Publications by authors named "Yifan Dai"

143 Publications

Indacaterol/glycopyrronium affects lung function and cardiovascular events in patients with chronic obstructive pulmonary diseases: A meta-analysis.

Heart Lung 2021 Apr 13;50(4):532-541. Epub 2021 Apr 13.

Division of Respiratory Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China. Electronic address:

Background: Bronchodilators are the cornerstone for treating patients with chronic obstructive pulmonary diseases (COPD), although some studies have shown that dual bronchodilators may exacerbate incidence of adverse cardiovascular events. Here, we evaluated the cardiopulmonary safety of indacaterol/glycopyrronium (IND/GLY) using a meta-analysis.

Methods: We searched PubMed, OVID, Cochrane Library and Web of Science databases, using "indacaterol/glycopyrronium", "indacaterol/glycopyrrolate", "IND/GLY", "QVA149", "chronic obstructive pulmonary diseases", "COPD", "chronic obstructive airway disease", "chronic obstructive lung disease" as key words. Acute exacerbation of COPD and FEV as indicators of pulmonary function and occurrence of hypertension, atrial fibrillation, myocardial infarction and heart failure as indicators of cardiovascular safety.

Results: A total of 23 articles, comprising 21,238 participants, were included in the analysis. FEV values were significantly different compared to IND/GLY and single bronchodilator therapy (LABA or LAMA), with the MD 0.11 L (95%CI: 0.10-0.13, P<0.01). Hypertension was more frequent in the IND/GLY, than the single bronchodilator therapy group, although this difference was insignificant (IND/GLY vs LABA, RR=1.88, P = 0.09; IND/GLY vs LAMA, RR=1.42, P = 0.08; IND/GLY vs LABA+ICS, RR=1.85, P = 0.23). In addition, IND/GLY did not significantly increase the risk of myocardial infarction (IND/GLY vs LAMA or double therapy, total RR: 1.49, 95%CI: 0.72-3.08, P = 0.28), atrial fibrillation (IND/GLY vs LAMA, RR: 1.62, 95%CI: 0.64-4.10, P = 0.31) and heart failure (IND/GLY vs LAMA, RR: 0.40, 95%CI: 0.07-2.33, P = 0.31) in COPD patients.

Conclusions: IND/GLY significantly reduced incidence of acute COPD exacerbations, and slowed down the decline of FEV. Adequate safety measures are needed to control incidence of adverse cardiovascular events.
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http://dx.doi.org/10.1016/j.hrtlng.2021.02.018DOI Listing
April 2021

Rapid fabrication technique for aluminum optics by inducing a MRF contamination layer modification with Ar ion beam sputtering.

Opt Express 2021 Mar;29(6):8951-8966

Aluminum optics are widely used in modern optical systems because of high specific stiffness and high reflectance. Magnetorheological finishing (MRF) provides a highly deterministic technology for high precision aluminum optics fabrication. However, the contamination layer will generate on the surface and bring difficulties for the subsequent processes, which highly limit the fabrication efficiency and precision. In this study, characteristics of the contamination layer and its formation process are firstly revealed through experimental and theoretical methods. Impurities such as abrasives are embedded into the aluminum substrate causing increasing surface hardness. The influence of the contaminant layer on machining accuracy and machining efficiency is analyzed in this study. Based on the analysis, ion beam sputtering (IBS) is induced as a contamination layer modification method. Impurities will be preferential sputtered during the process. Surface hardness and brightness will restore to the state before MRF. Moreover, the thickness of the contamination layer reduces dynamically during IBS because of the bombardment-induced Gibbsian segregation and sputter yield amplification mechanism. Consequently, we proposed a combined technique that includes MRF, IBS and smoothing polishing. Comparative experiments are performed on an elliptical shape plane surface. The results indicate that the efficiency has been increased sevenfold and surface precision is also highly improved. Our research will promote the application of aluminum optics to the visible and even ultraviolet band.
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http://dx.doi.org/10.1364/OE.420965DOI Listing
March 2021

High efficiency removal of single point diamond turning marks on aluminum surface by combination of ion beam sputtering and smoothing polishing.

Opt Express 2021 Feb;29(3):3738-3753

Single point diamond turning (SPDT) is highly versatile in fabricating axially symmetric form, non-axially-symmetric form and free form surfaces. However, inevitable microstructure known as turning marks left on the surface have limited the mirror's optical performance. Based on chemical mechanical polishing (CMP) mechanism, smoothing polishing (SP) process is believed to be an effective method to remove turning marks. However, the removal efficiency is relatively low. In this paper, based on Greenwood-Williamson (GW) theory, the factors that limit removal efficiency of SP are discussed in details. Influences of process parameters (work pressure and rotational speed) are firstly discussed. With further analysis, surface spectral characteristics are identified as the inherent factor affecting further efficiency improvement. According to theoretical analysis, the removal efficiency of isotropic surface is nearly 1.8 times higher than anisotropy surface like surface with turning marks. A high efficiency turning marks removal process combining ion beam sputtering (IBS) and SP is proposed in our research. With removal depth exceeding 100 nm, the isotropic aluminum surface can be constructed by IBS so that the efficiency of SP process can be greatly improved. Though deteriorated by IBS, the surface roughness will be rapidly reduced by SP process. Finally, experiments are conducted to verify our analysis. A 3.7 nm roughness surface without turning marks is achieved by new method while direct SP can only reach roughness of 4.3 nm with evident turning marks. Experimental results show that removal efficiency nearly doubled which matches well with the theoretical analysis. Our research not only can be used as a high efficiency turning marks removal and surface quality improvement method but also can be a new method for high precision aluminum optics fabrication.
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http://dx.doi.org/10.1364/OE.417537DOI Listing
February 2021

Computational Efficiency of a Modular Reservoir Network for Image Recognition.

Front Comput Neurosci 2021 5;15:594337. Epub 2021 Feb 5.

Research Institute of Electrical Communication, Tohoku University, Sendai, Japan.

Liquid state machine (LSM) is a type of recurrent spiking network with a strong relationship to neurophysiology and has achieved great success in time series processing. However, the computational cost of simulations and complex dynamics with time dependency limit the size and functionality of LSMs. This paper presents a large-scale bioinspired LSM with modular topology. We integrate the findings on the visual cortex that specifically designed input synapses can fit the activation of the real cortex and perform the Hough transform, a feature extraction algorithm used in digital image processing, without additional cost. We experimentally verify that such a combination can significantly improve the network functionality. The network performance is evaluated using the MNIST dataset where the image data are encoded into spiking series by Poisson coding. We show that the proposed structure can not only significantly reduce the computational complexity but also achieve higher performance compared to the structure of previous reported networks of a similar size. We also show that the proposed structure has better robustness against system damage than the small-world and random structures. We believe that the proposed computationally efficient method can greatly contribute to future applications of reservoir computing.
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http://dx.doi.org/10.3389/fncom.2021.594337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892762PMC
February 2021

A Bama miniature pig model of monoallelic TSC1 mutation for human tuberous sclerosis complex.

J Genet Genomics 2021 Jan 13. Epub 2021 Jan 13.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China; Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China. Electronic address:

Tuberous sclerosis complex (TSC) is a dominant genetic neurocutaneous syndrome characterized by multiple organ hamartomas. Although rodent models bearing a germline mutation in either TSC1 or TSC2 genes have been generated, they do not develop pathogenic lesions matching those seen in patients with TSC because of the significant differences between mice and humans, highlighting the need for an improved large animal model of TSC. Here, we successfully generated monoallelic TSC1-modified Bama miniature pigs using the CRISPR/Cas9 system along with somatic cell nuclear transfer (SCNT) technology. The expression of phosphorylated target ribosomal protein S6 was significantly enhanced in the piglets, indicating that disruption of a TSC1 allele activated the mechanistic target of rapamycin (mTOR) signaling pathway. Notably, differing from the mouse TSC models reported previously, the TSC1 Bama miniature pig developed cardiac rhabdomyoma and subependymal nodules, resembling the major clinical features that occur in patients with TSC. These TSC1 Bama miniature pigs could serve as valuable large animal models for further elucidation of the pathogenesis of TSC and the development of therapeutic strategies for TSC disease.
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http://dx.doi.org/10.1016/j.jgg.2020.11.005DOI Listing
January 2021

Potential roles of mesenchymal stromal cells in islet allo- and xenotransplantation for type 1 diabetes mellitus.

Xenotransplantation 2021 Feb 10:e12678. Epub 2021 Feb 10.

Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Islet transplantation is poised to play an important role in the treatment of type 1 diabetes mellitus (T1DM). However, there are several challenges limiting its widespread use, including the instant blood-mediated inflammatory reaction, hypoxic/ischemic injury, and the immune response. Mesenchymal stem/stromal cells (MSCs) are known to exert regenerative, immunoregulatory, angiogenic, and metabolic properties. Here, we review recent reports on the application of MSCs in islet allo- and xenotransplantation. We also document the clinical trials that have been undertaken or are currently underway, relating to the co-transplantation of islets and MSCs. Increasing evidence indicates that co-transplantation of MSCs prolongs islet graft survival by locally secreted protective factors that reduce immune reactivity and promote vascularization, cell survival, and regeneration. MSC therapy may be a promising option for islet transplantation in patients with T1DM.
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http://dx.doi.org/10.1111/xen.12678DOI Listing
February 2021

Fabrication and evaluation of complicated microstructures on cylindrical surface.

PLoS One 2020 15;15(12):e0242918. Epub 2020 Dec 15.

Laboratory of Science and Technology on Integrated Logistics Support, College of Artificial Intelligence, National University of Defense Technology, Changsha, China.

Various items of roll molds are popularly used to fabricate different kinds of optical films for optoelectronic information and other new and high-tech fields, while the fabrication and evaluation of optical microstructures on a cylindrical roller surface is more difficult than ecumenically manufactured products. In this study, the machinability of microstructures on the roll based on a fast tool servo (FTS) system is investigated. First, the flexible hinge holder for a FTS is designed and its structural parameters are optimized with finite-element analysis and fatigue reliability theory. The tool radius compensation algorithm for complicated microstructures is then deduced based on the surface fitting and bilinear interpolation algorithm of discrete data. Meanwhile, the evaluation index and method are proposed by the medium section method. Finally, a machining test of aspheric arrays on a cylindrical aluminum surface is carried out, and the high quality of the microstructure indicates that the proposed method is able to be used to fabricate optical microstructures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242918PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737994PMC
January 2021

Surface roughness evolution mechanism of the optical aluminum 6061 alloy during low energy Ar ion beam sputtering.

Opt Express 2020 Nov;28(23):34054-34068

Ultra-smooth surfaces with low contamination and little damage are a great challenge for aluminum optical fabrication. Ion beam sputtering (IBS) has obvious advantages of low contamination and non-contact that make it a perfect method for processing aluminum optics. However, the evolution laws of aluminum surface morphology are quite different from conventional amorphous materials, which affects the roughness change and needs systematic research. Thus, in this paper, the roughness evolution of an aluminum optical surface (i.e., aluminum mirror) subjected to IBS has been studied with experimental and theoretical methods. The surface morphology evolution mechanisms of turning marks and second phase during IBS are revealed. The newly emerging relief morphology and its evolution mechanism are studied in depth. The experimental results find that IBS causes the coarsening of optical surfaces and the appearance of microstructures, leading to the surface quality deterioration. Turning marks have been through the process of deepening and vanish, while second phase generates microstructures on the original surface. The corresponding mechanism is discussed exhaustively. Preferential sputtering, curvature-dependent sputtering and material properties play important roles on surface quality deterioration. A modified roughness evolution mechanism and an improved binary sputtering theory are proposed to describe the polycrystalline sputtering phenomena. The current research can provide a guidance for the application of IBS in aluminum optics manufacture fields.
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http://dx.doi.org/10.1364/OE.410023DOI Listing
November 2020

Frequency Domain Analysis and Precision Realization in Deterministic Figuring of Ultra-Precision Shaft Parts.

Materials (Basel) 2020 Oct 14;13(20). Epub 2020 Oct 14.

College of Intelligent Science and Technology, National University of Defense Technology, Changsha 410073, China.

An aerostatic spindle is a core component in ultra-precision machine tools. The rotor of the spindle has extremely high manufacturing accuracy, which cannot be directly achieved via traditional machining, but always via manual grinding. The deterministic figuring theory is introduced into the machining of shaft parts, which overcomes many shortcomings of manual grinding. The manufacturing error of the shaft's surface contains different frequency components, which have different effects on its working performance and the figuring process. Because the deterministic figuring method can only correct the error within a limited frequency range, in order to ensure high efficiency and high precision of the figuring process, we need to use reasonable filtering parameters to filter out the error with unnecessary frequencies. In this paper, the influence of contour error with different frequencies and amplitudes on the air film are analyzed using computational fluid dynamics (CFD) software, and the amplitude-frequency analysis as a function of the power spectral density (PSD) characteristic curve is used to study the filtering parameters of the measured data. After the figuring experiment using the filtering parameters obtained from the analysis, the average roundness of the shaft converged from 0.419 μm to 0.101 μm, and the cylindricity converged from 0.76 μm to 0.35 μm. The precision reached the level of manual grinding, which proves the rationality of the analysis using filtering parameters in a shaft's deterministic figuring.
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http://dx.doi.org/10.3390/ma13204561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602269PMC
October 2020

Quantification of Circulating Pig-Specific DNA in the Blood of a Xenotransplantation Model.

J Vis Exp 2020 09 22(163). Epub 2020 Sep 22.

Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital;

Xenotransplantation is a feasible method to treat organ failure. However, how to effectively monitor the immune rejection of xenotransplantation is a problem for physicians and researchers. This manuscript describes a simple and effective method to monitor immune rejection in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. Circulating DNA is a potentially non-invasive biomarker for organ damage. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection by quantitative real-time PCR (qPCR). In this protocol, porcine specific primers were designed, plasmids-containing porcine specific DNA fragments were constructed, and standard curves for quantitation were established. Species-specific primers were then used to quantify cpsDNA by qPCR in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. The value of this method suggests that it can be used as a simple, convenient, low cost, and less invasive method to monitor the immune rejection of xenotransplantation.
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http://dx.doi.org/10.3791/61579DOI Listing
September 2020

Chemical Translational Biology-Guided Molecular Diagnostics: The Front Line To Mediate the Current SARS-CoV-2 Pandemic.

Authors:
Yifan Dai

Chembiochem 2020 12 22;21(24):3492-3494. Epub 2020 Sep 22.

Department of Biomedical Engineering, Duke University, 101 Science Drive, Durham, NC, 27705, USA.

The spread of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) has disrupted our global society in unprecedented ways. The very front line in defense against this pandemic is molecular diagnosis, which is an exceptional representation of how chemical translational biology can benefit our lives. In this viewpoint, I emphasize the imperative demand for a simple and rapid point-of-care system in order to mediate the spread of COVID-19. I further describe how the interdisciplinary combination of chemistry and biology advances biosensing systems, which potentially lead to integrated and automated point-of-care systems capable of relieving the current pandemic.
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http://dx.doi.org/10.1002/cbic.202000518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537211PMC
December 2020

An Integrated Multi-Function Heterogeneous Biochemical Circuit for High-Resolution Electrochemistry-Based Genetic Analysis.

Angew Chem Int Ed Engl 2020 11 24;59(46):20545-20551. Epub 2020 Sep 24.

Department of Chemical and Biomolecular Engineering, Electronics Design Center, Case Western Reserve University, Cleveland, OH, 44106, USA.

Modular construction of an autonomous and programmable multi-functional heterogeneous biochemical circuit that can identify, transform, translate, and amplify biological signals into physicochemical signals based on logic design principles can be a powerful means for the development of a variety of biotechnologies. To explore the conceptual validity, we design a CRISPR-array-mediated primer-exchange-reaction-based biochemical circuit cascade, which probes a specific biomolecular input, transform the input into a structurally accessible form for circuit wiring, translate the input information into an arbitrary sequence, and finally amplify the prescribed sequence through autonomous formation of a signaling concatemer. This upstream biochemical circuit is further wired with a downstream electrochemical interface, delivering an integrated bioanalytical platform. We program this platform to directly analyze the genome of SARS-CoV-2 in human cell lysate, demonstrating the capability and the utility of this unique integrated system.
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http://dx.doi.org/10.1002/anie.202010648DOI Listing
November 2020

CRISPR Mediated Biosensing Toward Understanding Cellular Biology and Point-of-Care Diagnosis.

Angew Chem Int Ed Engl 2020 11 25;59(47):20754-20766. Epub 2020 Aug 25.

School of Chemistry, Australian Centre for NanoMedicine, and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW, 2052, Australia.

Recent advances in CRISPR based biotechnologies have greatly expanded our capabilities to repurpose CRISPR for the development of biomolecular sensors for diagnosing diseases and understanding cellular pathways. The key attribute that allows CRISPR to be widely utilized is the programmable and highly selective mechanism. In this Minireview, we first illustrate the molecular principle of CRISPR functioning process from sensing to actuating. Next, the CRISPR based biosensing strategies for nucleic acids, proteins and small molecules are summarized. We highlight some of recent advances in applications for in vitro detection of biomolecules and in vivo imaging of cellular networks. Finally, the challenges with, and exciting prospects of, CRISPR based biosensing developments are discussed.
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http://dx.doi.org/10.1002/anie.202005398DOI Listing
November 2020

Research on Deterministic Figuring of Ultra-Precision Shaft Parts Based on Analysis and Control of Figuring Ability.

Materials (Basel) 2020 May 28;13(11). Epub 2020 May 28.

College of Intelligent Science and Technology, National University of Defense Technology, Changsha 410073, China.

The application of ultra-precision shaft parts is widely used, such as the spindle core of the air bearing spindle in ultra-precision machine tools. The precision of the spindle core is extremely high, and it is very difficult to obtain directly by traditional Computer Numerical Control (CNC) machine tools but is mostly obtained by manual grinding, whose machining efficiency is greatly limited. Based on the deterministic figuring theory, this paper focuses on the ultra-precision roundness, optimizing the filtering parameters of the measurement error data and studying the generation mechanism of the removal function morphology; the shape of the removal function is adjusted by combining the analysis of the figuring ability and positioning error. Finally, the optimized removal function is used on an experimental steel shaft, the average roundness convergence ratio is 72% higher than that of the original removal function, and the roundness reaches a 0.1 μm level. The result shows that a reasonable filtering of measured data and the removal function adjusted for the surface feature can improve the efficiency and precision of deterministic figuring on shaft parts.
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http://dx.doi.org/10.3390/ma13112458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321206PMC
May 2020

Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways.

Mol Med 2020 05 24;26(1):49. Epub 2020 May 24.

Department of Pneumology, The Affiliated Hospital of Hangzhou Normal University, No. 126, Wenzhou Road, Hangzhou, 31000, Zhejiang, China.

Background: Pirfenidone (PFD) is effective for pulmonary fibrosis (PF), but its action mechanism has not been fully explained. This study explored the signaling pathways involved in anti-fibrosis role of PFD, thus laying a foundation for clinical application.

Methods: Pulmonary fibrosis mice models were constructed by bleomycin (BLM), and TGF-β1 was used to treat human fetal lung fibroblasts (HLFs). Then, PFD was added into treated mice and cells alone or in combination with β-catenin vector. The pathological changes, inflammatory factors levels, and Collagen I levels in mice lung tissues were assessed, as well as the activity of HLFs was measured. Levels of indices related to extracellular matrix, epithelial-mesenchymal transition (EMT), Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were determined in tissues or cells.

Results: After treatment with BLM, the inflammatory reaction and extracellular matrix deposition in mice lung tissues were serious, which were alleviated by PFD and aggravated by the addition of β-catenin. In HLFs, PFD reduced the activity of HLFs induced by TGF-β1, inhibited levels of vimentin and N-cadherin and promoted levels of E-cadherin, whereas β-catenin produced the opposite effects to PFD. In both tissues and cells, Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were activated, which could be suppressed by PFD.

Conclusions: PFD alleviated pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways, which might further improve the action mechanism of anti-fibrosis effect of PFD.
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http://dx.doi.org/10.1186/s10020-020-00173-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245944PMC
May 2020

Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin.

Animal Model Exp Med 2020 Mar 20;3(1):79-86. Epub 2020 Mar 20.

Shenzhen Xenotransplantation Medical Engineering Research and Development Center Institute of Translational Medicine Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University Health Science Center Shenzhen China.

Backgrounds: Streptozotocin (STZ)- induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. There are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. In order to reduce the side effects, diabetic monkeys were induced using clinical-grade STZ. However, clinical-grade STZ is not available in China. Here, we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal.

Methods: Three cynomolgus monkeys were used in this study. 100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein. After the STZ administration, blood glucose levels were examined every 1 or 2 hours in the first 48 hours. Then, blood glucose levels were examined twice per day during the first week after the STZ injection. Insulin and C-peptide levels were measured by ELISA. Blood chemistry of hepatic and renal function tests were performed. Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays.

Results: The stimulated C-peptide level (Intravenous glucose tolerance test) which is less than 0.5 ng/mL, the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model. No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection.

Conclusion: In summary, we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.
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http://dx.doi.org/10.1002/ame2.12109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167243PMC
March 2020

Phase-Regulated Sensing Mechanism of MoS Based Nanohybrids toward Point-of-Care Prostate Cancer Diagnosis.

Small 2020 05 6;16(18):e2000307. Epub 2020 Apr 6.

Department of Chemical and Biomolecular Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.

Alpha-methylacyl-CoA racemase (AMACR) has been proven to be consistently overexpressed in prostate cancer epitheliums, and is expected to act as a positive biomarker for the diagnosis of prostate carcinoma in clinical practice. Here, a strategy for specific determination of AMACR in real human serum by using an electrochemical microsensor system is presented. In order to implement the protocol, a self-organized nanohybrid consisting of metal nanopillars in a 2D MoS matrix is developed as material for the sensing interface. The testing signal outputs are strongly enhanced with the presence of the nanohybrids owing to that the metal pillars provide an efficient mass difussion and electron transfer path to the MoS film surface. Furthermore, the phase-regulated sensing mechanism over MoS is noticed and demonstrated by density functional theory calculation and experiments. The explored MoS based nanohybrids are employed for the fabrication of an electrochemical microsensor, presenting good linear relationship in both ng µL and pg µL ranges for AMACR quantification. The sampling analysis of human serum indicates that this microsensor has good diagnostic specificity and sensitivity toward AMACR. The proposed electrochemical microsensor system also demonstrates the advantages of convenience, cost-effectiveness, and disposability, resulting in a potential integrated microsystem for point-of-care prostate cancer diagnosis.
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http://dx.doi.org/10.1002/smll.202000307DOI Listing
May 2020

Effects of Ion Beam Etching on the Nanoscale Damage Precursor Evolution of Fused Silica.

Materials (Basel) 2020 Mar 13;13(6). Epub 2020 Mar 13.

Laboratory of Science and Technology on Integrated Logistics Support, College of Intelligence Science and Technology, National University of Defense Technology, 109 Deya Road, Changsha 410073, Hunan, China.

Nanoscale laser damage precursors generated from fabrication have emerged as a new bottleneck that limits the laser damage resistance improvement of fused silica optics. In this paper, ion beam etching (IBE) technology is performed to investigate the evolutions of some nanoscale damage precursors (such as contamination and chemical structural defects) in different ion beam etched depths. Surface material structure analyses and laser damage resistance measurements are conducted. The results reveal that IBE has an evident cleaning effect on surfaces. Impurity contamination beneath the polishing redeposition layer can be mitigated through IBE. Chemical structural defects can be significantly reduced, and surface densification is weakened after IBE without damaging the precision of the fused silica surface. The photothermal absorption on the fused silica surface can be decreased by 41.2%, and the laser-induced damage threshold can be raised by 15.2% after IBE at 250 nm. This work serves as an important reference for characterizing nanoscale damage precursors and using IBE technology to increase the laser damage resistance of fused silica optics.
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http://dx.doi.org/10.3390/ma13061294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143300PMC
March 2020

Inguinal Subcutaneous White Adipose Tissue (ISWAT) Transplantation Model of Murine Islets.

J Vis Exp 2020 02 16(156). Epub 2020 Feb 16.

Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Health Science Center;

Pancreatic islet transplantation is a well-established therapeutic treatment for type 1 diabetes. The kidney capsule is the most commonly used site for islet transplantation in rodent models. However, the tight kidney capsule limits the transplantation of sufficient islets in large animals and humans. The inguinal subcutaneous white adipose tissue (ISWAT), a new subcutaneous space, was found to be a potentially valuable site for islet transplantation. This site has better blood supply than other subcutaneous spaces. Moreover, the ISWAT accommodates a larger islet mass than the kidney capsule, and transplantation into it is simple. This manuscript describes the procedure of mouse islet isolation and transplantation in the ISWAT site of syngeneic diabetic mouse recipients. Using this protocol, murine pancreatic islets were isolated by standard collagenase digestion and a basement membrane matrix hydrogel was used for fixing the purified islets in the ISWAT site. The blood glucose levels of the recipient mice were monitored for more than 100 days. Islet grafts were retrieved at day 100 after transplantation for histological analysis. The protocol for islet transplantation in the ISWAT site described in this manuscript is simple and effective.
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http://dx.doi.org/10.3791/60679DOI Listing
February 2020

Surpassing the detection limit and accuracy of the electrochemical DNA sensor through the application of CRISPR Cas systems.

Biosens Bioelectron 2020 May 18;155:112100. Epub 2020 Feb 18.

Department of Chemical and Biomolecular Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA; Electronics Design Center, Case Western Reserve University, Cleveland, OH, 44106, USA.

Robust developments of personalized medicine for next-generation healthcare highlight the need for sensitive and accurate point-of-care platforms for quantification of disease biomarkers. Broad presentations of clustered regularly interspaced short palindromic repeats (CRISPR) as an accurate gene editing tool also indicate that the high-specificity and programmability of CRISPR system can be utilized for the development of biosensing systems. Herein, we present a CRISPR Cas system enhanced electrochemical DNA (E-DNA) sensor with unprecedented sensitivity and accuracy. The principle of the E-DNA sensor is the target induced conformational change of the surface signaling probe (containing an electrochemical tag), leading to the variation of the electron transfer rate of the electrochemical tag. With the introduction of CRISPR cleavage activity into the E-DNA sensor, a more apparent signal change between with and without the presence of the target can be achieved. We compared the performance of Cas9 and Cas12a enhanced E-DNA sensor and optimized the chemical environment of CRISPR, achieving a femto-molar detection limit without enzymatic amplification. Moreover, we correlated the CRISPR cleavage signal with the original E-DNA signal as a strategy to indicate potential mismatches in the target sequence. Comparing with classic DNA electrochemistry based mutation detection strategy, CRISPR enhanced E-DNA sensor can determine the presence of a single mutation at an unknown concentration condition. Overall, we believe that the CRISPR enhanced E-DNA sensing strategy will be of especially high utility for point-of-care systems owing to the programmability, modularity, high-sensitivity and high-accuracy.
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http://dx.doi.org/10.1016/j.bios.2020.112100DOI Listing
May 2020

Immunoglobulin G-Based Steric Hindrance Assay for Protein Detection.

ACS Sens 2020 01 27;5(1):140-146. Epub 2019 Dec 27.

With the imminent needs of rapid, accurate, simple point-of-care systems for global healthcare industry, electrochemical biosensors have been widely developed owing to their cost-effectiveness and simple instrumentation. However, typical electrochemical biosensors for direct analysis of proteins in the human biological sample still suffer from complex biosensor fabrication, lack of general method, limited sensitivity, and matrix-caused biofouling effect. To resolve these challenges, we developed a general electrochemical sensing strategy based on a designed steric hindrance effect on an antibody surface layer. This strategy utilizes the interaction pattern of protein-G and immunoglobulin G (Fc and Fab regions), providing a steric hindrance effect during the target capturing process. The provided steric hindrance effect minimizes the matrix effect-caused fouling surface and altered the path of electron transfer, delivering a low-fouling and high-sensitivity detection of protein in complex matrices. Also, an enzyme-based horseradish peroxidase/hydroquinone/HO transduction system can also be applied to the system, demonstrating the versatility of this sensing strategy for general electrochemical sensing applications. We demonstrated this platform through the detection of Tau protein and programming death ligand 1 with a subpico molar detection limit within 10 min, satisfying the clinical point-of-care requirements for rapid turnaround time and ultrasensitivity.
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http://dx.doi.org/10.1021/acssensors.9b01902DOI Listing
January 2020

Improving the properties of straw biomass rattan by corn starch.

Bioengineered 2019 12;10(1):659-667

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, China.

As a kind of renewable resource and natural biomass, starch has been widely used to substitute plastics in the modern industry and is regarded as one of the most promising biodegradable materials. The newly developmental rattan, straw biomass rattan (SBR) as weaving material, has been exploited as per our previous work, which possessed advantages of both natural rattan and pure plastic rattan. The main objective of the work was to improve the properties of SBR by corn starch (CS). Based on the manufacturing of the above composites, the experiments of SBR that enhanced with CS on mechanical properties, melting performance, hydroscopicity, thermogravimetric analysis, and microstructures were tested in this study. The results revealed that when the content of CS increased gradually within the range of 0, 3, 6, 9 12, and 15 wt.%, the mechanical properties and melt index of the composite both increased first and then decreased, with 6 to 12 wt.% as the optimal dosage range. In contrast, the water absorption of SBR kept increased in this range, indicating an easier biodegradable. With CS added, the microstructure of SBR was examined by scanning electron microscope and found the microscopic surfaces and sections to become smoother, and that could improve the compatibility and tenacity between the materials. As a result, CS in moderation can be used as a supplement to enhance SBR, and improve their characteristics which will enhance the mechanical properties of the composites for future perspectives.
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http://dx.doi.org/10.1080/21655979.2019.1688127DOI Listing
December 2019

Strand Displacement Strategies for Biosensor Applications.

Trends Biotechnol 2019 12 1;37(12):1367-1382. Epub 2019 Nov 1.

Department of Chemical and Biomolecular Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Electronics Design Center, Case Western Reserve University, Cleveland, OH 44106, USA.

DNA has many unique properties beyond encoding genetic information, one of which is its physicochemical stability based on Watson-Crick base pairing. Differences in sequence complementarity between multiple DNA strands can lead to the strand displacement reaction (SDR). SDRs have been regularly applied in synthetic biology, drug delivery, and, importantly, biosensing. SDR-based biosensors have high controllability, high sensitivity, and low interference, and can be used for multiplexed detection. Such biosensors have been demonstrated to detect nearly every class of biomolecule. As the field continues to mature, such platforms can be used as an integral tool for the manipulation of biomolecular reactions, bringing biosensors one step closer to the ultimate goal of point-of-care systems.
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http://dx.doi.org/10.1016/j.tibtech.2019.10.001DOI Listing
December 2019

Exploring the Trans-Cleavage Activity of CRISPR-Cas12a (cpf1) for the Development of a Universal Electrochemical Biosensor.

Angew Chem Int Ed Engl 2019 11 17;58(48):17399-17405. Epub 2019 Oct 17.

Department of Chemical and Biomolecular Engineering, Electronics Design Center, Case Western Reserve University, Cleveland, OH, 44106, USA.

An accurate, rapid, and cost-effective biosensor for the quantification of disease biomarkers is vital for the development of early-diagnostic point-of-care systems. The recent discovery of the trans-cleavage property of CRISPR type V effectors makes CRISPR a potential high-accuracy bio-recognition tool. Herein, a CRISPR-Cas12a (cpf1) based electrochemical biosensor (E-CRISPR) is reported, which is more cost-effective and portable than optical-transduction-based biosensors. Through optimizing the in vitro trans-cleavage activity of Cas12a, E-CRIPSR was used to detect viral nucleic acids, including human papillomavirus 16 (HPV-16) and parvovirus B19 (PB-19), with a picomolar sensitivity. An aptamer-based E-CRISPR cascade was further designed for the detection of transforming growth factor β1 (TGF-β1) protein in clinical samples. As demonstrated, E-CRISPR could enable the development of portable, accurate, and cost-effective point-of-care diagnostic systems.
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http://dx.doi.org/10.1002/anie.201910772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938695PMC
November 2019

Preparation and characterization of coffee hull fiber for reinforcing application in thermoplastic composites.

Bioengineered 2019 12;10(1):397-408

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University , Nanjing , Jiangsu , China.

Nowadays, there is an increasing concern toward substituting the scarce wood fibers with alternative lignocellulosic fibers that originate from crop residue to reinforce biocomposites. In this paper, the potential application of coffee hull (CH) of the reinforced polyethylene (PE) matrix composites was studied for the first time. Experiments of composite that enhanced with CH on mechanical properties, hydroscopicity, thermogravimetric analysis, fiber treatment, and microstructures were tested in this study. The PE matrix was reinforced with varying volume fractions of CH and was studied. The results show that incorporation of coffee hull markedly improved the mechanical properties of the reinforced high-density polyethylene (HDPE) matrix composites. Micrographs show a strong interfacial adhesion between the CH fiber particles. This property may be the main reason for the stability between composites. At the same time this work investigated the effect of different treatments on the mechanical properties and water absorption behavior of composites. The fiber surface treatments were done using active chemicals such as calcium hydroxide (Ca(OH)), silane coupling agent (SCA), maleic anhydride grafted polypropylene (MA-g-PP), stearic acid (SA), ethylene bis stearamide (EBS) and the combination (MA-g-PP, SA, EBS). The results show that (Ca(OH))treatment is the best way to improve its properties. Probably because attributed to removal of surface active functional groups (-OH) from the CH fiber and induction of hydrophobicity that in turn improved the compatibility with the polymer matrix. As a result, the use of coffee hull in composites could have great significance for the industry.
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http://dx.doi.org/10.1080/21655979.2019.1661694DOI Listing
December 2019

OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia.

J Genet Genomics 2019 08 13;46(8):379-387. Epub 2019 Aug 13.

Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Oxysterol binding protein like 2 (OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotype-phenotype associations, the OSBPL2-disrupted Bama miniature (BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer (SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss (HL) with degeneration/apoptosis of cochlea hair cells (HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet (HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss (NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.
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http://dx.doi.org/10.1016/j.jgg.2019.06.006DOI Listing
August 2019

Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells.

Xenotransplantation 2019 11 21;26(6):e12537. Epub 2019 Aug 21.

Shenzhen Xenotransplantation Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, Shenzhen, China.

After hyperacute rejection in pig-to-primate xenotransplantation had been overcome by the introduction of α1,3-galactosyltransferase gene-knockout (GTKO) pigs, acute and chronic antibody-mediated rejection became one of the major barriers to long-term graft survival. This was associated with exposure of non-Gal antigens to the recipient's immune system and indicated that further genetic engineering of the pigs would be necessary. We here report that Gabarapl1, a regulator of tumorigenesis, plays a role in the regulation of immunogenicity of porcine aortic endothelial cells (PAECs). Knockdown of Gabarapl1 in PAECs results in a remarkable reduction in binding of serum antibody from PAEC-immunized monkeys, associated with decreased serum cytotoxicity of pig cells. Expression of swine leukocyte antigens (SLA) II DR was downregulated by Gabarapl1 knockdown. However, suppression of expression of SLA II is associated with less reduction of antibody binding than achieved by Gabarapl1 knockdown, suggesting that other Gabarapl1-regulated xenoantigens may be more important. These findings indicate a hitherto unknown relationship between Gabarapl1 and xenoimmunogenicity, suggesting a potential new strategy to reduce rejection initiated by the presence of non-Gal antigens.
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http://dx.doi.org/10.1111/xen.12537DOI Listing
November 2019

Dynamic Control of Peptide Strand Displacement Reaction Using Functional Biomolecular Domain for Biosensing.

ACS Sens 2019 08 18;4(8):1980-1985. Epub 2019 Jul 18.

Lerner Research Institute , Cleveland Clinic , Cleveland , Ohio 44106 , United States.

Nature's great repository provides nucleic acids and amino acids as the fundamental elements of life. Inspired by the programmability of nucleic acids, DNA nanotechnology has been extensively developed based on the strand displacement reaction of nucleic acids. In comparison with nucleic acids, amino acids possess higher programmability and more functionalities owing to the diversity of the amino acid unit. However, the design of the peptide-based bimolecular cascade is still limited. We herein describe a peptide-based strand displacement reaction, which was granted with a specific biological function by addition of a functional domain onto the coiled-coil peptide based displacement substrate. The displacement substrate was specifically designed to response to Tau protein based on a well-established Tau inhibition sequence. We demonstrated that the kinetics of the designed displacement reaction can be dynamically tuned through blocking the toehold region to prevent migration. A nanomolar Tau detection linear range was achieved through the designed displacement reaction within a rapid turnaround time of 30 min. We also presented the capability of the peptide strand displacement based sensing system operating in real human biological samples and its excellent orthogonality on response to irrelevant biological components. We envision that this will be of especially high utility for the development of next-generation biotechnology.
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http://dx.doi.org/10.1021/acssensors.9b00831DOI Listing
August 2019

Derivation of novel naive-like porcine embryonic stem cells by a reprogramming factor-assisted strategy.

FASEB J 2019 08 24;33(8):9350-9361. Epub 2019 May 24.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.

The establishment of ungulate embryonic stem cells (ESCs) has been notoriously difficult a conventional approach. We combined a traditional ESC culture method with reprogramming factors to assist the establishment of porcine naive-like ESCs (nESCs). Pig embryonic fibroblasts were transfected with a tetracycline-inducible vector carrying 4 classic mouse reprogramming factors, followed by somatic cell nuclear transfer and culturing to the blastocyst stage. Then, the inner cell mass was isolated and seeded in culture medium. The naive-like ESCs had characteristic verys similar to those of mouse ESCs and showed no signs of altered morphology or differentiation, even after 130 passages. They depended on leukemia inhibitory factor signals for maintenance of pluripotency, and the female cell lines had low expression of the X-inactive specific transcript gene and no histone H3 lysine 27 trimethylation spot. Notably, the ESCs differentiated into 3 germ layers and could be induced to undergo directional neural and kidney precursor differentiation under defined conditions, and the ESCs could keep proliferating after doxycycline was removed. nESCs can be established, and the well-characterized ESC lines will be useful for the research of transgenic pig models for human disease.-Zhang, M., Wang, C., Jiang, H., Liu, M., Yang, N., Zhao, L., Hou, D., Jin, Y., Chen, Q., Chen, Y., Wang, J., Dai, Y., Li, R. Derivation of novel naive-like porcine embryonic stem cells by a reprogramming factor-assisted strategy.
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http://dx.doi.org/10.1096/fj.201802809RDOI Listing
August 2019

Circulating pig-specific DNA as a novel biomarker for monitoring xenograft rejection.

Xenotransplantation 2019 07 11;26(4):e12522. Epub 2019 May 11.

Shenzhen Xenotransplantation Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Monitoring for immune rejection is crucial for long-term survival of pig xenografts. Circulating DNA is a promising non-invasive biomarker for either organ injury or response to therapy. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection. Potential targets of cpsDNA were selected by in silico analysis, and species specificity of selected primers was confirmed by PCR. Subsequently, cpsDNA as a biomarker was evaluated using a complement-dependent cytotoxicity (CDC) assay in vitro. Then, early diagnosis and response to rapamycin were assessed by an in vivo imaging model of pig-to-mouse cell transplantation. Finally, cpsDNA was monitored in a pig-to-monkey artery patch transplantation model. The results showed that (a) a method of cpsDNA quantitation was established for application in mouse and nonhuman primate models; (b) cpsDNA reflected CDC in vitro; (c) cpsDNA in vivo mirrored xenograft rejection, and correlated with xenograft loss in pig-to-mouse cell transplantation; (d) cpsDNA was significantly reduced when rapamycin was administered; and (e) dynamic cpsDNA was detectable in pig-to-monkey artery patch transplantation. In conclusion, measurement of cpsDNA could prove to be a less invasive, but more specific and sensitive low-cost biomarker enabling monitoring of xenograft rejection and the response to immunosuppressive therapy.
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http://dx.doi.org/10.1111/xen.12522DOI Listing
July 2019