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1.
Nanoscale Adv ; 6(11): 2919-2927, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38817424

ABSTRACT

Phonon transport in two-dimensional materials has been the subject of intensive studies both theoretically and experimentally. Recently observed unique phenomena such as Poiseuille flow at low temperature in graphene nanoribbons (GNRs) initiated strong interest in similar effects at higher temperatures. Here, we carry out massive molecular dynamics simulations to examine thermal transport in GNRs at room temperature (RT) and demonstrate that non-diffusive behaviors including Poiseuille-like local thermal conductivity and second sound are obtained, indicating quasiballistic thermal transport. For narrow GNRs, a Poiseuille-like thermal conductivity profile develops across the nanoribbon width, and wider GNRs exhibit a mixed nature of phonon transport in that diffusive transport is dominant in the middle region whereas non-uniform behavior is observed near lateral GNR boundaries. In addition, transient heating simulations reveal that the driftless second sound can propagate through GNRs regardless of the GNR width. By decomposing the atomic motion into out-of-plane and in-plane modes, it is further shown that the observed quasiballistic thermal transport is primarily contributed by the out-of-plane motion of C atoms in GNRs.

2.
Nanoscale ; 14(8): 3004-3012, 2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35170602

ABSTRACT

Low- or self-powered infrared sensors can be used in a broad range of applications, including networking mobile edge devices and image recognition for autonomous driving technology. Here, we show state-of-the-art self-powered near-infrared (NIR) sensors using graphene/In/InSe/Au as a photoactive region. The self-powered NIR sensors show outstanding performance, achieving a photoresponsivity of ∼8.5 A W-1 and a detectivity of ∼1012 Jones at 850 nm light. Multiple self-powered InSe photodetectors with different device structures and contacts were systematically investigated. In particular, the asymmetrically assembled graphene/In/InSe/Au vertical heterostructure offers a high built-in field, which gives rise to efficient electron-hole pair separation and transit time that is shorter than the photocarrier lifetime. The built-in potential across the InSe was estimated using the Schottky barrier height at each metal contact with InSe, obtained using density functional theory calculations. We also demonstrate InSe vertical field-effect transistors and provide an out-of-plane carrier mobility of InSe. Using the out-of-plane mobility and structural parameters of each device, the built-in field, drift velocity, and corresponding transit time are estimated.

3.
ACS Appl Mater Interfaces ; 13(40): 47749-47755, 2021 Oct 13.
Article in English | MEDLINE | ID: mdl-34582182

ABSTRACT

The natural abundance of magnesium together with its high volumetric energy capacity and less-dendritic anodes makes Mg-ion batteries an appealing alternative to the widely used Li-ion batteries. However, Mg cathode materials under current investigation suffer from various shortcomings such as low operation voltage and high energy barrier for ion migration, resulting in poor battery performance. Here, we propose a garnet-type intercalation cathode active material, Mg3Si3(MoO6)2, for high-performance Mg-ion batteries. Through first-principles density functional theory calculations, it is demonstrated that Mg3Si3(MoO6)2 possesses a high average discharge voltage (2.35 V vs Mg/Mg2+), a low ion migration barrier (∼0.2 eV), and a minimal volume change (∼4%) concurrently, which comprises excellent intercalation cathode chemistry. The small energy barrier for ion migration is shown to arise from the favorable change in the Mg coordination along the migration route within the garnet host. These findings present an additional direction to develop competent Mg-ion batteries for future energy storage applications.

4.
ACS Appl Mater Interfaces ; 13(1): 531-540, 2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33390000

ABSTRACT

The influence of N-substituent and pKa of azole rings has been investigated for the performance of high-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs). Imidazole, benzimidazole, and triazole groups were functionalized on the side chains of poly(phenylene oxide), respectively. Each azole group is categorized by their N-substituent into two types: unsubstituted and methyl-substituted azoles. The membranes with methyl-substituted azoles showed higher phosphoric acid (PA) doping levels with an average increase of 20% compared to those with unsubstituted azoles in the full-doped states. However, unsubstituted azoles more effectively improved the proton conductivity and the membrane with unsubstituted imidazole (IMPPO-H) showed a high anhydrous proton conductivity of 153 mS/cm at 150 °C. In contrast, the membranes with methyl-substituted azoles showed a higher PA retention with an average increase of 81% compared to those with unsubstituted azoles. The higher PA retention of methyl-substituted azoles also led to the higher fuel cell performance with the maximum increase of 95% in the power density. It was also revealed that higher pKa of azoles enhanced the PA retention and the fuel cell performance. Based on the experimental results of PA retention and density functional theory calculations, the PA loss mechanism was also proposed.

5.
Appl Microbiol Biotechnol ; 105(1): 67-76, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33191460

ABSTRACT

Our previous work showed that there is a limitation in the use of dihydrofolate reductase (dhfr)/methotrexate (MTX)-mediated gene amplification systems in dhfr-non-deficient HEK293 cells, as endogenous dhfr may interfere with the amplification process. In the present study, we successfully generated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-amplified HEK293 cells in a dhfr-non-deficient HEK293 cell background using a single-plasmid vector-based gene amplification system with shRNA targeting the 3'-UTR of endogenous dhfr. The introduction of this shRNA efficiently downregulated the expression of endogenous dhfr in the HEK293 cells without affecting exogenous dhfr expression. The downregulation of endogenous dhfr improved the efficiency of EBNA-1 amplification, as evidenced by a comparison with the amplification extent in cells lacking shRNA expression at the same MTX concentration. The EBNA-1 expression levels from the EBNA-1-amplified clones selected in this study were higher than those obtained from EBNA-1-amplified clones that were generated using the conventional amplification in our previous study. Consistent with previous studies, EBNA-1 amplification improved the production of the Fc-fusion protein through a specific protein productivity (qp)-enhancing effect, rather than by improving cell growth or transfection efficiency. In addition, the N-glycan profiles in the Fc-fusion protein produced using this transient gene expression (TGE) system were not affected by EBNA-1 amplification. These results indicate the potential utility of EBNA-1-amplified mammalian cells, developed using a single-plasmid vector-based gene amplification system, for efficient protein production. KEY POINTS: • EBNA-1-amplified HEK293 cells were established using gene amplification system. • EBNA-1 amplification in TGE system can increase the Fc-fusion protein productivity. • EBNA-1 amplification does not affect the N-glycan profile in the Fc-fusion protein.


Subject(s)
Epstein-Barr Virus Infections , Gene Amplification , Animals , CHO Cells , Cricetinae , Epstein-Barr Virus Nuclear Antigens/genetics , Gene Expression , HEK293 Cells , Herpesvirus 4, Human/genetics , Humans , Methotrexate , Plasmids/genetics , Tetrahydrofolate Dehydrogenase/genetics , Tetrahydrofolate Dehydrogenase/metabolism
6.
Mol Cancer Ther ; 19(12): 2585-2597, 2020 12.
Article in English | MEDLINE | ID: mdl-33199500

ABSTRACT

Complexities in treating breast cancer with bone metastasis are enhanced by a vicious protumorigenic pathology, involving a shift in skeletal homeostasis toward aggressive osteoclast activity and polarization of immune cells supporting tumor growth and immunosuppression. Recent studies signify the role of receptor activator of NF-κB ligand (RANKL) beyond skeletal pathology in breast cancer, including tumor growth and immunosuppression. By using an osteoprotegerin (OPG) variant, which we developed recently through protein engineering to uncouple TNF-related apoptosis-inducing ligand (TRAIL) binding, this study established the potential of a cell-based OPGY49R therapy for both bone damage and immunosuppression in an immunocompetent mouse model of orthotopic and metastatic breast cancers. In combination with agonistic death receptor (DR5) activation, the OPGY49R therapy significantly increased both bone remolding and long-term antitumor immunity, protecting mice from breast cancer relapse and osteolytic pathology. With limitations, cost, and toxicity issues associated with the use of denosumab, bisphosphonates, and chemotherapy for bone metastatic disease, use of OPGY49R combination could offer a viable alternate therapeutic approach.


Subject(s)
Bone Remodeling/drug effects , Bone Remodeling/genetics , Neoplasms/immunology , Neoplasms/metabolism , Osteoprotegerin/genetics , TNF-Related Apoptosis-Inducing Ligand/antagonists & inhibitors , TNF-Related Apoptosis-Inducing Ligand/metabolism , Animals , Antineoplastic Agents, Immunological/pharmacology , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Cell Line, Tumor , Cytokines , Disease Models, Animal , Female , Humans , Immunohistochemistry , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Neoplasms/drug therapy , Neoplasms/pathology , Osteoprotegerin/metabolism , Protein Binding , Receptor Activator of Nuclear Factor-kappa B/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , X-Ray Microtomography
7.
Nanomedicine (Lond) ; 15(11): 1113-1126, 2020 05.
Article in English | MEDLINE | ID: mdl-32292108

ABSTRACT

Aims: We investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. Materials & methods: After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. Results: miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia. Conclusion: The anti-inflammatory effects of miR 146a-5p along with nanoparticle-based materials make miR NPs promising tools for treating neuropathic pain.


Subject(s)
MicroRNAs , Nanoparticles , Neuralgia , Animals , Glycolates , Glycols , Lactic Acid , MicroRNAs/genetics , Microglia , Neuralgia/drug therapy , Rats , Rats, Sprague-Dawley
8.
Nanoscale ; 12(16): 8701-8705, 2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32270150

ABSTRACT

Understanding the mechanism of thermal energy transport in a single nanotube (NT) is essential for successfully engineering nanostructured conducting polymers to apply to thermoelectrics or flexible electronic devices. We report the characterization of the in-plane thermal energy transport in a single poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) NT via direct measurement of the in-plane thermal conductivity (κ). We also demonstrate that the in-plane κ of PEDOT:PSS NT can be tuned within the range of 0.19 to 1.92 W·m-1·K-1 merely by changing the solvent used to treat the NTs in the post-fabrication stage. The in-plane thermal energy transport in a pristine NT, with its low in-plane κ, is primarily due to phonons; in a sulfuric acid-treated NT however, significant electronic contributions lead to a high in-plane κ. The present study will contribute to understanding the mechanism of thermal energy transport in highly disordered structures, such as conducting polymers, and to designing highly efficient polymer-based devices in which in-plane κ plays a pivotal role in determining the energy conversion efficiency.

9.
Cancer Res ; 80(8): 1615-1623, 2020 04 15.
Article in English | MEDLINE | ID: mdl-32066566

ABSTRACT

Therapeutic interventions to harness the immune system against tumor cells have provided mixed results in the past for several solid tumors and hematologic malignancies. However, immunotherapy has advanced considerably over the last decade and is becoming an integral combination for treating patients with advanced solid tumors. In particular, prostate cancer immunotherapy has shown modest efficacy for patients in the past. With several key discoveries on immune mechanisms and advanced molecular diagnostic platforms recently, immunotherapy is re-emerging as a viable option for prostate cancer, especially castration-resistant prostate cancer (CRPC), to stimulate antitumor immunity. Combination of patient-tailored immunotherapy and immune checkpoint blockers with conventional cytotoxic agents and androgen receptor-targeted therapies should move the field forward. With a recent adaptation that the application of immune checkpoint inhibitors has been successful in the treatment of more than a dozen solid tumors, including melanoma, lymphoma, liver, cervical, gastrointestinal, and breast cancers, it is a timely endeavor to harness immunotherapy for prostate cancer. Here, we provide an account on the progression of immunotherapy with new discoveries and precision approaches for tumors, in particular CRPC, from mechanistic standpoint to emerging limitations and future directions.


Subject(s)
Immunotherapy/methods , Prostatic Neoplasms/therapy , Androgen Receptor Antagonists/therapeutic use , Antibodies, Bispecific/therapeutic use , Antineoplastic Agents/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors , Combined Modality Therapy/methods , Forecasting , Humans , Immunization, Passive/methods , Immunotherapy/trends , Immunotherapy, Active/methods , Male , Neoplastic Stem Cells/immunology , Precision Medicine/methods , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Prostatic Neoplasms/etiology , Prostatic Neoplasms/immunology , Prostatic Neoplasms, Castration-Resistant/immunology , Prostatic Neoplasms, Castration-Resistant/therapy , Prostatitis/complications
10.
ACS Appl Mater Interfaces ; 12(3): 4129-4134, 2020 Jan 22.
Article in English | MEDLINE | ID: mdl-31880145

ABSTRACT

Contact engineering for two-dimensional (2D) transition metal dichalcogenides (TMDCs) is crucial for realizing high-performance 2D TMDC devices, and most studies on contact properties of 2D TMDCs have mainly focused on Fermi level unpinning. Here, we investigated electrical and photoelectrical properties of chemical vapor deposition (CVD)-grown molybdenum disulfide (MoS2) monolayer devices depending on metal contacts, Ti/Pt, Ti/Au, Ti, and Ag, and particularly demonstrated the essential role of defects in MoS2 in contact properties. Remarkably, MoS2 devices with Ag contacts show a field-effect mobility of 12.2 cm2 V-1 s-1, an on/off current ratio of 7 × 107, and a photoresponsivity of 1020 A W-1, which are outstanding compared to similar devices with other metal contacts. These improvements are attributed to a reduced Schottky barrier height, thanks to the small work function of Ag and Ag-MoS2 orbital hybridization at the interface, which facilitates efficient charge transfer between MoS2 and Ag. Interestingly, X-ray photoelectron spectroscopic analysis reveals that Ag2S was formed in our defect-containing CVD-grown MoS2 monolayer, but such orbital hybridization is not observed in a nearly defect-free exfoliated MoS2. This distinction shows that defects existing in MoS2 enable Ag to effectively couple to MoS2 and correspondingly enhance multiple electrical and photoelectrical properties.

11.
FASEB Bioadv ; 1(3): 180-190, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31225515

ABSTRACT

The short half-life and use of recombinant bone morphogenetic protein (BMP)-2 in large doses poses major limitations in the clinic. Events regulating post-translational processing and degradation of BMP2 in situ, linked to its secretion, have not been understood. Towards identifying mechanisms regulating intracellular BMP2 stability, we first discovered that inhibiting proteasomal degradation enhances both intracellular BMP2 level and its extracellular secretion. Next, we identified BMP2 degradation occurs through an ubiquitin-mediated mechanism. Since ubiquitination precedes proteasomal turnover and mainly occurs on lysine residues of nascent proteins, we systematically mutated individual lysine residues within BMP2 and tested them for enhanced stability. Results revealed that substitutions on four lysine residues within the pro-BMP2 region and three in the mature region increased both BMP2 turnover and extracellular secretion. Structural modeling revealed key lysine residues involved in proteasomal degradation occupy a lysine cluster near proprotein convertase cleavage site. Interestingly, mutations within these residues did not affect biological activity of BMP2. These data suggest preventing intracellular proteasomal loss of BMP2 through genetic modifications can overcome limitations related to its short half-life.

12.
J Biotechnol ; 283: 37-42, 2018 Oct 10.
Article in English | MEDLINE | ID: mdl-30012463

ABSTRACT

Sodium butyrate (NaBu) is an efficient supplement for increasing recombinant protein production in Chinese hamster ovary (CHO) cell culture. To elucidate the effects of NaBu on miRNA expression profile in recombinant CHO (rCHO) cells, differentially expressed miRNAs in NaBu-treated rCHO cells were assessed by NanoString nCounter analysis. This result showed that eight mature mouse miRNAs (let-7b, let-7d, miR-15b, miR-25, miR-27a, miR-99a, miR-125a-5p, and miR-125b-5p) were differentially expressed. Furthermore, quantitative real-time RT-PCR analysis of eight mature CHO miRNAs, annotated using a miRBase database, confirmed the transcriptomic findings. Among the potential corresponding target mRNAs for the selected mature miRNAs, seven cell growth-related target genes (e2f2, akt2, mtor, bcl-2, bim, p38α, and bmf) and five N-glycosylation-related target genes (neu1, b4galt3, gale, man1b1 and mgat4a) were selected by considering the effectiveness of NaBu on rCHO cell culture. The altered expression patterns of the 12 target mRNAs were inversely correlated with those of the selected mature miRNAs. Altogether, NanoString nCounter analysis may be useful for identifying differentially expressed miRNAs in rCHO cells.


Subject(s)
Butyric Acid/pharmacology , Gene Expression Profiling/methods , MicroRNAs/genetics , Recombinant Proteins/genetics , Animals , CHO Cells , Cell Proliferation/drug effects , Cell Survival/drug effects , Cricetinae , Cricetulus , Gene Expression Regulation/drug effects , Glycosylation , Mice , Molecular Sequence Annotation
13.
Appl Microbiol Biotechnol ; 102(11): 4729-4739, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29654557

ABSTRACT

Despite the relatively low transfection efficiency and low specific foreign protein productivity (qp) of Chinese hamster ovary (CHO) cell-based transient gene expression (TGE) systems, TGE-based recombinant protein production technology predominantly employs CHO cells for pre-clinical research and development purposes. To improve TGE in CHO cells, Epstein-Barr virus nuclear antigen-1 (EBNA-1)/polyoma virus large T antigen (PyLT)-co-amplified recombinant CHO (rCHO) cells stably expressing EBNA-1 and PyLT were established using dihydrofolate reductase/methotrexate-mediated gene amplification. The level of transiently expressed Fc-fusion protein was significantly higher in the EBNA-1/PyLT-co-amplified pools compared to control cultures. Increased Fc-fusion protein production by EBNA-1/PyLT-co-amplification resulted from a higher qp attributable to EBNA-1 but not PyLT expression. The qp for TGE-based production with EBNA-1/PyLT-co-amplified rCHO cells (EP-amp-20) was approximately 22.9-fold that of the control culture with CHO-DG44 cells. Rather than improved transfection efficiency, this cell line demonstrated increased levels of mRNA expression and replicated DNA, contributing to an increased qp. Furthermore, there was no significant difference in N-glycan profiles in Fc-fusion proteins produced in the TGE system. Taken together, these results showed that the use of rCHO cells with co-amplified expression of the viral elements EBNA-1 and PyLT improves TGE-based therapeutic protein production dramatically. Therefore, EBNA-1/PyLT-co-amplified rCHO cells will likely be useful as host cells in CHO cell-based TGE systems.


Subject(s)
Antigens, Polyomavirus Transforming/genetics , Epstein-Barr Virus Nuclear Antigens/genetics , Gene Amplification , Nucleic Acid Amplification Techniques/methods , Animals , CHO Cells , Cricetinae , Cricetulus , Recombinant Proteins/genetics , Transfection
14.
Small ; 14(6)2018 02.
Article in English | MEDLINE | ID: mdl-29211321

ABSTRACT

Black phosphorus (BP) has drawn enormous attention for both intriguing material characteristics and electronic and optoelectronic applications. In spite of excellent advantages for semiconductor device applications, the performance of BP devices is hampered by the formation of phosphorus oxide on the BP surface under ambient conditions. It is thus necessary to resolve the oxygen-induced degradation on the surface of BP to recover the characteristics and stability of the devices. To solve this problem, it is demonstrated that a 1,2-ethanedithiol (EDT) treatment is a simple and effective way to remove the bubbles formed on the BP surface. The device characteristics of the degraded BP field-effect transistor (FET) are completely recovered to the level of the pristine cases by the EDT treatment. The underlying principle of bubble elimination on the BP surface by the EDT treatment is systematically analyzed by density functional theory calculation, atomic force microscopy, and X-ray photoelectron spectroscopy analysis. In addition, the performance of the hexagonal boron nitride-protected BP FET is completely retained without changing device characteristics even when exposed to 30 d or more in air. The EDT-induced recovering effect will allow a new route for the optimization of electronic and optoelectronic devices based on BP.

15.
Sci Rep ; 7(1): 9994, 2017 08 30.
Article in English | MEDLINE | ID: mdl-28855591

ABSTRACT

Fabrication of epitaxial FeSexTe1-x thin films using pulsed laser deposition (PLD) enables improving their superconducting transition temperature (T c) by more than ~40% than their bulk T c. Intriguingly, T c enhancement in FeSexTe1-x thin films has been observed on various substrates and with different Se content, x. To date, various mechanisms for T c enhancement have been reported, but they remain controversial in universally explaining the T c improvement in the FeSexTe1-x films. In this report, we demonstrate that the controversies over the mechanism of T c enhancement are due to the abnormal changes in the chalcogen ratio (Se:Te) during the film growth and that the previously reported T c enhancement in FeSe0.5Te0.5 thin films is caused by a remarkable increase of Se content. Although our FeSexTe1-x thin films were fabricated via PLD using a Fe0.94Se0.45Te0.55 target, the precisely measured composition indicates a Se-rich FeSexTe1-x (0.6 < x < 0.8) as ascertained through accurate compositional analysis by both wavelength dispersive spectroscopy (WDS) and Rutherford backscattering spectrometry (RBS). We suggest that the origin of the abnormal composition change is the difference in the thermodynamic properties of ternary FeSexTe1-x, based on first principle calculations.

16.
Sci Rep ; 7(1): 8678, 2017 08 17.
Article in English | MEDLINE | ID: mdl-28819116

ABSTRACT

Transforming growth factor (TGF)-ß1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-ß1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-ß1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells. Knockdown of TGF-ß1 expression in the tumor cells negatively affected matrix metalloproteinase (MMP)-9 gene expression. Fibroblasts, cultured in the presence of tumor cells with intact TGF-ß1, showed a significant increase in proliferation rate, as well as expression of VEGF, bFGF, and SDF-1, which was not seen when TGF-ß1 expression was abrogated in tumor cells. Absence of TGF-ß1 in tumor cells also failed to result in myofibroblast differentiation. Co-implantation of CAFs and tumor cells with either intact TGF-ß1 expression or devoid of TGF-ß1 in vivo showed a significant increase in tumor growth kinetics in both cell types, suggesting a possible activation TGF-ß receptor signaling in tumor cells in response to TGF-ß from the TME.


Subject(s)
Gene Silencing , Matrix Metalloproteinase 9/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Transforming Growth Factor beta1/genetics , Tumor Microenvironment/genetics , Biomarkers , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Cell Proliferation , Chemokines/genetics , Chemokines/metabolism , Coculture Techniques , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Neoplasms/pathology , Paracrine Communication , Signal Transduction/drug effects , Stromal Cells/metabolism
17.
Phys Chem Chem Phys ; 19(7): 5121-5126, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28138674

ABSTRACT

We propose a novel hybrid structure for improving the efficiency of crystalline silicon solar cells. By employing first-principles calculations, we demonstrate that ordered, nanoporous silicon (np-Si), when filled with polythiophene (PT) inside the pores, exhibits a substantially enhanced absorption coefficient compared to both np-Si and the bulk, which makes the np-Si/PT heterojunction a superior light absorbing material. In addition, the PT-filled porous structure forms a staggered gap, or type II, heterojunction at the interfaces, where the valence band maximum and conduction band minimum of the composite reside on PT and np-Si, respectively. Moreover, the pore-filling polymer brings about a highly dispersive valence band, which provides a major pathway for hole transport. These results suggest that such a hybrid structure, which may be easier to scale up than nanowire-based approaches, will efficiently dissociate photo-induced electron-hole pairs and reduce the amount of material for light absorption, thus leading to a cost-effective and high-performance solar cell.

18.
FASEB J ; 31(4): 1608-1619, 2017 04.
Article in English | MEDLINE | ID: mdl-28069826

ABSTRACT

Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling. This reversal after ES treatment significantly decreased PCa cell proliferation through down-regulation of GR and up-regulation of manganese superoxide dismutase and reduced glutathione levels. Proteome and biochemical analyses of ES-treated PCa cells further indicated a significant up-regulation of enzymes in the major reactive oxygen species (ROS) scavenging machinery, including catalase, glutathione synthetase, glutathione reductase, NADPH-cytochrome P450 reductase, biliverdin reductase, and thioredoxin reductase, resulting in a concomitant reduction of intracellular ROS. ES further augmented the antioxidant system through up-regulation of glucose influx, the pentose phosphate pathway, and NAD salvaging pathways. This shift in cancer cell redox homeostasis by ES significantly decreased the effect of protumorigenic oxidative machinery on androgen-independent PCa growth, suggesting that ES can suppress GR-induced resistant phenotype upon AR antagonism and that the dual targeting action of ES on AR and GR can be further translated to PCa therapy.-Lee, J. H., Kang, M., Wang, H., Naik, G., Mobley, J. A., Sonpavde, G., Garvey, W. T., Darley-Usmar, V. M., Ponnazhagan, S. Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Endostatins/pharmacology , Oxidative Stress , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Catalase/genetics , Catalase/metabolism , Cell Line, Tumor , Down-Regulation , Glutathione Reductase/genetics , Glutathione Reductase/metabolism , Humans , Male , NADPH-Ferrihemoprotein Reductase/genetics , NADPH-Ferrihemoprotein Reductase/metabolism , Receptors, Glucocorticoid/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Thioredoxin-Disulfide Reductase/genetics , Thioredoxin-Disulfide Reductase/metabolism
19.
Blood Adv ; 1(25): 2375-2385, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-29296887

ABSTRACT

The current treatment options for multiple myeloma (MM) osteolytic lesions are mainly combinations of chemotherapy and other small-molecule inhibitors, but toxic side effects still remain a major concern. Studies have shown that osteoclast activity is enhanced in MM patients through increased expression of receptor activator of nuclear factor κB ligand (RANKL), triggering RANK signaling on osteoclast precursors, which results in aggressive bone resorption. Furthermore, osteoprotegerin (OPG), a decoy receptor for RANKL, and the osteogenic potential of mesenchymal stem cells (MSCs) are significantly decreased in myeloma patients with multiple bone lesions. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, in addition to inhibiting osteoclast activation, OPG binds to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), thereby rendering the tumor cells resistant to TRAIL-induced apoptosis and limiting the use of OPG for therapy. The present study developed a bone-disseminated myeloma disease model in mouse and successfully tested a cell therapy approach using MSCs, genetically engineered to express OPG variants that retain the capacity to bind RANKL, but do not bind TRAIL. Our results of skeletal remodeling following this regenerative stem cell therapy with OPG variants indicated a significant protection against myeloma-induced osteolytic bone damage in areas of major myeloma skeletal dissemination, suggesting the potential of this therapy for treating osteolytic damage in myeloma patients.

20.
Phys Chem Chem Phys ; 18(31): 21949-53, 2016 Aug 03.
Article in English | MEDLINE | ID: mdl-27440199

ABSTRACT

The Poisson's ratio νij = -ε/ε, where ε and ε (i,j = x, y, z) are applied and resulting strain, respectively, are computed from first-principles for Si with an array of cylindrical, nanometer-sized pores aligned in the z direction (nanoporous Si, or np-Si). Through density functional theory calculations, it is demonstrated that the periodic arrangement of pores introduces strong anisotropy in the Poisson's ratio of np-Si: while νyz remains close to the Poisson's ratio of the bulk, νzx and νxy exhibit an increase and a sharp decrease from the bulk value, respectively, as the volume fraction of pores (ϕ) becomes large. It is shown that the characteristic dependence of the Poisson's ratio on ϕ originates from the difference in the actual stress on np-Si, which is caused by the dissimilar surface geometry. Unlike random porous materials, this finding signifies the importance of structural details in determining the mechanical response of ordered systems at a nanoscale.

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