Search

As an electrocatalyst for water electrolysis, nickel oxide (NiO) has received significant attention due to its cost-effectiveness and high reactivity among non-noble-metal-based catalytic materials. However, NiO still exhibits poor alkaline hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) kinetics compared to conventional noble metal-based catalysts. This is because NiO has a strong interaction with protons for the HER and too low free energy of the OH* state, resulting in slower rate-determining step (RDS) kinetics for the OER. To address these issues, adding a dopant is suggested as an efficient method to modify the electron structure of the NiO electrocatalyst favorably for each reaction kinetics. In this context, we demonstrate that Bismuth (Bi), due to its higher electronegativity than that of Nickel (Ni), induces a positive charge on Ni sites. This enhances the catalytic activity by reducing the number of excessive cation interactions with the NiO electrocatalyst. Moreover, as the Bi ratio increases, the Ni reaction sites in NiO become more positively charged, and these changes in the electronic structure directly impact the free energy of the reaction mechanism. Particularly, it is confirmed that for the HER, Bi additives increase the proton-adsorbed free energy toward a near-zero value and, additionally, decrease the free energy difference of the second step considered as the RDS in the OER, as calculated by density functional theory. The positive effects of Bi in both the HER and the OER are demonstrated in practical electrochemical evaluations of half/single cells. Notably, the Bi-containing catalysts Bi05:NiO and Bi02:NiO exhibit remarkable alkaline HER and OER kinetics, showing performance improvements of 97.0% and 21.9%, respectively.

Rational reforming of metal oxide has a potential importance to modulate their inherent properties toward appealing characteristics for various applications. Here, we present a detailed fundamental study of the proton migration phenomena between mediums and propose the methodology for controllable metal oxide hydrogenation through galvanic reactions with metallic cation under ambient atmosphere. As a proof of concept for hydrogenation, we study the role of proton adoption on the structural properties of molybdenum trioxide, as a representative, and its impact on redox characteristics in Li-ion battery (LiB) systems using electrochemical experiments and first-principles calculation. The proton adoption contributes to a lattice rearrangement facilitating the faster Li-ion diffusion along the selected layered and mediates the diffusion pathway that promote the enhancements of high-rate performance and cyclic stability. Our work provides physicochemical insights of hydrogenations and underscores the viable approach for improving the redox characteristics of layered oxide materials., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

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 ∼10 12 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.

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, Mg 3 Si 3 (MoO 6 ) 2 , for high-performance Mg-ion batteries. Through first-principles density functional theory calculations, it is demonstrated that Mg 3 Si 3 (MoO 6 ) 2 possesses a high average discharge voltage (2.35 V vs Mg/Mg 2+ ), 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.

The influence of N-substituent and p K a 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 p K a 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.

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 (q p )-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.

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 OPG Y49R 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 OPG Y49R 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 OPG Y49R combination could offer a viable alternate therapeutic approach., (©2020 American Association for Cancer Research.)

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.

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.

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., (©2020 American Association for Cancer Research.)

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 (MoS 2 ) monolayer devices depending on metal contacts, Ti/Pt, Ti/Au, Ti, and Ag, and particularly demonstrated the essential role of defects in MoS 2 in contact properties. Remarkably, MoS 2 devices with Ag contacts show a field-effect mobility of 12.2 cm 2 V -1 s -1 , an on/off current ratio of 7 × 10 7 , 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-MoS 2 orbital hybridization at the interface, which facilitates efficient charge transfer between MoS 2 and Ag. Interestingly, X-ray photoelectron spectroscopic analysis reveals that Ag 2 S was formed in our defect-containing CVD-grown MoS 2 monolayer, but such orbital hybridization is not observed in a nearly defect-free exfoliated MoS 2 . This distinction shows that defects existing in MoS 2 enable Ag to effectively couple to MoS 2 and correspondingly enhance multiple electrical and photoelectrical properties.

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., Competing Interests: DISCLOSURE OF CONFLICT OF INTEREST There is not financial conflict with any of the authors.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Despite the relatively low transfection efficiency and low specific foreign protein productivity (q p ) 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 q p attributable to EBNA-1 but not PyLT expression. The q p 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 q p . 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.

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., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Fabrication of epitaxial FeSe x Te 1-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 FeSe x Te 1-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 FeSe x Te 1-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 FeSe 0.5 Te 0.5 thin films is caused by a remarkable increase of Se content. Although our FeSe x Te 1-x thin films were fabricated via PLD using a Fe 0.94 Se 0.45 Te 0.55 target, the precisely measured composition indicates a Se-rich FeSe x Te 1-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 FeSe x Te 1-x , based on first principle calculations.

Transforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 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-β1 expression in the tumor cells negatively affected matrix metalloproteinase (MMP)-9 gene expression. Fibroblasts, cultured in the presence of tumor cells with intact TGF-β1, showed a significant increase in proliferation rate, as well as expression of VEGF, bFGF, and SDF-1, which was not seen when TGF-β1 expression was abrogated in tumor cells. Absence of TGF-β1 in tumor cells also failed to result in myofibroblast differentiation. Co-implantation of CAFs and tumor cells with either intact TGF-β1 expression or devoid of TGF-β1 in vivo showed a significant increase in tumor growth kinetics in both cell types, suggesting a possible activation TGF-β receptor signaling in tumor cells in response to TGF-β from the TME.

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., (© FASEB.)

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.

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.

Background/aims: Smoking and alcohol intake are two wellknown risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis., Methods: In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking., Results: The median duration of followup was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008)., Conclusions: Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis.

Background: A growing body of evidence indicates a positive correlation between expression of human antimicrobial peptide leucin leucin 37 (LL-37) and progression of epithelial cancers, including prostate cancer (PCa). Although the molecular mechanisms for this correlation has not yet been elucidated, the primary function of LL-37 as a chemotactic molecule for innate immune effector cells suggests its possible association in coordinating protumorigenic mechanisms, mediated by tumor-infiltrating immune cells., Methods: To investigate protumorigenic role(s) of cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of LL-37, the present study compared tumor growth kinetics between mouse PCa cell lines with and without CRAMP expression (TRAMP-C1 and TRAMP-C1(CRAMP-sh) , respectively) in immunocompetent mice. CRAMP-mediated chemotaxis of different innate immune cell types to the tumor microenvironment (TME) was observed in vivo and confirmed by in vitro chemotaxis assay. The role of CRAMP in differentiation and polarization of immature myeloid progenitors (IMPs) to protumorigenic type 2 macrophages (M2) in TME was determined by adoptive transfer of IMPs into mice bearing CRAMP(+) and CRAMP(-) tumors. To differentiate protumorigenic events mediated by tumor-derived CRAMP from host immune cell-derived CRAMP, tumor challenge study was performed in CRAMP-deficient mice. To identify mechanisms of CRAMP function, macrophage colony stimulating factor (M-CSF) and monocyte chemoattractant protein 1 (MCP-1) gene expression was analyzed by QRT-PCR and STAT3 signaling was determined by immunoblotting., Results: Significantly delayed tumor growth was observed in wild-type (WT) mice implanted with TRAMP-C1(CRAMP-sh) cells compared to mice implanted with TRAMP-C1 cells. CRAMP(+) TME induced increased number of IMP differentiation into protumorigenic M2 macrophages compared to CRAMP(-) TME, indicating tumor-derived CRAMP facilitates differentiation and polarization of IMPs toward M2. Tumor challenge study in CRAMP deficient mice showed comparable tumor growth kinetics with WT mice, suggesting tumor-derived CRAMP plays a crucial role in PCa progression. In vitro study demonstrated that overexpressed M-CSF and MCP-1 in TRAMP-C1 cells through CRAMP-mediated autocrine signaling, involving p65, regulates IMP-to-M2 differentiation/polarization through STAT3 activation., Conclusion: Altogether, the present study suggests that overexpressed CRAMP in prostate tumor initially chemoattracts IMPs to TME and mediates differentiation and polarization of early myeloid progenitors into protumorigenic M2 macrophages during PCa progression. Thus, selective downregulation of CRAMP in tumor cells in situ may benefit overcoming immunosuppressive mechanisms in PCa., (© 2016 Wiley Periodicals, Inc.)

Unlabelled: Osteolytic bone damage is a major cause of morbidity in several metastatic pathologies. Current therapies using bisphosphonates provide modest improvement, but cytotoxic side effects still occur prompting the need to develop more effective therapies to target aggressive osteoclastogenesis. Increased levels of receptor activator of NF-κB ligand (TNFSF11/RANKL), leading to RANKL-RANK signaling, remain the key axis for osteoclast activation and bone resorption. Osteoprotegerin (TNFRSF11B/OPG), a decoy receptor for RANKL, is significantly decreased in patients who present with bone lesions. Despite its potential in inhibiting osteoclast activation, OPG also binds to TNF-related apoptosis-inducing ligand (TNFSF10/TRAIL), making tumor cells resistant to apoptosis. Toward uncoupling the events of TRAIL binding of OPG and to improve its utility for bone remodeling without inducing tumor resistance to apoptosis, OPG mutants were developed by structural homology modeling based on interactive domain identification and by superimposing models of OPG, TRAIL, and its receptor DR5 (TNFRSF10B) to identify regions of OPG for rational design. The OPG mutants were purified and extensively characterized for their ability to decrease osteoclast damage without affecting tumor apoptosis pathway both in vitro and in vivo, confirming their potential in bone remodeling following cancer-induced osteolytic damage., Implications: OPG variants were developed that lack TRAIL binding, yet retain RANKL binding and suggest new possibilities for therapeutic targeting in osteolytic malignancies., (©2015 American Association for Cancer Research.)

Acquired resistance to androgen receptor (AR)-targeted therapies compels the development of novel treatment strategies for castration-resistant prostate cancer (CRPC). Here, we report a profound effect of endostatin on prostate cancer cells by efficient intracellular trafficking, direct interaction with AR, reduction of nuclear AR level, and down-regulation of AR-target gene transcription. Structural modeling followed by functional analyses further revealed that phenylalanine-rich α1-helix in endostatin-which shares structural similarity with noncanonical nuclear receptor box in AR-antagonizes AR transcriptional activity by occupying the activation function (AF)-2 binding interface for coactivators and N-terminal AR AF-1. Together, our data suggest that endostatin can be recognized as an endogenous AR inhibitor that impairs receptor function through protein-protein interaction. These findings provide new insights into endostatin whose antitumor effect is not limited to inhibiting angiogenesis, but can be translated to suppressing AR-mediated disease progression in CRPC.

Elastic properties of nanoporous Si (np-Si), which is composed of bulk Si containing ordered, nanometer-sized cylindrical pores, are investigated based on first-principles density functional theory calculations. By separately varying the pore size and spacing, it is demonstrated that the elastic stiffness of np-Si under the shear strain perpendicular to the pore axis turns negative when the volume fraction of pores becomes greater than a critical value. The total energy calculations reveal that the negative values in the stiffness originate from the enhanced strain energy, which leads to significant rotation in bonds near the pore surface. Moreover, the high sensitivity of the elastic stiffness to shear induces a structural transformation in np-Si from tetragonal (D2d) to orthorhombic (C2v) phase, which makes it necessary to properly take the effect of external strain due to substrates or electrical leads into account in np-Si-based applications.

Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, β3 and β4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.

Increasing demand for energy with fossil fuel supplies decreasing makes it an urgent task to develop novel and cost-effective materials that can supply environmentally benign and sustainable energy. To address this important issue, in the present work we carry out a systematic study on the effect of external strain on the room-temperature thermoelectric properties of Si containing cylindrical pores in a periodic arrangement (nanoporous Si, or np-Si), based on density functional theory and the Boltzmann transport equation. Within the relaxation time approximation, it is demonstrated that the electrical conductivity (σ) and Seebeck coefficient (S) of np-Si remain unchanged from the strain-free values under biaxial or shear strain. However, orthorhombic strain increases σ and S by as large as 68% and 110% compared to the unstrained structure, respectively, which is found to originate from the broken planar symmetry induced by the applied strain. Combined with the thermal conductivity, the improvement in σ and S of orthorhombically strained np-Si can enhance the maximum value of the thermoelectric figure of merit to as high as 0.8, which makes strain engineering particularly attractive for high-performance thermoelectrics.

Although the stoichiometry of bulk lead sulfide (PbS) is exactly 1:1, that of quantum dots (QDs) can be considerably different from this crystalline limit. Employing first-principles calculations, we show that the impact of PbS QD stoichiometry on the electronic structure can be enormous, suggesting that control over the overall stoichiometry in the QD will play a critical role for improving the efficiency of optoelectronic devices made with PbS QDs. In particular, for bare PbS QDs, we find that: (i) stoichiometric PbS QDs are free from midgap states even without ligand passivation and independent of shape, (ii) off stoichiometry in PbS QDs introduces new states in the gap that are highly localized on certain surface atoms, and (iii) further deviations in stoichiometry lead to QDs with "metallic" behavior, with a dense number of energy states near the Fermi level. We further demonstrate that this framework holds for the case of passivated QDs by considering the attachment of ligand molecules as stoichiometry variations. Our calculations show that an optimal number of ligands makes the QD stoichiometric and heals unfavorable electronic structure, whereas too few or too many ligands cause effective off stoichiometry, resulting in QDs with defect states in the gap.

We investigate the effects of two-dimensional (2D) periodic patterns of functional groups on the thermal transport in a graphene monolayer by employing molecular and lattice dynamics simulations. Our calculations show that the use of patterned 2D shapes on graphene reduces the room temperature thermal conductivity, by as much as 40 times lower than that of the pristine monolayer, due to a combination of boundary and clamping effects. Lattice dynamics calculations elucidate the correlation between this large reduction in thermal conductivity and two dynamical properties of the main heat carrying phonon modes: (1) decreased phonon lifetimes by an order of magnitude due to scattering, and (2) direction-dependent group velocities arising from phonon confinement. Taken together, these results suggest that patterned graphene nanoroads provide a method for tuning the thermal conductivity of graphene without the introduction of defects in the lattice, opening an important possibility for thermoelectric applications.

Short tandem repeat (STR) loci are routinely analyzed by capillary electrophoresis. However, this method has several disadvantages, including long operational time, low throughput, and inaccuracy. As a result of the introduction of matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization (ESI), mass spectrometry has become an alternative method for genotyping polymorphic STR loci. Here we established a restriction fragment mass polymorphism (RFMP) assay for genotyping STR locus, TPOX, by typeIIS restriction endonuclease cleavage of polymerase chain reaction (PCR) amplicon followed by MALDI-TOF mass spectrometry. The resulting TPOX genotypes from this assay were in good agreement with the results from direct DNA sequencing and GeneScan assays. Our results showed that the RFMP assay is an accurate and high-throughput method for analyzing long DNA fragments such as STR markers. Further research with multiple STR loci may allow this assay to be used for diverse applications such as forensics, paternity tests, and detection of genetic disorders., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We present molecular and lattice dynamics calculations of the thermal conductivity of nanoporous silicon, and we show that it may attain values 10-20 times smaller than in bulk Si for porosities and surface-to-volume ratios similar to those obtained in recently fabricated nanomeshes. Further reduction of almost an order of magnitude is obtained in thin films with thickness of 20 nm, in agreement with experiment. We show that the presence of pores has two main effects on heat carriers: appearance of non-propagating, diffusive modes and reduction of the group velocity of propagating modes. The former effect is enhanced by the presence of disorder at the pore surfaces, while the latter is enhanced by decreasing film thickness.

Aberrant hyaluronan production has been implicated in many types of tumor. In this context, hyaluronidase has been explored as a viable therapeutic approach to reduce tumoral hyaluronan. However, elevated levels of hyaluronan in tumors are often associated with high expression levels of cellular hyaluronidases, which consequently produce various sizes of saturated hyaluronan fragments with divergent pro-tumoral activities. The current study shows that different hyaluronan metabolisms of mammalian and microbial hyaluronidases could elicit distinct alterations in cancer cell behavior. Unlike saturated hyaluronan metabolites, unsaturated hyaluronan oligosaccharides produced by bacteriophage hyaluronidase, HylP, had no biological effect on growth of breast carcinoma cells. More importantly, HylP's metabolic process of hyaluronan into non-detrimental oligosaccharides significantly decreased breast cancer cell proliferation, migration and invasion by disrupting Erk1/2 activation and RhoA expression. Our results suggest that it may be possible to exploit HylP's unique enzymatic activity in suppressing hyaluronan-mediated tumor growth and progression., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We investigate the effect of O impurities on the thermoelectric properties of ZnSe from a combination of first-principles and analytic calculations. It is demonstrated that dilute amounts of O impurities introduce peaks in the density of states (DOS) above the conduction band minimum, and that the charge density near the DOS peaks is substantially attracted toward O atoms due to their high electronegativity. The impurity-induced peaks in the DOS result in a sharp increase of the room-temperature Seebeck coefficient and power factor from those of O-free ZnSe by a factor of 30 and 180, respectively. Furthermore, this effect is found to be absent when the impurity electronegativity well matches the host that it substitutes. The results suggest that highly electronegativity-mismatched alloys can be designed for high performance thermoelectric applications.

Purpose: To evaluate the efficacy and safety of single-session OK-432 sclerotherapy for the treatment of renal cysts., Materials and Methods: From October 2005 to November 2006, 48 patients (61 simple renal cysts) were included in the study. Indications were determined as flank discomfort (n = 37) or patient reassurance due to increasing size (n = 11). The simple renal cysts were aspirated under ultrasonography (US), at which point OK-432 was injected into the cyst. Follow-up was performed with US or computed tomography scan every 3 months until 1 year. Complete regression of the renal cyst or more than 70% reduction in size with no symptoms indicated a successful treatment., Results: Among 61 renal cysts of 48 patients, the overall success rate was 98.4%. Complete regression occurred in 46 cysts (75.4%), and more than 90% reduction in size occurred in 6 cysts (9.8%). A size reduction of 80% to 90% and 70% to 80% occurred in five (8.2%) and three cysts (4.9%), respectively. A size reduction less than 70% occurred in only one cyst (1.6%). The success of cyst regression was correlated with cyst volume. Clinical symptoms resolved in 100% of patients with symptomatic cysts, and there was no enlargement of the aspirated cysts at the 1-year follow-up. After the procedure, there were only some minor complications, such as mild fever, flank pain, and leukocytosis, which subsided with the conservative treatment., Conclusions: Percutaneous OK-432 sclerotherapy is simple, safe, and effective, and it can be an alternative first-line therapy for simple renal cysts.

Purpose: We compared the efficacy and safety of multiple session 99% ethanol sclerotherapy to single session OK-432 sclerotherapy for the treatment of simple renal cysts., Materials and Methods: Between September 2004 and November 2006, 41 patients (50 cysts, group 1) underwent sclerotherapy with 99% ethanol at least twice and 48 (61 cysts, group 2) underwent a single session of OK-432 sclerotherapy. Followup was performed with ultrasound or computerized tomography every 3 months for 1 year. Complete regression of the renal cyst or more than 70% reduction with no symptoms was considered successful treatment., Results: There was no significant difference in the mean size of renal cysts between the 2 treatment groups. The overall success rate was 84.0% in group 1 and 98.4% in group 2. For cysts smaller than 500 ml there was a similar complete regression rate between the 2 groups whereas in cysts 500 ml or larger the complete regression ratio of group 2 was higher than group 1. The symptom relief rate of group 2 was higher than group 1. In group 1 there were 2 patients with a recurrent cyst but in group 2 there was no enlargement of the aspirated cysts. For cysts smaller than 200 ml neither treatment group had complications whereas in cysts 200 ml or larger the frequency of complications was higher in group 1., Conclusions: Single session OK-432 sclerotherapy is simpler, safer and more effective than multiple session 99% ethanol sclerotherapy for the treatment of simple renal cysts, especially large cysts.

Room-temperature thermoelectric properties of n-type crystalline Si with periodically arranged nanometer-sized pores are computed using a combination of classical molecular dynamics for lattice thermal conductivity and ab initio density functional theory for electrical conductivity, Seebeck coefficient, and electronic contribution to the thermal conductivity. The electrical conductivity is found to decrease by a factor of 2-4, depending on doping levels, compared to that of bulk due to confinement. The Seebeck coefficient S yields a 2-fold increase for carrier concentrations less than 2 x 10(19) cm(-3), above which S remains closer to the bulk value. Combining these results with our calculations of lattice thermal conductivity, we predict the figure of merit ZT to increase by 2 orders of magnitude over that of bulk. This enhancement is due to the combination of the nanometer size of pores which greatly reduces the thermal conductivity and the ordered arrangement of pores which allows for only a moderate reduction in the power factor. We find that while alignment of pores is necessary to preserve power factor values comparable to those of bulk Si, a symmetric arrangement is not required. These findings indicate that nanoporous semiconductors with aligned pores may be highly attractive materials for thermoelectric applications.

Objectives: An analysis of differentially expressed genes (DEGs) between bladder transitional cell carcinoma (TCC) and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. We sought to find a new DEG related to the development of bladder TCC., Methods: Thirty-nine bladder TCC tissues paired with normal-appearing urothelium tissues obtained from the same patient were used as subjects. Initially, we compared the messenger RNA (mRNA) profiles between normal-appearing urothelium and TCC tissue of 1 patient by using annealing control primer (ACP)-based GeneFishing polymerase chain reaction (PCR) and selective amplification of family members (SAFM) PCR to identify potential DEGs. To validate the results of the ACP data, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on those of all 39 patients., Results: Among the several DEGs discovered in the ACP data, 1 DEG was chosen as the candidate for the RT-PCR, that is present or markedly upregulated in normal-appearing urothelial tissue compared with TCC tissue. Gene sequence searching revealed that this DEG is chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Downregulation of COUP-TFI mRNA expression in TCC tissue compared to normal-appearing urothelium tissue of the same patient, irrespective of tumor stage and grade, was confirmed by RT-PCR in 39 patients., Conclusions: Our results suggest that the loss of COUP-TFI may play a role in the transition from normal epithelium to TCC. Further characterization of the COUP-TFI gene is expected to give us informations about bladder TCC tumorigenesis.

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).

We experienced one fatal case of biliary cast syndrome after cadaveric liver transplantation involving both intrahepatic ducts. A 58-year-old man underwent cadaveric liver transplantation because of hepatitis B virus related liver cirrhosis and concomitant hepatocellular carcinoma. Five weeks after the liver transplantation, postoperative course was complicated by development of acute cholangitis. Subsequent endoscopic retrograde cholangiography revealed diffuse intrahepatic bile duct strictures without filling defects. Percutaneous liver biopsy, which was done to exclude rejection, revealed biliary cast. Successful endoscopic removal was precluded due to its diffuse involvement. Because of the deterioration of patient's condition by refractory biliary obstruction and cholangitis, retransplantation from cadaveric donor was performed. Debridement of the biliary tree after graft removal yielded a near-complete cast of the intrahepatic ductal system. Biliary cast syndrome should be suspected when jaundice or cholangitis is associated with dilated ducts on abdominal imaging studies in cadaveric liver transplantation recipients. Initial therapeutic options include removal of biliary cast after endoscopic or percutaneous cholangiography. Although endoscopic retrieval of biliary cast by endoscopic retrograde cholangiopancreatography could be employed as a first-line management, other modalities such as endoscopic nasobiliary drainage, percutaneous transhepatic drainage, or retransplantation should be considered when complete removal is not feasible and the condition of the recipient deteriorates.

This article summarizes the major categories of ethical violations encountered during submission, review, and publication of scientific articles. We discuss data fabrication and falsification, plagiarism, redundant and duplicate publication, conflict of interest, authorship, animal and human welfare, and reviewer responsibility. In each section, pertinent historical background and citation of relevant regulations and statutes are provided. Furthermore, a specific case(s) derived from actual situations is(are) presented. These cases were chosen to highlight the complexities that investigators and journals must face when dealing with ethical issues. A series of discussion questions follow each case. It is our hope that by increasing education and awareness of ethical matters relevant to scientific investigation and publication, deviations from appropriate conduct will be reduced.