Publications by authors named "Cheng-Hao Wen"

49 Publications

Generation of IBMS-iPSC-021, -022, -023 human induced pluripotent stem cells (IBMSi016-A, IBMSi017-A, and IBMSi018-A) derived from patients with the ALDH2 rs671 polymorphism.

Stem Cell Res 2021 Jul 10;54:102416. Epub 2021 Jun 10.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation). These cell lines were characterized in terms of pluripotency and differentiation potential. They serve as useful platforms to study alcohol metabolism and other chronic diseases associated with alcohol consumption.
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http://dx.doi.org/10.1016/j.scr.2021.102416DOI Listing
July 2021

High-Performance Organic Solar Cells Featuring Double Bulk Heterojunction Structures with Vertical-Gradient Selenium Heterocyclic Nonfullerene Acceptor Concentrations.

ACS Appl Mater Interfaces 2021 Jun 6;13(23):27227-27236. Epub 2021 Jun 6.

Department of Materials Science and Engineering, Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University, Hsinchu 3001, Taiwan.

In this study, we prepared organic photovoltaics (OPVs) featuring an active layer comprising double bulk heterojunction (BHJ) structures, featuring binary blends of a polymer donor and concentration gradients of two small-molecule acceptors. After forming the first BHJ structure by spin-coating, the second BHJ layer was transfer-printed onto the first using polydimethylsiloxane stamps. A specially designed selenium heterocyclic small-molecule acceptor (Y6-Se-4Cl) was employed as the second acceptor in the BHJ. X-ray photoelectron spectroscopy revealed that the two acceptors formed a gradient concentration profile across the active layer, thereby facilitating charge transportation. The best power conversion efficiencies (PCEs) for the double-BHJ-structured devices incorporating PM6:Y6-Se-4Cl/PM6:Y6 and PM6:Y6-Se-4Cl/PM6:IT-4Cl were 16.4 and 15.8%, respectively; these values were higher than those of devices having one-BHJ structures based on PM6:Y6-Se-4Cl (15.0%), PM6:Y6 (15.4%), and PM6:IT-4Cl (11.6%), presumably because of the favorable vertical concentration gradient of the selenium-containing small-molecule Y6-Se-4Cl in the active layer as well as some complementary light absorption. Thus, combining two BHJ structures with a concentration gradient of the two small-molecule acceptors can be an effective approach for enhancing the PCEs of OPVs.
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http://dx.doi.org/10.1021/acsami.1c06762DOI Listing
June 2021

Microlens Array Fabrication by Using a Microshaper.

Micromachines (Basel) 2021 Feb 28;12(3). Epub 2021 Feb 28.

Department of Mechanical and Computer-Aided Engineering, Feng Chia University, Taichung City 407, Taiwan.

A simple, easy, inexpensive, and quick nonsilicon-based micromachining method was developed to manufacture a microlens array. The spherical surface of the microlens was machined using a microshaper mounted on a three-axis vertical computer numerical control (CNC) machine with cutter-path-planning. The results show the machined profiles of microlens agree well with designed profiles. The focus ability of the machined microlens array was verified. The designed and measured focal lengths have average 1.5% error. The results revealed that the focal lengths of micro lens agreed with the designed values. A moderate roughness of microlens surface is obtained by simply polishing. The roughness of the lens surface is 43 nm in feed direction (x-direction) and 56 nm in path interval direction (y-direction). It shows the simple, scalable, and reproducible method to manufacture microlenses by microshaper with cutter-path-planning is feasible.
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http://dx.doi.org/10.3390/mi12030244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997474PMC
February 2021

High-Performance Organic Photovoltaics Incorporating an Active Layer with a Few Nanometer-Thick Third-Component Layer on a Binary Blend Layer.

Nano Lett 2021 Mar 18;21(5):2207-2215. Epub 2021 Feb 18.

Department of Materials Science and Engineering, Center for Emergent Functional Matter Science, National Chiao Tung University, Hsinchu 3001, Taiwan.

In this paper, a universal approach toward constructing a new bilayer device architecture, a few-nanometer-thick third-component layer on a bulk-heterojunction (BHJ) binary blend layer, has been demonstrated in two different state-of-the-art organic photovoltaic (OPV) systems. Through a careful selection of a third component, the power conversion efficiency (PCE) of the device based on PM6/Y6/layered PTQ10 layered third-component structure was 16.8%, being higher than those of corresponding devices incorporating the PM6/Y6/PTQ10 BHJ ternary blend (16.1%) and the PM6/Y6 BHJ binary blend (15.5%). Also, the device featuring PM7/Y1-4F/layered PTQ10 layered third-component structure gave a PCE of 15.2%, which is higher than the PCEs of the devices incorporating the PM7/Y1-4F/PTQ10 BHJ ternary blend and the PM7/Y1-4F BHJ binary blend (14.2 and 14.0%, respectively). These enhancements in PCE based on layered third-component structure can be attributed to improvements in the charge separation and charge collection abilities. This simple concept of the layered third-component structure appears to have great promise for achieving high-performance OPVs.
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http://dx.doi.org/10.1021/acs.nanolett.0c05045DOI Listing
March 2021

Generation of induced pluripotent stem cells FIRDIi001-A from a Taiwanese subject carrying ALDH2 pE487K mutation.

Stem Cell Res 2021 04 11;52:102229. Epub 2021 Feb 11.

Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan. Electronic address:

The ALDH2 mutation (ALDH2*2) is caused by an amino acid substitution ALDH2 rs671 G>A (pE487K) which reduces ALDH2 enzyme activity. When individuals with the ALDH2 mutation consume alcohol, accumulating acetaldehyde in the blood can cause reddened face, headache, nausea, and palpitations; symptoms referred to as Alcohol Flushing Reaction. We report the production of an induced pluripotent stem cell (iPSC) line, FIRDIi001-A, developed from peripheral blood mononuclear cells of a 39-year-old male subject with the ALDH2*2 mutation. The ALDH2-pE487K iPSCs will be valuable in investigating pathogenic mechanisms involved in the link between the ALDH2 polymorphism and alcohol-related diseases.
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http://dx.doi.org/10.1016/j.scr.2021.102229DOI Listing
April 2021

Characterization and detection of Passiflora mottle virus and other two potyviruses causing passionfruit woodiness disease in Vietnam.

Phytopathology 2021 Jan 24. Epub 2021 Jan 24.

National Chung Hsing University, 34916, Plant Pathology, 145 Xingda Road, Taichung, Taiwan, 402;

Passionfruit plantation in Vietnam increased to 10,000 ha in 2019. However, the outbreaks of passionfruit woodiness disease (PWD) have become a serious threat for the production. In this study, five virus isolates DN1, DN4, NA1, GL1 and GL2 were collected from different areas of Vietnam. Their causal roles for PWD were verified by back inoculation to passionfruit. Analyses of coat protein (CP) and genomic sequences revealed that GL1 isolate is closely related to East Asia Passiflora virus (EAPV) AO strain of Japan (polyprotein nt/aa identities of 98.1% / 98.2%), while GL2 isolate is related to Telosma mosaic virus (TelMV) isolate PasFru, China (polyprotein nt/aa identities of 87.1% / 90.9%). CP comparison, host range and cytological characterization indicated that DN1, DN4 and NA1 are potyviruses, but different from EAPV and TelMV. Phylogenic analyses of their CP and genome sequences indicated that these three isolates and passionfruit severe mottle-associated virus Fujian isolate of China belong to a distinct clade, which does not satisfy the threshold (76% nt identity of polyprotein) to be regarded as any of potyviral species. Thus, a new species name of "" has been proposed by ICTV. A rabbit antiserum was produced against the CP of DN1 and it can discriminate Passiflora mottle virus (PaMoV) from TelMV and EAPV in western blotting and ELISA without cross reactions. Field surveys of 240 samples by ELISA and RT-PCR disclosed that PWD in Vietnam is mainly caused by PaMoV; followed by EAPV, mixed-infection of PaMoV/EAPV, and rare cases of TelMV.
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http://dx.doi.org/10.1094/PHYTO-10-20-0481-RDOI Listing
January 2021

Incorporating Indium Selenide Nanosheets into a Polymer/Small Molecule Binary Blend Active Layer Enhances the Long-Term Stability and Performance of Its Organic Photovoltaics.

ACS Appl Mater Interfaces 2020 Dec 25;12(49):55023-55032. Epub 2020 Nov 25.

Department of Materials Science and Engineering, National Chiao Tung University 30010 Hsinchu, Taiwan.

In this report, we demonstrated that the incorporation of 15 wt % two-dimensional transition-metal dichalcogenide materials indium selenide (InSe) nanosheets into a polymer (PM6)/small molecule (Y6) active layer not only increased its light absorption but also enhanced the long-term stability of the PM6/Y6/InSe ternary blend organic photovoltaic (OPV) devices. The power conversion efficiency (PCE) of the device was improved from 15.7 to 16.5% for the corresponding PM6/Y6 binary blend device. Moreover, the PM6/Y6/InSe device retained 80% of its initial PCE after thermal treatment at 100 °C for 600 h; in comparison, the binary blend device retained only 62% of its initial value. This relative enhancement of 29% resulted from the InSe nanosheets retarding or facilitating molecule packing in different orientations that stabilizes the morphology of the active layer. We adopted a modified kinetics model to account for the intrinsic degradation of the OPV; the degradation-facilitated energy for the degradation kinetics of the PCE for the ternary blend device was 5.3 kJ/mol, half of that (11.3 kJ/mol) of the binary blend device, indicating a slower degradation rate occurring for the case of incorporating InSe nanosheets. Therefore, the incorporation of transition metal dichalcogenide nanosheets having tunable band gaps and large asymmetric shape appears to be a new way to improve the long-term stability of devices and realize the practical use of OPVs.
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http://dx.doi.org/10.1021/acsami.0c14461DOI Listing
December 2020

Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing the Taiwan human disease iPSC Consortium Bank.

J Biomed Sci 2020 Sep 4;27(1):92. Epub 2020 Sep 4.

Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.

Background: The Taiwan Human Disease iPSC Service Consortium was established to accelerate Taiwan's growing stem cell research initiatives and provide a platform for researchers interested in utilizing induced pluripotent stem cell (iPSC) technology. The consortium has generated and characterized 83 iPSC lines: 11 normal and 72 disease iPSC lines covering 21 different diseases, several of which are of high incidence in Taiwan. Whether there are any reprogramming-induced recurrent copy number variant (CNV) hotspots in iPSCs is still largely unknown.

Methods: We performed genome-wide copy number variant screening of 83 Han Taiwanese iPSC lines and compared them with 1093 control subjects using an Affymetrix genome-wide human SNP array.

Results: In the iPSCs, we identified ten specific CNV loci and seven "polymorphic" CNV regions that are associated with the reprogramming process. Additionally, we established several differentiation protocols for our iPSC lines. We demonstrated that our iPSC-derived cardiomyocytes respond to pharmacological agents and were successfully engrafted into the mouse myocardium demonstrating their potential application in cell therapy.

Conclusions: The CNV hotspots induced by cell reprogramming have successfully been identified in the current study. This finding may be used as a reference index for evaluating iPSC quality for future clinical applications. Our aim was to establish a national iPSC resource center generating iPSCs, made available to researchers, to benefit the stem cell community in Taiwan and throughout the world.
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http://dx.doi.org/10.1186/s12929-020-00682-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487458PMC
September 2020

Dosimetric comparison of helical tomotherapy, volumetric-modulated arc therapy, intensity-modulated radiotherapy, and field-in-field technique for synchronous bilateral breast cancer.

Med Dosim 2020 Autumn;45(3):271-277. Epub 2020 Feb 29.

Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Purpose: To compare the dosimetric characteristics of helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), intensity-modulated radiotherapy (IMRT), and tangential field-in-field technique (FIF) for the treatment of synchronous bilateral breast cancer (SBBC).

Methods And Materials: Ten patients with early-stage unilateral breast cancer were selected for simulating the patients with SBBC in this retrospective analysis. Treatment plans with HT, VMAT, IMRT, and FIF were generated for each patient with a total dose of 50.4 Gy in 28 fractions to the target. Plan quality, namely conformity index (CI), homogeneity index (HI), dose-volume statistics of organs at risk (OARs), and beam-on time (BOT), were evaluated.

Results: HT plans showed a lower mean heart dose (3.53 ± 0.31Gy) compared with the other plans (VMAT = 5.6 ± 1.36 Gy, IMRT = 3.80 ± 0.76 Gy, and FIF = 4.84 ± 2.13 Gy). Moreover, HT plans showed a significantly lower mean lung dose (p < 0.01) compared with the other plans: mean right lung doses were 6.81 ± 0.67, 10.32 ± 1.04, 9.07 ± 1.21, and 10.03 ± 1.22 Gy and mean left lung doses were 6.33 ± 0.87, 8.82 ± 0.91, 7.84 ± 1.07, and 8.64 ± 0.99 Gy for HT, VMAT, IMRT, and FIF plans, respectively. The mean dose to the left anterior descending artery was significantly lower in HT plans (p < 0.01) than in the other plans: HT = 19.41 ± 0.51 Gy, VMAT = 25.77 ± 7.23 Gy, IMRT = 27.87 ± 6.48 Gy, and FIF = 30.95 ± 10.17 Gy. FIF plans showed a worse CI and HI compared with the other plans. VMAT plans showed shorter BOT (average, 3.9 ± 0.2 minutes) than did HT (average, 11.0 ± 3.0 minutes), IMRT (average, 6.1 ± 0.5 minutes), and FIF (average, 4.6 ± 0.7 minutes) plans.

Conclusions: In a dosimetric comparison for SBBC, HT provided the most favorable dose sparing of OARs. However, HT with longer BOT may increase patient discomfort and treatment uncertainty. VMAT enabled shorter BOT with acceptable doses to OARs and had a better CI than did FIF and IMRT.
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http://dx.doi.org/10.1016/j.meddos.2020.01.006DOI Listing
July 2021

Potassium-Presenting Zinc Oxide Surfaces Induce Vertical Phase Separation in Fullerene-Free Organic Photovoltaics.

Nano Lett 2020 Jan 26;20(1):715-721. Epub 2019 Dec 26.

Department of Materials Science and Engineering , California NanoSystems Institute, University of California , Los Angeles , California 90095 , United States.

Bulk heterojunction (BHJ) structure based organic photovoltaics (OPVs) have recently showed great potential for achieving high power conversion efficiencies (PCEs). An ideal BHJ structure would feature large donor/acceptor interfacial areas for efficient exciton dissociation and gradient distributions with high donor and acceptor concentrations near the anode and cathode, respectively, for efficient charge extraction. However, the random mixing of donors and acceptors in the BHJ often suffers the severe charge recombination in the interface, resulting in poor charge extraction. Herein, we propose a new approach-treating the surface of the zinc oxide (ZnO) as an electron transport layer with potassium hydroxide-to induce vertical phase separation of an active layer incorporating the nonfullerene acceptor IT-4F. Density functional theory calculations suggested that the binding energy difference between IT-4F and the PBDB-T-2Cl, to the potassium (K)-presenting ZnO interface, is twice as strong as that for IT-4F and PBDB-T-2Cl to the untreated ZnO surface, such that it would induce more IT-4F moving toward the K-presenting ZnO interface than the untreated ZnO interface thermodynamically. Benefiting from efficient charge extraction, the best PCEs increased to 12.8% from 11.8% for PBDB-T-2Cl:IT-4F-based devices, to 12.6% from 11.6% for PBDB-T-2Cl:Y1-4F-based devices, to 13.5% from 12.2% for PBDB-T-2Cl:Y6-based devices, and to 15.7% from 15.1% for PM6:Y6-based devices.
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http://dx.doi.org/10.1021/acs.nanolett.9b04586DOI Listing
January 2020

Hydrogen plasma-treated MoSe nanosheets enhance the efficiency and stability of organic photovoltaics.

Nanoscale 2019 Oct 18;11(37):17460-17470. Epub 2019 Sep 18.

Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan. and Center for Emergent Functional Matter Science, National Chiao Tung University, Hsinchu 30010, Taiwan.

In this paper we report the effect on the power conversion efficiency (PCE) and stability of photovoltaic devices after incorporating hydrogenated two-dimensional (2D) MoSe nanosheets into the active layer of bulk heterojunction (BHJ) organic photovoltaics (OPV). The surface properties of 2D MoSe nanosheets largely affect their dispersion in the active layer blend and, thus, influence the carrier mobility, PCE, and stability of corresponding devices. We treated MoSe nanosheets with hydrogen plasma and investigated their influence on the polymer packing and fullerene domain size of the active layer. For the optimized devices incorporating 37.5 wt% of untreated MoSe, we obtained a champion PCE of 9.82%, compared with the champion reference PCE of approximately 9%. After incorporating the hydrogen plasma-treated MoSe nanosheets, we achieved a champion PCE of 10.44%-a relative increase of 16% over that of the reference device prepared without MoSe nanosheets. This PCE is the one of the highest ever reported for OPVs incorporating 2D materials. We attribute this large enhancement to the enhanced exciton generation and dissociation at the MoSe-fullerene interface and, consequently, the balanced charge carrier mobility. The device incorporating the MoSe nanosheets maintained 70% of its initial PCE after heat-treatment at 100 °C for 1 h; in contrast, the PCE of the reference device decreased to 60% of its initial value-a relative increase in stability of 17% after incorporating these nanosheets. We also incorporated MoSe nanosheets (both with and without treatment) into a polymer donor (PBDTTBO)/small molecule (IT-4F) acceptor system. The champion PCEs reached 7.85 and 8.13% for the devices incorporating the MoSe nanosheets with and without plasma treatment, respectively-relative increases of 8 and 12%, respectively, over that of the reference. These results should encourage a push toward the implementation of transition metal dichalcogenides to enhance the performances of BHJ OPVs.
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http://dx.doi.org/10.1039/c9nr06611jDOI Listing
October 2019

Realizing Efficient Charge/Energy Transfer and Charge Extraction in Fullerene-Free Organic Photovoltaics via a Versatile Third Component.

Nano Lett 2019 Aug 16;19(8):5053-5061. Epub 2019 Jul 16.

Department of Materials Science and Engineering, California NanoSystems Institute , University of California , Los Angeles , California 90095 , United States.

Solution-processed organic photovoltaics (OPVs) based on bulk-heterojunctions have gained significant attention to alleviate the increasing demend of fossil fuel in the past two decades. OPVs combined of a wide bandgap polymer donor and a narrow bandgap nonfullerene acceptor show potential to achieve high performance. However, there are still two reasons to limit the OPVs performance. One, although this combination can expand from the ultraviolet to the near-infrared region, the overall external quantum efficiency of the device suffers low values. The other one is the low open-circuit voltage () of devices resulting from the relatively downshifted lowest unoccupied molecular orbital (LUMO) of the narrow bandgap. Herein, the approach to select and incorporate a versatile third component into the active layer is reported. A third component with a bandgap larger than that of the acceptor, and absorption spectra and LUMO levels lying within that of the donor and acceptor, is demonstrated to be effective to conquer these issues. As a result, the power conversion efficiencies (PCEs) are enhanced by the elevated short-circuit current and ; the champion PCEs are 11.1% and 13.1% for PTB7-Th:IEICO-4F based and PBDB-T:Y1 based solar cells, respectively.
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http://dx.doi.org/10.1021/acs.nanolett.9b01344DOI Listing
August 2019

Generation of induced pluripotent stem cells (IBMSi011-A) from a patient with Parkinson's disease carrying LRRK2 p.I1371V mutation.

Stem Cell Res 2019 05 22;37:101447. Epub 2019 Apr 22.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Leucine rich repeat kinase 2 (LRRK2) is the causative gene for autosomal-dominant familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with LRRK2 c.4111A > G (p.I1371V) mutation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the three germ layers in vivo. This cellular model will provide a platform for studying the role of LRRK2 in the disease process.
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http://dx.doi.org/10.1016/j.scr.2019.101447DOI Listing
May 2019

Unraveling Sunlight by Transparent Organic Semiconductors toward Photovoltaic and Photosynthesis.

ACS Nano 2019 02 4;13(2):1071-1077. Epub 2019 Jan 4.

Department of Materials Science and Engineering , University of California , Los Angeles , California 90095 , United States.

Because the visible and the infrared (IR) regions take up ∼47% and ∼51% of the energy in the solar spectrum (AM 1.5G standard), respectively, utilizing the visible light for plant growth and the IR light for power generation is potentially extremely exciting. IR-absorbing organic semiconductors, with localized IR absorption and visible-light transmittance, would be promising materials for this purpose. Here, flexible transparent organic photovoltaics (TOPVs) based on IR-absorbing organic materials were proposed, which can be a simple, low-cost, and promising way to utilize the IR light for electricity generation, and the penetrated visible light will be utilized for photosynthesis in plants. A power-conversion efficiency of ∼10% with an average visible transmittance of 34% was achieved for TOPV devices. Meanwhile, the side-by-side comparison showed that plants grown under the TOPVs filtered light, and those under normal sunlight yielded very similar results. These outcomes demonstrated the results from TOPV devices beyond simple photovoltaic applications.
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http://dx.doi.org/10.1021/acsnano.8b08577DOI Listing
February 2019

Unique Energy Alignments of a Ternary Material System toward High-Performance Organic Photovoltaics.

Adv Mater 2018 Jul 21;30(28):e1801501. Epub 2018 May 21.

Department of Materials Science and Engineering, University of California, Los Angeles, CA, 90095, USA.

Incorporating narrow-bandgap near-infrared absorbers as the third component in a donor/acceptor binary blend is a new strategy to improve the power conversion efficiency (PCE) of organic photovoltaics (OPV). However, there are two main restrictions: potential charge recombination in the narrow-gap material and miscompatibility between each component. The optimized design is to employ a third component (structurally similar to the donor or acceptor) with a lowest unoccupied molecular orbital (LUMO) energy level similar to the acceptor and a highest occupied molecular orbital (HOMO) energy level similar to the donor. In this design, enhanced absorption of the active layer and enhanced charge transfer can be realized without breaking the optimized morphology of the active layer. Herein, in order to realize this design, two new narrow-bandgap nonfullerene acceptors with suitable energy levels and chemical structures are designed, synthesized, and employed as the third component in the donor/acceptor binary blend, which boosts the PCE of OPV to 11.6%.
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http://dx.doi.org/10.1002/adma.201801501DOI Listing
July 2018

Generation of novel induced pluripotent stem cell (iPSC) line from a 16-year-old sialidosis patient with NEU-1 gene mutation.

Stem Cell Res 2018 04 31;28:39-43. Epub 2018 Jan 31.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Sialidosis is a rare autosomal recessive disorder that affects the intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in NEU1, which encodes the sialidase enzyme, result in sialidosis. Sialidosis is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. In this study, we used Sendai virus reprogramming to generate an induced pluripotent stem cell (iPSC) line carrying the A544G mutation combined with the 667-679 deletion of the NEU1 gene from a sialidosis patient. The patient-specific iPSCs expressed pluripotent markers, possessed a normal karyotype, and displayed the capability to differentiate into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2018.01.024DOI Listing
April 2018

Ternary System with Controlled Structure: A New Strategy toward Efficient Organic Photovoltaics.

Adv Mater 2018 Feb 10;30(8). Epub 2018 Jan 10.

Department of Materials Science and Engineering, University of California, Los Angeles, CA, 90095, USA.

Recently, a new type of active layer with a ternary system has been developed to further enhance the performance of binary system organic photovoltaics (OPV). In the ternary OPV, almost all active layers are formed by simple ternary blend in solution, which eventually leads to the disordered bulk heterojunction (BHJ) structure after a spin-coating process. There are two main restrictions in this disordered BHJ structure to obtain higher performance OPV. One is the isolated second donor or acceptor domains. The other is the invalid metal-semiconductor contact. Herein, the concept and design of donor/acceptor/acceptor ternary OPV with more controlled structure (C-ternary) is reported. The C-ternary OPV is fabricated by a sequential solution process, in which the second acceptor and donor/acceptor binary blend are sequentially spin-coated. After the device optimization, the power conversion efficiencies (PCEs) of all OPV with C-ternary are enhanced by 14-21% relative to those with the simple ternary blend; the best PCEs are 10.7 and 11.0% for fullerene-based and fullerene-free solar cells, respectively. Moreover, the averaged PCE value of 10.4% for fullerene-free solar cell measured in this study is in great agreement with the certified one of 10.32% obtained from Newport Corporation.
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http://dx.doi.org/10.1002/adma.201705243DOI Listing
February 2018

Generation of an induced pluripotent stem cell (iPSC) line from a 40-year-old patient with the A8344G mutation of mitochondrial DNA and MERRF (myoclonic epilepsy with ragged red fibers) syndrome.

Stem Cell Res 2018 03 19;27:10-14. Epub 2017 Dec 19.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Mitochondrial defects are associated with clinical manifestations from common diseases to rare genetic disorders. Myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome results from an A to G transition at nucleotide position 8344 in the tRNA gene of mitochondrial DNA (mtDNA) and is characterized by myoclonus, myopathy and severe neurological symptoms. In this study, Sendai reprogramming method was used to generate an iPS cell line carrying the A8344G mutation of mtDNA from a MERRF patient. This patient-specific iPSC line expressed pluripotent stem cell markers, possessed normal karyotype, and displayed the capability to differentiate into mature cells in three germ layers.
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http://dx.doi.org/10.1016/j.scr.2017.12.013DOI Listing
March 2018

Generation of induced pluripotent stem cells from a patient with Parkinson's disease carrying LRRK2 p.I2012T mutation.

Stem Cell Res 2017 12 31;25:123-127. Epub 2017 Oct 31.

Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan. Electronic address:

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by interactions between genetic and environmental factors. Leucine rich repeat kinase (LRRK2) is the most prevalent mutation in autosomal-dominant inheritance of PD. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with p.I2012T mutation in LRRK2 gene by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the 3 germ layers in vivo. This cellular model will provide a useful platform for further pathophysiological studies of PD.
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http://dx.doi.org/10.1016/j.scr.2017.10.020DOI Listing
December 2017

Induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient carrying a PKD1 Q533X mutation.

Stem Cell Res 2017 12 28;25:83-87. Epub 2017 Oct 28.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent monogenic kidney disorder leading to kidney failure. We generated induced pluripotent stem cells (iPSCs) from a 37-year-old man carrying a PKD1 Q533X mutation who suffered from kidney failure and a myocardial infarction. The iPSCs were reprogrammed from the patient's peripheral blood mononuclear cells using the Sendai virus system, and were confirmed to possess the specific PKD1 Q533X mutation and normal karyotype. Pluripotency was confirmed using in vitro and in vivo assays. This iPSC line will be useful for studying the mechanisms driving the complicated pathophysiology of ADPKD.
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http://dx.doi.org/10.1016/j.scr.2017.10.026DOI Listing
December 2017

Potyviral Gene-Silencing Suppressor HCPro Interacts with Salicylic Acid (SA)-Binding Protein 3 to Weaken SA-Mediated Defense Responses.

Mol Plant Microbe Interact 2018 01 1;31(1):86-100. Epub 2017 Nov 1.

1 Department of Plant Pathology, National Chung-Hsing University, Taichung City 40227, Taiwan, R.O.C.

The viral infection process is a battle between host defense response and pathogen antagonizing action. Several studies have established a tight link between the viral RNA silencing suppressor (RSS) and the repression of salicylic acid (SA)-mediated defense responses, nonetheless host factors directly linking an RSS and the SA pathway remains unidentified. From yeast two-hybrid analysis, we identified an interaction between the potyviral RSS helper-component proteinase (HCPro) and SA-binding protein SABP3. Co-localization and bimolecular fluorescence complementation analyses validated the direct in vivo interaction between Turnip mosaic virus (TuMV) HCPro and the Arabidopsis homologue of SABP3, AtCA1. Additionally, transient expression of TuMV HCPro demonstrated its ability to act as a negative regulator of AtCA1. When the plants of the AtCA1 knockout mutant line were inoculated with TuMV, our results indicated that AtCA1 is essential to restrict viral spreading and accumulation, induce SA accumulation, and trigger the SA pathway. Unexpectedly, the AtCA1 overexpression line also displayed a similar phenotype, suggesting that the constitutive expression of AtCA1 antagonizes the SA pathway. Taken together, our results depict AtCA1 as an essential regulator of SA defense responses. Moreover, the interaction of potyviral HCPro with this regulator compromises the SA pathway to weaken host defense responses and facilitate viral infection.
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http://dx.doi.org/10.1094/MPMI-06-17-0128-FIDOI Listing
January 2018

Forward treatment planning techniques to reduce the normalization effect in Gamma Knife radiosurgery.

J Appl Clin Med Phys 2017 Nov 27;18(6):114-122. Epub 2017 Sep 27.

Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications.
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http://dx.doi.org/10.1002/acm2.12193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689927PMC
November 2017

Evaluation of Clinical Application and Dosimetric Comparison of Treatment Plans of Gamma Knife and CyberKnife in Treating Arteriovenous Malformations.

Stereotact Funct Neurosurg 2017 10;95(3):142-148. Epub 2017 May 10.

Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC.

Purpose: To analyze and compare the characteristics of dose distributions for Leksell Gamma Knife Perfexion (LGK-PFX) and CyberKnife (CK) in treating arteriovenous malformations (AVMs).

Subjects And Methods: Twenty-four patients with AVMs who received CK radiosurgery at a prescribed dose (PD) of 16-25 Gy in a single fraction were selected. A LGK-PFX treatment plan with the same PD was designed for each patient. Dosimetric values for both systems were compared with respect to the conformity index (CI); selectivity index (SI); gradient index (GI) of 75, 50, and 25% of the PD; heterogeneity index; volume of the brain tissue covered by doses of 10 and 12 Gy; maximum dose delivered to the brainstem; and beam-on time.

Results: The CIs of LGK-PFX and CK were 0.744 ± 0.075 and 0.759 ± 0.071 (p = 0.385), respectively. The SIs of LGK-PFX and CK were 0.764 ± 0.081 and 0.780 ± 0.076 (p = 0.424), respectively. The GI75%, GI50%, and GI25% values of LGK-PFX and CK were 1.028 ± 0.123 and 2.439 ± 0.338 (p < 0.001), 3.169 ± 0.265 and 4.972 ± 0.852 (p < 0.001), and 8.650 ± 0.914 and 14.261 ± 2.476 (p < 0.001), respectively. Volumes of the brain tissue covered by 10 Gy and 12 Gy for LGK-PFX and CK (p < 0.001) exhibited a significant difference.

Conclusions: LGK-PFX and CK exhibited similar dose conformity. LGK-PFX showed superior normal tissue sparing.
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http://dx.doi.org/10.1159/000460259DOI Listing
September 2017

Generation of induced pluripotent stem cells from a patient with spinocerebellar ataxia type 3.

Stem Cell Res 2017 01 9;18:29-32. Epub 2016 Dec 9.

Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan. Electronic address:

Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a trinucleotide repeat (CAG) expansion in the coding region of ATXN3 gene resulting in production of ataxin-3 with an elongated polyglutamine tract. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a male patient with SCA3 by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, retained the disease-causing ATXN3 mutation, expressed pluripotent markers and could differentiate into the three germ layers. Potentially, the iPSCs could be a useful tool for the investigation of disease mechanisms of SCA3.
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http://dx.doi.org/10.1016/j.scr.2016.12.017DOI Listing
January 2017

Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

Biomed Res Int 2016 12;2016:2106342. Epub 2016 Dec 12.

Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.

Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, = 20) and control (normal saline, = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group ( < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.
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http://dx.doi.org/10.1155/2016/2106342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183754PMC
January 2017

Recovery of CD45(-)/Lin(-)/SSEA-4(+) very small embryonic-like stem cells by cord blood bank standard operating procedures.

Cytotherapy 2014 Apr 22;16(4):560-5. Epub 2013 Dec 22.

Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan. Electronic address:

Background Aims: Very small embryonic-like (VSEL) stem cells are a rare cell population present in bone marrow, cord blood and other tissues that displays a distinct small cell size and the ability to give rise to cells of the three germ layers. VSEL stem cells were reported to be discarded in the red blood cell fraction by Ficoll-Paque density gradient centrifugation during the processing of bone marrow and cord blood specimens. However, most cord blood banks do not include density gradient centrifugation in their procedures while red blood cells are removed by Hespan sedimentation following the Cord Blood Transplantation Study cord blood bank standard operating procedures (COBLT SOP). To clarify the retention of VSEL stem cells, we investigated the recovery of VSEL stem cells following COBLT SOP guidelines.

Methods: The recovery of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells of umbilical cord blood was examined by flow cytometry before and after COBLT SOP processing, and relative expression of pluripotent genes was analyzed by quantitative polymerase chain reaction.

Results: CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells were mostly recovered in the final products following COBLT SOP guidelines. The expression of pluripotent genes could be maintained at >80% in products after hetastarch (Hespan; B. Braun Medical Inc., Irvine, CA, USA) processing.

Conclusions: The rare sub-population of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells survived after Hespan sedimentation. This finding suggests that umbilical cord blood units cryopreserved by COBLT SOP in cord blood banks should retain most VSEL stem cells present in the un-processed specimens.
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http://dx.doi.org/10.1016/j.jcyt.2013.10.009DOI Listing
April 2014

An efficient tag derived from the common epitope of tospoviral NSs proteins for monitoring recombinant proteins expressed in both bacterial and plant systems.

J Biotechnol 2013 Apr 10;164(4):510-9. Epub 2013 Feb 10.

Department of Plant Pathology, National Chung Hsing University, Taichung 40227, Taiwan, ROC.

NSscon (23 aa), a common epitope in the gene silencing suppressor NSs proteins of the members of the Watermelon silver mottle virus (WSMoV) serogroup, was previously identified. In this investigation, we expressed different green fluorescent protein (GFP)-fused deletions of NSscon in bacteria and reacted with NSscon monoclonal antibody (MAb). Our results indicated that the core 9 amino acids, "(109)KFTMHNQIF(117)", denoted as "nss", retain the reactivity of NSscon. In bacterial pET system, four different recombinant proteins labeled with nss, either at N- or C-extremes, were readily detectable without position effects, with sensitivity superior to that for the polyhistidine-tag. When the nss-tagged Zucchini yellow mosaic virus (ZYMV) helper component-protease (HC-Pro) and WSMoV nucleocapsid protein were transiently expressed by agroinfiltration in tobacco, they were readily detectable and the tag's possible efficacy for gene silencing suppression was not noticed. Co-immunoprecipitation of nss-tagged and non-tagged proteins expressed from bacteria confirmed the interaction of potyviral HC-Pro and coat protein. Thus, we conclude that this novel nss sequence is highly valuable for tagging recombinant proteins in both bacterial and plant expression systems.
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http://dx.doi.org/10.1016/j.jbiotec.2013.02.002DOI Listing
April 2013

Single nucleotide polymorphism barcoding to evaluate oral cancer risk using odds ratio-based genetic algorithms.

Kaohsiung J Med Sci 2012 Jul 14;28(7):362-8. Epub 2012 May 14.

Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan.

Cancers often involve the synergistic effects of gene-gene interactions, but identifying these interactions remains challenging. Here, we present an odds ratio-based genetic algorithm (OR-GA) that is able to solve the problems associated with the simultaneous analysis of multiple independent single nucleotide polymorphisms (SNPs) that are associated with oral cancer. The SNP interactions between four SNPs-namely rs1799782, rs2040639, rs861539, rs2075685, and belonging to four genes (XRCC1, XRCC2, XRCC3, and XRCC4)-were tested in this study, respectively. The GA decomposes the SNPs sets into different SNP combinations with their corresponding genotypes (called SNP barcodes). The GA can effectively identify a specific SNP barcode that has an optimized fitness value and uses this to calculate the difference between the case and control groups. The SNP barcodes with a low fitness value are naturally removed from the population. Using two to four SNPs, the best SNP barcodes with maximum differences in occurrence between the case and control groups were generated by GA algorithm. Subsequently, the OR provides a quantitative measure of the multiple SNP synergies between the oral cancer and control groups by calculating the risk related to the best SNP barcodes and others. When these were compared to their corresponding non-SNP barcodes, the estimated ORs for oral cancer were found to be great than 1 [approx. 1.72-2.23; confidence intervals (CIs): 0.94-5.30, p < 0.03-0.07] for various specific SNP barcodes with two to four SNPs. In conclusion, the proposed OR-GA method successfully generates SNP barcodes, which allow oral cancer risk to be evaluated and in the process the OR-GA method identifies possible SNP-SNP interactions.
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http://dx.doi.org/10.1016/j.kjms.2012.02.002DOI Listing
July 2012

Lysophosphatidic acid induces erythropoiesis through activating lysophosphatidic acid receptor 3.

Stem Cells 2011 Nov;29(11):1763-73

Institute of Zoology, National Taiwan University, Taipei, Taiwan, Republic of China.

Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through activating G protein-coupled receptors. LPA receptor 3 (LPA(3)) is a member of the endothelial differentiation gene family, which regulates differentiation and development of the circulation system. However, the relationship among the LPA receptors (LPARs) and erythropoiesis is still not clear. In this study, we found that erythroblasts expressed both LPA(1) and LPA(3), and erythropoietic defects were observed in zLPA(3) antisense morpholino oligonucleotide-injected zebrafish embryos. In human model, our results showed that LPA enhanced the erythropoiesis in the cord blood-derived human hematopoietic stem cells (hHSCs) with erythropoietin (EPO) addition in the plasma-free culture. When hHSCs were treated with Ki16425, an antagonist of LPA(1) and LPA(3), erythropoietic process of hHSCs was also blocked, as detected by mRNA and protein expressions of CD71 and GlyA. In the knockdown study, we further demonstrated that specific knockdown of LPA(3), not LPA(1), blocked the erythropoiesis. The translocation of β-catenin into the nucleus, a downstream response of LPAR activation, was blocked by Ki16425 treatment. In addition, upregulation of erythropoiesis by LPA was also blocked by quercetin, an inhibitor of the β-catenin/T-cell factor pathway. Furthermore, the enhancement of LPA on erythropoiesis was diminished by blocking c-Jun-activated kinase/signal transducer and activator of transcription and phosphatidylinositol 3-kinase/AKT activation, the downstream signaling pathways of EPO receptor, suggested that LPA might play a synergistic role with EPO to regulate erythropoietic process. In conclusion, we first reported that LPA participates in EPO-dependent erythropoiesis through activating LPA(3).
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http://dx.doi.org/10.1002/stem.733DOI Listing
November 2011

Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts.

Peptides 2011 Sep 16;32(9):1832-9. Epub 2011 Aug 16.

Department of Biological Science and Technology, National Chiao Tung University, No. 75 Po-Ai Street, Hsinchu 30068, Taiwan.

Angiotensin-converting enzyme 2 (ACE2) has been proposed as a potential target for cardioprotection in regulating cardiovascular functions, owing to its key role in the formation of the vasoprotective peptides angiotensin-(1-7) from angiotensin II (Ang II). The regulatory mechanism of ace2 expression, however, remains to be explored. In this study, we investigated the regulatory element within the upstream of ace2. The human ace2 promoter region, from position -2069 to +20, was cloned and a series of upstream deletion mutants were constructed and cloned into a luciferase reporter vector. The reporter luciferase activity was analyzed by transient transfection of the constructs into human cardiofibroblasts (HCFs) and an activating domain was identified in the -516/-481 region. Deletion or reversal of this domain within ace2 resulted in a significant decrease in promoter activity. The nuclear proteins isolated from the HCFs formed a DNA-protein complex with double stranded oligonucleotides of the -516/-481 domain, as detected by electrophoretic mobility shift assay. Site-directed mutagenesis of this region identified a putative protein binding domain and a potential binding site, ATTTGGA, homologous to that of an Ikaros binding domain. This regulatory element was responsible for Ang II stimulation via the Ang II-Ang II type-1 receptor (AT1R) signaling pathway, but was not responsible for pro-inflammatory cytokines TGF-β1 and TNF-α. Our results suggest that the nucleotide sequences -516/-481 of human ace2 may be a binding domain for an as yet unidentified regulatory factor(s) that regulates ace2 expression and is associated with Ang II stimulation.
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http://dx.doi.org/10.1016/j.peptides.2011.08.009DOI Listing
September 2011