Publications by authors named "Weiqiang Wang"

72 Publications

Biliopancreatic Limb Length of Small Intestinal Bypass in Non-obese Goto-Kakizaki (GK) Rats Correlates with Gastrointestinal Hormones, Adipokines, and Improvement in Type 2 Diabetes.

Obes Surg 2021 Oct 26;31(10):4419-4426. Epub 2021 Jul 26.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.

Background: The purpose of this study was to explore the effects on type 2 diabetes, gastrointestinal hormones, and adipokines after the small intestinal bypass of different biliopancreatic limb (BPL) lengths in non-obese type 2 diabetic rats.

Method: Small intestinal bypass with the BPL length at 10cm, 20cm, 30cm, and 40cm, respectively, and sham surgery were performed in non-obese GK rats. Fasting serum was collected at 2 days preoperatively and 1, 3, 6, and 9 weeks postoperatively. Body weight and fasting blood glucose (FBG) were measured during the experiment. Glycated hemoglobin (GHb), fasting insulin (FINS), C-peptide, ghrelin, leptin, adiponectin, and somatostatin were measured postoperatively.

Result: Rats with a bypassed length of 40cm died within 5-9 weeks. No statistically significant was observed in body weight between the sham group and the bypass groups at the 9th week postoperatively. FBG, GHb, FINS, C-peptide, and HOMA-IR in the bypass groups were lower than those in the sham group postoperatively and were negatively correlated with BPL length. Ghrelin and leptin declined compared with preoperative but were not associated with BPL length. Adiponectin of the bypass groups increased after operation and was positively correlated with BPL length. Somatostatin remained stable among groups during the experiment.

Conclusion: Ghrelin and leptin of non-obese GK rats decreased postoperatively without a linear relationship with the BPL length, while adiponectin increased with positively correlation with the BPL length. In addition, somatostatin remained steady after small intestinal bypass. Further studies are expected to confirm the effect of the BPL length of small intestinal bypass on gastrointestinal hormones and adipokines.
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http://dx.doi.org/10.1007/s11695-021-05604-6DOI Listing
October 2021

Electrical actuation of dielectric droplets by negative liquid dielectrophoresis.

Electrophoresis 2021 Jul 26. Epub 2021 Jul 26.

Department of Instruments Science and Technology, Nanjing University of Science and Technology, Nanjing, P. R. China.

This paper presents an electrical actuation scheme of dielectric droplet by negative liquid dielectrophoresis. A general model of lumped parameter electromechanics for evaluating the electromechanical force acting on the droplets is established. The model reveals the influence of actuation voltage, device geometry, and dielectric parameter on the actuation force for both conductive and dielectric medium. Using this model, we compare the actuation forces for four liquid combinations in the parallel-plate geometry and predict the low voltage actuation of dielectric droplets by negative dielectrophoresis. Parallel experimental results demonstrate such electric actuation of dielectric droplets, including droplet transport, splitting, merging, and dispending. All these dielectric droplet manipulations are achieved at voltages < 100 V . The frequency dependence of droplet actuation velocity in aqueous solution is discussed and the existence of surfactant molecules is believed to play an important role by realigning with the AC electric field. Finally, we present coplanar manipulation of oil and water droplets and formation of oil-in-water emulsion droplet by applying the same low voltage.
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http://dx.doi.org/10.1002/elps.202100093DOI Listing
July 2021

GopGAN: Gradients Orthogonal Projection Generative Adversarial Network With Continual Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jul 16;PP. Epub 2021 Jul 16.

The generative adversarial networks (GANs) in continual learning suffer from catastrophic forgetting. In continual learning, GANs tend to forget about previous generation tasks and only remember the tasks they just learned. In this article, we present a novel conditional GAN, called the gradients orthogonal projection GAN (GopGAN), which updates the weights in the orthogonal subspace of the space spanned by the representations of training examples, and we also mathematically demonstrate its ability to retain the old knowledge about learned tasks in learning a new task. Furthermore, the orthogonal projection matrix for modulating gradients is mathematically derived and its iterative calculation algorithm for continual learning is given so that training examples for learned tasks do not need to be stored when learning a new task. In addition, a task-dependent latent vector construction is presented and the constructed conditional latent vectors are used as the inputs of generator in GopGAN to avoid the disappearance of orthogonal subspace of learned tasks. Extensive experiments on MNIST, EMNIST, SVHN, CIFAR10, and ImageNet-200 generation tasks show that the proposed GopGAN can effectively cope with the issue of catastrophic forgetting and stably retain learned knowledge.
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http://dx.doi.org/10.1109/TNNLS.2021.3093319DOI Listing
July 2021

Comparison Between Laparoscopic Sleeve Gastrectomy and Laparoscopic Greater Curvature Plication Treatments for Obesity: an Updated Systematic Review and Meta-Analysis.

Obes Surg 2021 09 5;31(9):4142-4158. Epub 2021 Jul 5.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, 2 Zheshan West Road, Wuhu, Anhui Province, China.

Bariatric surgery has been widely performed to treat morbid obesity. Our meta-analysis aims to provide an updated comparison between laparoscopic sleeve gastrectomy (LSG) and laparoscopic greater curvature plication (LGCP). Medline, EMBASE, Scopus, and Cochrane Central were searched. Ongoing clinical trials were identified from the clinicaltrials.gov website. References of the chosen literatures were manually reviewed for additional relevant studies. As a result, a total of 18 studies involving 1329 patients were selected. We demonstrated a significant higher excess weight loss (%EWL) after LSG at the 1-, 3-, 6-, 12-, and 18-month follow-up time points. However, no significant difference was found at 36 months. Body Mass Index Loss (BMIL) was better after LSG than LGCP at 12 and 24 months. The difference in the improvement of comorbidities (i.e., T2-DM, hypertension, and sleep apnea) did not reach statistical significance. The complications (i.e., bleeding, stenosis, leak, and abdominal pain), operative time, and length of hospital stay were comparable. More patients undergoing LGCP experienced nausea and vomiting. We obtained some different and new results compared to the previously published meta-analysis. Our meta-analysis showed significantly higher %EWL at 24 months (Z=2.08, p=0.04), significantly higher BMIL at 36 months (Z=9.11, p <0.00001), and significantly higher costs (Z=2.87, p=0.004) in the LSG group. In addition, for the first time, complications (i.e., GERD, wound infection, port-site hernia, and mortality) and improvement of dyslipidemia were compared between the two techniques. According to our pooled data, no significant differences were found in any of the above aspects. In conclusion, LSG is superior to LGCP with regard to providing effective weight loss in the short- and mid-term. LSG has a lower rate of minor complications, but was less effective when considering cost. The two procedures are similar in terms of improvement of comorbidities, major complications, operative time, and length of stay.
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http://dx.doi.org/10.1007/s11695-021-05538-zDOI Listing
September 2021

Synthesized soliton crystals.

Nat Commun 2021 May 26;12(1):3179. Epub 2021 May 26.

State Key Laboratory of Transient Optics and Photonics, Xi'an Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi'an, China.

Dissipative Kerr soliton (DKS) featuring broadband coherent frequency comb with compact size and low power consumption, provides an unparalleled tool for nonlinear physics investigation and precise measurement applications. However, the complex nonlinear dynamics generally leads to stochastic soliton formation process and makes it highly challenging to manipulate soliton number and temporal distribution in the microcavity. Here, synthesized and reconfigurable soliton crystals (SCs) are demonstrated by constructing a periodic intra-cavity potential field, which allows deterministic SCs synthesis with soliton numbers from 1 to 32 in a monolithic integrated microcavity. The ordered temporal distribution coherently enhanced the soliton crystal comb lines power up to 3 orders of magnitude in comparison to the single-soliton state. The interaction between the traveling potential field and the soliton crystals creates periodic forces on soliton and results in forced soliton oscillation. Our work paves the way to effectively manipulate cavity solitons. The demonstrated synthesized SCs offer reconfigurable temporal and spectral profiles, which provide compelling advantages for practical applications such as photonic radar, satellite communication and radio-frequency filter.
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http://dx.doi.org/10.1038/s41467-021-23172-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154952PMC
May 2021

Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell-Cell Interactions.

ACS Appl Mater Interfaces 2021 Apr 24;13(13):14875-14884. Epub 2021 Mar 24.

Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra (Barcelona) 08193, Spain.

Grafting biomolecules on nanostructures' surfaces is an increasingly used strategy to target pathogenic cells, with both diagnostic and therapeutic applications. However, nanomaterials monofunctionalized by conjugating a single type of ligand find limited uses in pathologies/therapies that require two or more targets/receptors to be targeted and/or activated with a single molecular entity simultaneously. Therefore, multivalent nanomaterials for dual- or multitargeting are attracting significant interest. This study provides a proof of concept of such nanostructures. We have recently developed a modular methodology that allows obtaining amyloid-based materials decorated with active globular domains. Here, this approach is exploited to generate functional amyloid fibrils displaying antibody capture moieties. A high antibody binding affinity and capacity for the resulting nanofibrils, whose size can be manipulated to obtain homogeneous nanorods with high biocompatibility, are demonstrated. These nanorods are then used for specific antibody-mediated targeting of different cell types. Simultaneous conjugation of these nanorods with different antibodies allows obtaining a mimic of a bispecific antibody that redirects T lymphocytes to tumoral cells, holding high potential for immunotherapy. Overall, the work illustrates a modular and straightforward strategy to obtain preparative quantities of multivalent antibody-functionalized nanomaterials with multitargeting properties without the need for covalent modification.
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http://dx.doi.org/10.1021/acsami.0c21996DOI Listing
April 2021

Runge-Kutta Numerical Method Followed by Richardson's Extrapolation for Efficient Ion Rejection Reassessment of a Novel Defect-Free Synthesized Nanofiltration Membrane.

Membranes (Basel) 2021 Feb 14;11(2). Epub 2021 Feb 14.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China.

A defect-free, loose, and strong layer consisting of zirconium (Zr) nanoparticles (NPs) has been successfully established on a polyacrylonitrile (PAN) ultrafiltration substrate by an in-situ formation process. The resulting organic-inorganic nanofiltration (NF) membrane, NF-PANZr, has been accurately characterized not only with regard to its properties but also its structure by the atomic force microscopy, field emission scanning electron microscopy, and energy dispersive spectroscopy. A sophisticated computing model consisting of the Runge-Kutta method followed by Richardson extrapolation was applied in this investigation to solve the extended Nernst-Planck equations, which govern the solute particles' transport across the active layer of NF-PANZr. A smart, adaptive step-size routine is chosen for this simple and robust method, also known as RK4 (fourth-order Runge-Kutta). The NF-PANZr membrane was less performant toward monovalent ions, and its rejection rate for multivalent ions reached 99.3%. The water flux of the NF-PANZr membrane was as high as 58 L · m · h. Richardson's extrapolation was then used to get a better approximation of Cl and Mg rejection, the relative errors were, respectively, 0.09% and 0.01% for Cl and Mg. While waiting for the rise and expansion of machine learning in the prediction of rejection performance, we strongly recommend the development of better NF models and further validation of existing ones.
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http://dx.doi.org/10.3390/membranes11020130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918593PMC
February 2021

Nonlinear calibration of frequency modulated continuous wave LIDAR based on a microresonator soliton comb.

Opt Lett 2021 Mar;46(5):1025-1028

Traditional frequency modulated continuous wave (FMCW) LIDAR ranging is based on heterodyne detection, calculating unknown distance by extracting the frequency of the interference signal, while the main error source is frequency modulation (FM) nonlinearity. In this paper, a ranging system based on a microresonator soliton comb is demonstrated to correct the nonlinearity by sampling the ranging signals at equal frequency intervals, producing a ranging error lower than 20 µm, while at the range of 2 m. Advantages of fast data acquisition, light computation requirements, and a simple optical path, without long optical fiber, give this method a high practical value in precision manufacturing.
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http://dx.doi.org/10.1364/OL.415524DOI Listing
March 2021

Successful Treatment of a 19-Month-Old Boy with Hepatitis Associated Aplastic Anemia by Infusion of Umbilical Cord-Derived Mesenchymal Stromal Cells: A Case Report.

Cell Transplant 2021 Jan-Dec;30:963689720977144

Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.

Here we presented a case of a 19-month-old boy who developed severe aplastic anemia postacute hepatitis. He was treated successfully with the umbilical cord-derived mesenchymal stromal cells (UC-MSCs) infusion and cyclosporine A (CsA). The boy achieved both hematopoietic recovery and normal lymphocyte proportion. So far, his condition still remains stable. To our knowledge, there is a rare previous report on the utility of MSCs infusion for the treatment of hepatitis-associated aplastic anemia (HAAA). Considering the efficacy, safety, and strong operability, particularly for pediatric patient, the infusion of UC-MSCs combined with CsA could be an effective alternative for the treatment of HAAA.
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http://dx.doi.org/10.1177/0963689720977144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863554PMC
February 2021

Improvement of the fabricated and application of aluminosilicate-based microfiltration membrane.

Chemosphere 2021 Jun 16;273:129628. Epub 2021 Jan 16.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

Aluminosilicate composite materials are characterized by their low cost, nontoxicity and facilely shaped. Membrane prepared using aluminosilicate composites have the following disadvantages: large mean pore size and low mechanical strength. To address these limitations, flat microfiltration membranes were fabricated using SiO powder and aluminosilicate composite as raw materials. The membrane performance was optimized by regulating the particle size of SiO, the ratio of SiO to aluminosilicate composite (s/a), and the type of chemical admixture. The X-ray diffraction results indicated that the crystalline SiO particles were favorable for the preparation of membranes with higher bending strengths. The decreasing particle sizes of SiO (1.33-0.15 μm) decreased the pore size distribution. The bending strength of the membrane reduced with an increase in s/a, while was effectively enhanced by adding dissolved NaSiO. The optimized inorganic microfiltration membrane could also catalyze ozone to remove 100% of benzophenone-4 with an initial concentration of 10 mg L within 15 min, and TOC removal by 52.67%. This paper presents a revised method for preparing an inorganic microfiltration membrane, which is an increasingly promising material for water treatment because of its low cost, low energy consumption, and high catalytic performance.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129628DOI Listing
June 2021

Multifunctional Amyloid Oligomeric Nanoparticles for Specific Cell Targeting and Drug Delivery.

Biomacromolecules 2020 10 21;21(10):4302-4312. Epub 2020 Sep 21.

Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

Natural selection has endorsed proteins with amazing structures and functionalities that cannot be matched by synthetic means, explaining the exponential interest in developing protein-based materials. Protein self-assembly allows fabricating complex supramolecular structures from relatively simple building blocks, a bottom-up strategy naturally employed by amyloid fibrils. However, the design of amyloid-inspired materials with biological activity is inherently difficult. Here, we exploit a modular procedure to generate functional amyloid nanostructures with tight control of their mesoscopic properties. The soft amyloid core of a yeast prion was fused to dihydrofolate reductase through flexible linkers of different sizes. This enabled us to produce, for the first time, biocompatible protein-only amyloid-like oligomeric nanoparticles with defined dimensions in which the embedded enzyme remained highly active, as assessed by biophysical and enzymatic assays. The modular design allowed one to obtain multifunctional nanoparticles by incorporating the antibody-binding Z-domain to the protein fusion. We show how these assemblies can be exploited for antibody-directed targeting of specific cell types and the localized delivery of methotrexate, resulting in the intracellular uptake of the drug by cancer cells and their death. Overall, the novel protein particles we describe in this work might find applications in areas as diverse as biocatalysis, bioimaging, or targeted therapies.
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http://dx.doi.org/10.1021/acs.biomac.0c01103DOI Listing
October 2020

Amyloidogenicity as a driving force for the formation of functional oligomers.

J Struct Biol 2020 10 14;212(1):107604. Epub 2020 Aug 14.

Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS, Université Montpellier, Montpellier, France; Institut de Biologie Computationnelle, Université Montpellier, Montpellier, France. Electronic address:

Insoluble amyloid fibrils formed by self-assembly of amyloidogenic regions of proteins have a cross-β-structure. In this work, by using targeted molecular dynamics and rigid body simulation, we demonstrate that if a protein consists of an amyloidogenic region and a globular domain(s) and if the linker between them is short enough, such molecules cannot assemble into amyloid fibrils, instead, they form oligomers with a defined and limited number of β-strands in the cross-β core. We show that this blockage of the amyloid growth is due to the steric repulsion of the globular structures linked to amyloidogenic regions. Furthermore, we establish a relationship between the linker length and the number of monomers in such nanoparticles. We hypothesise that such oligomerisation can be a yet unrecognised way to form natural protein complexes involved in biological processes. Our results can also be used in protein engineering for designing soluble nanoparticles carrying different functional domains.
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http://dx.doi.org/10.1016/j.jsb.2020.107604DOI Listing
October 2020

Prion domains as a driving force for the assembly of functional nanomaterials.

Prion 2020 12;14(1):170-179

Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona , Bellaterra (Barcelona), Spain.

Amyloids display a highly ordered fibrillar structure. Many of these assemblies appear associated with human disease. However, the controllable, stable, tunable, and robust nature of amyloid fibrils can be exploited to build up remarkable nanomaterials with a wide range of applications in biomedicine and biotechnology. Functional prions constitute a particular class of amyloids. These transmissible proteins exhibit a modular architecture, with a disordered prion domain responsible for the assembly and one or more globular domains that account for the activity. Importantly, the original globular protein can be replaced with any protein of interest, without compromising the fibrillation potential. These genetic fusions form fibrils in which the globular domain remains folded, rendering functional nanostructures. However, in some cases, steric hindrance restricts the activity of these fibrils. This limitation can be solved by dissecting prion domains into shorter sequences that keep their self-assembling properties while allowing better access to the active protein in the fibrillar state. In this review, we will discuss the properties of prion-like functional nanomaterials and the amazing applications of these biocompatible fibrillar arrangements.
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http://dx.doi.org/10.1080/19336896.2020.1785659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518758PMC
December 2020

Characterization and cytocompatibility of hierarchical porous TiO coatings incorporated with calcium and strontium by one-step micro-arc oxidation.

Mater Sci Eng C Mater Biol Appl 2020 Apr 28;109:110610. Epub 2019 Dec 28.

School of Materials Science and Engineering, Dalian University of Technology, 116024 Dalian, China. Electronic address:

Calcium (Ca) and strontium (Sr) are beneficial for bone reconstruction. This study incorporated Ca and Sr into the TiO coatings by one-step micro-arc oxidation (MAO) treatment with CaO and SrO added in tetraborate electrolytes. The structure, composition, hydrophilicity, ion release, and cytocompatibility of the coatings were studied. The coatings combine layered micron-scale pores in various sizes and nano-scaled pores, forming a hierarchical structure. This hierarchical structure is highly porous and super-hydrophilic. The coatings are composed of Ti, O, and B, as well as Ca or Sr. Ca and Sr mainly distribute in the outer layer of the coatings and exist in the forms of carbonates and oxides. The formation of the coatings was discussed. Ca and Sr incorporated into the coatings are readily released into aqueous solutions. The homogeneous surface structure of the coatings leads to an excellent and approximating performance in hydrophilicity, as well as the adhesion and spreading of the human bone marrow-derived mesenchymal stem cells (hBMSCs). The simultaneous incorporation of Ca and Sr incorporation exhibits superior facilitation in the proliferation of hBMSCs compared with single Ca or Sr incorporation. This study shows a promising method to incorporate bioactive elements into the MAO coatings on titanium surfaces.
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http://dx.doi.org/10.1016/j.msec.2019.110610DOI Listing
April 2020

Mid-infrared dual-comb generation via the cross-phase modulation effect in a normal-dispersion microcavity.

Appl Opt 2020 Mar;59(7):2101-2107

We numerically demonstrate orthogonally polarized dual-comb generation in a single microcavity with normal dispersion assisted by the cross-phase modulation (XPM) effect. It is found that the XPM effect facilitates the emission of a secondary polarized comb with different temporal properties in a wide existence range covering the blue- to red-detuned regime and thus releases the requirements for delicate control on the detuned region of pump frequency. Also, the energy transfer between two polarization components together with the normal-dispersion property contributes to a more balanced intensity difference and significantly increased conversion efficiency from the pump light into the comb operation. This work could provide a route to a low-cost and compact mid-infrared dual-comb system with a lower power requirement as well as an effective approach to higher comb teeth power with improved efficiency for practical applications.
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http://dx.doi.org/10.1364/AO.385401DOI Listing
March 2020

Toward enhancing the separation and antifouling performance of thin-film composite nanofiltration membranes: A novel carbonate-based preoccupation strategy.

J Colloid Interface Sci 2020 Jul 12;571:155-165. Epub 2020 Mar 12.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

High-performance nanofiltration (NF) membranes with simultaneously improved antifouling and separation performance are of great significance for environmental water purification. In this work, a high-performance thin-film composite (TFC) NF membrane (TFC-Ca) was constructed through in-situ incorporation of calcium bicarbonate during interfacial reaction. The surface morphology and chemical structure of the TFC-Ca membrane were systematically investigated by FTIR, XPS, AFM, and SEM. The results indicated that the surface characteristics of the pristine NF membrane were greatly changed by the incorporation of calcium bicarbonate. The TFC-Ca membrane exhibited improved hydrophilicity, narrowed pore size, declined negative charge, and increased surface area. Compared to the control membrane, the TFC-Ca membrane possessed a much greater water permeability and higher molecule rejections. For the TFC-Ca membrane, an optimized water permeance of 13.4 ± 0.3 L m h bar with 99.9% NaSO rejection was obtained. Impressively, the TFC-Ca membrane exhibited excellent antifouling performance during 5 cycles of humic acid fouling tests. A satisfactory flux recovery up to 90.0% was achieved after physical cleaning for the optimized membrane. Furthermore, the TFC-Ca membrane also presented superior performance stability when treated with strong acid and chelating agents for 7 days. Overall, this facile preoccupation strategy via in-situ incorporation of calcium bicarbonate allows the fabrication of high-performance TFC membranes with outstanding separation and antifouling properties.
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http://dx.doi.org/10.1016/j.jcis.2020.03.044DOI Listing
July 2020

Identification of prototypes from Ligustri Lucidi Fructus in rat plasma based on a data-dependent acquisition and multicomponent pharmacokinetic study.

Biomed Chromatogr 2020 Jul 20;34(7):e4833. Epub 2020 Apr 20.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

The identification and quantization of traditional Chinese medicine (TCM) are a challenge for researchers and industry. Using untargeted analytical methods, the in vivo detection and identification of TCM compounds are difficult because of the significant interference of endogenous substances. Fortunately, the ongoing development of new analytical technologies, especially Q-Orbitrap-MS, offers some solutions. Our team developed a holistic MS method, combining untargeted data-dependent MS (dd-MS ) modes to extensively identify TCM prototypes in vivo. The method was successfully applied to the analysis of Ligustri Lucidi Fructus (LLF). LLF is a widely used TCM with a remarkable nourishing effect on the liver and kidney. In the study, we aimed to identify the prototypes in rat plasma after oral administration of LLF extract. Following separation on an HSS T column, LLF extract and rat plasma were performed in untargeted dd-MS mode. Forty-seven compounds were characterized in rats plasma as prototypes of LLF extract. Furthermore, seven major prototypes were chosen as pharmacokinetic markers to investigate LLF's pharmacokinetic properties. The results provides comprehensive determination of compounds in LLF both in vitro and in vivo, which is important for quality control, pharmacology studies and clinical use of LLF.
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http://dx.doi.org/10.1002/bmc.4833DOI Listing
July 2020

miR-4999-5p Predicts Colorectal Cancer Survival Outcome and Reprograms Glucose Metabolism by Targeting PRKAA2.

Onco Targets Ther 2020 11;13:1199-1210. Epub 2020 Feb 11.

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui, People's Republic of China.

Purpose: Colorectal cancer (CRC) is the third most common cancer, and the second leading cause of cancer death worldwide. Dysregulation of microRNAs has been shown to modulate glucose metabolic reprogramming in CRC. However, the functional role of miR-4999-5p in the CRC glucose metabolic shift has not been characterized.

Patients And Methods: The levels of miR-4999-5p and PRKAA2 were evaluated by RT-qPCR. Univariate and multivariate survival analyses were conducted to evaluate the prognostic value of miR-4999-5p. Cell proliferation was assessed using the CCK-8 and colony formation assays. Extracellular acidification rate, glucose uptake, cellular glucose-6-phosphate level, and lactate production were evaluated to assess the effects of miR-4999-5p on CRC glycolysis. Dual-luciferase reporter assay was conducted to investigate the direct interaction between miR-4999-5p and PRKAA2. Mouse xenograft models were established to assess the functions of miR-4999-5p in vivo.

Results: miR-4999-5p was highly expressed in CRC tissues and cell lines. In addition, miR-4999-5p was associated with tumor differentiation and TNM stage, and elevated expression of miR-4999-5p was an independent predictor of poorer overall survival. Furthermore, miR-4999-5p promoted cell proliferation and glycolysis in CRC. miR-4999-5p targeted PRKAA2 to exert its tumor-promoting functions, and PRKAA2 knockdown rescued decreased cell proliferation and glycolysis in miR-4999-5p-silenced CRC cells. In vivo experiments showed that miR-4999-5p promoted CRC growth.

Conclusion: miR-4999-5p facilitated cell growth and glucose metabolic reprogramming through direct targeting of PRKAA2. Our results showed that miR-4999-5p may be a novel prognostic marker and therapeutic target for CRC.
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http://dx.doi.org/10.2147/OTT.S234666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024870PMC
February 2020

Effect of Hyperbaric Oxygen on Neurologic Sequelae and All-Cause Mortality in Patients with Carbon Monoxide Poisoning: A Meta-Analysis of Randomized Controlled Trials.

Med Sci Monit 2019 10 13;25:7684-7693. Epub 2019 Oct 13.

Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).

BACKGROUND Hyperbaric oxygen (HBO) is used in patients with carbon monoxide (CO) poisoning to prevent the occurrence of delayed neurological sequelae. However, inconsistent results were obtained regarding the treatment effects of HBO. Therefore, the current meta-analysis was conducted based on published randomized controlled trials (RCTs) to determine the effect of HBO on neurologic sequelae and all-cause mortality in patients with CO poisoning. MATERIAL AND METHODS Electronic databases MedLine, EmBase, and the Cochrane Library were searched for relevant RCTs from inception to March 1, 2019. The pooled relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the outcomes by using a random-effects model. Sensitivity, subgroup, and publication bias analyses were also conducted. RESULTS Seven RCTs, including 9 cohorts and a total of 2023 patients with CO poisoning, were enrolled in this study. The summary results revealed that HBO showed an association with lower risk of memory impairment compared to patients receiving normobaric oxygen (NBO), whereas 2 sessions of HBO showed an association with higher risk of memory impairment compared to those who received 1 session of HBO. Moreover, HBO was associated with increased neuropsychologic scores of block design and trail making when compared with NBO. No other significant differences regarding the treatment effects of HBO were observed. CONCLUSIONS These results indicate that HBO therapy significantly reduces the risk of memory impairment compared to NBO, but 2 sessions of HBO might not be better for memory impairment than 1 session of HBO.
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http://dx.doi.org/10.12659/MSM.917065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807531PMC
October 2019

Comparative Investigation of Phenomenological Modeling for Hysteresis Responses of Magnetorheological Elastomer Devices.

Int J Mol Sci 2019 Jun 30;20(13). Epub 2019 Jun 30.

Centre for Built Infrastructure Research, School of Civil and Environmental Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia.

Magnetorheological elastomer (MRE) is a type of magnetic soft material consisting of ferromagnetic particles embedded in a polymeric matrix. MRE-based devices have characteristics of adjustable stiffness and damping properties, and highly nonlinear and hysteretic force-displacement responses that are dependent on external excitations and applied magnetic fields. To effectively implement the devices in mitigating the hazard vibrations of structures, numerically traceable and computationally efficient models should be firstly developed to accurately present the unique behaviors of MREs, including the typical Payne effect and strain stiffening of rubbers etc. In this study, the up-to-date phenomenological models for describing hysteresis response of MRE devices are experimentally investigated. A prototype of MRE isolator is dynamically tested using a shaking table in the laboratory, and the tests are conducted based on displacement control using harmonic inputs with various loading frequencies, amplitudes and applied current levels. Then, the test results are used to identify the parameters of different phenomenological models for model performance evaluation. The procedure of model identification can be considered as solving a global minimization optimization problem, in which the fitness function is the root mean square error between the experimental data and the model prediction. The genetic algorithm (GA) is employed to solve the optimization problem for optimal model parameters due to its advantages of easy coding and fast convergence. Finally, several evaluation indices are adopted to compare the performances of different models, and the result shows that the improved LuGre friction model outperforms other models and has optimal accuracy in predicting the hysteresis response of the MRE device.
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http://dx.doi.org/10.3390/ijms20133216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651070PMC
June 2019

Prion soft amyloid core driven self-assembly of globular proteins into bioactive nanofibrils.

Nanoscale 2019 Jul 25;11(26):12680-12694. Epub 2019 Jun 25.

Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Amyloids have been exploited to build amazing bioactive materials. In most cases, short synthetic peptides constitute the functional components of such materials. The controlled assembly of globular proteins into active amyloid nanofibrils is still challenging, because the formation of amyloids implies a conformational conversion towards a β-sheet-rich structure, with a concomitant loss of the native fold and the inactivation of the protein. There is, however, a remarkable exception to this rule: yeast prions. They are singular proteins able to switch between a soluble and an amyloid state. In both states, the structure of their globular domains remains essentially intact. The transit between these two conformations is encoded in prion domains (PrDs): long and disordered sequences to which the active globular domains are appended. PrDs are much larger than typical self-assembling peptides. This seriously limits their use for nanotechnological applications. We have recently shown that these domains contain soft amyloid cores (SACs) that suffice to nucleate their self-assembly reaction. Here we genetically fused a model SAC with different globular proteins. We demonstrate that this very short sequence acts as a minimalist PrD, driving the selective and slow assembly of the initially soluble fusion proteins into amyloid fibrils in which the globular proteins retain their native structure and display high activity. Overall, we provide here a novel, modular and straightforward strategy to build active protein-based nanomaterials at a preparative scale.
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http://dx.doi.org/10.1039/c9nr01755kDOI Listing
July 2019

Preparation of discrete cage-like oxidized hollow carbon spheres with vertically aligned graphene-like nanosheet surface for high performance Pb absorption.

J Colloid Interface Sci 2019 Oct 17;553:484-493. Epub 2019 Jun 17.

College of Materials Science and Engineering, Fuzhou University, Fuzhou 350116, PR China. Electronic address:

A novel oxidized hollow carbon sphere (OHCS) as absorbent for the removal of Pb was fabricated from the mixture of coal-tar pitch and aluminum isopropoxide followed by nitric acid oxidation. The as-prepared OHCSs were characterized by FESEM, TEM, BET, TG, FTIR and XPS, and meanwhile the effects of adsorption conditions on the Pb removal were investigated by batch experiments. Results show that the OHCSs prepared possess discrete cage-like structures and well-defined inner/outer surface features, exhibiting vertically aligned graphene-like nanosheets on their surfaces with mesoporous nature and high hydrophobicity. The maximum absorption capacity for Pb of the OHCSs can reach 280.79 mg g at the optimum condition. The adsorption kinetic of Pb onto the OHCSs was found to be well modeled by pseudo-second-order kinetic model, and the experimental equilibrium data were represented well by Langmuir isotherm model. Moreover, the OHCSs still exhibit excellent adsorption ability and stability after recycling 5 times, indicating its excellent reusability performance. Overall, the OHCS is a promising adsorbent for Pb removal.
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http://dx.doi.org/10.1016/j.jcis.2019.06.050DOI Listing
October 2019

Micro/nano-hierarchical structured TiO coating on titanium by micro-arc oxidation enhances osteoblast adhesion and differentiation.

R Soc Open Sci 2019 Apr 24;6(4):182031. Epub 2019 Apr 24.

School of Stomatology, China Medical University, Shenyang 110013, People's Republic of China.

Nano-structured and micro/nano-hierarchical structured TiO coatings were produced on polished titanium by the micro-arc oxidation (MAO) technique. This study was conducted to screen a suitable structured TiO coating for osteoblast adhesion and differentiation in dental implants. The formulation was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and wettability testing. Adhesion, proliferation and osteogenic differentiation of MG63 cells were analysed by SEM, Cell Counting Kit-8 (CCK-8) and quantitative real-time PCR. The micro/nano-hierarchical structured TiO coating with both slots and pores showed the best morphology and wettability. XRD analysis revealed that rutile predominated along with a minor amount of anatase in both TiO coatings. Adhesion and extension of MG63 cells on the micro/nano-hierarchical structured TiO coating were the most favourable. MG63 cells showed higher growth rates on the micro/nano-hierarchical structured TiO coating at 1 and 3 days. Osteogenic-related gene expression was markedly increased in the micro/nano-hierarchical structured TiO coating group compared with the polished titanium group at 7, 14 and 21 days. These results revealed the micro/nano-hierarchical structured TiO coating as a promising surface modification and suitable biomaterial for use with dental implants.
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http://dx.doi.org/10.1098/rsos.182031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502366PMC
April 2019

Heterogeneity of Human Mesenchymal Stromal/Stem Cells.

Adv Exp Med Biol 2019 ;1123:165-177

National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, China.

Increasing evidence has shown that mesenchymal stem cells (MSCs) isolated from body tissues are heterogeneous while being examined in vitro and in vivo. Besides some common characteristics, MSCs derived from different tissues exhibit unique biological properties. In addition, the therapeutic effects of MSCs may vary widely due to their heterogeneity and the technical differences in large-scale ex vivo expansion. In this chapter, the heterogeneity of MSCs will be discussed in three levels: the individual donors, the tissue sources, and the cell surface markers.
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http://dx.doi.org/10.1007/978-3-030-11096-3_10DOI Listing
August 2019

Ce as a facile and versatile surface modification reagent for templated synthesis in electrical applications.

Nanoscale 2019 Jan;11(5):2138-2142

State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China.

Surface modification for templated synthesis is crucial to achieving three-dimensional (3D) architectured materials for catalysis, photonics, energy storage, etc. However, the existing facile and versatile modification methods (e.g. with dopamine and catechol) generate modification layers that are unstable in harsh environments. These methods are thus unsuitable for electrical applications. Here we report that Ce4+ can act as an effective surface modification reagent for a broad range of substrates (chitinous butterfly wings, carbon paper, nickel foam, and polyethylene terephthalate planks) with various structural features owing to its strong oxidizing ability and Lewis acid nature. The modification yields discrete CeO2 seed layers on substrate surfaces in ca. 0.25-2 h, important for the subsequent conformal growth of CeO2 nanoparticles, Ni(OH)2 nanowires, FeOOH nanosheets, and WO3 nanosheets into 3D architectured materials. The conformally synthesized FeOOH on nickel foam (NF) yields an overpotential of 241 mV at 10 mA cm-1 for an oxygen evolution reaction. This value is comparable to a typical catalyst Ni(Fe)OOH-NF for which the Ni/Fe ratio must be well-optimized. This facile and versatile strategy might have broad applications in the conformal fabrication and application of 3D architectured materials, especially when applied in electrical applications of architectured materials (e.g. Li-ion battery).
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http://dx.doi.org/10.1039/c8nr09538hDOI Listing
January 2019

Microstructure, mechanical properties and springback behaviour of Ti‑6Al‑4V alloy connection rod for spinal fixation device.

Mater Sci Eng C Mater Biol Appl 2019 Jan 6;94:811-820. Epub 2018 Oct 6.

School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, PR China.

The effect of annealing condition on microstructure, mechanical properties and springback behaviour was examined in the connection rod of Ti-6Al-4V alloy for spinal fixation devices. Compared with the deformed microstructure in the sample before annealing, relatively few equiaxed grains were present after annealing at 1003 K after 1.8 ks, and a considerable amount appeared at 7.2 ks. When annealing time was extended to 36 ks, the recrystallised grains further grew. Vickers hardness, tensile strength and bending strength decreased with increasing annealing time, whereas the elastic and bending moduli showed no significant change with annealing time of up to 7.2 ks and then slightly decreased at 36 ks. The springback ratio was closely associated with strength and modulus and applied bending deflection. The springback ratio reached the highest and lowest values in the sample before and after annealing for 7.2 ks, respectively. A good combination of strength, modulus and springback ratio was obtained in the sample after annealing for 7.2 ks.
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http://dx.doi.org/10.1016/j.msec.2018.10.030DOI Listing
January 2019

Preclinical pharmacokinetics of a novel anti-c-Met antibody-drug conjugate, SHR-A1403, in rodents and non-human primates.

Xenobiotica 2019 Sep 4;49(9):1097-1105. Epub 2019 Jan 4.

a Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University , Nanjing , China.

1. The pharmacokinetics (PK) profiles of a novel c-Met antibody-drug conjugate (ADC), SHR-A1403, were investigated and characterized in mice, rats and monkeys. 2. Serum concentrations of ADC and total antibody were detected using validated ELISA methods. The results showed low systemic clearance of both ADC and total antibody in all three species as reflected by gradual decrease in serum concentrations. Half-life () of ADC ranged from 4.6 to 11.3 days in the three species. 3. Tissue distribution study in tumor-bearing mice showed high accumulation of I-SHR-A1403 in tumor tissues over the other organs/tissues, indicating the favorable safety of SHR-A1403 and characteristics of an ADC drug. 4. Relatively low grade of anti-drug antibody (ADA) in monkeys had no impact on PK profile of the ADC. 5. During discovery stage, undesirable exposure and/or ADA incidence were observed for SHR-A1403 with high or low drug-antibody ratio (DAR), which was DAR = 5 to 6 and DAR = 1, respectively, and therefore prompted selection of an appropriate DAR value (DAR = 2) for SHR-A1403 used in preclinical development and clinical trials. 6. In conclusion, our work demonstrated favorable PK characterization of SHR-A1403, and supported for investigational new drug application (IND) and the ongoing first-in-human trial in the US.
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http://dx.doi.org/10.1080/00498254.2018.1534030DOI Listing
September 2019

Comparison of Teratoma Formation between Embryonic Stem Cells and Parthenogenetic Embryonic Stem Cells by Molecular Imaging.

Stem Cells Int 2018 25;2018:7906531. Epub 2018 Mar 25.

Nankai University School of Medicine, Tianjin 300071, China.

With their properties of self-renewal and differentiation, embryonic stem (ES) cells hold great promises for regenerative therapy. However, teratoma formation and ethical concerns of ES cells may restrict their potential clinical applications. Currently, parthenogenetic embryonic stem (pES) cells have attracted the interest of researchers for its self-renewing and pluripotent differentiation while eliciting less ethic concerns. In this study, we established a model with ES and pES cells both stably transfected with a double-fusion reporter gene containing renilla luciferase (Rluc) and red fluorescent protein (RFP) to analyze the mechanisms of teratoma formation. Transgenic mouse, which expresses firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (), was used to trace the growth of new blood vessel recruited by transplanted cells. Bioluminescence imaging (BLI) of Rluc/Fluc provides an effective tool in estimating the growth and angiogenesis of teratoma We found that the tumorigenesis and angiogenesis capacity of ES cells were higher than those of pES cells, in which VEGF/VEGFR2 signal pathway plays an important role. In conclusion, pES cells have the decreased potential of teratoma formation but meanwhile have similar differentiating capacity compared with ES cells. These data demonstrate that pES cells provide an alternative source for ES cells with the risk reduction of teratoma formation and without ethical controversy.
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http://dx.doi.org/10.1155/2018/7906531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889892PMC
March 2018

Egocentric Temporal Action Proposals.

IEEE Trans Image Process 2018 Feb;27(2):764-777

We present an approach to localize generic actions in egocentric videos, called temporal action proposals (TAPs), for accelerating the action recognition step. An egocentric TAP refers to a sequence of frames that may contain a generic action performed by the wearer of a head-mounted camera, e.g., taking a knife, spreading jam, pouring milk, or cutting carrots. Inspired by object proposals, this paper aims at generating a small number of TAPs, thereby replacing the popular sliding window strategy, for localizing all action events in the input video. To this end, we first propose to temporally segment the input video into action atoms, which are the smallest units that may contain an action. We then apply a hierarchical clustering algorithm with several egocentric cues to generate TAPs. Finally, we propose two actionness networks to score the likelihood of each TAP containing an action. The top ranked candidates are returned as output TAPs. Experimental results show that the proposed TAP detection framework performs significantly better than relevant approaches for egocentric action detection.
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http://dx.doi.org/10.1109/TIP.2017.2772904DOI Listing
February 2018

Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction.

Stem Cell Res Ther 2018 05 11;9(1):129. Epub 2018 May 11.

National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, People's Republic of China.

Background: Multipotent mesenchymal stromal cell (MSC) therapy has been widely recognized as a feasible strategy for regenerating injured myocardial tissue. However, little is known about the efficacy of intravenous injection of allogeneic umbilical cord (UC) MSCs in preclinical models of porcine myocardial infarction.

Methods: Different dosages of allogeneic UC-MSCs or the vehicle [phosphate-buffered saline (PBS)] were delivered intravenously into an acute myocardial infarction (AMI) porcine model twice after coronary ligation. Echocardiography was performed to examine the cardiac function and single photon emission computed tomography (SPECT) and positron emission tomography (PET)/computed tomography (CT) was performed to detect cardiac perfusion and nonviable myocardium. At the end of the experiment, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Masson T staining were performed to determine the infarct area. The protein and gene expression levels associated with cardiac function, inflammation, and angiogenesis were examined by Western blot and real time polymerase chain reaction (PCR). In vivo trafficking of intravenous injection of allogeneic UC-MSCs enhanced green fluorescent protein (eGFP) was detected by real time PCR and immunofluorescence.

Results: After systemic delivery, allogeneic UC-MSCs were largely distributed in the lungs and some in the infracted myocardium. At week 8 following AMI, echocardiography demonstrated significantly improved fractional shortening in the high-dose (1.5 × 10 cells/kg) group. SPECT-PET/CT showed that UC-MSC treatment in both high and low doses markedly ameliorated the left ventricle (LV) infarct area but did not significantly improve the myocardial perfusion defect. LV remodeling was inhibited by UC-MSC therapy, as reflected by a marked reduction in rthe fibrosis area at basal, middle, and apical levels and reduced extracellular matrix deposition in the total myocardial area. Inflammatory biomarkers (tumor necrosis factor alpha and interleukin-6) were reduced and pro-angiogenesis factors (vascular endothelial growth factor and platelet/endothelial cell adhesion molecule 1) were augmented in the myocardial infarct and border area. High-dose UC-MSCs increased the connexin 43 (Cx43) (myocardium preservation) expression in remote area of the LV myocardium after AMI.

Conclusions: Intravenous injection of UC-MSCs is a feasible and effective way to preserve LV function and ameliorate myocardial remodeling in porcine AMI. The cardioprotective effects of UC-MSCs were attributed to paracrine factors that appear to augment angiogenesis, limit inflammation, and preserve Cx43 gap junction.
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http://dx.doi.org/10.1186/s13287-018-0888-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948807PMC
May 2018
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