Publications by authors named "Chia-Ching Lin"

40 Publications

Spin-Charge Interconversion in KTaO 2D Electron Gases.

Adv Mater 2021 Sep 9:e2102102. Epub 2021 Sep 9.

Unité Mixte de Physique, CNRS, Thales, Université Paris-Saclay, 1 avenue Augustin Fresnel, Palaiseau, 91767, France.

Oxide interfaces exhibit a broad range of physical effects stemming from broken inversion symmetry. In particular, they can display non-reciprocal phenomena when time reversal symmetry is also broken, e.g., by the application of a magnetic field. Examples include the direct and inverse Edelstein effects (DEE, IEE) that allow the interconversion between spin currents and charge currents. The DEE and IEE have been investigated in interfaces based on the perovskite SrTiO (STO), albeit in separate studies focusing on one or the other. The demonstration of these effects remains mostly elusive in other oxide interface systems despite their blossoming in the last decade. Here, the observation of both the DEE and IEE in a new interfacial two-dimensional electron gas (2DEG) based on the perovskite oxide KTaO is reported. 2DEGs are generated by the simple deposition of Al metal onto KTaO single crystals, characterized by angle-resolved photoemission spectroscopy and magnetotransport, and shown to display the DEE through unidirectional magnetoresistance and the IEE by spin-pumping experiments. Their spin-charge interconversion efficiency is then compared with that of STO-based interfaces, related to the 2DEG electronic structure, and perspectives are given for the implementation of KTaO 2DEGs into spin-orbitronic devices is compared.
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http://dx.doi.org/10.1002/adma.202102102DOI Listing
September 2021

Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation.

Nat Commun 2021 06 29;12(1):3878. Epub 2021 Jun 29.

Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan.

Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3' ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3'-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7 cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.
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http://dx.doi.org/10.1038/s41467-021-24177-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241994PMC
June 2021

ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling-Driven Epithelial-to-Mesenchymal Transition.

Cancer Res 2021 Aug 18;81(15):4094-4109. Epub 2021 Jun 18.

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.

ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Activation of these signaling axes decreased GSK3β activity via Src-PI3K-AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer. SIGNIFICANCE: This study shows that ENO1 promotes lung cancer metastasis via HGFR and WNT signaling and introduces a novel anti-ENO1 antibody for potential therapeutic use in lung cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3543DOI Listing
August 2021

Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation.

Stem Cell Res Ther 2021 05 29;12(1):314. Epub 2021 May 29.

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

Background: The major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear.

Methods: Gain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA).

Results: CXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs.

Conclusions: CXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.
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http://dx.doi.org/10.1186/s13287-021-02402-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164772PMC
May 2021

Toward Intrinsic Ferroelectric Switching in Multiferroic BiFeO_{3}.

Phys Rev Lett 2020 Aug;125(6):067601

Department of Physics, University of California, Berkeley, California 94720, USA.

Using pulsed ferroelectric measurements, we probe switching dynamics in multiferroic BiFeO_{3}, revealing low-ns switching times and a clear pathway to sub-ns switching. Our data is well described by a nucleation and growth model, which accounts for the various timescales in the switching process, namely (1) the ferroelectric polarization switching (bound-charge) dynamics and (2) the RC-limited movement of free charge in the circuit. Our model shows good agreement with observed data and begins to bridge the gap between experiment and theory, indicating pathways to study ferroelectric switching on intrinsic timescales.
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http://dx.doi.org/10.1103/PhysRevLett.125.067601DOI Listing
August 2020

X-ray Studies of High-Performance Lithium-Ion Storage in Keplerate-Type Polyoxometalate Anodes.

ACS Appl Mater Interfaces 2020 Sep 25;12(36):40296-40309. Epub 2020 Aug 25.

Department of Materials Science and Engineering, National Tsing Hua University, 101, Sec. 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.

Polyoxometalates (POMs) have emerged as potential anode materials for lithium-ion batteries (LIBs) owing to their ability to transfer multiple electrons. Although POM anode materials exhibit notable results in LIBs, their energy-storage mechanisms have not been well-investigated. Here, we utilize various and techniques to verify the charge-storage mechanisms of a Keplerate-type POM NaK{[(Mo)MoO(HO)(KSO)] [(VO)(HO)(SO)]}·ca200HO () anode in LIBs. The anode provides a high reversible capacity of up to ∼1300 mA h g without capacity fading for up to 100 cycles. The lithium-ion storage mechanism was studied systematically through synchrotron X-ray absorption near-edge structure, X-ray diffraction, extended X-ray absorption fine structure, transmission electron microscopy, synchrotron transmission X-ray microscopy, and Raman spectroscopy. Based on the abovementioned results, we propose that the open hollow-ball structure of the molecular cluster serves as an electron/ion sponge that can store a large number of lithium ions and electrons reversibly via multiple and reversible redox reactions (Mo ↔ Mo and V/V↔ V) with fast lithium diffusion kinetics (: 10-10 cm s). No obvious volumetric expansion of the microsized particle is observed during the lithiation/delithiation process, which leads to high cycling stability. This study provides comprehensive analytical methods for understanding the lithium-ion storage mechanism of such complicated POMs, which is important for further studies of POM electrodes in energy-storage applications.
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http://dx.doi.org/10.1021/acsami.0c09344DOI Listing
September 2020

Long-range air pollution transport in East Asia during the first week of the COVID-19 lockdown in China.

Sci Total Environ 2020 Nov 15;741:140214. Epub 2020 Jun 15.

Department of Atmospheric Sciences, National Central University, Taoyuan 32001, Taiwan; Center for Environmental Monitoring and Technology, National Central University, Taoyuan 32001, Taiwan. Electronic address:

Long-range transport (LRT) of air pollutants from East Asia during the northeast monsoon season impacts several downwind locations. In 2020, the initial COVID-19 lockdowns in China overlapped with Week 3 of the Chinese New Year (CNY) holiday, and an Asian outflow event. Thus, movement of the Chinese populace from city to city was already greatly reduced by the time of the LRT episode, although the reductions in industrial output are less clear. We found NO column concentrations were reduced by 24% during the CNY Week 3 this year compared to previous years. The attenuated transport event arrived to northern Taiwan with a PM concentration <45 μg m and most often <35 μg m, which is 2-3 times lower than LRT episodes of similar back-trajectory and synoptic patterns. The whole episode persisted for about 60 h, longer than most LRT episodes from China to Taiwan. CMAQ v5.2.1 modeling of the LRT event with 100% emission and reduced emission scenarios, revealed emissions in China were approximately 50% less than normal periods. Due to the length of the episode and the significant reduction in emissions, Taiwan avoided a PM surplus of 19.2 μg m on average during the episode, equivalent to a 0.5 μg m reduction for the whole 3-month winter season. Employing the 100% emission model scenario and scaling up to the average episode hours each winter, the PM surplus delivered via plumes on the northeast monsoon is equivalent to a 0.5 μg m surplus for the whole year.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295523PMC
November 2020

Manipulating magnetoelectric energy landscape in multiferroics.

Nat Commun 2020 Jun 5;11(1):2836. Epub 2020 Jun 5.

Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, CA, 94720, USA.

Magnetoelectric coupling at room temperature in multiferroic materials, such as BiFeO, is one of the leading candidates to develop low-power spintronics and emerging memory technologies. Although extensive research activity has been devoted recently to exploring the physical properties, especially focusing on ferroelectricity and antiferromagnetism in chemically modified BiFeO, a concrete understanding of the magnetoelectric coupling is yet to be fulfilled. We have discovered that La substitutions at the Bi-site lead to a progressive increase in the degeneracy of the potential energy landscape of the BiFeO system exemplified by a rotation of the polar axis away from the 〈111〉 towards the 〈112〉 discretion. This is accompanied by corresponding rotation of the antiferromagnetic axis as well, thus maintaining the right-handed vectorial relationship between ferroelectric polarization, antiferromagnetic vector and the Dzyaloshinskii-Moriya vector. As a consequence, La-BiFeO films exhibit a magnetoelectric coupling that is distinctly different from the undoped BiFeO films.
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http://dx.doi.org/10.1038/s41467-020-16727-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275047PMC
June 2020

Ultralow Voltage Manipulation of Ferromagnetism.

Adv Mater 2020 Jul 28;32(28):e2001943. Epub 2020 May 28.

Department of Materials Science and Engineering, University of California, Berkeley, CA, 94720, USA.

Spintronic elements based on spin transfer torque have emerged with potential for on-chip memory, but they suffer from large energy dissipation due to the large current densities required. In contrast, an electric-field-driven magneto-electric storage element can operate with capacitive displacement charge and potentially reach 1-10 µJ cm switching operation. Here, magneto-electric switching of a magnetoresistive element is shown, operating at or below 200 mV, with a pathway to get down to 100 mV. A combination of phase detuning is utilized via isovalent La substitution and thickness scaling in multiferroic BiFeO to scale the switching energy density to ≈10 µJ cm . This work provides a template to achieve attojoule-class nonvolatile memories.
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http://dx.doi.org/10.1002/adma.202001943DOI Listing
July 2020

Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities.

Neuron 2020 06 21;106(6):992-1008.e9. Epub 2020 Apr 21.

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. How these roles are regulated by transcription factors is unknown. Moreover, there is emerging evidence that astrocytes exhibit regional heterogeneity, and the mechanisms controlling this diversity remain nascent. Here, we show that conditional deletion of the transcription factor nuclear factor I-A (NFIA) in astrocytes in the adult brain results in region-specific alterations in morphology and physiology that are mediated by selective DNA binding. Disruptions in astrocyte function following loss of NFIA are most pronounced in the hippocampus, manifested by impaired interactions with neurons, coupled with diminution of learning and memory behaviors. These changes in hippocampal astrocytes did not affect basal neuronal properties but specifically inhibited synaptic plasticity, which is regulated by NFIA in astrocytes through calcium-dependent mechanisms. Together, our studies reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits.
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http://dx.doi.org/10.1016/j.neuron.2020.03.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879989PMC
June 2020

PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis.

Nature 2020 02 29;578(7793):166-171. Epub 2020 Jan 29.

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.

Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment. Recent studies have shown that increases in neuronal activity have an important role in the proliferation and progression of glioblastoma. Whether there is reciprocal crosstalk between glioblastoma and neurons remains poorly defined, as the mechanisms that underlie how these tumours remodel the neuronal milieu towards increased activity are unknown. Here, using a native mouse model of glioblastoma, we develop a high-throughput in vivo screening platform and discover several driver variants of PIK3CA. We show that tumours driven by these variants have divergent molecular properties that manifest in selective initiation of brain hyperexcitability and remodelling of the synaptic constituency. Furthermore, secreted members of the glypican (GPC) family are selectively expressed in these tumours, and GPC3 drives gliomagenesis and hyperexcitability. Together, our studies illustrate the importance of functionally interrogating diverse tumour phenotypes driven by individual, yet related, variants and reveal how glioblastoma alters the neuronal microenvironment.
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http://dx.doi.org/10.1038/s41586-020-1952-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577741PMC
February 2020

Synthesizing electronic health records using improved generative adversarial networks.

J Am Med Inform Assoc 2019 03;26(3):228-241

Institute of Information Science, Academia Sinica, Taipei, Taiwan.

Objective: The aim of this study was to generate synthetic electronic health records (EHRs). The generated EHR data will be more realistic than those generated using the existing medical Generative Adversarial Network (medGAN) method.

Materials And Methods: We modified medGAN to obtain two synthetic data generation models-designated as medical Wasserstein GAN with gradient penalty (medWGAN) and medical boundary-seeking GAN (medBGAN)-and compared the results obtained using the three models. We used 2 databases: MIMIC-III and National Health Insurance Research Database (NHIRD), Taiwan. First, we trained the models and generated synthetic EHRs by using these three 3 models. We then analyzed and compared the models' performance by using a few statistical methods (Kolmogorov-Smirnov test, dimension-wise probability for binary data, and dimension-wise average count for count data) and 2 machine learning tasks (association rule mining and prediction).

Results: We conducted a comprehensive analysis and found our models were adequately efficient for generating synthetic EHR data. The proposed models outperformed medGAN in all cases, and among the 3 models, boundary-seeking GAN (medBGAN) performed the best.

Discussion: To generate realistic synthetic EHR data, the proposed models will be effective in the medical industry and related research from the viewpoint of providing better services. Moreover, they will eliminate barriers including limited access to EHR data and thus accelerate research on medical informatics.

Conclusion: The proposed models can adequately learn the data distribution of real EHRs and efficiently generate realistic synthetic EHRs. The results show the superiority of our models over the existing model.
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http://dx.doi.org/10.1093/jamia/ocy142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647178PMC
March 2019

Regeneration After Radiation- and Immune-Mediated Tissue Injury Is Not Enhanced by Type III Interferon Signaling.

Int J Radiat Oncol Biol Phys 2019 03 29;103(4):970-976. Epub 2018 Nov 29.

Klinik und Poliklinik für Innere Medizin 3, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Purpose: Type I interferon (IFN-I) and interleukin (IL)-22 modulate regeneration of the thymus and intestinal epithelial cells (IECs) after cytotoxic stress such as irradiation. Radiation-induced damage to thymic tissues and IECs is a crucial aspect during the pathogenesis of inadequate immune reconstitution and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative total body irradiation (TBI), respectively. IL-22 and IFN-I reduce the severity of acute GVHD after allo-HSCT with myeloablative TBI. However, the role of biologically related type III interferon (IFN-III), also known as interferon lambda (IFN-λ) or IL-28, in this context is unclear. We therefore studied the role of the IFN-III pathway in thymic regeneration and GVHD after TBI and allo-HSCT.

Methods And Materials: Cohoused wild-type (WT) and IFN-III receptor-deficient (IL-28 receptor alpha subunit-deficient/IL-28Ra) mice were analyzed in models of TBI-induced thymus damage and a model of GVHD after allo-HSCT with myeloablative TBI. PASylated IFN-III (PASylated IL-28A, XL-protein GmbH) was generated to prolong the plasma half-life of IFN-III. Pharmacologic activity and the effects of PASylated IL-28A on radiation-induced thymus damage and the course of GVHD after allo-HSCT with myeloablative TBI were tested.

Results: The course and severity of GVHD after myeloablative TBI and allo-HSCT in IL-28Ra mice was comparable to those in WT mice. Activation of the IFN-III pathway by PASylated IL-28A did not significantly modulate GVHD after allo-HSCT with TBI. Furthermore, IL28Ra mice and WT mice showed similar thymus regeneration after radiation, which could also not be significantly modulated by IFN-III receptor engagement using PASylated IL-28A.

Conclusions: We analyzed the role of IFN-III signaling during radiation-mediated acute tissue injury. Despite molecular and biologic homologies with IFN-I and IL-22, IFN-III signaling did not improve thymus regeneration after radiation or the course of GVHD after myeloablative TBI and allo-HSCT.
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http://dx.doi.org/10.1016/j.ijrobp.2018.11.038DOI Listing
March 2019

Scalable energy-efficient magnetoelectric spin-orbit logic.

Nature 2019 01 3;565(7737):35-42. Epub 2018 Dec 3.

Components Research, Intel Corporation, Hillsboro, OR, USA.

Since the early 1980s, most electronics have relied on the use of complementary metal-oxide-semiconductor (CMOS) transistors. However, the principles of CMOS operation, involving a switchable semiconductor conductance controlled by an insulating gate, have remained largely unchanged, even as transistors are miniaturized to sizes of 10 nanometres. We investigated what dimensionally scalable logic technology beyond CMOS could provide improvements in efficiency and performance for von Neumann architectures and enable growth in emerging computing such as artifical intelligence. Such a computing technology needs to allow progressive miniaturization, reduce switching energy, improve device interconnection and provide a complete logic and memory family. Here we propose a scalable spintronic logic device that operates via spin-orbit transduction (the coupling of an electron's angular momentum with its linear momentum) combined with magnetoelectric switching. The device uses advanced quantum materials, especially correlated oxides and topological states of matter, for collective switching and detection. We describe progress in magnetoelectric switching and spin-orbit detection of state, and show that in comparison with CMOS technology our device has superior switching energy (by a factor of 10 to 30), lower switching voltage (by a factor of 5) and enhanced logic density (by a factor of 5). In addition, its non-volatility enables ultralow standby power, which is critical to modern computing. The properties of our device indicate that the proposed technology could enable the development of multi-generational computing.
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http://dx.doi.org/10.1038/s41586-018-0770-2DOI Listing
January 2019

Voltage control of unidirectional anisotropy in ferromagnet-multiferroic system.

Sci Adv 2018 11 23;4(11):eaat4229. Epub 2018 Nov 23.

Components Research, Intel Corp., Hillsboro, OR 97124, USA.

Demonstration of ultralow energy switching mechanisms is imperative for continued improvements in computing devices. Ferroelectric (FE) and multiferroic (MF) order and their manipulation promise an ideal combination of state variables to reach attojoule range for logic and memory (i.e., ~30× lower switching energy than nanoelectronics). In BiFeO (BFO), the coupling between the antiferromagnetic (AFM) and FE order is robust at room temperature, scalable in voltage, stabilized by the FE order, and can be integrated into a fabrication process for a beyond-CMOS (complementary metal-oxide semiconductor) era. The presence of the AFM order and a canted magnetic moment in this system causes exchange interaction with a ferromagnet such as CoFe or LaSrMnO. Previous research has shown that exchange coupling (uniaxial anisotropy) can be controlled with an electric field. However, voltage modulation of unidirectional anisotropy, which is preferred for logic and memory technologies, has not yet been demonstrated. Here, we present evidence for electric field control of exchange bias of laterally scaled spin valves that is exchange coupled to BFO at room temperature. We show that the exchange bias in this bilayer is robust, electrically controlled, and reversible. We anticipate that magnetoelectricity at these scaled dimensions provides a powerful pathway for computing beyond modern nanoelectronics by enabling a new class of nonvolatile, ultralow energy computing elements.
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http://dx.doi.org/10.1126/sciadv.aat4229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251722PMC
November 2018

Predicting financial trouble using call data-On social capital, phone logs, and financial trouble.

PLoS One 2018 23;13(2):e0191863. Epub 2018 Feb 23.

School of Communication and Information, Rutgers University, New Brunswick, New Jersey, United States of America.

An ability to understand and predict financial wellbeing for individuals is of interest to economists, policy designers, financial institutions, and the individuals themselves. According to the Nilson reports, there were more than 3 billion credit cards in use in 2013, accounting for purchases exceeding US$ 2.2 trillion, and according to the Federal Reserve report, 39% of American households were carrying credit card debt from month to month. Prior literature has connected individual financial wellbeing with social capital. However, as yet, there is limited empirical evidence connecting social interaction behavior with financial outcomes. This work reports results from one of the largest known studies connecting financial outcomes and phone-based social behavior (180,000 individuals; 2 years' time frame; 82.2 million monthly bills, and 350 million call logs). Our methodology tackles highly imbalanced dataset, which is a pertinent problem with modelling credit risk behavior, and offers a novel hybrid method that yields improvements over, both, a traditional transaction data only approach, and an approach that uses only call data. The results pave way for better financial modelling of billions of unbanked and underbanked customers using non-traditional metrics like phone-based credit scoring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191863PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825009PMC
March 2018

Daam2 driven degradation of VHL promotes gliomagenesis.

Elife 2017 10 20;6. Epub 2017 Oct 20.

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, United States.

Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. These in silico insights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.
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http://dx.doi.org/10.7554/eLife.31926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650470PMC
October 2017

RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury.

Sci Transl Med 2017 04;9(386)

III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice. This phenotype was not associated with changes in the intestinal microbiota but was associated with reduced gut epithelial integrity. Conversely, targeted activation of the RIG-I pathway during tissue injury promoted gut barrier integrity and reduced GVHD. Recombinant IFN-I or IFN-I expression induced by RIG-I promoted growth of intestinal organoids in vitro and production of the antimicrobial peptide regenerating islet-derived protein 3 γ (RegIIIγ). Our findings were not confined to RIG-I/MAVS signaling because targeted engagement of the STING (stimulator of interferon genes) pathway also protected gut barrier function and reduced GVHD. Consistent with this, STING-deficient mice suffered worse GVHD after allo-HSCT than did wild-type mice. Overall, our data suggest that activation of either RIG-I/MAVS or STING pathways during acute intestinal tissue injury in mice resulted in IFN-I signaling that maintained gut epithelial barrier integrity and reduced GVHD severity. Targeting these pathways may help to prevent acute intestinal injury and GVHD during allogeneic transplantation.
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http://dx.doi.org/10.1126/scitranslmed.aag2513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604790PMC
April 2017

The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury.

Neurotherapeutics 2017 Jul;14(3):792-809

Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.

Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.
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http://dx.doi.org/10.1007/s13311-016-0509-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509620PMC
July 2017

Amantadine Use as a Risk Factor for Corneal Edema: A Nationwide Cohort Study in Taiwan.

Am J Ophthalmol 2016 Nov 2;171:122-129. Epub 2016 Sep 2.

Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Purpose: To evaluate the association between amantadine use and corneal toxicity in a nationwide population.

Design: Retrospective cohort study of nationwide population-based administrative database.

Methods: This study analyzed data in the Taiwan Longitudinal Insurance Database for a group of 8195 patients diagnosed with Parkinson disease during a 15-year period (January 1, 1996 to December 31, 2010). A control group of 8195 patients without Parkinson disease was randomly matched with the Parkinson group by age, sex, and comorbidity index. The Kaplan-Meier method was used to calculate the cumulative incidence of corneal edema. Incident rate ratios and Cox proportional hazard regressions were estimated to compare the risk of corneal edema. The same methods were then used to compare the risk between patients with and without amantadine treatment.

Results: The incidence of corneal edema in the Parkinson group (123 patients; 1.50%) was significantly higher than that in the control group (82 patients; 1.0%) (P = .004). The incidence ratio for corneal edema in the Parkinson group vs the controls was 5.77. When the Parkinson group was further subgrouped by use and non-use of amantadine, the hazard ratio for corneal edema was 1.79 times higher in the amantadine subgroup. Analyses of the amantadine subgroup by cumulative dose revealed that the 30-day hazard ratio for corneal edema was 2.05 higher in patients given moderate doses (2000-4000 mg) of amantadine and 2.84 times higher in the subgroup of patients given high doses (>4000 mg).

Conclusions: Amantadine increases the risk of corneal edema in a dose-dependent manner.
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http://dx.doi.org/10.1016/j.ajo.2016.08.034DOI Listing
November 2016

Enhanced external quantum efficiency in GaN-based vertical-type light-emitting diodes by localized surface plasmons.

Sci Rep 2016 Mar 3;6:22659. Epub 2016 Mar 3.

Institute of Electro-Optical Science and Technology, National Taiwan Normal University, 88, Sec. 4, Ting-Chou Rd., Taipei, 116, Taiwan.

Enhancement of the external quantum efficiency of a GaN-based vertical-type light emitting diode (VLED) through the coupling of localized surface plasmon (LSP) resonance with the wave-guided mode light is studied. To achieve this experimentally, Ag nanoparticles (NPs), as the LSP resonant source, are drop-casted on the most top layer of waveguide channel, which is composed of hydrothermally synthesized ZnO nanorods capped on the top of GaN-based VLED. Enhanced light-output power and external quantum efficiency are observed, and the amount of enhancement remains steady with the increase of the injected currents. To understand the observations theoretically, the absorption spectra and the electric field distributions of the VLED with and without Ag NPs decorated on ZnO NRs are determined using the finite-difference time-domain (FDTD) method. The results prove that the observation of enhancement of the external quantum efficiency can be attributed to the creation of an extra escape channel for trapped light due to the coupling of the LSP with wave-guided mode light, by which the energy of wave-guided mode light can be transferred to the efficient light scattering center of the LSP.
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http://dx.doi.org/10.1038/srep22659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776147PMC
March 2016

Enhancing UV-emissions through optical and electronic dual-function tuning of Ag nanoparticles hybridized with n-ZnO nanorods/p-GaN heterojunction light-emitting diodes.

Nanoscale 2016 Feb;8(8):4463-74

Institute of Electro-Optical Science and Technology, National Taiwan Normal University, 88, Sec. 4, Ting-Chou Road, Taipei 116, Taiwan.

ZnO nanorods (NRs) and Ag nanoparticles (NPs) are known to enhance the luminescence of light-emitting diodes (LEDs) through the high directionality of waveguide mode transmission and efficient energy transfer of localized surface plasmon (LSP) resonances, respectively. In this work, we have demonstrated Ag NP-incorporated n-ZnO NRs/p-GaN heterojunctions by facilely hydrothermally growing ZnO NRs on Ag NP-covered GaN, in which the Ag NPs were introduced and randomly distributed on the p-GaN surface to excite the LSP resonances. Compared with the reference LED, the light-output power of the near-band-edge (NBE) emission (ZnO, λ = 380 nm) of our hybridized structure is increased almost 1.5-2 times and can be further modified in a controlled manner by varying the surface morphology of the surrounding medium of the Ag NPs. The improved light-output power is mainly attributed to the LSP resonance between the NBE emission of ZnO NRs and LSPs in Ag NPs. We also observed different behaviors in the electroluminescence (EL) spectra as the injection current increases for the treatment and reference LEDs. This observation might be attributed to the modification of the energy band diagram for introducing Ag NPs at the interface between n-ZnO NRs and p-GaN. Our results pave the way for developing advanced nanostructured LED devices with high luminescence efficiency in the UV emission regime.
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http://dx.doi.org/10.1039/c5nr08561fDOI Listing
February 2016

Taking advantage of neural development to treat glioblastoma.

Eur J Neurosci 2014 Sep 25;40(6):2859-66. Epub 2014 Jun 25.

Department of Neurosurgery, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Jiangsu Province, China; Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.

Glioblastoma (GBM) is by far the most common and most malignant primary adult brain tumor (World Health Organization grade IV), containing a fraction of stem-like cells that are highly tumorigenic and multipotent. Recent research has revealed that GBM stem-like cells play important roles in GBM pathogenesis. GBM is thought to arise from genetic anomalies in glial development. Over the past decade, a wide range of studies have shown that several signaling pathways involved in neural development, including basic helix-loop-helix, Wnt-β-catenin, bone morphogenetic proteins-Smads, epidermal growth factor-epidermal growth factor receptor, and Notch, play important roles in GBM pathogenesis. In this review, we highlight the significance of these pathways in the context of developing treatments for GBM. Extrapolating knowledge and concepts from neural development will have significant implications for designing better strategies with which to treat GBM.
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http://dx.doi.org/10.1111/ejn.12655DOI Listing
September 2014

Improvement of spin transfer torque in asymmetric graphene devices.

ACS Nano 2014 Apr 21;8(4):3807-12. Epub 2014 Mar 21.

School of Electrical and Computer Engineering and Birck Nanotechnology Center, Purdue University , West Lafayette, Indiana, United States.

A graphene lateral spin valve structure with asymmetric contacts is presented for the first time, with enhancement of spin angular momentum absorption in its receiving magnet. The asymmetric device with tunneling barrier only at the injector magnet shows a comparable spin valve signal but lower electrical noises compared to the device with two tunneling barriers. We also report experimental measurements of spin transfer torque. Assisted by an external magnetic field of 2.5 mT, spin diffusion current-induced magnetization reversal occurs at a nonlocal charge current density of 33 mA/μm(2), smaller than that needed in devices with two tunneling barriers.
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http://dx.doi.org/10.1021/nn500533bDOI Listing
April 2014

Spin transfer torque in a graphene lateral spin valve assisted by an external magnetic field.

Nano Lett 2013 Nov 17;13(11):5177-81. Epub 2013 Oct 17.

School of Electrical and Computer Engineering and Birck Nanotechnology Center, Purdue University , West Lafayette, Indiana 47907, United States.

Spin-based devices are widely discussed for post-complementary metal-oxide-semiconductor (CMOS) applications. A number of spin device ideas propose using spin current to carry information coherently through a spin channel and transfering it to an output magnet by spin transfer torque. Graphene is an ideal channel material in this context due to its long spin diffusion length, gate-tunable carrier density, and high carrier mobility. However, spin transfer torque has not been demonstrated in graphene or any other semiconductor material as of yet. Here, we report the first experimental measurement of spin transfer torque in graphene lateral nonlocal spin valve devices. Assisted by an external magnetic field, the magnetization reversal of the ferromagnetic receiving magnet is induced by pure spin diffusion currents from the input magnet. The magnetization switching is reversible between parallel and antiparallel configurations, depending on the polarity of the applied charged current. The presented results are an important step toward developing graphene-based spin logic and understanding spin-transfer torque in systems with tunneling barriers.
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http://dx.doi.org/10.1021/nl402547mDOI Listing
November 2013

Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue.

Cell Mol Life Sci 2013 Nov 23;70(22):4399-410. Epub 2013 Jun 23.

Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, 79104, Freiburg, Germany.

Borna disease virus (BDV) persistently infects neurons of the central nervous system of various hosts, including rats. Since type I IFN-mediated antiviral response efficiently blocks BDV replication in primary rat embryo fibroblasts, it has been speculated that BDV is not effectively sensed by the host innate immune system in the nervous system. To test this assumption, organotypical rat hippocampal slice cultures were infected with BDV for up to 4 weeks. This resulted in the secretion of IFN and the up-regulation of IFN-stimulated genes. Using the rat Mx protein as a specific marker for IFN-induced gene expression, astrocytes and microglial cells were found to be Mx positive, whereas neurons, the major cell type in which BDV is replicating, lacked detectable levels of Mx protein. In uninfected cultures, neurons also remained Mx negative even after treatment with high concentrations of IFN-α. This non-responsiveness correlated with a lack of detectable nuclear translocation of both pSTAT1 and pSTAT2 in these cells. Consistently, neuronal dissemination of BDV was not prevented by treatment with IFN-α. These data suggest that the poor innate immune response in rat neurons renders this cell type highly susceptible to BDV infection even in the presence of exogenous IFN-α. Intriguingly, in contrast to rat neurons, IFN-α treatment of mouse neurons resulted in the up-regulation of Mx proteins and block of BDV replication, indicating species-specific differences in the type I IFN response of neurons between mice and rats.
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http://dx.doi.org/10.1007/s00018-013-1402-5DOI Listing
November 2013

Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.

Proc Natl Acad Sci U S A 2013 Jan 14;110(5):1899-904. Epub 2013 Jan 14.

Department of Virology, Spemann Graduate School of Biology and Medicine, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.

Infection of newborn rats with Borne disease virus (BDV) results in selective degeneration of granule cell neurons of the dentate gyrus (DG). To study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this BDV-induced neuronal degeneration. To this end, we infected hippocampal slice cultures of different rat strains with BDV and analyzed for the preservation of the DG. Whereas infected cultures of five rat strains, including Lewis (LEW) rats, exhibited a disrupted DG cytoarchitecture, slices of three other rat strains, including Sprague-Dawley (SD), were unaffected. However, efficiency of viral replication was comparable in susceptible and resistant cultures. Moreover, these rat strain-dependent differences in vulnerability were replicated in vivo in neonatally infected LEW and SD rats. Intriguingly, conditioned media from uninfected cultures of both LEW and SD rats could prevent BDV-induced DG damage in infected LEW hippocampal cultures, whereas infection with BDV suppressed the availability of these factors from LEW but not in SD hippocampal cultures. To gain further insights into the genetic basis for this rat strain-dependent susceptibility, we analyzed DG granule cell survival in BDV-infected cultures of hippocampal neurons derived from the F1 and F2 offspring of the crossing of SD and LEW rats. Genome-wide association analysis revealed one resistance locus on chromosome (chr) 6q16 in SD rats and, surprisingly, a locus on chr3q21-23 that was associated with susceptibility. Thus, BDV-induced neuronal degeneration is dependent on the host genetic background and is prevented by soluble protective factors in the disease-resistant SD rat strain.
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http://dx.doi.org/10.1073/pnas.1214939110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562833PMC
January 2013

Exploration of long-term care institution managers' perceptions of institutional indoor environment quality and ease of administration.

Care Manag J 2012 ;13(3):121-33

Department of Senior Citizen Service Management of National Taichung University of Science and Technology.

This study investigated the level of management's perception of the importance of indoor environment indicators at long-term care facilities as well as the differences between the level of perceived importance and the level of implementation. This study also analyzed the indicators for improving indoor environments. This study selected Taiwanese long-term care facility managers as its subjects to whom questionnaires were distributed by mail Descriptive statistics, a one-way analysis of variance (ANOVA), and an importance-performance analysis were used to conduct analyses on the data retrieved from the questionnaires. The results indicate that, of the indoor environment indicators of four facility spaces, bedrooms had the highest perceived level of importance. The lounge was the easiest space in which to implement the indicators. Differences were found between the perceived level of importance and the level of implementation for six of the indoor environment indicators of the four facility spaces. In these four spaces, the ventilation indicator was the most important, whereas implementing the temperature and humidity indicators was the most difficult. The highest priority for indicator improvement was given to the temperature in the bedrooms and bathrooms, whereas control over temperature, humidity, and sound had a low priority. The indicators seen as requiring continuous maintenance were lighting and ventilation. Facility managers had a high level of awareness and competence in implementing the ventilation indicator. However, although they were aware of the importance of the temperature, humidity, and sound indicators, their implementation was difficult, suggesting that they needed to be improved.
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http://dx.doi.org/10.1891/1521-0987.13.3.121DOI Listing
November 2012

Pain relief assessment by aromatic essential oil massage on outpatients with primary dysmenorrhea: a randomized, double-blind clinical trial.

J Obstet Gynaecol Res 2012 May 22;38(5):817-22. Epub 2012 Mar 22.

Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan.

Aim: This study assessed the effectiveness of blended essential oils on menstrual cramps for outpatients with primary dysmenorrhea and explored the analgesic ingredients in the essential oils.

Material And Methods: A randomized, double-blind clinical trial was conducted. Forty-eight outpatients were diagnosed with primary dysmenorrhea by a gynecologist and had 10-point numeric rating scales that were more than 5. The patients were randomly assigned to an essential oil group (n = 24) and a synthetic fragrance group (n = 24). Essential oils blended with lavender (Lavandula officinalis), clary sage (Salvia sclarea) and marjoram (Origanum majorana) in a 2:1:1 ratio was diluted in unscented cream at 3% concentration for the essential oil group. All outpatients used the cream daily to massage their lower abdomen from the end of the last menstruation continuing to the beginning of the next menstruation.

Results: Both the numeric rating scale and the verbal rating scale significantly decreased (P < 0.001) after one menstrual cycle intervention in the two groups. The duration of pain was significantly reduced from 2.4 to 1.8 days after aromatherapy intervention in the essential oil group.

Conclusion: Aromatic oil massage provided relief for outpatients with primary dysmenorrhea and reduced the duration of menstrual pain in the essential oil group. The blended essential oils contain four key analgesic components that amount to as much as 79.29%; these analgesic constitutes are linalyl acetate, linalool, eucalyptol, and β-caryophyllene. This study suggests that this blended formula can serve as a reference for alternative and complementary medicine on primary dysmenorrhea.
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http://dx.doi.org/10.1111/j.1447-0756.2011.01802.xDOI Listing
May 2012

Differential effects of LY294002 and wortmannin on inducible nitric oxide synthase expression in glomerular mesangial cells.

Int Immunopharmacol 2012 Mar 9;12(3):471-80. Epub 2012 Jan 9.

Department of Internal Medicine, China Medical University Beigang Hospital, 123 Sinde Road, Beigang Township, Yunlin County 65152, Taiwan, ROC.

Nitric oxide (NO) that is produced by inducible nitric oxide synthase (iNOS) is associated with the pathophysiology of glomerulonephritis. Numerous studies have focused on the regulation of NO production by iNOS to reduce NO-mediated cytotoxicity. In the present study, we demonstrated the differential effects of two phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin, on lipopolysaccharide- (LPS) and interferon (IFN)-γ-induced NO production in a glomerular mesangial cell line, MES-13 cells. At dosages without affecting cell viability of MES-13 cells, 5μM LY294002 showed a more-significant inhibitory effect on LPS/IFN-γ-induced NO production, and iNOS protein and gene expressions than did 1μM wortmannin. Akt phosphorylation in MES-13 cells declined upon the addition of wortmannin, but not upon treatment with LY294002. Suppression of PI3K expression by small interfering (si)RNA exhibited no effect on LPS/IFN-γ-stimulated NO production or iNOS protein expression in MES-13 cells. Neither LY294002 nor wortmannin reduced IFN-γ-induced STAT-1α phosphorylation. LY294002 exhibited a more-significant inhibitory effect on NF-κB luciferase activities than wortmannin in LPS/IFN-γ-stimulated MES-13 cells. Moreover, LY294002, but not wortmannin, accelerated iNOS protein degradation and reduced the iNOS dimer/monomer ratio in MES-13 cells. Although both LY294002 and wortmannin are known as PI3K inhibitors, their differential effects on iNOS expression in MES-13 cells indicate that the effects of LY294002 on inhibiting NF-κB activation and accelerating iNOS protein degradation are through a mechanism independent of PI3K.
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http://dx.doi.org/10.1016/j.intimp.2011.12.017DOI Listing
March 2012
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