Publications by authors named "Xia Zhao"

1,007 Publications

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Occupational Health Risk Assessment of Benzene, Toluene, and Xylene in Shanghai.

Biomed Environ Sci 2021 Apr;34(4):290-298

Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200000, China.

Objective: This study was designed to conduct a retrospective and systematic occupational health risk assessment (OHRA) of enterprises that used benzene, toluene, and xylene (BTX) in Shanghai, China.

Methods: All data for the study were obtained from 1,705 occupational health examination and evaluation reports from 2013 to 2017, and a semiquantitative model following Chinese OHRA guidelines (GBZ/T 298-2017) was applied for the assessment.

Results: The selected enterprises using BTX were mainly involved in manufacturing of products. Using the exposure level method, health risk levels associated with exposure to BTX were classified as medium, negligible, or low. However, the risk levels associated with benzene and toluene were significantly different according to job types, with gluers and inkers exhibiting greater health risks. For the same job type, the health risk levels assessed using the comprehensive index method were higher than those using the exposure level method.

Conclusion: Our OHRA reveals that workers who are exposed to BTX still face excessive health risk. Additionally, the risk level varied depending on job categories and exposure to specific chemicals. Therefore, additional control measures recommended by OHRA guidelines are essential to reduce worker exposure levels.
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http://dx.doi.org/10.3967/bes2021.038DOI Listing
April 2021

BC-TFdb: a database of transcription factor drivers in breast cancer.

Database (Oxford) 2021 Apr;2021

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.

Transcription factors (TFs) are DNA-binding proteins, which regulate many essential biological functions. In several cancer types, TF function is altered by various direct mechanisms, including gene amplification or deletion, point mutations, chromosomal translocations, expression alterations, as well as indirectly by non-coding DNA mutations influencing the binding of the TF. TFs are also actively involved in breast cancer (BC) initiation and progression. Herein, we have developed an open-access database, BC-TFdb (Breast Cancer Transcription Factors database), of curated, non-redundant TF involved in BC. The database provides BC driver TFs related information including genomic sequences, proteomic sequences, structural data, pathway information, mutations information, DNA binding residues, survival and therapeutic resources. The database will be a useful platform for researchers to obtain BC-related TF-specific information. High-quality datasets are downloadable for users to evaluate and develop computational methods for drug designing against BC. Database URL: https://www.dqweilab-sjtu.com/index.php.
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http://dx.doi.org/10.1093/database/baab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060005PMC
April 2021

Association of Opioid Use Disorder With 2016 Presidential Voting Patterns: Cross-sectional Study in New York State at Census Tract Level.

JMIR Public Health Surveill 2021 Apr 21;7(4):e23426. Epub 2021 Apr 21.

Stony Brook University, Stony Brook, NY, United States.

Background: Opioid overdose-related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP) and opioid use disorder (OUD).

Objective: We aimed to discover geospatial patterns in nonmedical opioid use and its correlations with demographic features related to despair and economic hardship, most notably the US presidential voting patterns in 2016 at census tract level in New York State.

Methods: This cross-sectional analysis used data from New York Statewide Planning and Research Cooperative System claims data and the presidential voting results of 2016 in New York State from the Harvard Election Data Archive. We included 63,958 patients who had at least one OUD diagnosis between 2010 and 2016 and 36,004 patients with at least one OP diagnosis between 2012 and 2016. Geospatial mappings were created to compare areas of New York in OUD rates and presidential voting patterns. A multiple regression model examines the extent that certain factors explain OUD rate variation.

Results: Several areas shared similar patterns of OUD rates and Republican vote: census tracts in western New York, central New York, and Suffolk County. The correlation between OUD rates and the Republican vote was .38 (P<.001). The regression model with census tract level of demographic and socioeconomic factors explains 30% of the variance in OUD rates, with disability and Republican vote as the most significant predictors.

Conclusions: At the census tract level, OUD rates were positively correlated with Republican support in the 2016 presidential election, disability, unemployment, and unmarried status. Socioeconomic and demographic despair-related features explain a large portion of the association between the Republican vote and OUD. Together, these findings underscore the importance of socioeconomic interventions in combating the opioid epidemic.
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http://dx.doi.org/10.2196/23426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100884PMC
April 2021

Recent trends in drug-delivery systems for the treatment of diabetic retinopathy and associated fibrosis.

Adv Drug Deliv Rev 2021 Apr 20;173:439-460. Epub 2021 Apr 20.

Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau. Electronic address:

Diabetic retinopathy is a frequent microvascular complication of diabetes and a major cause of visual impairment. In advanced stages, the abnormal neovascularization can lead to fibrosis and subsequent tractional retinal detachment and blindness. The low bioavailability of the drugs at the target site imposed by the anatomic and physiologic barriers within the eye, requires long term treatments with frequent injections that often compromise patient's compliance and increase the risk of developing more complications. In recent years, much effort has been put towards the development of new drug delivery platforms aiming to enhance their permeation, to prolong their retention time at the target site and to provide a sustained release with reduced toxicity and improved efficacy. This review provides an overview of the etiology and pathophysiology of diabetic retinopathy and current treatments. It addresses the specific challenges associated to the different ocular delivery routes and provides a critical review of the most recent developments made in the drug delivery field.
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http://dx.doi.org/10.1016/j.addr.2021.04.007DOI Listing
April 2021

Antifungal activity and potential mechanism of Asiatic acid alone and in combination with fluconazole against Candida albicans.

Biomed Pharmacother 2021 Apr 10;139:111568. Epub 2021 Apr 10.

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong Province 250014, People's Republic of China. Electronic address:

Candida albicans (C. albicans) infection remains a challenge to clinicians due to the limited available antifungals. With the widespread use of antifungals in the clinic, the drug resistance has been emerging continuously, especially fluconazole. Therefore, searching for new antifungals, active constituents of natural or traditional medicines, and approaches to overcome antifungals resistance is needed. This study investigated the activity of Asiatic acid (AA) alone and in combination with fluconazole (FLC) against C. albicans in vitro and in vivo. The in vitro studies indicated that the drug combination had a synergistic effect on FLC-resistant C. albicans, with fractional inhibitory concentration index (FICI) of 0.25. And when AA at the dose of 32 µg/mL, the drug combination group could decrease the sessile minimum inhibitory concentration (sMIC) of FLC from > 1024 µg/mL to 0.125-0.25 µg/mL within 8 h against C. albicans biofilms, even with the FICI > 0.5. In vivo, the antifungal efficacy of AA used alone and in combination with FLC was evaluated by Galleria mellonella (G. mellonella) larvae. The drug combination group prolonged the survival rate and reduced tissue invasion of larvae infected with resistant C. albicans. Furthermore, mechanism studies indicated that the antifungal effects of AA in combination with FLC might be associated with the inhibition of drug efflux pump, the accumulation of reactive oxygen species (ROS) and the inhibition of hyphal growth. These findings might provide novel insights for overcoming drug resistance of C. albicans and bring new reference data for the development and application of AA in future.
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http://dx.doi.org/10.1016/j.biopha.2021.111568DOI Listing
April 2021

Applications of Biocompatible Scaffold Materials in Stem Cell-Based Cartilage Tissue Engineering.

Front Bioeng Biotechnol 2021 25;9:603444. Epub 2021 Mar 25.

Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States.

Cartilage, especially articular cartilage, is a unique connective tissue consisting of chondrocytes and cartilage matrix that covers the surface of joints. It plays a critical role in maintaining joint durability and mobility by providing nearly frictionless articulation for mechanical load transmission between joints. Damage to the articular cartilage frequently results from sport-related injuries, systemic diseases, degeneration, trauma, or tumors. Failure to treat impaired cartilage may lead to osteoarthritis, affecting more than 25% of the adult population globally. Articular cartilage has a very low intrinsic self-repair capacity due to the limited proliferative ability of adult chondrocytes, lack of vascularization and innervation, slow matrix turnover, and low supply of progenitor cells. Furthermore, articular chondrocytes are encapsulated in low-nutrient, low-oxygen environment. While cartilage restoration techniques such as osteochondral transplantation, autologous chondrocyte implantation (ACI), and microfracture have been used to repair certain cartilage defects, the clinical outcomes are often mixed and undesirable. Cartilage tissue engineering (CTE) may hold promise to facilitate cartilage repair. Ideally, the prerequisites for successful CTE should include the use of effective chondrogenic factors, an ample supply of chondrogenic progenitors, and the employment of cell-friendly, biocompatible scaffold materials. Significant progress has been made on the above three fronts in past decade, which has been further facilitated by the advent of 3D bio-printing. In this review, we briefly discuss potential sources of chondrogenic progenitors. We then primarily focus on currently available chondrocyte-friendly scaffold materials, along with 3D bioprinting techniques, for their potential roles in effective CTE. It is hoped that this review will serve as a primer to bring cartilage biologists, synthetic chemists, biomechanical engineers, and 3D-bioprinting technologists together to expedite CTE process for eventual clinical applications.
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http://dx.doi.org/10.3389/fbioe.2021.603444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026885PMC
March 2021

The diagnostic value of miR-145 and miR-205 in patients with cervical cancer.

Am J Transl Res 2021 15;13(3):1825-1832. Epub 2021 Mar 15.

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of University of South China Hengyang, Hu'nan Province, China.

Objective: To investigate the diagnostic value of miRNA-145 (miR-145) and miRNA-205 (miR-205) in cervical cancer patients.

Methods: Cervical tissue samples were collected from 144 patients diagnosed with and suspected to have cervical cancer in our hospital. Confirmed by pathology, 84 samples were obtained from cervical cancer patients and 60 samples were from patients with cervical intraepithelial neoplasia. Meanwhile, 30 patients with cervicitis were also selected, and the expression levels of miR-145, miR-205 and human papillomavirus (HPV) were detected in cervical lesions and normal cervical tissue.

Results: In comparison to normal cervical tissue, cervicitis and cervical intraepithelial neoplasia groups, the relative expression level of miR-145 was significantly lower, whereas the relative expression level of miR-205 was notably higher in the cervical cancer group, respectively (P<0.001). The area under the receiver operating characteristic (ROC) curve of miR-145 for diagnosis of cervical cancer in patients was 0.878, of which the sensitivity and the specificity were 0.905 and 0.822, respectively. The area under the ROC curve of miR-205 was 0.881, of which the sensitivity and the specificity was 0.869 and 0.889, respectively. Among all patients, the relative expression level of miR-145 was significantly lower while the relative expression level of miR-205 was considerably higher in HPV-positive patients than those of HPV-negative groups (P<0.001). Parauterine invasion, FIGO stage III-IV and lymphatic metastasis were considered as independent factors that affect the expression of miR-145. FIGO stage III-IV and lymphatic metastasis were independent factors affecting the expression of miR-205.

Conclusion: The low expression level of miR-145 and the high expression level of miR-205 in patients with cervical cancer demonstrate a certain diagnostic value in cervical cancer. The expression level of miR-145 and miR-205 is correlated with HPV infection and cervical tumor malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014394PMC
March 2021

Do Migrants Receive Tuberculosis Education in China? Evidence From the China Migrants Dynamic Survey.

Health Educ Behav 2021 Apr 7:10901981211000309. Epub 2021 Apr 7.

Fudan University School of Nursing, Shanghai, China.

Background: Migrants are the key population for tuberculosis (TB) transmission in China. However, it remains unknown how many migrants have received TB education and through what means.

Objectives: To identify the rate and methods of TB education among migrants in China by using nationally representative data.

Method: This study used secondary data analysis. The data were derived from the China Migrants Dynamic Survey 2014-2017. A total sample of 745,926 migrants was included in the following analysis. Information on TB education was collected through a self-report questionnaire. We used hierarchical logistic regression models to explore the relationship between the independent variables and the receipt of TB education.

Results: Only 30.4% ( = 226,458) received TB education. Among all age-groups, participants between 65 and 69 years old had the highest TB education rate (33.4%). Bulletin boards (86.5%-91%), media (73% to 86.7%), and books/magazines (59.2%-67.4%) were the most common ways for migrants to receive TB education.

Conclusions: Our study showed the rates of TB education in each region of China and indicated the significant disparity among the seven regions. Traditional media, off-line medical consultation, community advocacy, and bulletin boards should be the primary methods of delivering TB education. TB education campaigns targeting migrants with a low socioeconomic status should be actively promoted.
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http://dx.doi.org/10.1177/10901981211000309DOI Listing
April 2021

Effects of Pulmonary Fibrosis and Surface Tension On Alveolar Sac Mechanics in Diffuse Alveolar Damage.

J Biomech Eng 2021 Apr 5. Epub 2021 Apr 5.

Department of Rheumatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210027, China.

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern in most cases of acute respiratory distress syndrome and severe viral pneumonia, such as COVID-19. DAD is characterized by an acute phase with edema, hyaline membranes and inflammation followed by an organizing phase with pulmonary fibrosis and hyperplasia. The degree of pulmonary fibrosis and surface tension is different in the pathological stages of DAD. The effects of pulmonary fibrosis and surface tension on alveolar sac mechanics in DAD are investigated by using the fluid-structure interaction (FSI) method. The human pulmonary alveolus is idealized by a three-dimensional honeycomb-like geometry, with alveolar geometries approximated as closely packed 14-sided polygons. A dynamic compression-relaxation model for surface tension effects is adopted. Compared to a healthy model, DAD models are created by increasing the tissue thickness and decreasing the concentration of the surfactant. The FSI results show that pulmonary fibrosis is more influential than the surface tension on flow rate, volume, P-V loop and resistance. The lungs of the disease models become stiffer than those of the healthy models. According to the P-V loop results, the surface tension plays a more important role in hysteresis than the material nonlinearity of the lung tissue. Our study demonstrates the differences in air flow and lung function on the alveolar sacs between the healthy and DAD models.
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http://dx.doi.org/10.1115/1.4050789DOI Listing
April 2021

Long-term corrosion protection for magnesium alloy by two-layer self-healing superamphiphobic coatings based on shape memory polymers and attapulgite.

J Colloid Interface Sci 2021 Jul 9;594:836-847. Epub 2021 Mar 9.

Key Laboratory of Clay Mineral Applied Research of Gansu Province, and Center of Eco-Material and Green Chemistry, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Magnesium (Mg) alloy has wide potential applications due to its unique properties, but is apt to corrosion. Recently, superhydrophobic coatings are receiving great interest for corrosion protection of metals but suffer from short lifespan. Here, we report a strategy for long-term corrosion protection of Mg alloy by designing two-layer self-healing superamphiphobic coatings based on shape memory polymers (SMP) and attapulgite. The superamphiphobic coatings are composed of a bottom SMP coating containing a corrosion inhibitor (1, 2, 3-benzotriazole, BTA) and ceresine wax microparticles and a top superamphiphobic attapulgite coating. The two-layer self-healing coatings have excellent superamphiphobicity and initial anti-corrosion performance. The Mg alloy with the coatings can withstand immersion in 3.5 wt% NaCl solution for 80 days and neutral salt spray with 5 wt% NaCl for 54 days. Furthermore, the coatings show excellent self-healing capability towards various physical damages, such as 10 scratching/self-healing cycles at the same position, hexagonal star scratching and grid scratching. Moreover, the physically damaged coatings exhibit self-healing behavior of the microstructure and superhydrophobicity, driven by the shape memory effect of the bottom SMP layer. Thus, the self-healed coatings can still withstand 60 days of 3.5 wt% NaCl solution immersion and 30 days of 5 wt% NaCl salt spray. This study paves the way for applying super anti-wetting coatings for long-term corrosion protection of metals.
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http://dx.doi.org/10.1016/j.jcis.2021.03.005DOI Listing
July 2021

Silencing of hsa_circ_0009035 suppresses cervical progression and enhances radiosensitivity through miR-889-3p-dependent regulation of HOXB7.

Mol Cell Biol 2021 Mar 29. Epub 2021 Mar 29.

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of University of South China, Hengyang City, Hunan Province, China.

Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA (miR)-889-3p and homeobox B7 (HOXB7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease R (RNase R) and Actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration and invasion were gauged by the Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, respectively. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP) or RNA pull-down assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and enhanced apoptosis and radiosensitivity and weakened tumor growth Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance , and hsa_circ_0009035 modulated CC progression and radioresistance by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulation of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.
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http://dx.doi.org/10.1128/MCB.00631-20DOI Listing
March 2021

New insights into crosstalk between apoptosis and necroptosis co-induced by chlorothalonil and imidacloprid in Ctenopharyngodon idellus kidney cells.

Sci Total Environ 2021 Mar 20;780:146591. Epub 2021 Mar 20.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Overuse and co-exposure of pesticides have become a public health problem and threat seriously water health and environmental organisms and even humans. Chlorothalonil (CT) and imidacloprid (IMI) are high-selling pesticides worldwide, which can persist in the environment, and present a series of severely toxic effects on non-target animals. However, the effect of co-application on aquatic organisms is unknown. Based on the concept of the toxic unit (TU), toxic interaction of CT and IMI was evaluated and showed the additive and synergistic toxicity on Ctenopharyngodon idellus (grass carp) kidney cell line (CIK cells). Cell death analysis found an obvious increase of the apoptosis and necrosis rates exposed to CT and IMI, and aggravation when applied together. Moreover, CT and IMI co-exposure accelerated the inhibition of CYP450s/ROS/HIF-1α signal, the decline of energy metabolism, mitochondrial dynamics disorder, activation of Bcl2/Bax/Cyt C/Casp3/Casp9 pathway and RIP1/RIP3/MLKL pathway. Bioinformatics analysis showed autophagy, cell response, NOD-like receptor signaling pathway might be affected by co-exposure. In summary, the above results indicate that co-exposure to CT and IMI has synergistic toxicity and aggravates cell death via inhibition of the CYP450s/ROS/HIF-1α signal. These data provide new insights for evaluating the stacking interaction and revealing the toxicological effects of pesticide mixture.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146591DOI Listing
March 2021

SLR-superscaffolder: a de novo scaffolding tool for synthetic long reads using a top-to-bottom scheme.

BMC Bioinformatics 2021 Mar 25;22(1):158. Epub 2021 Mar 25.

BGI-Qingdao, BGI-Shenzhen, Qingdao, 266555, China.

Background: Synthetic long reads (SLR) with long-range co-barcoding information are now widely applied in genomics research. Although several tools have been developed for each specific SLR technique, a robust standalone scaffolder with high efficiency is warranted for hybrid genome assembly.

Results: In this work, we developed a standalone scaffolding tool, SLR-superscaffolder, to link together contigs in draft assemblies using co-barcoding and paired-end read information. Our top-to-bottom scheme first builds a global scaffold graph based on Jaccard Similarity to determine the order and orientation of contigs, and then locally improves the scaffolds with the aid of paired-end information. We also exploited a screening algorithm to reduce the negative effect of misassembled contigs in the input assembly. We applied SLR-superscaffolder to a human single tube long fragment read sequencing dataset and increased the scaffold NG50 of its corresponding draft assembly 1349 fold. Moreover, benchmarking on different input contigs showed that this approach overall outperformed existing SLR scaffolders, providing longer contiguity and fewer misassemblies, especially for short contigs assembled by next-generation sequencing data. The open-source code of SLR-superscaffolder is available at https://github.com/BGI-Qingdao/SLR-superscaffolder .

Conclusions: SLR-superscaffolder can dramatically improve the contiguity of a draft assembly by integrating a hybrid assembly strategy.
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http://dx.doi.org/10.1186/s12859-021-04081-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993450PMC
March 2021

A review of the interfacial stability mechanism of aging oily sludge: Heavy components, inorganic particles, and their synergism.

J Hazard Mater 2021 Mar 10;415:125624. Epub 2021 Mar 10.

College of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resource Reuse, Ministry of Education Key Laboratory of Yangtze River Water Environment, Shanghai Institute of Pollution Control and Ecological Security, Tongji University, Shanghai 200092, China. Electronic address:

Oily sludge is widely produced in the processes of petroleum exploitation, storage, transportation, and refining, and becomes more stable during aging. The interfacial stability of aging oily sludge hinders the recovery and disposal of oil resources. This review summarizes the interfacial film stability of aging oily sludge, which occurs through the formation of viscoelastic and rigid bilayer interfacial films between heavy components (asphaltenes and resins) and inorganic particles. The bilayer interfacial films enhance interfacial film strength and hinder the aggregation of droplets, contributing to the formation of a stable and high-viscosity oil-water-solid three-phase mixture. Recent demulsification technologies for reducing the stability of interfacial films have been classified as follows: removing heavy components, changing asphaltene aggregate structure, and reducing inorganic particle content. More efficient demulsification technologies are expected to be developed by deeply analyzing the microstructure and interfacial properties of asphaltenes and resins, as well as comprehensively studying the complex interactions among various components. This review constructs a bridge between the stability mechanism and the corresponding destabilization methods, which would promote future studies in aging oily sludge treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125624DOI Listing
March 2021

Long non-coding RNA FOXD2-AS1 promotes proliferation, migration and invasion of ovarian cancer cells via regulating the expression of miR-4492.

Exp Ther Med 2021 Apr 1;21(4):307. Epub 2021 Feb 1.

Department of Gynecology, Laizhou People's Hospital, Yantai, Shandong 261400, P.R. China.

The aim of the present study was to determine the role of long non-coding RNA (lncRNA) forkhead box D2 antisense 1 (FOXD2-AS1) in the development of ovarian cancer, investigate the underlying mechanisms and provide a potential diagnostic biomarker for ovarian cancer. A total of 39 ovarian cancer patients were included, and the ovarian cancer tissues and paracancer tissues were obtained. The ovarian cancer cell lines SKOV3 and OVCAR3 and the human ovarian normal epithelial cell line IOSE80 were cultured. The expression of lncRNA FOXD2-AS1 and miR-4492 was detected by reverse transcription-quantitative PCR. Small interfering RNA targeting FOXD2-AS1 (si-FOXD2-AS1), microRNA (miR)-4492 mimics, miR-4492 inhibitor and their corresponding controls were transfected into cells. The proliferation was detected with a Cell-Couting-Kit-8 assay, and migration and invasion were determined using Transwell assays. The mutual binding site of lncRNA FOXD2-AS1 and miR-4492 was predicted with the miRDB database and verified by a luciferase reporter assay. Finally, a rescue assay was performed. The results suggested that lncRNA FOXD2-AS1 was upregulated in ovarian cancer tissues and cell lines. si-FOXD2-AS1 was able to inhibit the proliferation, migration and invasion of ovarian cancer cells. lncRNA FOXD2-AS1 was confirmed to directly target miR-4492. The expression of lncRNA FOXD2-AS1 and miR-4492 exhibited a negative correlation. In a rescue experiment, miR-4492 inhibitor abrogated the effect of siFOXD2-AS1 in SKOV3 and OVCAR3 cell lines. In conclusion, lncRNA FOXD2-AS1 promotes the proliferation and invasion of ovarian cancer cells via regulating the expression of miR-4492. It may be a novel potential diagnostic biomarker and therapeutic target for ovarian cancer.
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http://dx.doi.org/10.3892/etm.2021.9738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885078PMC
April 2021

Gu-Ben-Fang-Xiao decoction modulates lipid metabolism by activating the AMPK pathway in asthma remission.

Biomed Pharmacother 2021 Jun 11;138:111403. Epub 2021 Mar 11.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China; Pediatric Institution of Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing 210023, China; Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Gu-Ben-Fang-Xiao decoction (GBFXD), derived from the traditional Chinese medicine Yu-Ping-Feng-San, is widely used in clinical settings and has obvious curative effects in respiratory diseases. GBFXD regulates cholesterol transport and lipid metabolism in chronic persistent asthma. There is evidence for its beneficial effects in the remission stage of asthma; however, its metabolic regulatory effects and underlying mechanisms during asthma remission are unclear. In the present study, we used liquid chromatography-mass spectrometry (LC-MS) to analyse the metabolic profile of mouse serum during asthma remission. The acquired LC-MS data were subjected to a multivariate analysis for identification of significantly altered metabolites. In total, 42 metabolites were significantly differentially expressed among the control, model, and GBFXD groups. In particular, levels of fatty acids, acylcarnitines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, triglycerides, and diacylglycerols were altered during asthma remission. GBFXD may maintain lipid homeostasis on the lung surface by modulating lipid metabolism and may thereby alleviate asthma. We further quantified hypogeic acid (FA 16:1) based on targeted metabolomics and found that GBFXD may regulate fatty acid metabolism by activating the AMP-activated protein kinase (AMPK) pathway. These results support the use of GBFXD in patients with asthma remission.
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http://dx.doi.org/10.1016/j.biopha.2021.111403DOI Listing
June 2021

H S catalysed by CBS regulates testosterone synthesis through affecting the sulfhydrylation of PDE.

J Cell Mol Med 2021 Apr 13;25(7):3460-3468. Epub 2021 Mar 13.

Department of Reproductive Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Testosterone deficiency resulted in increased mortality in men. Our previous work found that hydrogen sulphide (H S) significantly alleviated the spermatogenesis disorder. To investigate whether H S could regulate testosterone synthesis and the relative signalling pathways. Disorder model of testosterone synthesis was constructed in vitro and in vivo. The cell viability was detected using CCK-8 method. The concentration of H S and testosterone were examined using ELISA kits. The relative mRNA and protein expression of CBS, PDE4A, PDE8A and proteins related to testosterone synthesis were detected by RT-qPCR and western blotting. PAS staining was used to detect the inflammatory status of testis. The sulfhydryl level of PDE4A and PDE8A was determined by Biotin Switch Technique. CBS overexpression inhibited while knockdown promoted LPS + H O induced injury in testosterone synthesis of MLTC-1 cells, though regulating the level of H S. The LPS + H O induced inhibition on cAMP and p-PKA was recovered by CBS overexpression, while addition of the specific inhibitor of PKA had opposite effects. CBS overexpression alleviated the inflammation status in testis and promoted the expression of StAR, P450scc, P450c17 and 3β-HSD. CBS could also exhibit its protective role through promoting sulfhydrylation of PDE4A and PDE8A. H S catalysed by CBS could recover testosterone synthesis in vitro and in vivo through inhibiting PDE expression via sulfhydryl modification and activating cAMP/PKA pathway.
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http://dx.doi.org/10.1111/jcmm.16428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034449PMC
April 2021

A large-scale retrospective study of opioid poisoning in New York State with implications for targeted interventions.

Sci Rep 2021 Mar 4;11(1):5152. Epub 2021 Mar 4.

Department of Biomedical Informatics, Stony Brook University, 2313D Computer Science, Stony Brook, NY, 11794-8330, USA.

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP). To discover trends and patterns of opioid poisoning and the demographic and regional disparities, we analyzed large scale patient visits data in New York State (NYS). Demographic, spatial, temporal and correlation analyses were performed for all OP patients extracted from the claims data in the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016, along with Decennial US Census and American Community Survey zip code level data. 58,481 patients with at least one OP diagnosis and a valid NYS zip code address were included. Main outcome and measures include OP patient counts and rates per 100,000 population, patient level factors (gender, age, race and ethnicity, residential zip code), and zip code level social demographic factors. The results showed that the OP rate increased by 364.6%, and by 741.5% for the age group > 65 years. There were wide disparities among groups by race and ethnicity on rates and age distributions of OP. Heroin and non-heroin based OP rates demonstrated distinct temporal trends as well as major geospatial variation. The findings highlighted strong demographic disparity of OP patients, evolving patterns and substantial geospatial variation.
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http://dx.doi.org/10.1038/s41598-021-84148-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933431PMC
March 2021

A Semi-Quantitative Risk Assessment and Management Strategies on COVID-19 Infection to Outpatient Health Care Workers in the Post-Pandemic Period.

Risk Manag Healthc Policy 2021 25;14:815-825. Epub 2021 Feb 25.

Hospital Infection Management Division, Xuan Wu Hospital Capital Medical University, Beijing, People's Republic of China.

Background: In the pandemic of COVID-19, due to asymptomatic patients and high personnel fluidity in outpatient clinics, health care workers (HCWs) in outpatients were facing severe threat from infection. There is an urgent need for a risk assessment to recognize and prevent infection risks.

Purpose: To establish a semi-quantitative risk assessment model on COVID-19 infections for HCWs in outpatient departments, and apply it to practices. Further to provide infection risk management strategies to reduce infection threats in the post-pandemic of COVID-19.

Methods: We used the method of Brainstorm, Literature study and Analytic Hierarchy Process (AHP) for risk factors selection and model construction, we also created corresponding indicators for each risk factors, in order to collect data in assessment practice.

Results: Eighteen risk factors were recognized and selected for model construction, by scatter plot, these risk factors had been classified into four parts, spanned the scopes of diagnosis and treatment, environment, personal protection and emergency handling, with specific management suggestions provided. In the practice, outpatient clinics were divided into three risk levels, 5 clinics in high risk level, 9 in medium risk level and 11 in low risk level.

Conclusion: A proper comprehensive risk assessment model for COVID-19 infections has been successfully established. With the model, the ability to COVID-19 prevention in outpatients can be easily evaluated. The strategies on disinfection, surveillance and personal protection were also valuable references in the post-pandemic of COVID-19.
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http://dx.doi.org/10.2147/RMHP.S293198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920612PMC
February 2021

[Study on liver diseases with zebrafish as an important tool].

Zhongguo Zhong Yao Za Zhi 2021 Jan;46(2):320-332

Beijing Key Laboratory of Chinese Medicine Quality Evaluation, College of Chinese Medicine, Beijing University of Chinese Medicine Beijing 102488, China.

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200916.601DOI Listing
January 2021

Casein Kinase 2-Interacting Protein-1 Alleviates High Glucose-Reduced Autophagy, Oxidative Stress, and Apoptosis in Retinal Pigment Epithelial Cells via Activating the p62/KEAP1/NRF2 Signaling Pathway.

J Ophthalmol 2021 11;2021:6694050. Epub 2021 Feb 11.

Department of Geriatrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China.

Background: Casein kinase 2-interacting protein-1 (CKIP-1) has been proved to be associated with complications of diabetes. Diabetic retinopathy is a main diabetic complication which usually leads to blindness. The current study aims to investigate the role of CKIP-1 in high glucose-treated retinal pigment epithelial (RPE) cells which is a component of blood-retinal barriers.

Methods: The RPE cells, ARPE-19, are treated with high glucose to mimic the diabetic stimulation. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively.

Results: CKIP-1 was expressed at a lower level in high glucose-treated cells than in normal glucose cells. Overexpression of CKIP-1 enhanced the Nrf2 translocation to the nucleus. Furthermore, high glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. Also, CKIP-1 regulates the p62/Keap1/Nrf2 signaling, which might be the potential mechanism in this model.

Conclusion: In conclusion, CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose.
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http://dx.doi.org/10.1155/2021/6694050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892229PMC
February 2021

Cadmium exposure induces TNF-α-mediated necroptosis via FPR2/TGF-β/NF-κB pathway in swine myocardium.

Toxicology 2021 04 21;453:152733. Epub 2021 Feb 21.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cadmium (Cd) is one common environmental pollutant with systemic toxicity. Lipoxin A4 (LXA4) can regulate transforming growth factor-β (TGF-β) pathway and alleviate tissue injury via binding to formyl peptide receptor 2 (FPR2). The activation of nuclear factor-κB (NF-κB) pathway can promote the occurence of necroptosis. However, whether Cd exposure induces necroptosis in swine myocardium and the role of FPR2/TGF-β/NF-κB pathway in this process are unclear. Hence, we established Cd-exposed swine myocardial injury model by feeding a CdCl added diet (20 mg Cd/kg diet). Hematoxylin-eosin (H&E) staining was used to observe the morphological changes, and inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect the levels of ion elements in myocardium. We further detected LXA4 and its receptor FPR2, TGF-β, Nrf2, NF-κB pathway and necroptosis related-genes expressions by RT-PCR and western blot. The results showed that Cd exposure induced necrotic cell death and ion homeostasis imbalance in swine myocardium. Moreover, Cd exposure increased the LXA4 content, inhibited the FPR2 expression, activated TGF-β pathway and suppressed Nrf2 pathway, activating the NF-κB pathway. In addition, Cd exposure increased the expressions of necroptosis related-genes TNF-α, TNFR1, RIP1, RIP3 and MLKL. It indicated Cd exposure induced necroptosis via FPR2/TGF-β/NF-κB pathway, revealing the potential mechanism of Cd-induced cardiotoxicity in swine myocardium.
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http://dx.doi.org/10.1016/j.tox.2021.152733DOI Listing
April 2021

Apigenin suppresses proliferation, invasion, and epithelial-mesenchymal transition of cervical carcinoma cells by regulation of miR-152/BRD4 axis.

Kaohsiung J Med Sci 2021 Feb 20. Epub 2021 Feb 20.

Department of Radiology, The first Affiliated Hospital of University of South China, Hengyang, China.

The present study aimed to investigate the role of apigenin and the molecular mechanism of miR-152-5p and bromodomain containing 4 (BRD4) in the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of cervical carcinoma cells. Quantitative real-time PCR was used to detect the transfection efficiency and the expression of miR-152-5p and BRD4. Western blotting was conducted to evaluate the protein level of BRD4, E-cadherin, N-cadherin, and MMP9. Luciferase reporter assay was performed to confirm whether miR-152-5p bound to BRD4. MTT and Transwell invasion assay were applied to determine the cell proliferation and invasion, respectively. MiR-152-5p was downregulated and BRD4 was upregulated in cervical carcinoma tissue. Besides, miR-152-5p could directly bind to BRD4 in Hela and CaSki cells. In addition, apigenin inhibited proliferation, invasion, and EMT of Hela and CaSki cells by regulating miR-152-5p/BRD4 axis. Apigenin suppresses proliferation, invasion, and induced EMT of cervical carcinoma cells by regulation of miR-152-5p/BRD4 axis.
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http://dx.doi.org/10.1002/kjm2.12370DOI Listing
February 2021

Identification of candidate genes influencing anthocyanin biosynthesis during the development and ripening of red and white strawberry fruits via comparative transcriptome analysis.

PeerJ 2021 2;9:e10739. Epub 2021 Feb 2.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou, China.

Strawberries are one of the most economically important berry fruits worldwide and exhibit colours ranging from white to dark red, providing a rich genetic resource for strawberry quality improvement. In the present study, we conducted transcriptome analyses of three strawberry cultivars, namely, 'Benihoppe', 'Xiaobai', and 'Snow White', and compared their gene expression profiles. Among the high-quality sequences, 5,049 and 53,200 differentially expressed genes (DEGs) were obtained when comparing the diploid and octoploid strawberry genomes and analysed to identify anthocyanin-related candidate genes. Sixty-five DEGs in the diploid genome (transcriptome data compared to the diploid strawberry genome) and 317 DEGs in the octoploid genome (transcriptome data compared to the octoploid strawberry genome) were identified among the three cultivars. Among these DEGs, 19 and 70 anthocyanin pathway genes, six and 42 sugar pathway genes, 23 and 101 hormone pathway genes, and 17 and 104 transcription factors in the diploid and octoploid genomes, respectively, correlated positively or negatively with the anthocyanin accumulation observed among the three cultivars. Real-time qPCR analysis of nine candidate genes showed a good correlation with the transcriptome data. For example, the expression of PAL was higher in 'Benihoppe' and 'Xiaobai' than in 'Snow White', consistent with the RNA-seq data. Thus, the RNA-seq data and candidate DEGs identified in the present study provide a sound basis for further studies of strawberry fruit colour formation.
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http://dx.doi.org/10.7717/peerj.10739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863778PMC
February 2021

Hepatocellular Carcinoma with Portal Vein Tumor Thrombus versus Hepatocellular Carcinoma with Biliary Tumor Thrombus: Better or Worse Prognoses? [Response to Letter].

Cancer Manag Res 2021 11;13:1323-1324. Epub 2021 Feb 11.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

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http://dx.doi.org/10.2147/CMAR.S304083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884955PMC
February 2021

Influence of gene polymorphisms on the pharmacokinetics of aripiprazole in healthy Chinese subjects.

Pharmacogenomics 2021 Mar 15;22(4):213-223. Epub 2021 Feb 15.

GCP Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Pharmacogenetics study was added into 2 bioequivalence trials of aripiprazole. The correlation between polymorphisms and aripiprazole pharmacokinetics (PK) was analyzed. A total of 140 subjects were included. A total of 26 gene alleles were detected. The plasma concentration of aripiprazole was measured by liquid chromatography-tandem mass spectrometry. was used to analyze the correlation between polymorphisms and aripiprazole PK parameters. All of the four PK parameters were significantly influenced by and . t and area under the concentration-time curve exhibited significant difference between extensive metabolizers and intermediate metabolizers. Aripiprazole PK was greatly influenced by . Attention should be paid to the possible dose adjustment for intermediate metabolizer population when the drug is used in Chinese patients.
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http://dx.doi.org/10.2217/pgs-2020-0134DOI Listing
March 2021

Cadmium exposure induces mitochondrial pathway apoptosis in swine myocardium through xenobiotic receptors-mediated CYP450s activation.

J Inorg Biochem 2021 Apr 2;217:111361. Epub 2021 Feb 2.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Cadmium (Cd) pollution has become an important public and environmental health issue. Xenobiotic receptors (XRs, aryl hydrocarbon receptor, AHR; constitutive androstane receptor, CAR; pregnane X receptor, PXR) modulate downstream cytochrome P450 enzymes (CYP450s) expression to metabolize xenobiotics and environmental contaminants. However, the underlying mechanisms of cardiotoxicity induced by Cd(II) in swine and the roles of XRs and CYP450s remain poorly understood. In this study, the cardiotoxicity of Cd(II) was investigated by establishing a Cd(II)-exposed swine model (CdCl, 20 mg Cd/Kg diet). Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay and transmission electron microscope were used to observe the apoptosis. Antioxidant capacity was evaluated by free radicals contents and antioxidant enzymes activities. RT-PCR and western blot were used to measure the expression of XRs, CYP450s and apoptosis-related genes. Our results revealed that Cd(II) exposure activated the XRs and increased the CYP450s expression, contributing to the production of reactive oxygen species (ROS). Cd(II) exposure restrained the antioxidant capacity, causing oxidative stress. Moreover, mitogen-activated protein kinase (MAPK) pathway including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (P38) was activated, triggering the mitochondrial apoptotic pathway. In brief, we concluded that Cd(II) caused mitochondrial pathway apoptosis in swine myocardium via the oxidative stress-MAPK pathway, and XRs-mediated CYP450s expression might participate in this process through promoting the ROS.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111361DOI Listing
April 2021

Notch signaling: Its essential roles in bone and craniofacial development.

Genes Dis 2021 Jan 11;8(1):8-24. Epub 2020 Apr 11.

Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.

Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.
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http://dx.doi.org/10.1016/j.gendis.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859553PMC
January 2021