Publications by authors named "Nan Jin"

105 Publications

Balanced Convolutional Neural Networks for Pneumoconiosis Detection.

Int J Environ Res Public Health 2021 Aug 28;18(17). Epub 2021 Aug 28.

Department of Automation, Tsinghua University, Beijing 100084, China.

Pneumoconiosis remains one of the most common and harmful occupational diseases in China, leading to huge economic losses to society with its high prevalence and costly treatment. Diagnosis of pneumoconiosis still strongly depends on the experience of radiologists, which affects rapid detection on large populations. Recent research focuses on computer-aided detection based on machine learning. These have achieved high accuracy, among which artificial neural network (ANN) shows excellent performance. However, due to imbalanced samples and lack of interpretability, wide utilization in clinical practice meets difficulty. To address these problems, we first establish a pneumoconiosis radiograph dataset, including both positive and negative samples. Second, deep convolutional diagnosis approaches are compared in pneumoconiosis detection, and a balanced training is adopted to promote recall. Comprehensive experiments conducted on this dataset demonstrate high accuracy (88.6%). Third, we explain diagnosis results by visualizing suspected opacities on pneumoconiosis radiographs, which could provide solid diagnostic reference for surgeons.
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http://dx.doi.org/10.3390/ijerph18179091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431598PMC
August 2021

Macroautophagy supports Sonic Hedgehog signaling by promoting Patched1 degradation.

Biochim Biophys Acta Mol Cell Res 2021 Aug 20;1868(12):119124. Epub 2021 Aug 20.

Department of Medical Genetics, Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Maternal & Child Health Hospital, Nanchang, Jiangxi 330006, PR China. Electronic address:

Autophagy is a highly conservative self-digestion process to maintain intracellular homeostasis and to ensure the survival of cells under stress. Activation of Sonic Hedgehog (Shh) signaling depends on the normal endocytic degradation of pathway receptor Patched1 (Ptch1). It is unclear whether autophagy participates in the receptor endocytosis and modulates Shh signaling transduction. Here we found that blocking macroautophagy attenuates Shh signaling due to the failed transport of Smoothened (Smo) into primary cilia. At the upstream of Smo, Ptch1 was poly-ubiquitinated through K63-conjugated ubiquitin chains. Macroautophagy participates Shh-induced degradation of poly-ubiquitinated Ptch1, contributing to the activation of Shh signaling.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119124DOI Listing
August 2021

Fixed-time ESO based fixed-time integral terminal sliding mode controller design for a missile.

ISA Trans 2021 Jul 13. Epub 2021 Jul 13.

College of Automation Engineering, Institute of Flight Control, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China. Electronic address:

This paper studies a novel fixed-time extended state observer based fixed-time integral terminal sliding mode controller for partial integrated guidance and control design. Firstly, a class of arbitrary-order systems with fixed-time stability is proposed by utilizing homogeneous approach, whose upper bound of convergence time is given. Then, an arbitrary-order fixed-time integral terminal sliding mode control is designed based on the proposed arbitrary-order fixed-time stable system, which avoids the singular problem. Subsequently, this paper constructs a new fixed-time extended state observer to further actively compensate for the disturbance caused by unknown target acceleration. Finally, numerical simulations show the effectiveness of the proposed controller.
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http://dx.doi.org/10.1016/j.isatra.2021.06.039DOI Listing
July 2021

Lag of accommodation predicts clinically significant change of spherical equivalents after cycloplegia.

Int J Ophthalmol 2021 18;14(7):1052-1058. Epub 2021 Jul 18.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.

Aim: To evaluate related factors with the change of spherical equivalents (ΔSE) and determine the suitable predictor of clinically significant ΔSE (≥0.50 D) with cyclopentolate hydrochloride on Chinese children.

Methods: A total of 145 right eyes of 145 children aged 4 to 15y were enrolled. Intraocular pressure, axial length and lag of accommodation (LOA) were assessed before cycloplegia induced by 3 drops of 1% cyclopentolate at 5-minute intervals. SE was measured before and 1h after the first drop of cyclopentolate. ΔSE was compared between different gender groups and among refractive groups. Multivariate linear regression analysis was performed to find related factors with ΔSE. ROC analysis was used to figure out the suitable predictor of clinically significant ΔSE.

Results: For the total 145 eyes, the mean SE reached up to -0.70±1.86 D from -1.30±1.62 D, with the mean ΔSE of 0.60±0.55 D. The mean ΔSE were 0.63±0.55 D and 0.57±0.56 D respectively in the male and female group (=0.40). The mean ΔSE was significantly different among different refractive groups (<0.0001), with the ΔSE of hyperopia group (1.12±0.64 D) larger than that of the emmetropia (0.56±0.43 D, =0.001) and myopia group (0.32±0.28 D, <0.0001). The ΔSE was correlated with LOA (=-0.54, <0.0001), cycloplegic SE (=0.10, <0.0001) and age (=-0.04, =0.015). ROC curve indicated that LOA predicted clinically significant ΔSE by 82% [area under the curve (AUC)=0.82] alone, while the value was slightly improved to 85% (AUC=0.85) in combination with axial length and 86% (AUC=0.86) in association with axial length as well as age.

Conclusion: After cycloplegia with cyclopentolate, the ΔSE decreases with larger LOA, longer axial length and older age. Specifically, LOA plays a more vital role in predicting clinically significant ΔSE.
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http://dx.doi.org/10.18240/ijo.2021.07.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243181PMC
July 2021

Fabrication and Evaluation of Glabridin Tip-loaded Dissolving Microneedles.

Curr Drug Deliv 2021 Jun 9. Epub 2021 Jun 9.

School of Pharmacy and Medical technology, Putian University, Fujian, China.

Background: The clinical application of glabridin in treating skin diseases has been constrained by the limitations of its poor chemical stability and low skin permeability.

Objective: Here, we describe tip-loading dissolving microneedles (TDMNs) encapsulating drugs only in the tips of needles for glabridin delivery with improved stability and skin permeability.

Methods And Results: The TDMNs fabricated by solvent casting technique had sufficient mechanical strength to penetrate through the excised rat's skin without fracture. Drug delivery efficiency and drug residual in the skin of TDMNs were 63.16% and 49.28%, respectively. Glabridin encapsulated in the tips of TDMNs was effectively delivered into the abdominal skin of rats, and the in vivo delivery efficiency was inversely proportional to the drug doses. Transepidermal water loss (TEWL) significantly increased to 34.80 g/m•h after the application of TDMNs and returned to normal levels (11.31 g/m•h) after 8 h, indicating that the TDMNs were well tolerated. The stability of glabridin at room temperature was appreciably improved when loaded in TDMNs.

Conclusion: These results suggest that intradermal delivery of glabridin by TDMNs is a safe and efficient alternative to currently available routes of administration.
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http://dx.doi.org/10.2174/1567201818666210609162852DOI Listing
June 2021

A microfluidic single-cell array for in situ laminar-flow-based comparative culturing of budding yeast cells.

Talanta 2021 Aug 20;231:122401. Epub 2021 Apr 20.

ETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, Basel, 4058, Switzerland.

To facilitate in situ comparative culturing of budding yeast cells in a precisely controlled microenvironment, we developed a microfluidic single-cell array (MiSCA) with 96 traps (16 rows × 6 columns) for single-cell immobilization. Through optimization of the distances between neighboring traps and the applied flow rates by using a hydraulic equivalent circuit of the fluidic network, yeast cells were delivered to each column of the array by laminar focused flows and reliably captured at the traps by hydrodynamic forces with about 90% efficiency of cell immobilization. Immobilized cells in different columns within the same device can then be cultured in parallel while being exposed to different media and compounds delivered by laminar flows. For biological validation of the comparative cell-culturing device, we used budding yeast that can express yellow fluorescent protein upon the addition of β-estradiol in cell-culturing medium. Experimental results show successful induction of fluorescence in cells immobilized in desired columns that have been dosed with β-estradiol. The MiSCA system allows for performing sets of experiments and control experiments in parallel in the same device, or for executing comparative experiments under well-defined laminar-perfusion conditions with different media, as well as in situ monitoring of dynamic cellular responses upon different analytical compounds or reagents for single-cell analysis.
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http://dx.doi.org/10.1016/j.talanta.2021.122401DOI Listing
August 2021

Structural basis of GABA receptor-G protein coupling.

Nature 2021 Jun 28;594(7864):594-598. Epub 2021 Apr 28.

ZJU-HUST Joint Laboratory of Cellular Signaling, Key Laboratory of Molecular Biophysics of MOE, International Research Center for Sensory Biology and Technology of MOST, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, China.

G-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABA receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with G protein. We found that a single G protein interacts with the GB2 subunit of the GABA receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABA receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex.
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http://dx.doi.org/10.1038/s41586-021-03507-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222003PMC
June 2021

Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin.

Biotechnol Appl Biochem 2021 Apr 20. Epub 2021 Apr 20.

School of Pharmacy and Medical technology, Putian University, Putian, Fujian, China.

Tyrosinase is a key metalloenzyme for the biosynthesis of melanin that plays a critical role in the prevention of skin damage caused by ultraviolet (UV) radiation. However, the overproduction of melanin may cause a variety of skin diseases. Due to the toxicity and inefficiency of existing tyrosinase inhibitors, it is urgent to identify safe and potent alternatives from natural sources. Theaflavin, a single-component extracted from black tea, has been found to possess a variety of pharmacological activities. Herein, the inhibition kinetics of theaflavin on tyrosinase and inhibitory mechanism were determined using spectroscopy, molecular docking, and zebrafish model. The results showed that theaflavin inhibited the diphenolase activity of tyrosinase in a reversible mixed type manner with IC of 229.75 μmol/L and hindered the synthesis of melanin in zebrafish. This may be due to the formation of eight hydrogen bonds and hydrophobic effects between theaflavin and tyrosinase according to the results of molecular docking. To study the possible effects on the prevention of free radical-mediated skin cancer and photoaging caused by UV radiation, the antioxidation and UV filter properties of theaflavin were further verified. This study demonstrates that theaflavin is a potential multifunctional compound that can be used in cosmetic and medicinal products.
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http://dx.doi.org/10.1002/bab.2166DOI Listing
April 2021

Maize transcription factor ZmNF-YC13 regulates plant architecture.

J Exp Bot 2021 06;72(13):4757-4772

Maize Research Institute, State Cultivation Base of Crop Stress Biology for Southern Mountainous Land, Southwest University, Beibei District, Chongqing, People's Republic of China.

Leaf angle and leaf orientation value (LOV) are critical agronomic traits for maize plant architecture. The functions of NUCLEAR FACTOR Y (NF-Y) members in regulating plant architecture have not been reported yet. Here, we identified a regulator of maize plant architecture, NF-Y subunit C13 (ZmNF-YC13). ZmNF-YC13 was highly expressed in the leaf base zone of maize plants. ZmNF-YC13 overexpressing plants showed upright leaves with narrow leaf angle and larger LOV, while ZmNF-YC13 knockout plants had larger leaf angle and smaller LOV compared with wild-type plants. The changes in plant architecture were due to the changes in the expression of cytochrome P450 family members. ZmNF-YC13 interacts with two NF-Y subunit B members (ZmNF-YB9 and ZmNF-YB10) of the LEAFY COTYLEDON1 sub-family, and further recruits NF-Y subunit A (ZmNF-YA3) to form two NF-Y complexes. The two complexes can both activate the promoters of transcriptional repressors (ZmWRKY76 and ZmBT2), and the promoters of PLASTOCHRON group genes can be repressed by ZmWRKY76 and ZmBT2 in maize protoplasts. We propose that ZmNF-YC13 functions as a transcriptional regulator and, together with ZmNF-YBs and ZmNF-YA3, affects plant architecture by regulating the expression of ZmWRKY76 and ZmBT2, which repress the expression of cytochrome P450 family members in PLASTOCHRON branch.
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http://dx.doi.org/10.1093/jxb/erab157DOI Listing
June 2021

Human cytomegalovirus infection: A considerable issue following allogeneic hematopoietic stem cell transplantation.

Oncol Lett 2021 Apr 23;21(4):318. Epub 2021 Feb 23.

Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Cytomegalovirus (CMV) is an opportunistic virus, whereby recipients are most susceptible following allogeneic hematopoietic stem cell transplantation (allo-HSCT). With the development of novel immunosuppressive agents and antiviral drugs, accompanied with the widespread application of prophylaxis and preemptive treatment, significant developments have been made in transplant recipients with human (H)CMV infection. However, HCMV remains an important cause of short- and long-term morbidity and mortality in transplant recipients. The present review summarizes the molecular mechanism and risk factors of HCMV reactivation following allo-HSCT, the diagnosis of CMV infection following allo-HSCT, prophylaxis and treatment of HCMV infection, and future perspectives. All relevant literature were retrieved from PubMed and have been reviewed.
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http://dx.doi.org/10.3892/ol.2021.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933754PMC
April 2021

Rational drug design of benzothiazole-based derivatives as potent signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors.

Eur J Med Chem 2021 Apr 2;216:113333. Epub 2021 Mar 2.

School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:

The cumulative evidence supports STAT3, a transcriptional mediator of oncogenic signaling, as a therapeutic target in cancer. The development of STAT3 inhibitors remain an active area of research as no inhibitors have yet to be approved for cancer treatment. In a continuing effort to develop more potent STAT3 inhibitors based on our previously identified hit compound 16w, a series of benzothiazole derivatives with unique binding mode in SH2 domain of STAT3 were designed, synthesized and biologically evaluated. Of note, compound B19 demonstrated excellent activity against IL-6/STAT3 signaling pathway with the IC value as low as 0.067 μM as determined by a luciferase reporter assay. Moreover, multiple compounds displayed potent antiproliferative activity against MDA-MB-468 and JAK2 mutant HEL cell lines. Further biochemical study using Western blot assay indicated that B19 blocked the phosphorylation of STAT3 at Tyr 705 and Ser 727 and thus suppressed STAT3-mediated gene expression of c-MYC and MCL-1. Simultaneously, it induced cancer cell G2/M phase arrest and apoptosis both in MDA-MB-468 and HEL cell lines. Finally, molecular docking study along with surface plasmon resonance (SPR) and fluorescence polarization (FP) assays disclosed the binding mode of B19 in STAT3 SH2 domain. Taken together, our finding suggests that B19 is a promising therapeutic STAT3 inhibitor for cancer treatment.
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http://dx.doi.org/10.1016/j.ejmech.2021.113333DOI Listing
April 2021

Age distribution and associated factors of cornea biomechanical parameter stress-strain index in Chinese healthy population.

BMC Ophthalmol 2020 Nov 3;20(1):436. Epub 2020 Nov 3.

Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Postal address: 251 Fukang Road, Nankai District, Tianjin, China.

Background: To investigate the new cornea biomechanical parameter stress-strain index (SSI) in Chinese healthy people and the factors associated with SSI.

Methods: A total of 175 eyes from 175 participants were included in this study. Axial length was measured with the Lenstar LS-900. Pentacam measured curvature of the cornea and anterior chamber volume (ACV). Cornea biomechanical properties assessments were performed by corneal visualization Scheimpflug technology (Corvis ST). Student's t-test, one-way ANOVA, partial least square linear regression (PLSLR) and linear mixed effects (LME) model were used in the statistical analysis.

Results: The mean (±SD) SSI was 1.14 ± 0.22 (range, 0.66-1.78) in all subjects and affected by age significantly after age of 35 (P < 0.05). In LME models, SSI was significantly associated with age (β = 0.526, P < 0.001), axial length (AL) (β = - 0.541, P < 0.001), intraocular pressure (IOP) (β = 0.326, P < 0.001) and steepest radius of anterior corneal curvature (RsF) (β = 0.229, P < 0.001) but not with ACV, biomechanical corrected intraocular pressure (bIOP), flattest radius of anterior corneal curvature (RfF) or central corneal thickness (CCT) (P > 0.05 for each).

Conclusions: SSI increased with age after the age of 35. In addition to age, SSI was positively correlated with RsF and IOP, while negatively correlated with AL.
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http://dx.doi.org/10.1186/s12886-020-01704-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607623PMC
November 2020

Comparison between two autorefractor performances in large scale vision screening in Chinese school age children.

Int J Ophthalmol 2020 18;13(10):1660-1666. Epub 2020 Oct 18.

Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.

Aim: To evaluate the effectiveness of Grand Seiko Ref/Keratometer WAM-5500 compared to Topcon KR800 autorefractor in detecting refractive error in large scale vision screening for Chinese school age children with the WHO criteria.

Methods: A total of 886 participants were enrolled with mean age of 9.49±1.88y from Tianjin, China. Spherical equivalent (SE) was obtained from un-cycloplegic autorefraction and cycloplegic autorefraction. Topcon KR 800 (Topcon) and Grand Seiko WAM-5500 (WAM) autorefractors were used. Bland-Altman Plot and regression were generated to compare their performance. The overall effectiveness of detecting early stage refractive error was analyzed with receiver operating characteristic (ROC) curves.

Results: The mean SE was -0.98±1.81 diopter (D) and the prevalence of myopia was 48.9% defined by WHO criteria according to the result of cycloplegic autorefraction. The mean SE of un-cycloplegic autorefraction with Topcon and WAM were -1.21±1.65 and -1.20±1.68 D respectively. There was a strong linear agreement between result obtained from WAM and cycloplegic autorefraction with an of 0.8318. Bland-Altman plot indicated a moderate agreement of cylinder values between the two methods. The sensitivity and specificity for detecting hyperopia were 90.52% and 83.51%; for detecting myopia were 95.60% and 90.24%; for detecting astigmatism were 79.40% and 90.21%; for detecting high myopia were 98.16% and 98.91% respectively.

Conclusion: These findings suggest that both Grand Seiko and Topcon autorefractor can be used in large-scale vision screening for detecting refractive error in Chinese population. Grand Seiko gives relatively better performance in detecting myopia, hyperopia, and high myopia for school age children.
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http://dx.doi.org/10.18240/ijo.2020.10.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511371PMC
October 2020

A prospective study of serum metabolomic and lipidomic changes in myopic children and adolescents.

Exp Eye Res 2020 10 8;199:108182. Epub 2020 Aug 8.

Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China. Electronic address:

Background: Myopia is a prevalent eye disorder, especially among children and adolescents in eastern Asian countries. Multiple measures have already been taken to prevent and treat myopia, including atropine and dopamine. However, the serum metabolic picture of myopia has not yet been studied as a whole and remains largely unclear. In this paper, a prospective and panoramic study was carried out to find out the whole serum metabolomic and lipidomic picture of myopia.

Methods: With untargeted mass spectrometry (MS), myopia among 211 children and adolescents was studied. The MS features were first grouped across the samples. Then, compound annotation was carried out based on these features. Finally, the metabolite features were mapped to pathways, whose biological functions in myopia were studied and discussed.

Results: A total of 275 metabolite features were derived from 92 aligned MS peak groups with significant fold changes, and then mapped to 33 pathways. By a comprehensive consideration of significance, fold change, importance score and appearance in different omics, 9 pathways were selected, and their biological functions were further analyzed. Among these selected pathways, 5 pathways were related with oxidative stress, a validated phenomenon during myopia development, while 5 pathways were related with dopamine receptor D2, whose molecular function in myopia treatment is not fully understood. A total of 177 metabolite features from 45 peak groups were related with the studied pathways.

Conclusion: This prospective study shed light on the whole picture of metabolomic mechanism underlying myopia and provided guidance to further elucidation of compounds and pathways in this whole picture.
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http://dx.doi.org/10.1016/j.exer.2020.108182DOI Listing
October 2020

Modification of the physicochemical and structural characteristics of zein suspension by dielectric barrier discharge cold plasma treatment.

J Food Sci 2020 Aug 20;85(8):2452-2460. Epub 2020 Jul 20.

State Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, 300457, China.

Owing to the strong hydrophobicity of zein, improved solubility is required to enhance the recovery of bioactive peptides. Using a zein suspension prepared by the antisolvent precipitation method, the impact of varying the voltage during dielectric barrier discharge (DBD) treatment on the physicochemical and conformational properties of zein in water was investigated. Analysis of the particle size, specific surface area, and free sulfhydryl content indicated that the protein solubility was maximized by treatment at 70 V for 70 s. DBD treatment destroyed covalent bonds and introduced some hydrophilic groups onto the zein surface, thus enhancing the contact area with water molecules and leading to a more uniform dispersion. A decrease in the hydrodynamic radius of zein micelles indicated that intermolecular interactions were disrupted, thus improving dispersion stability. A more hydrophilic microenvironment was formed owing to the reduction in hydrophobic interactions. Additionally, evaluation of the secondary structure demonstrated that DBD treatment broke hydrogen bonds, resulting in a loose conformation with more exposed sites of action for water. These results are expected to facilitate the development of technologies for improving utilization of zein. PRACTICAL APPLICATION: Strong hydrophobicity limits the application of zein in the food industry. The study indicated that DBD treatment could promote loose structure, and improve dispersion stability and hydrophilicity of zein suspension prepared by antisolvent precipitation method. This work revealed the potential of cold plasma treatment for modifying zein and other insoluble proteins, which would expand their scope of application.
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http://dx.doi.org/10.1111/1750-3841.15350DOI Listing
August 2020

Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease.

Cancer Cell Int 2020 7;20:114. Epub 2020 Apr 7.

Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Dingjiaqiao 87, Gulou District, Nanjing, 210009 Jiangsu People's Republic of China.

It is well acknowledged that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for numerous malignant blood diseases, which has also been applied to autoimmune diseases for more than a decade. Whereas graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a common serious complication, seriously affecting the efficacy of transplantation. Mesenchymal stem cells (MSCs) derived from a wealth of sources can easily isolate and expand with low immunogenicity. MSCs also have paracrine and immune regulatory functions, leading to a broad application prospect in treatment and tissue engineering. This review focuses on immunoregulatory function of MSCs, factors affecting mesenchymal stem cells to exert immunosuppressive effects, clinical application of MSCs in GVHD and researches on MSC-derived extracellular vesicles (EVs). The latest research progress on MSC in related fields is reviewed as well. The relevant literature from PubMed databases is reviewed in this article.
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http://dx.doi.org/10.1186/s12935-020-01193-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137413PMC
April 2020

Inhibition of Tyrosinase by Mercury Chloride: Spectroscopic and Docking Studies.

Front Pharmacol 2020 6;11:81. Epub 2020 Mar 6.

School of Pharmacy and Medical Technology, Putian University, Fujian, China.

Inorganic mercury compounds have been used in skin-lightening products since ancient times. Although a previous study demonstrated that mercury impeded the transfer of Cu to the apotyrosinase, the effect of mercury on tyrosinase is still unclear. In the present study, the mechanism of mercury chloride (HgCl) induced inactivation of tyrosinase was investigated for the first time. The IC values were 29.97 and 77.93 μmol/L for monophenolase and diphenolase, respectively. A kinetic analysis revealed that HgCl inhibited tyrosinase activity in an irreversible non-competitive manner. The strong intrinsic fluorescence quenching suggested that the formation of the HgCl-tyrosinase complex induced conformational changes of the enzyme, and HgCl had only one single binding site or a single class of binding site on tyrosinase. The molecular docking and further experiments demonstrated that HgCl bound to the amino residuals (His) in the catalytic center of tyrosinase. To our knowledge, these findings presented in this paper were the first evidence of the direct interactions between HgCl and tyrosinase, which provided a deep understanding of the inhibition mechanism of mercury on tyrosinase.
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http://dx.doi.org/10.3389/fphar.2020.00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068222PMC
March 2020

Meibomian Gland Dropout, not Distortion, Can Distinguish Dry Eyes from Normal Eyes in Contact Lens Wearers.

Curr Eye Res 2020 08 2;45(8):897-903. Epub 2020 Mar 2.

Department of Optometry, Tianjin Medical University Eye Hospital , Tianjin, China.

Purpose: To examine the effectiveness of using meibomian gland (MG) dropout and distortion for dry eye disease (DED) diagnosis in a young population with long-term contact lens (CL) wear.

Methods: Seventy-three CL-wearers and 68 non-CL-wearers (20-28 years old) participated in the study. The diagnosis of DED was based on an ocular surface disease index ≥ 13, and a noninvasive breakup time < 10 seconds or positive corneal fluorescein staining. The MG dropout and distortion in each subject were quantified with non-invasive meibography. Receiver operating characteristic (ROC) curves were created to evaluate the effectiveness of using MG dropout and distortion to determine the presence of DED in CL-wearers and non-CL-wearers.

Results: In non-CL-wearers, the MG distortion was significantly higher in DED subjects than in normal subjects (3.83 ± 1.81 versus 1.59 ± 1.04). In CL-wearers, MG distortion was not significantly different (5.12 ± 4.11 versus 5.51 ± 3.15 in normal and DED subjects respectively). The area under the ROC curve (AUC) for MG distortion was 0.783 in the non-CL-wearers, but 0.507 in CL-wearers. In non-CL-wearers, MG dropout was significantly higher in DED subjects than in normal subjects (0.22 ± 0.08 versus 0.15 ± 0.06). In CL-wearers, MG dropout was also significantly higher in DED subjects than in normal subjects (0.29 ± 0.11 versus 0.22 ± 0.08). The AUC for MG dropout used to classify DED was 0.740 in the non-CL-wearers and 0.715 in CL-wearers.

Conclusions: MG dropout was effective in distinguishing subjects with DED from normal subjects in both CL wearers and non-CL wearers. MG distortion can only distinguish DED subjects from normal ones in non-CL wearers, but not in CL wearers.
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http://dx.doi.org/10.1080/02713683.2020.1731829DOI Listing
August 2020

Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer.

Biochim Biophys Acta Mol Cell Res 2020 06 19;1867(6):118679. Epub 2020 Feb 19.

Department of Otolaryngology, University of California, San Francisco, USA. Electronic address:

Head and neck squamous cell carcinoma (HNSCC) is a highly morbid, genetically unstable disease derived from the mucoepithelium of the upper aerodigestive tract. Recent characterization of this disease has implicated the PI3K-Akt-mTOR pathway as one of the most frequently dysregulated pathways. As such, there are several classes of PI3K inhibitors currently undergoing clinical trials. In this article, we review the PI3K pathway, mutations of this pathway in HNSCC, drugs that target PI3K, the impact of these agents on the PI3K and GSK-3 signaling axes, ongoing clinical trials evaluating PI3K inhibitors, and the challenges of using these drugs in the clinic. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.
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http://dx.doi.org/10.1016/j.bbamcr.2020.118679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671657PMC
June 2020

Enhanced penetration and anti-psoriatic efficacy of curcumin by improved smartPearls technology with the addition of glycyrrhizic acid.

Int J Pharm 2020 Mar 5;578:119101. Epub 2020 Feb 5.

College of Pharmacy and Medical Technology, Putian University, Fujian, China; Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine (Putian University), Fujian, China.

smartPearls technology is one appropriate method to produce anti-psoriatic curcumin (Cur) topical delivery system. To prevent the sedimentation of loaded silica and release changing over the storage, which are disadvantages of smartPearls production, extra glycyrrhizic acid (GA) was added in classical smartPearls ingredients (active and porous material) to get an improved smartPearls production (Cur-GA-silica). The capacity of Cur-GA-silica to remain the gelation state after mixing with water was superior compared to that of the solid cluster without GA and that of the physical mixture of Cur, GA and silica. The Cur-GA-silica practically contained Cur with 1.68% ± 0.12% and showed significant difference with Cur raw drug powder in kinetic solubilities (4.55 ± 0.78 µg/mL vs 0 in 5 min; 3.26 ± 0.17 µg/mL vs 0 in 4 h) which was traceable to the amorphous state of Cur-GA-silica detected by X-ray diffractometer. With the amorphous Cur, two times as much penetrated Cur in Cur-GA-silica as in Cur raw drug powder was achieved on the imiquimod-induced psoriasis-like mice model. The anti-psoriatic efficacy of Cur-GA-silica was confirmed by Psoriasis Area and Severity Index (PASI) evaluation, histological evaluation and decreased IL-17A in the imiquimod-induced psoriasiform mouse skin analyzed by enzyme-linked immunosorbent assay. In conclusion, with the addition of GA, a stable amorphous curcumin topical vehicle fabricated by smartPearls technology without extra dermal matrix is available and facilitates penetration efficacy and anti-psoriatic capacity in imiquimod-induced psoriasiform mice.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119101DOI Listing
March 2020

Study on the atmospheric cold plasma (ACP) treatment of zein film: Surface properties and cytocompatibility.

Int J Biol Macromol 2020 Jun 19;153:1319-1327. Epub 2019 Nov 19.

State Key Laboratory of Food Nutrition and Safety, College of Food Engineering and Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

The cell adhesion and proliferation of zein-based biomaterials in cell culture application are limited by the strong hydrophobic surface with low surface energy. In this study, atmospheric cold plasma (ACP) was developed as a modification approach in enhancing the surface hydrophilic and cytocompatibility of zein films. The results indicated that water contact angles decreased from 72.85° (untreated) to 47.43° under the voltage of 100 V. The improvement of the surface free energy (SFE) was mainly attributed to the polar component rather than dispersive component. X-ray photoelectron spectroscopy (XPS) results indicated the change of surface physicochemical properties was mainly due to the partially transformation of long-chain aliphatic hydrocarbons (CH and/or CC) to oxygen- and nitrogen-containing bonds (CO, CO and CN). Furthermore, the content of secondary structure demonstrated β-turn and α-helix were transformed into β-sheet and random coil after ACP treatment. Combining with the cell experiment results, plasma treatment could significantly improve the adhesion rate and proliferation activity of C2C12 cells on zein films. With better cytocompatibility, the potentials of zein in tissue engineering scaffold could be readily exploited.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.10.268DOI Listing
June 2020

Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 10;226:117642. Epub 2019 Oct 10.

School of Pharmacy and Medical Technology, Putian University, Fujian, China; Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine (Putian University), Fujian Province University, Fujian, China.

Tyrosinase is the rate-limiting enzyme for controlling the production of melanin in the human body, and overproduction of melanin can lead to a variety of skin disorders. In this paper, the inhibitory kinetics of phloretin on tyrosinase and their binding mechanism were determined using spectroscopy, molecular docking, antioxidant assays and chromatography. The spectroscopic results indicate that phloretin reversibly inhibits tyrosinase in a mix-type manner through a multiphase kinetic process with the IC of 169.36 μmol/L. It is shown that phloretin has a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting that a stable phloretin-tyrosinase complex is generated. Molecular docking results suggest that the dominant conformation of phloretin binds to the gate of the active site of tyrosinase. Moreover, the antioxidant assays demonstrate that phloretin has powerful antioxidant capacity and has the ability to reduce o-dopaquinone to l-dopa just like ascorbic acid. Interestingly, the results of spectroscopy and chromatography indicate that phloretin is a substrate of tyrosinase but also an inhibitor. The possible inhibitory mechanism is proposed, which will be helpful to design and search for tyrosinase inhibitors.
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http://dx.doi.org/10.1016/j.saa.2019.117642DOI Listing
February 2020

Fabrication of sponge-forming microneedle patch for rapidly sampling interstitial fluid for analysis.

Biomed Microdevices 2019 07 4;21(3):63. Epub 2019 Jul 4.

School of Pharmacy and Medical Technology, Putian University, Fujian, 351100, China.

Microneedle (MN) patch has been used for collecting dermal interstitial fluid (ISF) containing biomarkers from patients with safety, pain-free and easy-to-use manner. However, long sampling time for biomarkers analysis still poses a significant challenge. Here, we describe a new sponge-forming MN patch consisting of polyvinyl formal (PVF) for rapidly extracting ISF from skin. Owing to the supreme water affinity of PVF, this MN patch can extract 1.6 mg ISF in 1 min without the assistance of extra devices, which remarkably facilitates timely analysis. The MN patch had preserved structural integrity in the swelling hydrated state without leaving residues in skin after usage, and the treated skin recovered within 8 h. More importantly, the extracted ISF can be efficiently recovered from the MN patch by simple centrifugation for the subsequent offline analysis of biomarkers such as glucose and cholesterol. Our results reveal that the new sponge-forming MN patch holds considerable promise for minimally invasive sampling ISF for biomarkers detection in real-life situations.
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http://dx.doi.org/10.1007/s10544-019-0413-xDOI Listing
July 2019

Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer.

Nat Commun 2019 06 20;10(1):2701. Epub 2019 Jun 20.

Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203, Shanghai, China.

One of the biggest hurdles for the development of metabolism-targeted therapies is to identify the responsive tumor subsets. However, the metabolic vulnerabilities for most human cancers remain unclear. Establishing the link between metabolic signatures and the oncogenic alterations of receptor tyrosine kinases (RTK), the most well-defined cancer genotypes, may precisely direct metabolic intervention to a broad patient population. By integrating metabolomics and transcriptomics, we herein show that oncogenic RTK activation causes distinct metabolic preference. Specifically, EGFR activation branches glycolysis to the serine synthesis for nucleotide biosynthesis and redox homeostasis, whereas FGFR activation recycles lactate to fuel oxidative phosphorylation for energy generation. Genetic alterations of EGFR and FGFR stratify the responsive tumors to pharmacological inhibitors that target serine synthesis and lactate fluxes, respectively. Together, this study provides the molecular link between cancer genotypes and metabolic dependency, providing basis for patient stratification in metabolism-targeted therapies.
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http://dx.doi.org/10.1038/s41467-019-10427-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586626PMC
June 2019

Maximum Loaded Amorphous Azithromycin Produced Using the Wetness Impregnation Method with Fractional Steps for Dermal Prophylaxis Against Lyme Disease.

Pharmazie 2019 06;74(6):345-349

Azithromycin was loaded onto the μm-sized mesoporous silica Davisil SP53D-11920 using the wetness impregnation method with fractional steps (WIFS) and further incorporated into a 5 % hydroxypropyl cellulose gel to prevent Lyme disease. Maximum loadings (32.0 % w/w and 33.2 % w/w) were produced by different concentrated loading solutions and determined by X-ray diffraction (XRD). A total of 24 months stability of the amorphous azithromycin state in the silica (33.2 % loading) and 18 months stability in the gel (33.2 % loading) at 4 °C were also confirmed by XRD. The higher kinetic solubility at 40 min (1,300 μg/mL versus 93 μg/mL) and higher porcine ear skin penetration compared to the raw drug powder indicated higher dermal bioavailability of the azithromycin-loaded silica (32.0 % loading), even when compared to the "gold standard" nanocrystals and another clinical effective azithromycin formulation with ethanol. In summary, maximum loaded silicas with azithromycin by WIFS is a promising dermal formulation for prophylaxis against Lyme disease.
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http://dx.doi.org/10.1691/ph.2019.8175DOI Listing
June 2019

Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing's syndrome: A case report and review of the literature.

World J Clin Cases 2019 Apr;7(8):961-971

Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.

Background: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) is mostly due to unilateral tumors, with bilateral tumors rarely reported. Its common causes include primary pigmented nodular adrenocortical disease, ACTH-independent macronodular adrenal hyperplasia, and bilateral adrenocortical adenomas (BAAs) or carcinomas. BAAs causing ACTH-independent CS are rare; up to now, fewer than 40 BAA cases have been reported. The accurate diagnosis and evaluation of BAAs are critical for determining optimal treatment options. Adrenal vein sampling (AVS) is a good way to diagnose ACTH-independent CS.

Case Summary: A 31-year-old woman had a typical appearance of CS. The oral glucose tolerance test showed impaired glucose tolerance and obviously increased insulin and C-peptide levels. Her baseline serum cortisol and urine free cortisol were elevated and did not show either a circadian rhythm or suppression with dexamethasone administration. The peripheral 1-deamino-8-D-arginine-vasopressin (DDVAP) stimulation test showed a delay of the peak level, which was 1.05 times as high as the baseline level. Bilateral AVS results suggested the possibility of BAAs. Abdominal computed tomography showed bilateral adrenal adenomas with atrophic adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). Magnetic resonance imaging of the pituitary gland demonstrated normal findings. A left adenomectomy by retroperitoneoscopy was performed first, followed by resection of the right-side adrenal mass 3 mo later. Biopsy results of both adenomas showed cortical tumors. Evaluations of ACTH and cortisol showed a significant decrease after left adenomectomy but could still not be suppressed, and the circadian rhythm was absent. Following bilateral adenomectomy, this patient has been administered with prednisone until now, all of her symptoms were alleviated, and she had normal blood pressure without edema in either of her lower extremities.

Conclusion: BAAs causing ACTH-independent CS are rare. AVS is of great significance for obtaining information on the functional state of BAAs before surgery.
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http://dx.doi.org/10.12998/wjcc.v7.i8.961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509263PMC
April 2019

Azithromycin nanocrystals for dermal prevention of tick bite infections.

Pharmazie 2019 05;74(5):277-285

Azithromycin was optimized as nanocrystals with a drug content of 10.0 % (w/w) and a surfactant D- -tocopheryl polyethylenglycol 1000 succinate (TPGS) content of 1.0 % (w/w) using bead milling for 10 min. The photon correlation spectroscopy (PCS) diameter of the bulk population was 189 nm, laser diffraction (LD) diameter 90 % was 370 nm. Spherical morphology of the optimal nanocrystals was observed by transmission electron microscope (TEM). They were stable over 1 year of storage at 4 °C with the particle size within the nanometer range which was confirmed by PCS, LD and light microscope. An acceptable physical stability of 2 years was also obtained when stored at 4 °C. No microbial attack to the nanocrystals was observed before 3 years storage at 4 °C. The saturation solubility of the nanocrystals was up to triple compared to the raw drug powder (RDP) in water. When incorporated into the gel base, highest penetration efficacy was achieved by the optimal nanocrystals compared to 1) the clinically effective ethanol-solution-gel, 2) the gel with propylene glycol and 3) the gel with RDP in the porcine ear penetration study. Even though propylene glycol improved saturation solubility of nanocrystals, it could not bring benefit to nanocrystals in the penetration study. Based on these optimized azithromycin nanocrystals, topical administration for enhanced dermal bioavailability of azithromycin seems to be feasible.
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http://dx.doi.org/10.1691/ph.2019.8169DOI Listing
May 2019

smartPearls - Novel physically stable amorphous delivery system for poorly soluble dermal actives.

Int J Pharm 2019 Jan 13;555:314-321. Epub 2018 Nov 13.

Freie Universität Berlin, Institute of Pharmacy, Germany. Electronic address:

Dermally applied poorly soluble actives whether in cosmetics or pharmaceuticals show insufficient skin penetration. Especially actives being insoluble in both phases of dermal vehicles, i.e. water and oil have no or less real effect. An approach to overcome this obstacle is the use of amorphous actives instead of the crystalline ones. The higher saturation solubility creates an increased concentration gradient between the formulation and skin. Thus, the diffusive flux into the skin is improved. However, the amorphous state of actives is highly labile, and the durability of such formulations would be too short for a marketable product. smartPearls is a novel technology efficiently long-term stabilize the amorphous state. They consist of µm sized particles with mesopores (e.g. silica: SYLOID, AEROPERL, Neusilin), in which the active can be loaded and preserved in amorphous state. Due to the tightness of the pores, not enough space is given for re-crystallization. In this work, the skin penetration of poorly soluble actives loaded in smartPearls is compared to the present "gold standards" in dermal delivery, e.g. amorphous microparticles, amorphous nanoparticles and nanocrystals. The performance was at least similar or even better than the gold standards, explainable by the increased saturation solubility of active due to a) amorphous state and b) nanostructure inside the µm-sized particles. Sedimentation investigations showed, that the physical stabilization of very dense smartPearls in semi-solid vehicles is possible by viscoelastic repulsion. Also, the technical, regulatory and marketing aspects for the use of smartPearls technology in products are discussed, e.g. status of excipients used, and advantages of not being a nanoparticle, but being as efficient as them. Overall, smartPearls proved to be a promising dermal delivery technology for poorly soluble actives with a high market potential.
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http://dx.doi.org/10.1016/j.ijpharm.2018.11.018DOI Listing
January 2019

The prevalence of vision impairment and refractive error in 3654 first year students at Tianjin Medical University.

Int J Ophthalmol 2018 18;11(10):1698-1703. Epub 2018 Oct 18.

Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute & Tianjin Medical University School of Optometry and Ophthalmology, Tianjin 300384, China.

Aim: To determine the prevalence of vision impairment (VI) and refractive error in first year university students at the Tianjin Medical University.

Methods: This is a cross-sectional observational cohort study of VI and refractive error among first year university students at the Tianjin Medical University. The first year university students were involved in this study and were given a detailed questionnaire including age, birth date, and spectacle wearing history. A standardized ophthalmologic examination including visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, objective refraction, fundus photography, and examination of their spectacles were recorded.

Results: A total of 3654 participants were included in this study. Totally 3436 (94.03%) individuals had VI in this population. Totally 150 (4.10%) individuals had VI due to ocular disease, including amblyopia, congenital cataract, retinal atrophy or degeneration, strabismus, congenital nystagmus, refractive surgery orthokeratology. Totally 3286 (89.93%) subjects had VI due to refractive error. Only 218 (5.97%) students were emmetropia. Moreover, refractive error was the main cause for the VI (95.63%). Totally 3242 (92.52%) students were myopia and the prevalence of mild, moderate, and high myopia subgroup was 27.05%, 44.35%, and 21.26% respectively. Totally 44 (1.29%) subjects were hyperopic. The rates of uncorrected visual acuity (UCVA), presenting visual acuity (PVA) and best corrected visual acuity (BCVA) which better than 20/20 in both eyes were 5.65%, 22.32% and 82.13% respectively. The rates of correction, under correction and well correction in myopia subjects were 82.73%, 84.39% and 15.61%, respectively.

Conclusion: We present a high prevalence of refractive errors and high rates of under correction refractive error among first year university students. These results may help to promote vision protection work in young adults.
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http://dx.doi.org/10.18240/ijo.2018.10.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192952PMC
October 2018
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