Publications by authors named "Wu Deng"

61 Publications

The amputation and mortality of inpatients with diabetic foot ulceration in the COVID-19 pandemic and postpandemic era: A machine learning study.

Int Wound J 2021 Nov 24. Epub 2021 Nov 24.

Department of Endocrinology, School of Medicine, Bioengineering College, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

This study aimed to explore the clinical characteristic and outcomes of inpatients with diabetic foot ulceration (DFU) in 2019 (prelockdown) and 2020 (postlockdown) due to the COVID-19 pandemic, at an emergency medical service unit. Prediction models for mortality and amputation were developed to describe the risk factors using a machine learning-based approach. Hospitalized DFU patients (N = 23) were recruited after the lockdown in 2020 and matched with corresponding inpatients (N = 23) before lockdown in 2019. Six widely used machine learning models were built and internally validated using 3-fold cross-validation to predict the risk of amputation and death in DFU inpatients under the COVID-19 pandemic. Previous DF ulcers, prehospital delay, and mortality were significantly higher in 2020 compared to 2019. Diabetic foot patients in 2020 had higher hs-CRP levels (P = .037) but lower hemoglobin levels (P = .017). The extreme gradient boosting (XGBoost) performed best in all models for predicting amputation and mortality with the highest area under the curve (0.86 and 0.94), accuracy (0.80 and 0.90), sensitivity (0.67 and 1.00), and negative predictive value (0.86 and 1.00). A long delay in admission and a higher risk of mortality was observed in patients with DFU who attended the emergency center during the COVID-19 post lockdown. The XGBoost model can provide evidence-based risk information for patients with DFU regarding their amputation and mortality. The prediction models would benefit DFU patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1111/iwj.13723DOI Listing
November 2021

Transglutaminase 3 expression in hepatocellular carcinoma patients: correlation with tumor features and survival profile.

Clin Res Hepatol Gastroenterol 2021 Sep 28:101812. Epub 2021 Sep 28.

Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, P.R. China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, P.R. China. Electronic address:

Background: Transglutaminase 3 (TGM3) regulates multiple oncogene pathways (GSK-3β/β-catenin pathway, Akt/ERK pathway, etc.) to promote hepatocellular carcinoma (HCC) cell proliferation, migration and invasion, however, its clinical value for HCC management is still limited. Therefore, we conducted this study to compare the TGM3 expression between tumor tissue and paired adjacent noncancerous tissue, aiming to explore the clinical application of TGM3 in HCC patients.

Methods: Totally, 208 HCC patients were enrolled and their clinicopathological features were collected. Then, 208 pairs of HCC specimens and adjacent noncancerous specimens were used to detect TGM3 protein expression by IHC assay and assessed by a semi-quantitative scoring method. Besides, 157 pairs were proposed to detect TGM3 mRNA expression by RT-qPCR.

Results: Both TGM3 protein (P<0.001) and mRNA (P<0.001) levels were increased in HCC specimens compared to adjacent noncancerous specimens. Besides, TGM3 high protein expression correlated with multifocal tumor nodules (P<0.001), advanced Barcelona Clinic Liver Cancer (BCLC) stage (P=0.006), higher carcinoembryonic antigen (P=0.038) and alpha-fetoprotein (AFP) (P<0.001). While TGM3 high mRNA expression correlated with multifocal tumor nodules (P=0.025), largest tumor size ≥ 5.0 cm (P=0.042) and higher AFP (P=0.019). Furthermore, both TGM3 protein (P=0.002) and mRNA (P=0.028) high expressions correlated with shorter overall survival (OS). While after adjustment by multivariant Cox's regression, TGM3 protein high expression (vs. low) independently predicted worse OS (P=0.004).

Conclusions: TMG3 expression is increased in tumor tissue, also its high expression correlates with multiple tumor nodules, higher BCLC stage, abnormal AFP and reduced OS in HCC patients.
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http://dx.doi.org/10.1016/j.clinre.2021.101812DOI Listing
September 2021

Time in range in relation to amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers.

Diabetes Metab Res Rev 2021 Sep 29:e3498. Epub 2021 Sep 29.

Department of Endocrinology, College of Medicine, College of Bioengineering, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

Aims: The aim of this study was to evaluate the association of time in range (TIR) with amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers (DFUs).

Materials And Methods: A retrospective analysis was performed on 303 hospitalised patients with DFUs. During hospitalisation, TIR, mean blood glucose (MBG), coefficient of variation (CV), time above range (TAR) and time below range (TBR) of patients were determined from seven-point blood glucose profiles. Participants were grouped based on their clinical outcomes (i.e., amputation and death). Logistic regression was employed to analyse the association of TIR with amputation and all-cause mortality of inpatients with DFUs.

Results: Among the 303 enrolled patients, 50 (16.5%) had undergone amputation whereas seven (2.3%) were deceased. Blood glucose was determined in 41,012 samples obtained from all participants. Patients who underwent amputation had significantly lower TIR and higher MBG, CV, level 2 TAR and level 1 TBR whereas deceased patients had significantly lower TIR and higher MBG and level 2 TAR. Both amputation and all-cause mortality rate declined with an increase in TIR quartiles. Logistic regression showed association of TIR with amputation (p = 0.034) and all-cause mortality (p = 0.013) after controlling for 15 confounders. This association was similarly significant in all-cause mortality after further adjustment for CV (p = 0.022) and level 1 TBR (p = 0.021), respectively.

Conclusions: TIR is inversely associated with amputation and all-cause mortality of hospitalised patients with DFUs. Further prospective studies are warranted to establish a causal relationship between TIR and clinical outcomes in patients with DFUs.
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http://dx.doi.org/10.1002/dmrr.3498DOI Listing
September 2021

An explainable machine learning model for predicting in-hospital amputation rate of patients with diabetic foot ulcer.

Int Wound J 2021 Sep 14. Epub 2021 Sep 14.

Department of Endocrinology and Metabolism, Chongqing Emergency Medical Center, Chongqing Key Laboratory of Emergency Medicine, Chongqing University Central Hospital, Chongqing University, Chongqing, China.

Diabetic foot ulcer (DFU) is one of the most serious and alarming diabetic complications, which often leads to high amputation rates in diabetic patients. Machine learning is a part of the field of artificial intelligence, which can automatically learn models from data and better inform clinical decision-making. We aimed to develop an accurate and explainable prediction model to estimate the risk of in-hospital amputation in patients with DFU. A total of 618 hospitalised patients with DFU were included in this study. The patients were divided into non-amputation, minor amputation or major amputation group. Light Gradient Boosting Machine (LightGBM) and 5-fold cross-validation tools were used to construct a multi-class classification model to predict the three outcomes of interest. In addition, we used the SHapley Additive exPlanations (SHAP) algorithm to interpret the predictions of the model. Our area under the receiver-operating-characteristic curve (AUC) demonstrated a 0.90, 0.85 and 0.86 predictive ability for non-amputation, minor amputation and major amputation outcomes, respectively. Taken together, our data demonstrated that the developed explainable machine learning model provided accurate estimates of the amputation rate in patients with DFU during hospitalisation. Besides, the model could inform individualised analyses of the patients' risk factors.
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http://dx.doi.org/10.1111/iwj.13691DOI Listing
September 2021

CCT6A expression in hepatocellular carcinoma and its correlation with clinical characteristics, liver function indexes, tumor markers and prognosis.

Clin Res Hepatol Gastroenterol 2021 Sep 6:101796. Epub 2021 Sep 6.

Clinical Medical College of Hubei University of Chinese Medicine, Wuhan, P.R. China; Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, P.R. China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, P.R. China. Electronic address:

Background: Chaperonin-containing tailless complex polypeptide 1 subunit 6A (CCT6A) plays roles in cancer progression, but its clinical implication in hepatocellular carcinoma (HCC) management needs further exploration. This study aimed to explore the correlation of CCT6A with clinical characteristics, liver function indexes, tumor markers and prognosis in HCC patients.

Methods: 240 HCC patients were retrospectively enrolled. 240 pairs of cancer and adjacent specimens were used to evaluate CCT6A protein expression by immunohistochemistry assay; among which 184 pairs were used to assess CCT6A mRNA expression by reverse transcription-quantitative polymerase chain reaction.

Results: Both CCT6A protein expression and CCT6A mRNA expression were higher in HCC tumor tissue than in adjacent tissue (P<0.001). The receiver operating characteristic (ROC) curve showed that CCT6A had certain potential in discriminating tumor tissues from adjacent tissues. In addition, CCT6A protein expression was positively correlated with multifocal tumor nodule (P=0.001), ≥5.0 cm tumor size (P=0.028), BCLC stage (P=0.002) and abnormal AFP (P=0.021). Besides, CCT6A mRNA expression was associated with multifocal tumor nodule (P=0.025), ≥5.0 cm tumor size (P=0.018), higher BCLC stage (P=0.036), abnormal CA199 (P=0.027) and abnormal AFP (P=0.008). However, no correlation was found in CCT6A with liver function indexes (all P>0.05). Moreover, CCT6A protein and mRNA high expressions were both correlated with poor accumulating overall survival (OS) (P=0.004, P=0.002, respectively). Furthermore, CCT6A protein high expression (vs. low) independently predicted shorter OS (P=0.027).

Conclusions: CCT6A serves as a possible biomarker reflecting tumor features and prognostication in HCC patients.
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http://dx.doi.org/10.1016/j.clinre.2021.101796DOI Listing
September 2021

A novel mathematical morphology spectrum entropy based on scale-adaptive techniques.

ISA Trans 2021 Jul 19. Epub 2021 Jul 19.

College of Electronic Information and Automation, Civil Aviation University of China, Tianjin 300300, China. Electronic address:

Mathematical morphology spectrum entropy is a signal feature extraction method based on information entropy and mathematical morphology. The scale of structure element is a critical parameter, whose value determines the accuracy of feature extraction. Existing scale selection methods depend on experiment parameters or external indicators including noise ratio, fault frequencies, etc. In many cases, existing methods obtain fix scale and they are not suitable for quantifying the performance degradation and the fault degree of bearings. There are few researches on scale selection based on the properties of mathematical morphology spectrum. In this study, a scale-adaptive mathematical morphology spectrum entropy (AMMSE) is proposed to improve the scale selection. To support the proposed method, two properties of the mathematical morphology spectrum (MMS), namely non-negativity and monotonic decreasing, are proved. It can be concluded from the two properties that the feature loss of MMS decreases with the increase of scale. Based on the conclusion, two adaptive scale selection strategies are proposed to automatically determine the scale by reducing the feature loss of MMS. AMMSE is the integration of two strategies. Compare to the existing methods, AMMSE is not constrained by the information of the experiment and the signal. The scale of AMMSE changes with the signal characteristics and is no longer fixed by experimental parameters. The parameters of AMMSE are more generalizable as well. The presented method is applied to identify fault degree on CWRU bearing data set and evaluate performance degradation on IMS bearing data set. The experiment result shows that AMMSE has better results in both experiments with the same parameters.
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http://dx.doi.org/10.1016/j.isatra.2021.07.017DOI Listing
July 2021

CT Image Analysis and Clinical Diagnosis of New Coronary Pneumonia Based on Improved Convolutional Neural Network.

Comput Math Methods Med 2021 20;2021:7259414. Epub 2021 Jul 20.

Information Center/Engineering Research Center of Medical Information Technology, West China Hospital of Sichuan University, Chengdu Sichuan 610000, China.

In this paper, based on the improved convolutional neural network, in-depth analysis of the CT image of the new coronary pneumonia, using the U-Net series of deep neural networks to semantically segment the CT image of the new coronary pneumonia, to obtain the new coronary pneumonia area as the foreground and the remaining areas as the background of the binary image, provides a basis for subsequent image diagnosis. Secondly, the target-detection framework Faster RCNN extracts features from the CT image of the new coronary pneumonia tumor, obtains a higher-level abstract representation of the data, determines the lesion location of the new coronary pneumonia tumor, and gives its bounding box in the image. By generating an adversarial network to diagnose the lesion area of the CT image of the new coronary pneumonia tumor, obtaining a complete image of the new coronary pneumonia, achieving the effect of the CT image diagnosis of the new coronary pneumonia tumor, and three-dimensionally reconstructing the complete new coronary pneumonia model, filling the current the gap in this aspect, provide a basis to produce new coronary pneumonia prosthesis and improve the accuracy of diagnosis.
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http://dx.doi.org/10.1155/2021/7259414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321746PMC
November 2021

Identification of Potential Therapeutic Targets of Alzheimer's Disease By Weighted Gene Co-Expression Network Analysis.

Chin Med Sci J 2020 Dec;35(4):330-341

Pharmacy School, Guangxi University of Chinese Medicine, Nanning 530200, China.

Objective Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of the disease mostly remains unearthed, thereby challenging drug development for AD. This study aims to screen high throughput gene expression data using weighted co-expression network analysis (WGCNA) to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus (GEO) database. Normalization, quality control, filtration, and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules. Furthermore, the correlation coefficients between the modules and clinical traits were computed to identify the key modules. Gene ontology and pathway enrichment analyses were performed on the key module genes. The STRING database was used to construct the protein-protein interaction (PPI) networks, which were further analyzed by Cytoscape app (MCODE). Finally, validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules, among which 6 modules were identified as the key module relating to AD occurrence. These key modules are primarily involved in chemical synaptic transmission (GO:0007268), the tricarboxylic acid (TCA) cycle and respiratory electron transport (R-HSA-1428517). , , , , , were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses, we identified the hub genes of AD, including , , , , and . Among them, three hub genes (, , ) might contribute to AD pathogenesis through pathway of TCA cycle.
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http://dx.doi.org/10.24920/003695DOI Listing
December 2020

Dysfunction of VIPR2 leads to myopia in humans and mice.

J Med Genet 2020 Dec 14. Epub 2020 Dec 14.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, China

Background: Myopia is the leading cause of refractive errors. As its pathogenesis is poorly understood, we determined if the retinal VIP-VIPR2 signalling pathway axis has a role in controlling signalling output that affects myopia development in mice.

Methods: Association analysis meta-study, single-cell transcriptome, bulk RNA sequencing, pharmacological manipulation and VIPR2 gene knockout studies were used to clarify if changes in the VIP-VIPR2 signalling pathway affect refractive development in mice.

Results: The SNP rs6979985 of the gene was associated with high myopia in a Chinese Han cohort (randomceffect model: p=0.013). After either 1 or 2 days' form deprivation (FD) retinal mRNA expression was downregulated. Retinal single-cell transcriptome sequencing showed that VIPR2 expressed mainly by bipolar cells. Furthermore, the cAMP signalling pathway axis was inhibited in some clusters after 2 days of FD. The selective VIPR2 antagonist PG99-465 induced relative myopia, whereas the selective VIPR2 agonist Ro25-1553 inhibited this response. In knockout (-KO) mice, refraction was significantly shifted towards myopia (p<0.05). The amplitudes of the bipolar cell derived b-waves in 7-week-old -KO mice were significantly larger than those in their WT littermates (p<0.05).

Conclusions: Loss of VIPR2 function likely compromises bipolar cell function based on presumed changes in signal transduction due to altered signature electrical wave activity output in these mice. As these effects correspond with increases in form deprivation myopia (FDM), the VIP-VIPR2 signalling pathway axis is a viable novel target to control the development of this condition.
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http://dx.doi.org/10.1136/jmedgenet-2020-107220DOI Listing
December 2020

Fault Diagnosis for Rolling Bearings Using Optimized Variational Mode Decomposition and Resonance Demodulation.

Entropy (Basel) 2020 Jul 3;22(7). Epub 2020 Jul 3.

School of Electronics and Information Engineering, Dalian Jiaotong University, Dalian 116028, China.

It is difficult to extract the fault signal features of locomotive rolling bearings and the accuracy of fault diagnosis is low. In this paper, a novel fault diagnosis method based on the optimized variational mode decomposition (VMD) and resonance demodulation technology, namely GNVRFD, is proposed to realize the fault diagnosis of locomotive rolling bearings. In the proposed GNVRFD method, the genetic algorithm and nonlinear programming are combined to design a novel parameter optimization algorithm to adaptively optimize the two parameters of the VMD. Then the optimized VMD is employed to decompose the collected vibration signal into a series of intrinsic mode functions (IMFs), and the kurtosis value of each IMF is calculated, respectively. According to the principle of maximum value, two most sensitive IMF components are selected to reconstruct the vibration signal. The resonance demodulation technology is used to decompose the reconstructed vibration signal in order to obtain the envelope spectrum, and the fault frequency of locomotive rolling bearings is effectively obtained. Finally, the actual data of rolling bearings is selected to testify the effectiveness of the proposed GNVRFD method. The experiment results demonstrate that the proposed GNVRFD method can more accurately and effectively diagnose the fault of locomotive rolling bearings by comparing with other fault diagnosis methods.
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http://dx.doi.org/10.3390/e22070739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517282PMC
July 2020

A systematic review of etiology, epidemiology, clinical manifestations, image findings, and medication of 2019 Corona Virus Disease-19 in Wuhan, China.

Medicine (Baltimore) 2020 Oct;99(42):e22688

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Unknown origin pneumonia has been furiously spreading since the late of December 2019, subsequently spread to approximately all provinces and areas in China and many countries, which was announced as a Public Health Emergency of International Concern by World Health Organization (WHO). The studies on 2019 Corona Virus Disease-19 (COVID-19) conducted from various fields around the world. Herein, the objective of the present study is to summarize the etiology, epidemiology, clinical manifestations, image findings, traceability analysis, and drug development of COVID-19.

Methods: The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Data. Other relevant literature will be manually searched as a compliment. We have reviewed etiology, epidemiology, clinical manifestations, image findings, and medication from case reports and retrospective clinical studies relating to COVID-19 published since the outbreak.

Results: The coronavirus is closely related to bat coronavirus and pangolin coronavirus. Besides, the infection pathway is confirmed to be the respiratory and digestive systems. The virus indicates person-to-person transmission and some patients present asymptomatic. The elderly have a higher mortality rate. Rapid and sensitive nucleic acid testing is usually used as a basis for diagnosis. Currently, there is no specific vaccine and antiviral drug. Intervention actions such as travel bans and quarantine adopted have effectively reduced the spread of the epidemic.

Conclusion: This systemic review will provide high-quality evidence to summarize etiology, epidemiology, clinical manifestations, image findings, traceability analysis, drug development in patients with COVID-19.
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http://dx.doi.org/10.1097/MD.0000000000022688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572017PMC
October 2020

Scleral HIF-1α is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis.

EBioMedicine 2020 Jul 8;57:102878. Epub 2020 Jul 8.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China. Electronic address:

Background: Myopia is a good model for understanding the interaction between genetics and environmental stimuli. Here we dissect the biological processes affecting myopia progression.

Methods: Human Genetic Analyses: (1) gene set analysis (GSA) of new genome wide association study (GWAS) data for 593 individuals with high myopia (refraction ≤ -6 diopters [D]); (2) over-representation analysis (ORA) of 196 genes with de novo mutations, identified by whole genome sequencing of 45 high-myopia trio families, and (3) ORA of 284 previously reported myopia risk genes. Contributions of the enriched signaling pathways in mediating the genetic and environmental interactions during myopia development were investigated in vivo and in vitro.

Results: All three genetic analyses showed significant enrichment of four KEGG signaling pathways, including amphetamine addiction, extracellular matrix (ECM) receptor interaction, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton pathways. In individuals with extremely high myopia (refraction ≤ -10 D), the GSA of GWAS data revealed significant enrichment of the HIF-1α signaling pathway. Using human scleral fibroblasts, silencing the key nodal genes within protein-protein interaction networks for the enriched pathways antagonized the hypoxia-induced increase in myofibroblast transdifferentiation. In mice, scleral HIF-1α downregulation led to hyperopia, whereas upregulation resulted in myopia. In human subjects, near work, a risk factor for myopia, significantly decreased choroidal blood perfusion, which might cause scleral hypoxia.

Interpretation: Our study implicated the HIF-1α signaling pathway in promoting human myopia through mediating interactions between genetic and environmental factors.

Funding: National Natural Science Foundation of China grants; Natural Science Foundation of Zhejiang Province.
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http://dx.doi.org/10.1016/j.ebiom.2020.102878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348000PMC
July 2020

Asian Pacific Association of Gastroenterology (APAGE) Inflammatory Bowel Disease (IBD) Working Party guidelines on IBD management during the COVID-19 pandemic.

JGH Open 2020 Jun 5;4(3):320-323. Epub 2020 Jun 5.

Duke-NUS Medical School Singapore.

The COVID-19 pandemic, secondary to SARS-CoV-2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long-term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face-to-face clinic follow ups and non-urgent procedures should be kept to a minimum.
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http://dx.doi.org/10.1002/jgh3.12362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273734PMC
June 2020

Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells.

Sci Rep 2019 07 9;9(1):9919. Epub 2019 Jul 9.

UC Irvine Diabetes Center, University of California, Irvine, California, USA.

The signaling mechanisms controlling somatic cell reprogramming are not fully understood. In this study, we report a novel role for mitochondrial Akt1 signaling that enhanced somatic cell reprogramming efficiency. The role of mitochondrial Akt1 in somatic cell reprogramming was investigated by transducing fibroblasts with the four reprogramming factors (Oct4, Sox2, Klf4, c-Myc) in conjunction with Mito-Akt1, Mito-dnAkt1, or control virus. Mito-Akt1 enhanced reprogramming efficiency whereas Mito-dnAkt1 inhibited reprogramming. The resulting iPSCs formed embryoid bodies in vitro and teratomas in vivo. Moreover, Oct4 and Nanog promoter methylation was reduced in the iPSCs generated in the presence of Mito-Akt1. Akt1 was activated and translocated into mitochondria after growth factor stimulation in embryonic stem cells (ESCs). To study the effect of mitochondrial Akt in ESCs, a mitochondria-targeting constitutively active Akt1 (Mito-Akt1) was expressed in ESCs. Gene expression profiling showed upregulation of genes that promote stem cell proliferation and survival and down-regulation of genes that promote differentiation. Analysis of cellular respiration indicated similar metabolic profile in the resulting iPSCs and ESCs, suggesting comparable bioenergetics. These findings showed that activation of mitochondrial Akt1 signaling was required during somatic cell reprogramming.
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http://dx.doi.org/10.1038/s41598-019-46359-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616364PMC
July 2019

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

Intest Res 2019 Jul 31;17(3):285-310. Epub 2019 May 31.

Department of Medicine, Chulalongkorn University, Bangkok, Thailand.

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
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http://dx.doi.org/10.5217/ir.2019.00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667368PMC
July 2019

Brain Tumor Segmentation Based on Improved Convolutional Neural Network in Combination with Non-quantifiable Local Texture Feature.

J Med Syst 2019 Apr 23;43(6):152. Epub 2019 Apr 23.

Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan, China.

Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis. According to deep learning model, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNN) and dense micro-block difference feature (DMDF) into a unified framework so as to obtain segmentation results with appearance and spatial consistency. Firstly, we propose a local feature to describe the rotation invariant property of the texture. In order to deal with the change of rotation and scale in texture image, Fisher vector encoding method is used to analyze the texture feature, which can combine with the scale information without increasing the dimension of the local feature. The obtained local features have strong robustness to rotation and gray intensity variation. Then, the non-quantifiable local feature is fused to the FCNN to perform fine boundary segmentation. Since brain tumors occupy a small portion of the image, deconvolutional layers are designed with skip connections to obtain a high quality feature map. Compared with the traditional MRI brain tumor segmentation methods, the experimental results show that the segmentation accuracy and stability has been greatly improved. Average Dice index can be up to 90.98%. And the proposed method has very high real-time performance, where brain tumor image can segment within 1 s.
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http://dx.doi.org/10.1007/s10916-019-1289-2DOI Listing
April 2019

Anticancer Effects of Extract in Rats Transplanted With Hepatocellular Carcinoma Cells.

Oncol Res 2019 Aug 2;27(8):889-899. Epub 2019 Apr 2.

Infectious Disease of Wuhan Medical Treatment Center, Wuhan, P.R. China.

The thorns of have been historically used in Chinese medicine and are considered one of the fundamental therapeutic herbs. Its anticancer effects are currently being explored. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and still requires the development of new drugs with higher efficiency. By using a rat HCC model implanted with cancerous Walker-256 cells, the therapeutic effects of extract (GSE) were assessed, as well as its regulatory effects on miRNAs. GSE significantly restored liver morphology and dramatically induced cell apoptosis in HCC rats. In addition, miR-21/181b/183 was upregulated in the HCC liver, and the elevation of these miRNAs could be alleviated by both GSE and sorafenib. PTEN/TIMP3/PDCD4 downregulation was consistent with the targets of miR-21/181b/183 in the HCC liver, and the alteration of these target genes was restored by both GSE and sorafenib. TIMP3 effects on MMP-2/9 expression were also determined. Our present findings indicate the potential of GSE in HCC treatment, and expand the understanding of miRNA-related mechanisms in the anticancer effects of GSE.
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http://dx.doi.org/10.3727/096504018X15482423944678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848454PMC
August 2019

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

J Gastroenterol Hepatol 2019 Aug 1;34(8):1296-1315. Epub 2019 Jul 1.

Department of Medicine, Chulalongkorn University, Bangkok, Thailand.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
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http://dx.doi.org/10.1111/jgh.14648DOI Listing
August 2019

A Novel Adaptive Signal Processing Method Based on Enhanced Empirical Wavelet Transform Technology.

Sensors (Basel) 2018 Oct 3;18(10). Epub 2018 Oct 3.

Software Institute, Dalian Jiaotong University, Dalian 116028, China.

Empirical wavelet transform (EWT) is a novel adaptive signal decomposition method, whose main shortcoming is the fact that Fourier segmentation is strongly dependent on the local maxima of the amplitudes of the Fourier spectrum. An enhanced empirical wavelet transform (MSCEWT) based on maximum-minimum length curve method is proposed to realize fault diagnosis of motor bearings. The maximum-minimum length curve method transforms the original vibration signal spectrum to scale space in order to obtain a set of minimum length curves, and find the maximum length curve value in the set of the minimum length curve values for obtaining the number of the spectrum decomposition intervals. The MSCEWT method is used to decompose the vibration signal into a series of intrinsic mode functions (IMFs), which are processed by Hilbert transform. Then the frequency of each component is extracted by power spectrum and compared with the theoretical value of motor bearing fault feature frequency in order to determine and obtain fault diagnosis result. In order to verify the effectiveness of the MSCEWT method for fault diagnosis, the actual motor bearing vibration signals are selected and the empirical mode decomposition (EMD) and ensemble empirical mode decomposition (EEMD) methods are selected for comparative analysis in here. The results show that the maximum-minimum length curve method can enhance EWT method and the MSCEWT method can solve the shortcomings of the Fourier spectrum segmentation and can effectively decompose the bearing vibration signal for obtaining less number of intrinsic mode function (IMF) components than the EMD and EEMD methods. It can effectively extract the fault feature frequency of the motor bearing and realize fault diagnosis. Therefore, the study provides a new method for fault diagnosis of rotating machinery.
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http://dx.doi.org/10.3390/s18103323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210451PMC
October 2018

Study on a Novel Fault Damage Degree Identification Method Using High-Order Differential Mathematical Morphology Gradient Spectrum Entropy.

Entropy (Basel) 2018 Sep 7;20(9). Epub 2018 Sep 7.

Software Institute, Dalian Jiaotong University, Dalian 116028, China.

A damage degree identification method based on high-order difference mathematical morphology gradient spectrum entropy (HMGSEDI) is proposed in this paper to solve the problem that fault signal of rolling bearings are weak and difficult to be quantitatively measured. In the HMGSEDI method, on the basis of mathematical morphology gradient spectrum and spectrum entropy, the changing scale influence of structure elements to damage degree identification is thoroughly analyzed to determine its optimal scale range. The high-order difference mathematical morphology gradient spectrum entropy is then defined in order to quantitatively describe the fault damage degree of bearing. The discrimination concept of fault damage degree is defined to quantitatively describe the difference between the high-order differential mathematical entropy and the general mathematical morphology entropy in order to propose a fault damage degree identification method. The vibration signal of motors under no-load and load states are used to testify the effectiveness of the proposed HMGSEDI method. The experiment shows that high-order differential mathematical morphology entropy can more effectively identify the fault damage degree of bearings and the identification accuracy of fault damage degree can be greatly improved. Therefore, the HMGSEDI method is an effective quantitative fault damage degree identification method, and provides a new way to identify fault damage degree and fault prediction of rotating machinery.
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http://dx.doi.org/10.3390/e20090682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513207PMC
September 2018

SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Infection.

Int J Mol Sci 2018 Aug 22;19(9). Epub 2018 Aug 22.

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.

The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic () infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to infection. Exposure of human AGS cells to induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to infection. We conclude that in the presence of SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state.
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http://dx.doi.org/10.3390/ijms19092482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163533PMC
August 2018

Scleral hypoxia is a target for myopia control.

Proc Natl Acad Sci U S A 2018 07 9;115(30):E7091-E7100. Epub 2018 Jul 9.

School of Optometry and Ophthalmology Wenzhou Medical University, Wenzhou, 325027 Zhejiang, China;

Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)-signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.
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http://dx.doi.org/10.1073/pnas.1721443115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064999PMC
July 2018

Symptom-based network classification identifies distinct clinical subgroups of liver diseases with common molecular pathways.

Comput Methods Programs Biomed 2019 Jun 22;174:41-50. Epub 2018 Feb 22.

School of Computer and Information Technology and Beijing Key Lab of Traffic Data Analysis and Mining, Beijing Jiaotong University, Beijing 100044, China. Electronic address:

Background And Objective: Liver disease is a multifactorial complex disease with high global prevalence and poor long-term clinical efficacy and liver disease patients with different comorbidities often incorporate multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of clinical liver population to help gain more accurate disease subtypes for personalized treatment.

Methods: Individualized treatment of the traditional Chinese medicine (TCM) provides a theoretical basis to the study of personalized classification of complex diseases. Utilizing the TCM clinical electronic medical records (EMRs) of 6475 liver inpatient cases, we built a liver disease comorbidity network (LDCN) to show the complicated associations between liver diseases and their comorbidities, and then constructed a patient similarity network with shared symptoms (PSN). Finally, we identified liver patient subgroups using community detection methods and performed enrichment analyses to find both distinct clinical and molecular characteristics (with the phenotype-genotype associations and interactome networks) of these patient subgroups.

Results: From the comorbidity network, we found that clinical liver patients have a wide range of disease comorbidities, in which the basic liver diseases (e.g. hepatitis b, decompensated liver cirrhosis), and the common chronic diseases (e.g. hypertension, type 2 diabetes), have high degree of disease comorbidities. In addition, we identified 303 patient modules (representing the liver patient subgroups) from the PSN, in which the top 6 modules with large number of cases include 51.68% of the whole cases and 251 modules contain only 10 or fewer cases, which indicates the manifestation diversity of liver diseases. Finally, we found that the patient subgroups actually have distinct symptom phenotypes, disease comorbidity characteristics and their underlying molecular pathways, which could be used for understanding the novel disease subtypes of liver conditions. For example, three patient subgroups, namely Module 6 (M6, n = 638), M2 (n = 623) and M1 (n = 488) were associated to common chronic liver disease conditions (hepatitis, cirrhosis, hepatocellular carcinoma). Meanwhile, patient subgroups of M30 (n = 36) and M36 (n = 37) were mostly related to acute gastroenteritis and upper respiratory infection, respectively, which reflected the individual comorbidity characteristics of liver subgroups. Furthermore, we identified the distinct genes and pathways of patient subgroups and the basic liver diseases (hepatitis b and cirrhosis), respectively. The high degree of overlapping pathways between them (e.g. M36 with 93.33% shared enriched pathways) indicates the underlying molecular network mechanisms of each patient subgroup.

Conclusions: Our results demonstrate the utility and comprehensiveness of disease classification study based on community detection of patient network using shared TCM symptom phenotypes and it can be used to other more complex diseases.
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http://dx.doi.org/10.1016/j.cmpb.2018.02.014DOI Listing
June 2019

Use of Pressure Transducers.

N Engl J Med 2017 07;377(4):401

Boston University School of Medicine, Boston, MA

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http://dx.doi.org/10.1056/NEJMc1705833DOI Listing
July 2017

Use of Pressure Transducers.

N Engl J Med 2017 Apr;376(14):e26

From the Department of Anesthesiology, Boston Medical Center, Boston University School of Medicine, Boston.

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http://dx.doi.org/10.1056/NEJMvcm1513613DOI Listing
April 2017

X-ray backlighting of imploding aluminium liners on PTS facility.

Rev Sci Instrum 2016 Sep;87(9):093706

Institute of Fluid Physics, CAEP, Mianyang 621999, China.

The x-ray backlighting systems, including a 1.865 keV (Si He line) spherically bent crystal imaging system and an ∼8.3 keV (Cu He line) point-projection imaging system, newly fielded on the Primary Test Stand facility are introduced and its preliminary experimental results in radiography of the aluminium (Al) liners with seeded sinusoidal perturbations are presented. The x-ray backlighter source is created using a 1 TW, 1 kJ Nd: glass high power laser, kilo-joule laser system, recently constructed at China Academy of Engineering Physics. The ablation melt and instability of the imploding Al liner outer edge under the driving current of ∼7.5 MA are successfully observed using these two backlighting systems, respectively.
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http://dx.doi.org/10.1063/1.4961366DOI Listing
September 2016

Regulator of G protein signaling 4 is a novel target of GATA-6 transcription factor.

Biochem Biophys Res Commun 2017 02 13;483(3):923-929. Epub 2016 Oct 13.

Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA. Electronic address:

GATA transcription factors regulate an array of genes important in cell proliferation and differentiation. Here we report the identification of regulator of G protein signaling 4 (RGS4) as a novel target for GATA-6 transcription factor. Although three sites (a, b, c) within the proximal region of rabbit RGS4 promoter for GATA transcription factors were predicted by bioinformatics analysis, only GATA-a site (16 bp from the core TATA box) is essential for RGS4 transcriptional regulation. RT-PCR analysis demonstrated that only GATA-6 was highly expressed in rabbit colonic smooth muscle cells but GATA-4/6 were expressed in cardiac myocytes and GATA-1/2/3 expressed in blood cells. Adenovirus-mediated expression of GATA-6 but not GATA-1 significantly increased the constitutive and IL-1β-induced mRNA expression of the endogenous RGS4 in colonic smooth muscle cells. IL-1β stimulation induced GATA-6 nuclear translocation and increased GATA-6 binding to RGS4 promoter. These data suggest that GATA factor could affect G protein signaling through regulating RGS4 expression, and GATA signaling may develop as a future therapeutic target for RGS4-related diseases.
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http://dx.doi.org/10.1016/j.bbrc.2016.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266638PMC
February 2017

The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2.

Pflugers Arch 2016 05 2;468(5):817-24. Epub 2016 Feb 2.

Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA, 23298, USA.

Inwardly rectifying K(+) (Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP2. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP2. Channels with high apparent affinity to PIP2 may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl(-) current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP2 determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP2 for a common binding site.
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http://dx.doi.org/10.1007/s00424-016-1794-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317042PMC
May 2016

Effectiveness of a 40-minute Ophthalmologic Examination Teaching Session on Medical Student Learning.

West J Emerg Med 2015 Sep 20;16(5):721-6. Epub 2015 Oct 20.

University of California, Irvine School of Medicine, Emergency Department, Irvine, California.

Introduction: Emergency physicians are among the few specialists besides ophthalmologists who commonly perform ophthalmologic examinations using the slit lamp and other instruments. However, most medical schools in the United States do not require an ophthalmology rotation upon completion. Teaching procedural skills to medical students can be challenging due to limited resources and instructor availability. Our study assesses the effectiveness of a 40-minute hands-on teaching session on ophthalmologic examination for medical students using only two instructors and low-cost equipment.

Methods: We performed an interventional study using a convenience sample of subjects. Pre- and post-workshop questionnaires on students' confidence in performing ophthalmologic examination were administered. We used a paired t-test and Wilcoxon rank test to analyze the data.

Results: Of the 30 participants in the study, the mean age was 25 and the majority were first-year medical students. The students' confidence in performing every portion of the ophthalmologic exam increased significantly after the teaching session. We found that the average confidence level before the teaching session were below 2 on a 1-5 Likert scale (1 being the least confident). Confidence levels in using the slit lamp had the highest improvement among the skills taught (2.17 95% CI [1.84-2.49]). Students reported the least improvement in their confidence in assessing extraocular movements (0.73, 95% CI [0.30-1.71]) and examining pupillary function (0.73, 95% CI [0.42-1.04]). We observed the biggest difference in median confidence level in the use of the tonometer (4 with a p-value of <0.05).

Conclusion: A 40-minute structured hands-on training session can significantly improve students' confidence levels in ophthalmologic skills.
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http://dx.doi.org/10.5811/westjem.2015.7.24933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644041PMC
September 2015

ncRDeathDB: A comprehensive bioinformatics resource for deciphering network organization of the ncRNA-mediated cell death system.

Autophagy 2015 ;11(10):1917-26

a College of Bioinformatics Science and Technology; Harbin Medical University ; Harbin , China.

Programmed cell death (PCD) is a critical biological process involved in many important processes, and defects in PCD have been linked with numerous human diseases. In recent years, the protein architecture in different PCD subroutines has been explored, but our understanding of the global network organization of the noncoding RNA (ncRNA)-mediated cell death system is limited and ambiguous. Hence, we developed the comprehensive bioinformatics resource (ncRDeathDB, www.rna-society.org/ncrdeathdb ) to archive ncRNA-associated cell death interactions. The current version of ncRDeathDB documents a total of more than 4600 ncRNA-mediated PCD entries in 12 species. ncRDeathDB provides a user-friendly interface to query, browse and manipulate these ncRNA-associated cell death interactions. Furthermore, this resource will help to visualize and navigate current knowledge of the noncoding RNA component of cell death and autophagy, to uncover the generic organizing principles of ncRNA-associated cell death systems, and to generate valuable biological hypotheses.
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http://dx.doi.org/10.1080/15548627.2015.1089375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824571PMC
September 2016
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