Publications by authors named "Xi Fang"

96 Publications

Ecosystem service multifunctionality of Chinese fir plantations differing in stand age and implications for sustainable management.

Sci Total Environ 2021 May 15;788:147791. Epub 2021 May 15.

Faculty of Life Science and Technology, Central South University of Forestry and Technology, Changsha 410004, China; Huitong National Station for Scientific Observation and Research of Chinese Fir Plantation Ecosystem in Hunan Province, Huitong 438107, China. Electronic address:

Establishing forest plantations is an important solution to the growing conflict between an increasing human population and mounting pressure to protect the natural forests, as plantations also harbor great potential for providing multiple ecosystem services (ESs). However, because of the trade-offs between multiple ESs and the conflicts between different stakeholders, the sustainable management of plantations has been exceedingly challenging. Especially in recent years, with China's emphasis on ecological civilization construction and sustainable development, forestry departments have begun to focus on long-term ecological benefits, which conflict with farmers' attention to short-term economic gains. In this study, we quantified 15 field-based ES indicators from the data measured in Chinese fir (Cunninghamia lanceolata) plantations aged 4 to 32 years. Corresponding to the concerns of two different stakeholders (forestry departments and farmers), we calculated ES-multifunctionality with different thresholds under four management scenarios: equal weight, production only, production multifunctionality, and supporting multifunctionality. Our results suggested pronounced stand age effects on both individual ESs and ES-multifunctionality of plantations. For individual ESs, stand age had a greater impact on provisioning services than on supporting services. High degree of trade-offs existed between plantation provisioning ESs and soil nutrient supporting ESs, and between water relevant ESs and the other ESs. With respect to ES-multifunctionality, the values under different scenarios were all augmented with stand age, but to differing degrees. The values for supporting multifunctionality were higher than those of production multifunctionality and production only before 21 years of stand development, but completely reversed once the fir plantations reached an age of 25 years. Finally, several stage-based plantation management recommendations are proposed to minimize conflicts between different stakeholders. Our results combined measures of temporal stability and multifunctionality, thereby providing valuable and timely insight into the multifunctional stability of plantations represented by Chinese fir.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147791DOI Listing
May 2021

Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure.

Front Mol Biosci 2021 15;8:630332. Epub 2021 Apr 15.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.

Heart failure is one of the leading causes of morbidity and mortality worldwide. In cardiomyocytes, mitochondria are not only essential organelles providing more than 90% of the ATP necessary for contraction, but they also play critical roles in regulating intracellular Ca signaling, lipid metabolism, production of reactive oxygen species (ROS), and apoptosis. Because mitochondrial DNA only encodes 13 proteins, most mitochondrial proteins are nuclear DNA-encoded, synthesized, and transported from the cytoplasm, refolded in the matrix to function alone or as a part of a complex, and degraded if damaged or incorrectly folded. Mitochondria possess a set of endogenous chaperones and proteases to maintain mitochondrial protein homeostasis. Perturbation of mitochondrial protein homeostasis usually precedes disruption of the whole mitochondrial quality control system and is recognized as one of the hallmarks of cardiomyocyte dysfunction and death. In this review, we focus on mitochondrial chaperones and proteases and summarize recent advances in understanding how these proteins are involved in the initiation and progression of heart failure.
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http://dx.doi.org/10.3389/fmolb.2021.630332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082175PMC
April 2021

Histone Lysine Methyltransferase SETD2 Regulates Coronary Vascular Development in Embryonic Mouse Hearts.

Front Cell Dev Biol 2021 9;9:651655. Epub 2021 Apr 9.

Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.

Congenital heart defects are the most common birth defect and have a clear genetic component, yet genomic structural variations or gene mutations account for only a third of the cases. Epigenomic dynamics during human heart organogenesis thus may play a critical role in regulating heart development. However, it is unclear how histone mark H3K36me3 acts on heart development. Here we report that histone-lysine N-methyltransferase SETD2, an H3K36me3 methyltransferase, is a crucial regulator of the mouse heart epigenome. is highly expressed in embryonic stages and accounts for a predominate role of H3K36me3 in the heart. Loss of in cardiac progenitors results in obvious coronary vascular defects and ventricular non-compaction, leading to fetus lethality in mid-gestation, without affecting peripheral blood vessel, yolk sac, and placenta formation. Furthermore, deletion of dramatically decreased H3K36me3 level and impacted the transcriptional landscape of key cardiac-related genes, including and . Taken together, our results strongly suggest that SETD2 plays a primary role in H3K36me3 and is critical for coronary vascular formation and heart development in mice.
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http://dx.doi.org/10.3389/fcell.2021.651655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063616PMC
April 2021

An image-based approach for quantitative assessment of uniformity in particle distribution of noise reduction material.

Microsc Res Tech 2021 Mar 9. Epub 2021 Mar 9.

School of Science, Wuhan University of Technology, Wuhan, China.

Under the background of noise pollution caused by railway development, noise reduction material is worthy of in-depth study. A uniform distribution of particles in the material has an important influence on sound absorption property. In this article, the relevant image processing technology is applied to get structure information to quantify the uniformity. The main contributions of this study are: (a) In the preprocessing stage, SEM cross-sectional image of material is processed by mean filter and histogram equalization. Therefore, the grayscale and the contrast between target and background are enhanced, and a low-quality image is transformed into a high-quality one. (b) In the locating stage, local details of the image are considered to discriminate each particle from the whole image. When a global threshold is combined with the local iteration threshold, an improved Otsu algorithm is designed to binarize the image. Through morphology transforming, area filtering, and hole filling, the connected domain of target can be found and particles are located. (c) In the assessing stage, area index, number index and local distance index are established for assessing the uniformity of pore distribution. The experimental results indicate that statistical analysis is consistent with human visual observation. The smaller the porosity is, the better the uniformity is. Compared with some important methods, the effectiveness and efficiency of the proposed approach could be illustrated.
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http://dx.doi.org/10.1002/jemt.23748DOI Listing
March 2021

Atypical protein kinase C is essential for embryonic vascular development in mice.

Genesis 2021 Mar 6;59(3):e23412. Epub 2021 Feb 6.

Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China.

The atypical PKC (aPKC) subfamily constitutes PKCζ and PKCλ in mice, and both aPKC isoforms have been proposed to be involved in regulating various endothelial cell (EC) functions. However, the physiological function of aPKC in ECs during embryonic development has not been well understood. To address this question, we utilized Tie2-Cre to delete PKCλ alone (PKCλ-SKO) or both PKCλ and PKCζ (DKO) in ECs, and found that all DKO mice died at around the embryonic day 11.5 (E11.5), whereas a small proportion of PKCλ-SKO mice survived till birth. PKCλ-SKO embryos also exhibited less phenotypic severity than DKO embryos at E10.5 and E11.5, suggesting a potential compensatory role of PKCζ for PKCλ in embryonic ECs. We then focused on DKO embryos and investigated the effects of aPKC deficiency on embryonic vascular development. At E9.5, deletion of both aPKC isoforms reduced the diameters of vitelline artery and vein, and decreased branching from both vitelline vessels in yolk sac. Ablation of both aPKC isoforms also disrupted embryonic angiogenesis in head and trunk at the same stage, increasing apoptosis of both ECs and non-ECs. Taken together, our results demonstrated that aPKC in ECs plays an essential role in regulating cell apoptosis, angiogenesis, and embryonic survival.
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http://dx.doi.org/10.1002/dvg.23412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109193PMC
March 2021

Association of AI quantified COVID-19 chest CT and patient outcome.

Int J Comput Assist Radiol Surg 2021 Mar 23;16(3):435-445. Epub 2021 Jan 23.

Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

Purpose: Severity scoring is a key step in managing patients with COVID-19 pneumonia. However, manual quantitative analysis by radiologists is a time-consuming task, while qualitative evaluation may be fast but highly subjective. This study aims to develop artificial intelligence (AI)-based methods to quantify disease severity and predict COVID-19 patient outcome.

Methods: We develop an AI-based framework that employs deep neural networks to efficiently segment lung lobes and pulmonary opacities. The volume ratio of pulmonary opacities inside each lung lobe gives the severity scores of the lobes, which are then used to predict ICU admission and mortality with three different machine learning methods. The developed methods were evaluated on datasets from two hospitals (site A: Firoozgar Hospital, Iran, 105 patients; site B: Massachusetts General Hospital, USA, 88 patients).

Results: AI-based severity scores are strongly associated with those evaluated by radiologists (Spearman's rank correlation 0.837, [Formula: see text]). Using AI-based scores produced significantly higher ([Formula: see text]) area under the ROC curve (AUC) values. The developed AI method achieved the best performance of AUC = 0.813 (95% CI [0.729, 0.886]) in predicting ICU admission and AUC = 0.741 (95% CI [0.640, 0.837]) in mortality estimation on the two datasets.

Conclusions: Accurate severity scores can be obtained using the developed AI methods over chest CT images. The computed severity scores achieved better performance than radiologists in predicting COVID-19 patient outcome by consistently quantifying image features. Such developed techniques of severity assessment may be extended to other lung diseases beyond the current pandemic.
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http://dx.doi.org/10.1007/s11548-020-02299-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822756PMC
March 2021

Mild manifestations of COVID-19 in healthcare workers.

PLoS Negl Trop Dis 2020 12 22;14(12):e0008950. Epub 2020 Dec 22.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Medical staff treating Coronavirus Disease 2019 (COVID-19) patients are at high risk for exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and many have been infected, which may cause panic among medical workers, their relatives, health professionals, and government leaders. We report the epidemiologic and clinical characteristics of healthcare workers and that the majority of infected medical staff had milder symptoms/conditions with a better prognosis than admitted patients. Timely improvement to medical staff's working conditions such as allowing adequate rest and providing sufficient medical protection is extremely important.
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http://dx.doi.org/10.1371/journal.pntd.0008950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755190PMC
December 2020

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model.

Front Neurosci 2020 3;14:587986. Epub 2020 Dec 3.

Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, GA, United States.

Stroke is a major cause of death and long-term disability affecting seven million adults in the United States each year. Recently, it has been demonstrated that neurological diseases, associated pathology, and susceptibility changes correlated with changes in the gut microbiota. However, changes in the microbial community in stroke has not been well characterized. The acute stage of stroke is a critical period for assessing injury severity, therapeutic intervention, and clinical prognosis. We investigated the changes in the gut microbiota composition and diversity using a middle cerebral artery (MCA) occlusion ischemic stroke pig model. Ischemic stroke was induced by cauterization of the MCA in pigs. Blood samples were collected prestroke and 4 h, 12 h, 1 day, and 5 days poststroke to evaluate circulating proinflammatory cytokines. Fecal samples were collected prestroke and 1, 3, and 5 days poststroke to assess gut microbiome changes. Results showed elevated systemic inflammation with increased plasma levels of tumor necrosis factor alpha at 4 h and interleukin-6 at 12 h poststroke, relative to prestroke. Microbial diversity and evenness were reduced at 1 day poststroke compared to prestroke. Microbial diversity at 3 days poststroke was negatively correlated with lesion volume. Moreover, beta-diversity analysis revealed trending overall differences over time, with the most significant changes in microbial patterns observed between prestroke and 3 days poststroke. Abundance of the Proteobacteria was significantly increased, while Firmicutes decreased at 3 days poststroke, compared to prestroke populations. Abundance of the lactic acid bacteria was reduced at 3 days poststroke. By day 5, the microbial pattern returned to similar values as prestroke, suggesting the plasticity of gut microbiome in an acute period of stroke in a pig model. These findings provide a basis for characterizing gut microbial changes during the acute stage of stroke, which can be used to assess stroke pathology and the potential development of therapeutic targets.
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http://dx.doi.org/10.3389/fnins.2020.587986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744295PMC
December 2020

Integrative analysis for COVID-19 patient outcome prediction.

Med Image Anal 2021 01 13;67:101844. Epub 2020 Oct 13.

Department of Biomedical Engineering and the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address:

While image analysis of chest computed tomography (CT) for COVID-19 diagnosis has been intensively studied, little work has been performed for image-based patient outcome prediction. Management of high-risk patients with early intervention is a key to lower the fatality rate of COVID-19 pneumonia, as a majority of patients recover naturally. Therefore, an accurate prediction of disease progression with baseline imaging at the time of the initial presentation can help in patient management. In lieu of only size and volume information of pulmonary abnormalities and features through deep learning based image segmentation, here we combine radiomics of lung opacities and non-imaging features from demographic data, vital signs, and laboratory findings to predict need for intensive care unit (ICU) admission. To our knowledge, this is the first study that uses holistic information of a patient including both imaging and non-imaging data for outcome prediction. The proposed methods were thoroughly evaluated on datasets separately collected from three hospitals, one in the United States, one in Iran, and another in Italy, with a total 295 patients with reverse transcription polymerase chain reaction (RT-PCR) assay positive COVID-19 pneumonia. Our experimental results demonstrate that adding non-imaging features can significantly improve the performance of prediction to achieve AUC up to 0.884 and sensitivity as high as 96.1%, which can be valuable to provide clinical decision support in managing COVID-19 patients. Our methods may also be applied to other lung diseases including but not limited to community acquired pneumonia. The source code of our work is available at https://github.com/DIAL-RPI/COVID19-ICUPrediction.
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http://dx.doi.org/10.1016/j.media.2020.101844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553063PMC
January 2021

Photoelectrochemical immunosensor for methylated RNA detection based on WS and poly(U) polymerase-triggered signal amplification.

Mikrochim Acta 2020 Oct 9;187(11):596. Epub 2020 Oct 9.

College of Chemistry and Material Science, Food Safety Analysis and Test Engineering Technology Research Center of Shandong Province, Shandong Agricultural University, Tai'an, 271018, People's Republic of China.

A novel photoelectrochemical immunosensor has been constructed for the determination of methylated RNA. MoS nanosheets with large specific area were employed as photoactive material, gold nanoparticles were used as signal amplification unit and immobilization matrix of 4-mercaptophenylboronic acid, anti-mA antibody was adopted as methylated RNA recognition reagent, and poly(U) polymerase-mediated RNA chain extension and Ru(NH) were used as assisted signal amplification unit. With the sensitization effect of Ru(NH), the photoactivity of WS nanosheets was improved greatly, which also improved the sensitivity. Using visible-light excitation and ascorbic acid as electron donor, the sensitive determination of methylated RNA was achieved by monitoring the photocurrent change with different concentrations of methylated RNA. This photoelectrochemical immunosensor has a wide linear relationship with methylated RNA concentration from 0.05 to 35 nM under optimal experimental conditions. The low detection limit of 14.5 pM was realized based on 3σ criterion. In addition to the good selectivity, this sensor also presents high reproducibility with a relative standard deviation of 1.4% for the photocurrent of seven electrodes. The applicability of the developed method was also investigated by detecting the level of methylated RNA in corn seedling leaves with and without sulfadiazine treatment. Graphical abstract A novel photoelectrochemical immunosensor was developed for methylated RNA detection using the photoactive material of MoS2 and poly(U) polymerase-mediated RNA chain extension.
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http://dx.doi.org/10.1007/s00604-020-04572-5DOI Listing
October 2020

Homozygous G650del nexilin variant causes cardiomyopathy in mice.

JCI Insight 2020 08 20;5(16). Epub 2020 Aug 20.

Department of Medicine, UCSD, La Jolla, California, USA.

Nexilin (NEXN) was recently identified as a component of the junctional membrane complex required for development and maintenance of cardiac T-tubules. Loss of Nexn in mice leads to a rapidly progressive dilated cardiomyopathy (DCM) and premature death. A 3 bp deletion (1948-1950del) leading to loss of the glycine in position 650 (G650del) is classified as a variant of uncertain significance in humans and may function as an intermediate risk allele. To determine the effect of the G650del variant on cardiac structure and function, we generated a G645del-knockin (G645del is equivalent to human G650del) mouse model. Homozygous G645del mice express about 30% of the Nexn expressed by WT controls and exhibited a progressive DCM characterized by reduced T-tubule formation, with disorganization of the transverse-axial tubular system. On the other hand, heterozygous Nexn global KO mice and genetically engineered mice encoding a truncated Nexn missing the first N-terminal actin-binding domain exhibited normal cardiac function, despite expressing only 50% and 20% of the Nexn, respectively, expressed by WT controls, suggesting that not only quantity but also quality of Nexn is necessary for a proper function. These findings demonstrated that Nexn G645 is crucial for Nexn's function in tubular system organization and normal cardiac function.
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http://dx.doi.org/10.1172/jci.insight.138780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455123PMC
August 2020

Multi-Organ Segmentation Over Partially Labeled Datasets With Multi-Scale Feature Abstraction.

Authors:
Xi Fang Pingkun Yan

IEEE Trans Med Imaging 2020 11 28;39(11):3619-3629. Epub 2020 Oct 28.

Shortage of fully annotated datasets has been a limiting factor in developing deep learning based image segmentation algorithms and the problem becomes more pronounced in multi-organ segmentation. In this paper, we propose a unified training strategy that enables a novel multi-scale deep neural network to be trained on multiple partially labeled datasets for multi-organ segmentation. In addition, a new network architecture for multi-scale feature abstraction is proposed to integrate pyramid input and feature analysis into a U-shape pyramid structure. To bridge the semantic gap caused by directly merging features from different scales, an equal convolutional depth mechanism is introduced. Furthermore, we employ a deep supervision mechanism to refine the outputs in different scales. To fully leverage the segmentation features from all the scales, we design an adaptive weighting layer to fuse the outputs in an automatic fashion. All these mechanisms together are integrated into a Pyramid Input Pyramid Output Feature Abstraction Network (PIPO-FAN). Our proposed method was evaluated on four publicly available datasets, including BTCV, LiTS, KiTS and Spleen, where very promising performance has been achieved. The source code of this work is publicly shared at https://github.com/DIAL-RPI/PIPO-FAN to facilitate others to reproduce the work and build their own models using the introduced mechanisms.
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http://dx.doi.org/10.1109/TMI.2020.3001036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665851PMC
November 2020

Integrative Analysis for COVID-19 Patient Outcome Prediction.

ArXiv 2020 Jul 20. Epub 2020 Jul 20.

While image analysis of chest computed tomography (CT) for COVID-19 diagnosis has been intensively studied, little work has been performed for image-based patient outcome prediction. Management of high-risk patients with early intervention is a key to lower the fatality rate of COVID-19 pneumonia, as a majority of patients recover naturally. Therefore, an accurate prediction of disease progression with baseline imaging at the time of the initial presentation can help in patient management. In lieu of only size and volume information of pulmonary abnormalities and features through deep learning based image segmentation, here we combine radiomics of lung opacities and non-imaging features from demographic data, vital signs, and laboratory findings to predict need for intensive care unit (ICU) admission. To our knowledge, this is the first study that uses holistic information of a patient including both imaging and non-imaging data for outcome prediction. The proposed methods were thoroughly evaluated on datasets separately collected from three hospitals, one in the United States, one in Iran, and another in Italy, with a total 295 patients with reverse transcription polymerase chain reaction (RT-PCR) assay positive COVID-19 pneumonia. Our experimental results demonstrate that adding non-imaging features can significantly improve the performance of prediction to achieve AUC up to 0.884 and sensitivity as high as 96.1%, which can be valuable to provide clinical decision support in managing COVID-19 patients. Our methods may also be applied to other lung diseases including but not limited to community acquired pneumonia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386508PMC
July 2020

Perinatal Docosahexaenoic Acid Supplementation Improves Cognition and Alters Brain Functional Organization in Piglets.

Nutrients 2020 Jul 15;12(7). Epub 2020 Jul 15.

Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, GA 30602, USA.

Epidemiologic studies associate maternal docosahexaenoic acid (DHA)/DHA-containing seafood intake with enhanced cognitive development; although, it should be noted that interventional trials show inconsistent findings. We examined perinatal DHA supplementation on cognitive performance, brain anatomical and functional organization, and the brain monoamine neurotransmitter status of offspring using a piglet model. Sows were fed a control (CON) or a diet containing DHA (DHA) from late gestation throughout lactation. Piglets underwent an open field test (OFT), an object recognition test (ORT), and magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at weaning. Piglets from DHA-fed sows spent 95% more time sniffing the walls than CON in OFT and exhibited an elevated interest in the novel object in ORT, while CON piglets demonstrated no preference. Maternal DHA supplementation increased fiber length and tended to increase fractional anisotropy in the hippocampus of offspring than CON. DHA piglets exhibited increased functional connectivity in the cerebellar, visual, and default mode network and decreased activity in executive control and sensorimotor network compared to CON. The brain monoamine neurotransmitter levels did not differ in healthy offspring. Perinatal DHA supplementation may increase exploratory behaviors, improve recognition memory, enhance fiber tract integrity, and alter brain functional organization in offspring at weaning.
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http://dx.doi.org/10.3390/nu12072090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400913PMC
July 2020

Heat Shock Protein 60 in Cardiovascular Physiology and Diseases.

Front Mol Biosci 2020 30;7:73. Epub 2020 Apr 30.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.

Heat shock protein 60 (HSP60) is a highly conserved protein abundantly expressed in both prokaryotic and eukaryotic cells. In mammals, HSP60 has been primarily considered to reside in the mitochondria, where HSP60 and HSP10 form a complex and facilitate mitochondrial protein folding. However, HSP60 is also observed in the cytoplasm, the plasma membrane, and the extracellular space. HSP60 regulates a broad spectrum of cellular events including protein trafficking, peptide hormone signaling, cell survival, cell proliferation, inflammation, and immunization. In the cardiovascular system, growing evidence indicates that HSP60 could not only play an important role under physiological conditions, but also regulate the initiation and progression of heart failure and atherosclerosis. In this review, we focus on recent progress in understanding the function of HSP60 in cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs), respectively, and discuss the related signaling pathways that have been found in these cells, so as to illustrate the role of HSP60 in the development of cardiovascular disease.
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http://dx.doi.org/10.3389/fmolb.2020.00073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203681PMC
April 2020

Emergent hospital reform in response to outbreak of COVID-19.

Brain Behav Immun 2020 08 6;88:954-955. Epub 2020 May 6.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Wuhan Red Cross Hospital, Wuhan, Hubei, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202825PMC
August 2020

Emerging Evidence for Neuropsycho-Consequences of COVID-19.

Curr Neuropharmacol 2021 ;19(1):92-96

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

The pandemic novel coronavirus disease (COVID-19) has become a global concern in which the respiratory system is not the only one involved. Previous researches have presented the common clinical manifestations including respiratory symptoms (i.e., fever and cough), fatigue and myalgia. However, there is limited evidence for neurological and psychological influences of SARS-CoV-2. In this review, we discuss the common neurological manifestations of COVID-19 including acute cerebrovascular disease (i.e., cerebral hemorrhage) and muscle ache. Possible viral transmission to the nervous system may occur via circulation, an upper nasal transcribrial route and/or conjunctival route. Moreover, we cannot ignore the psychological influence on the public, medical staff and confirmed patients. Dealing with public psychological barriers and performing psychological crisis intervention are an important part of public health interventions.
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http://dx.doi.org/10.2174/1570159X18666200507085335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903490PMC
January 2021

Inositol 1,4,5-trisphosphate receptors are essential for fetal-maternal connection and embryo viability.

PLoS Genet 2020 04 22;16(4):e1008739. Epub 2020 Apr 22.

School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of intracellular Ca2+ release channels located on the ER membrane, which in mammals consist of 3 different subtypes (IP3R1, IP3R2, and IP3R3) encoded by 3 genes, Itpr1, Itpr2, and Itpr3, respectively. Studies utilizing genetic knockout mouse models have demonstrated that IP3Rs are essential for embryonic survival in a redundant manner. Deletion of both IP3R1 and IP3R2 has been shown to cause cardiovascular defects and embryonic lethality. However, it remains unknown which cell types account for the cardiovascular defects in IP3R1 and IP3R2 double knockout (DKO) mice. In this study, we generated conditional IP3R1 and IP3R2 knockout mouse models with both genes deleted in specific cardiovascular cell lineages. Our results revealed that deletion of IP3R1 and IP3R2 in cardiomyocytes by TnT-Cre, in endothelial / hematopoietic cells by Tie2-Cre and Flk1-Cre, or in early precursors of the cardiovascular lineages by Mesp1-Cre, resulted in no phenotypes. This demonstrated that deletion of both IP3R genes in cardiovascular cell lineages cannot account for the cardiovascular defects and embryonic lethality observed in DKO mice. We then revisited and performed more detailed phenotypic analysis in DKO embryos, and found that DKO embryos developed cardiovascular defects including reduced size of aortas, enlarged cardiac chambers, as well as growth retardation at embryonic day (E) 9.5, but in varied degrees of severity. Interestingly, we also observed allantoic-placental defects including reduced sizes of umbilical vessels and reduced depth of placental labyrinth in DKO embryos, which could occur independently from other phenotypes in DKO embryos even without obvious growth retardation. Furthermore, deletion of both IP3R1 and IP3R2 by the epiblast-specific Meox2-Cre, which targets all the fetal tissues and extraembryonic mesoderm but not extraembryonic trophoblast cells, also resulted in embryonic lethality and similar allantoic-placental defects. Taken together, our results demonstrated that IP3R1 and IP3R2 play an essential and redundant role in maintaining the integrity of fetal-maternal connection and embryonic viability.
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http://dx.doi.org/10.1371/journal.pgen.1008739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176088PMC
April 2020

Deep learning-based liver segmentation for fusion-guided intervention.

Int J Comput Assist Radiol Surg 2020 Jun 21;15(6):963-972. Epub 2020 Apr 21.

Department of Biomedical Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

Purpose: Tumors often have different imaging properties, and there is no single imaging modality that can visualize all tumors. In CT-guided needle placement procedures, image fusion (e.g. with MRI, PET, or contrast CT) is often used as image guidance when the tumor is not directly visible in CT. In order to achieve image fusion, interventional CT image needs to be registered to an imaging modality, in which the tumor is visible. However, multi-modality image registration is a very challenging problem. In this work, we develop a deep learning-based liver segmentation algorithm and use the segmented surfaces to assist image fusion with the applications in guided needle placement procedures for diagnosing and treating liver tumors.

Methods: The developed segmentation method integrates multi-scale input and multi-scale output features in one single network for context information abstraction. The automatic segmentation results are used to register an interventional CT with a diagnostic image. The registration helps visualize the target and guide the interventional operation.

Results: The segmentation results demonstrated that the developed segmentation method is highly accurate with Dice of 96.1% on 70 CT scans provided by LiTS challenge. The segmentation algorithm is then applied to a set of images acquired for liver tumor intervention for surface-based image fusion. The effectiveness of the proposed methods is demonstrated through a number of clinical cases.

Conclusion: Our study shows that deep learning-based image segmentation can obtain useful results to help image fusion for interventional guidance. Such a technique may lead to a number of other potential applications.
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http://dx.doi.org/10.1007/s11548-020-02147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305971PMC
June 2020

Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.

Brain Res 2020 06 16;1736:146778. Epub 2020 Mar 16.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States; Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, United States; Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA, United States. Electronic address:

The acute stroke phase is a critical time frame used to evaluate stroke severity, therapeutic options, and prognosis while also serving as a major tool for the development of diagnostics. To further understand stroke pathophysiology and to enhance the development of treatments, our group developed a translational pig ischemic stroke model. In this study, the evolution of acute ischemic tissue damage, immune responses, and functional deficits were further characterized. Stroke was induced by middle cerebral artery occlusion in Landrace pigs. At 24 h post-stroke, magnetic resonance imaging revealed a decrease in ipsilateral diffusivity, an increase in hemispheric swelling resulting in notable midline shift, and intracerebral hemorrhage. Stroke negatively impacted white matter integrity with decreased fractional anisotropy values in the internal capsule. Like patients, pigs showed a reduction in circulating lymphocytes and a surge in neutrophils and band cells. Functional responses corresponded with structural changes through reductions in open field exploration and impairments in spatiotemporal gait parameters. Characterization of acute ischemic stroke in pigs provided important insights into tissue and functional-level assessments that could be used to identify potential biomarkers and improve preclinical testing of novel therapeutics.
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http://dx.doi.org/10.1016/j.brainres.2020.146778DOI Listing
June 2020

A method of rapid quantification of patient-specific organ doses for CT using deep-learning-based multi-organ segmentation and GPU-accelerated Monte Carlo dose computing.

Med Phys 2020 Jun 3;47(6):2526-2536. Epub 2020 Apr 3.

Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

Purpose: One technical barrier to patient-specific computed tomography (CT) dosimetry has been the lack of computational tools for the automatic patient-specific multi-organ segmentation of CT images and rapid organ dose quantification. When previous CT images are available for the same body region of the patient, the ability to obtain patient-specific organ doses for CT - in a similar manner as radiation therapy treatment planning - will open the door to personalized and prospective CT scan protocols. This study aims to demonstrate the feasibility of combining deep-learning algorithms for automatic segmentation of multiple radiosensitive organs from CT images with the GPU-based Monte Carlo rapid organ dose calculation.

Methods: A deep convolutional neural network (CNN) based on the U-Net for organ segmentation is developed and trained to automatically delineate multiple radiosensitive organs from CT images. Two databases are used: The lung CT segmentation challenge 2017 (LCTSC) dataset that contains 60 thoracic CT scan patients, each consisting of five segmented organs, and the Pancreas-CT (PCT) dataset, which contains 43 abdominal CT scan patients each consisting of eight segmented organs. A fivefold cross-validation method is performed on both sets of data. Dice similarity coefficients (DSCs) are used to evaluate the segmentation performance against the ground truth. A GPU-based Monte Carlo dose code, ARCHER, is used to calculate patient-specific CT organ doses. The proposed method is evaluated in terms of relative dose errors (RDEs). To demonstrate the potential improvement of the new method, organ dose results are compared against those obtained for population-average patient phantoms used in an off-line dose reporting software, VirtualDose, at Massachusetts General Hospital.

Results: The median DSCs are found to be 0.97 (right lung), 0.96 (left lung), 0.92 (heart), 0.86 (spinal cord), 0.76 (esophagus) for the LCTSC dataset, along with 0.96 (spleen), 0.96 (liver), 0.95 (left kidney), 0.90 (stomach), 0.87 (gall bladder), 0.80 (pancreas), 0.75 (esophagus), and 0.61 (duodenum) for the PCT dataset. Comparing with organ dose results from population-averaged phantoms, the new patient-specific method achieved smaller absolute RDEs (mean ± standard deviation) for all organs: 1.8% ± 1.4% (vs 16.0% ± 11.8%) for the lung, 0.8% ± 0.7% (vs 34.0% ± 31.1%) for the heart, 1.6% ± 1.7% (vs 45.7% ± 29.3%) for the esophagus, 0.6% ± 1.2% (vs 15.8% ± 12.7%) for the spleen, 1.2% ± 1.0% (vs 18.1% ± 15.7%) for the pancreas, 0.9% ± 0.6% (vs 20.0% ± 15.2%) for the left kidney, 1.7% ± 3.1% (vs 19.1% ± 9.8%) for the gallbladder, 0.3% ± 0.3% (vs 24.2% ± 18.7%) for the liver, and 1.6% ± 1.7% (vs 19.3% ± 13.6%) for the stomach. The trained automatic segmentation tool takes <5 s per patient for all 103 patients in the dataset. The Monte Carlo radiation dose calculations performed in parallel to the segmentation process using the GPU-accelerated ARCHER code take <4 s per patient to achieve <0.5% statistical uncertainty in all organ doses for all 103 patients in the database.

Conclusion: This work shows the feasibility to perform combined automatic patient-specific multi-organ segmentation of CT images and rapid GPU-based Monte Carlo dose quantification with clinically acceptable accuracy and efficiency.
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http://dx.doi.org/10.1002/mp.14131DOI Listing
June 2020

Loss of Filamin C Is Catastrophic for Heart Function.

Circulation 2020 03 9;141(10):869-871. Epub 2020 Mar 9.

Departments of Medicine-Cardiology (Y.Z., Z.C., L.Z., M.Z., C.T., S.M.E., X.F., W.F., J.C.), University of California San Diego, La Jolla.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583669PMC
March 2020

Antibacterial Activity and Pharmacokinetic Profile of a Promising Antibacterial Agent: 22-(2-Amino-phenylsulfanyl)-22-Deoxypleuromutilin.

Molecules 2020 Feb 17;25(4). Epub 2020 Feb 17.

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China.

A new pleuromutilin derivative, 22-(2-amino-phenylsulfanyl)-22-deoxypleuromutilin (amphenmulin), has been synthesized and proved excellent in vitro and in vivo efficacy than that of tiamulin against methicillin-resistant (MRSA), suggesting this compound may lead to a promising antibacterial agent to treat MRSA infections. In this study, the effectiveness and safety of amphenmulin were further investigated. Amphenmulin showed excellent antibacterial activity against MRSA (minimal inhibitory concentration = 0.0156~8 µg/mL) and performed time-dependent growth inhibition and a concentration-dependent postantibiotic effect (PAE). Acute oral toxicity test in mice showed that amphenmulin was a practical non-toxic drug and possessed high security as a new drug with the 50% lethal dose (LD) above 5000 mg/kg. The pharmacokinetic properties of amphenmulin were then measured. After intravenous administration, the elimination half-life (T), total body clearance (Cl), and area under curve to infinite time (AUC) were 1.92 ± 0.28 h, 0.82 ± 0.09 L/h/kg, and 12.23 ± 1.35 μg·h/mL, respectively. After intraperitoneal administration, the T, Cl and AUC were 2.64 ± 0.72 h, 4.08 ± 1.14 L/h/kg, and 2.52 ± 0.81 μg·h/mL, respectively, while for the oral route were 2.91 ± 0.81 h, 6.31 ± 2.26 L/h/kg, 1.67 ± 0.66 μg·h/mL, respectively. Furthermore, we evaluated the antimicrobial activity of amphenmulin in an experimental model of MRSA wound infection. Amphenmulin enhanced wound closure and promoted the healing of wound, which inhibited MRSA bacterial counts in the wound and decreased serum levels of the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1.
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http://dx.doi.org/10.3390/molecules25040878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071076PMC
February 2020

Overexpression of Na-HCO cotransporter contributes to the exacerbation of cardiac remodeling in mice with myocardial infarction by increasing intracellular calcium overload.

Biochim Biophys Acta Mol Basis Dis 2020 03 26;1866(3):165623. Epub 2019 Nov 26.

Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

The role of the cardiac isoform of the electrogenic sodium-bicarbonate ion cotransporter (NBCe1) in cardiac remodeling is not fully understood. The aim of this study was to assess the effects of NBCe1 overexpression on cardiac remodeling induced by myocardial infarction (MI) in mice. We generated NBCe1 transgenic (Tg) mice and NBCe1 overexpressing adult mouse ventricular myocytes (AMVMs) to investigate the role of NBCe1 on post-MI remodeling and calcium kinetics. Tg mice showed a markedly higher mortality rate and larger infarct size after MI. At 6 weeks after MI, the maximum rising rates of left ventricular pressure (dp/dt), contractility index, and the exponential time constant of relaxation (τ) were markedly lower, and there was higher cardiomyocyte apoptosis, in Tg mice compared with WT mice. In cultured AMVMs, overexpression of NBCe1 decreased sarcomere shortening and calcium amplitude. In WT AMVMs, the rates of the rise and decay phase of calcium transients, indicated by the rising time (T, time to peak) and decay time constant (τ), and the number of apoptotic cells, were increased following hypoxia, while overexpression of NBCe1 further increased T and cellular apoptosis, but not τ. Intracellular resting calcium and sodium concentrations were significantly increased following both hypoxia and NBCe1 overexpression. Co-treatment with S0859, an NBCe1 antagonist, blocked the hypoxia-induced increase in T, τ intracellular resting calcium and sodium concentrations, and apoptosis in cardiomyocytes. These findings indicate that NBCe1 overexpression promotes cardiac remodeling by increasing intracellular calcium overload. Therefore, NBCe1 should be a potential target for treatment of cardiac remodeling.
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http://dx.doi.org/10.1016/j.bbadis.2019.165623DOI Listing
March 2020

Heat shock protein 60 regulates yolk sac erythropoiesis in mice.

Cell Death Dis 2019 10 10;10(10):766. Epub 2019 Oct 10.

School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, 518055, Shenzhen, China.

The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-CreHspd1 (HSP60) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60 yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.
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http://dx.doi.org/10.1038/s41419-019-2014-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786998PMC
October 2019

MiR-20b Down-Regulates Intestinal Ferroportin Expression In Vitro and In Vivo.

Cells 2019 09 24;8(10). Epub 2019 Sep 24.

Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.

Ferroportin (FPN) is the only known cellular iron exporter in mammalian. However, post-transcriptional regulation of intestinal FPN has not yet been completely understood. In this study, bioinformatics algorithms (TargetScan, PicTar, PITA, and miRanda) were applied to predict, screen and obtain microRNA-17 family members (miR-17, miR-20a, miR-20b, and miR-106a) targeting FPN, 'seed sequence' and responding binding sites on the 3'untranslated region (3'UTR) region of FPN. Dual-luciferase reporter assays revealed miRNA-17 family members' mimics decreased the luciferase activity, whereas their inhibitors increased the luciferase activity. Compared with the FPN 3'UTR wild type reporter, co-transfection of a miRNA-17 family members' over-expression plasmids and FPN 3'UTR mutant reporters enhanced the luciferase activity in HCT116 cells. Transfection with miR-20b overexpression plasmid significantly enhanced its expression, and it inhibited endogenous FPN protein expression in Caco-2 cells. Additionally, tail-vein injection of miR-20b resulted in increasing duodenal miR-20b expression, decreasing duodenal FPN protein expression, which was closely related to lower plasma iron level in mice. Taken together, these data suggest that the miR-20b is identified to regulate intestinal FPN expression in vitro and in vivo, which will provide a potential target for intestinal iron exportation.
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http://dx.doi.org/10.3390/cells8101135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829237PMC
September 2019

Preoperative albumin-to-fibrinogen ratio predicts chemotherapy resistance and prognosis in patients with advanced epithelial ovarian cancer.

J Ovarian Res 2019 Sep 18;12(1):88. Epub 2019 Sep 18.

Department of Gynecology, HwaMei Hospital, University Of Chinese Academy Of Sciences, NO 41, Xibei Street, Ningbo City, 315000, Zhejiang Province, China.

Background: Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery.

Methods: A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan-Meier method using log-rank test.

Results: The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan-Meier method by log-rank test (P < 0.001).

Conclusions: A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery.
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http://dx.doi.org/10.1186/s13048-019-0563-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751810PMC
September 2019

Identification of TAF1, SAT1, and ARHGEF9 as DNA methylation biomarkers for hepatocellular carcinoma.

J Cell Physiol 2020 01 8;235(1):611-618. Epub 2019 Jul 8.

Department of Rehabilitation, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. More than 90% of primary HCC is HCC. Hepatitis C virus (HCV) infection and alcohol consumption have been widely accepted as two major risk factors for developing HCC. Herein, we aimed to identify DNA methylation genes related to both HCV infection and alcohol consumption. In this study, we identified methylation genes that were associated with the risk of HCV infection and alcohol consumption, respectively, by a large-scale bioinformatic analysis. Through PPI network analysis, we revealed the associations between the two types of genes and found six hub genes-TAF1, SAT1, Phospholipase C-beta 2, FGD1, ARHGAP4, and ARHGEF9-that may be associated with both HCV infection and alcohol consumption. Gene Ontology enrichment analysis was used to analyze the function which these genes in the network enriched. Among them, TAF1, SAT1, and ARHGEF9 were methylated genes that have been found to be related to tumor progression in HCC patients. Through independent data sets, we verified the methylation pattern of these six genes in HCC samples that had both HCV infection and alcohol consumption risks. Furthermore, we found that three of the six methylated genes were also associated with the prognosis of HCC patients. To summarize, we identified six hub genes that were associated with both HCV infection and alcohol consumption in the progress of HCC. The six methylation genes that might play an important role in both HCV infection and alcohol consumption would be potential therapy targets for HCC.
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http://dx.doi.org/10.1002/jcp.28999DOI Listing
January 2020

Effect of Acute Ingestion of Green Tea Extract and Lemon Juice on Oxidative Stress and Lipid Profile in Pigs Fed a High-Fat Diet.

Antioxidants (Basel) 2019 Jun 23;8(6). Epub 2019 Jun 23.

Department of Foods and Nutrition, University of Georgia, Athens, GA 30602, USA.

Green tea and its catechins have been shown to ameliorate high fat diet-induced oxidative stress and hyperlipidemia. However, low bioavailability of catechins limits their therapeutic potential. Lemon juice (LJ) has been suggested to enhance the bioavailability of catechins in vitro. This study investigated the antioxidative and hypolipidemic efficacy of a single dose of green tea extract (GTE) or GTE plus LJ (GTE + LJ) in high-fat diet fed pigs. Sixteen pigs ingested a single dose of GTE (190 mg/kg/day) or GTE + LJ (0.75 mL/kg/day) mixed with low-fat (LF; 5% fat) or high-fat (HF; 22% fat) diets and blood samples were collected for 24 h. Plasma catechin level peaked at two hours, and gradually returned to baseline after six hours following the intake. The addition of LJ significantly increased plasma catechin level. The diet containing GTE did not lower plasma cholesterol and triacylglycerol (TG) concentrations, superoxide dismutase (SOD) and catalase activity, or malondialdehyde concentration in 24 h in HF-fed pigs. Addition of a single dose of LJ, however, significantly decreased plasma TG level in LF groups but did not cause further changes on any other markers compared to the GTE alone. Our findings indicate limited effect of a single meal containing GTE on plasma antioxidant enzymes, lipid profile, and lipid peroxidation in pigs and no significant synergistic/additive action of adding LJ to GTE within 24 h in pigs. A study with a longer treatment period is warranted to further understand the potential role of GTE in reducing HF diet-induced oxidative stress and the possible synergistic role of LJ.
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http://dx.doi.org/10.3390/antiox8060195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617406PMC
June 2019

Deletion of heat shock protein 60 in adult mouse cardiomyocytes perturbs mitochondrial protein homeostasis and causes heart failure.

Cell Death Differ 2020 02 17;27(2):587-600. Epub 2019 Jun 17.

School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, 518055, Shenzhen, China.

To maintain healthy mitochondrial enzyme content and function, mitochondria possess a complex protein quality control system, which is composed of different endogenous sets of chaperones and proteases. Heat shock protein 60 (HSP60) is one of these mitochondrial molecular chaperones and has been proposed to play a pivotal role in the regulation of protein folding and the prevention of protein aggregation. However, the physiological function of HSP60 in mammalian tissues is not fully understood. Here we generated an inducible cardiac-specific HSP60 knockout mouse model, and demonstrated that HSP60 deletion in adult mouse hearts altered mitochondrial complex activity, mitochondrial membrane potential, and ROS production, and eventually led to dilated cardiomyopathy, heart failure, and lethality. Proteomic analysis was performed in purified control and mutant mitochondria before mutant hearts developed obvious cardiac abnormalities, and revealed a list of mitochondrial-localized proteins that rely on HSP60 (HSP60-dependent) for correctly folding in mitochondria. We also utilized an in vitro system to assess the effects of HSP60 deletion on mitochondrial protein import and protein stability after import, and found that both HSP60-dependent and HSP60-independent mitochondrial proteins could be normally imported in mutant mitochondria. However, the former underwent degradation in mutant mitochondria after import, suggesting that the protein exhibited low stability in mutant mitochondria. Interestingly, the degradation could be almost fully rescued by a non-specific LONP1 and proteasome inhibitor, MG132, in mutant mitochondria. Therefore, our results demonstrated that HSP60 plays an essential role in maintaining normal cardiac morphology and function by regulating mitochondrial protein homeostasis and mitochondrial function.
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http://dx.doi.org/10.1038/s41418-019-0374-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205885PMC
February 2020