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and fibroblast growth factor 21 (FGF21) from differentiated C3H10T1/2 clone8 cells induced by palmitate, which was accompanied by a reduction of lipid accumulation in HepG2 cells and LO2 cells cultured by the corresponding collected media of C3H10T1/2 clone8 cells.

Conclusions: These results indicate that Cy-3-G can regulate the thermogenic and secretory functions of BAT. Furthermore, our data suggest that the protective effect of Cy-3-G on hepatic lipid accumulation is probably via regulating the secretion of adipokines from BAT.
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http://dx.doi.org/10.1016/j.biopha.2018.06.018DOI Listing
September 2018