The Expression and Prognostic Value of Cancer Stem Cell Markers, NRF2, and Its Target Genes in TAE/TACE-Treated Hepatocellular Carcinoma.

Background and Objectives: Activation of NRF2, a key transcription factor of cytoprotectant against oxidative stress, and its target genes are associated with aggressive tumor progression, metastasis and poor survival. In addition, NRF2 signaling mediates cancer stem cell (CSC)-like properties in hepatocellular carcinoma (HCC) cells. Moreover, CSCs have been associated with HCC onset and unfavorable prognosis. Transcatheter arterial embolization (TAE) and/or transcatheter arterial chemoembolization (TACE), which attempt to restrict blood supply to diminish tumor growth, can create a hypoxic environment. However, its effect on NRF2 signaling and CSC marker CD133 in the context of prognosis of HCCs have not been investigated. Therefore, we studied the possible role of the expressions of NRF2, its target genes and CSC markers CD133 and EpCAM on the survival of HCC patients after TAE/TACE. Materials and Methods: RT-qPCR was performed with 120 tumor (T) and adjacent tumor (N) tissue pairs. Expression of a single marker or combination was assessed for associations with survival of HCC patients after TAE/TACE. Results: The result of multivariate Cox regression showed that vascular invasion (HR, 1.821; p = 0.015), metastasis (HR, 2.033; p = 0.049) and CD133 overexpression (HR, 2.013; p = 0.006) were associated with poor survival. In a Kaplan-Meier survival analysis, patients with high expression of CD133 had shorter overall survival (OS) than those with low expression of CD133 in post-TAE/TACE HCC (p < 0.001). In contrast, neither NRF2 nor components of its signaling pathway correlated with survival. Combination marker analysis showed that co-expression of NQO1 and CD133 was associated with poor outcome. Conclusions: This study suggests that analyzing the expression status of CD133 alone and co-expression of NQO1 and CD133 may have additional value in predicting the outcome of TAE/TACE-treated HCC patients.

Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma.

The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation. An elevated PREX2 protein expression accompanied by activation of AKT was observed in the liver of Gnmt knockout mice. PREX2 protein expression was upregulated in 54.9% of human HCC samples, while its mRNA level was comparable in tumor and tumor-adjacent tissue, suggesting a post-translational alteration of PREX2 expression. Higher level of PREX2 in the tumor tissues was associated with poorer survival. These results reveal a novel mechanism in which GNMT participates in AKT signaling and HCC tumorigenesis by promoting HectH9-mediated PREX2 degradation.

Discovery of 5,7-Dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one with Lipid Lowering Effects in Hepatocytes.

The population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing. However, no medicine is indicated for treating these diseases clinically nowadays. Therefore, there is an urgent need to develop a new drug to overcome NAFLD and NASH. Capillarisin, a 2-phenoxychromone originating from Artemisia capillaris Thunb., is well-known for its liver-protective effects. As a result, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells by means of high-content screening. In the light of the results, the compounds with trimethoxy groups on the phenyl ring possessed better inhibitory properties against lipid accumulation in Huh7 cells, compared to other functional groups on the same ring. Nonetheless, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one (7e), with an IC50 value of 32.2 ± 2.1 µM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.

Continuous Speech for Improved Learning Pathological Voice Disorders.

Goal: Numerous studies had successfully differentiated normal and abnormal voice samples. Nevertheless, further classification had rarely been attempted. This study proposes a novel approach, using continuous Mandarin speech instead of a single vowel, to classify four common voice disorders (i.e. functional dysphonia, neoplasm, phonotrauma, and vocal palsy). Methods: In the proposed framework, acoustic signals are transformed into mel-frequency cepstral coefficients, and a bi-directional long-short term memory network (BiLSTM) is adopted to model the sequential features. The experiments were conducted on a large-scale database, wherein 1,045 continuous speech were collected by the speech clinic of a hospital from 2012 to 2019. Results: Experimental results demonstrated that the proposed framework yields significant accuracy and unweighted average recall improvements of 78.12-89.27% and 50.92-80.68%, respectively, compared with systems that use a single vowel. Conclusions: The results are consistent with other machine learning algorithms, including gated recurrent units, random forest, deep neural networks, and LSTM.The sensitivities for each disorder were also analyzed, and the model capabilities were visualized via principal component analysis. An alternative experiment based on a balanced dataset again confirms the advantages of using continuous speech for learning voice disorders.

1.8 V Aqueous Symmetric Carbon-Based Supercapacitors with Agarose-Bound Activated Carbons in an Acidic Electrolyte.

The specific energy of an aqueous carbon supercapacitor is generally small, resulting mainly from a narrow potential window of aqueous electrolytes. Here, we introduced agarose, an ecologically compatible polymer, as a novel binder to fabricate an activated carbon supercapacitor, enabling a wider potential window attributed to a high overpotential of the hydrogen-evolution reaction (HER) of agarose-bound activated carbons in sulfuric acid. Assembled symmetric aqueous cells can be galvanostatically cycled up to 1.8 V, attaining an enhanced energy density of 13.5 W h/kg (9.5 µW h/cm2) at 450 W/kg (315 µW/cm2). Furthermore, a great cycling behavior was obtained, with a 94.2% retention of capacitance after 10,000 cycles at 2 A/g. This work might guide the design of an alternative material for high-energy aqueous supercapacitors.

Few-Layer Graphene Sheet-Passivated Porous Silicon Toward Excellent Electrochemical Double-Layer Supercapacitor Electrode.

Few-layer graphene sheet-passivated porous silicon (PSi) as an outstanding electrochemical double-layer supercapacitor electrode was demonstrated. The PSi matrix was formed by electrochemical etching of a doped silicon wafer and was further surface-passivated with few-layer graphene sheets by a Ni-assisted chemical vapor deposition process where a wide range of porous PSi structures, including mesoporous, macroporous, and hybrid porous structures were created during the graphene growth as temperature increases. The microstructural and graphene-passivation effects on the capacitive performance of the PSi were investigated in detail. The hybrid porous PSi electrode, optimized in terms of capacitive performances, achieves a high areal capacitance of 6.21 mF/cm2 at an ultra-high scan rate of 1000 mV/s and an unusual progressing cyclic stability of 131% at 10,000 cycles. Besides mesopores and macropores, micropores were introduced onto the surfaces of the passivating few-layer graphene sheets with a KOH activation process to further increase the functioning surface area of the hierarchical porous PSi electrode, leading to a boost in the areal capacitance by 31.4% up to 8.16 mF/cm2. The present designed hierarchical porous PSi-based supercapacitor proves to be a robust energy storage device for microelectronic applications that require stable high rate capability.

Characterization of a new murine cell line of sarcomatoid hepatocellular carcinoma and its application for biomarker/therapy development.

Sarcomatoid hepatocellular carcinoma (SHC) is a rare type of HCC with significantly poorer survival than ordinary HCC. Little is known about the mechanism associated with SHC and its biomarkers and therapy. Here, we established a mouse liver cancer cell line and designated as Ymac-1. A sarcomatous appearance was observed in the allograft tumor arose from Ymac-1. Liver-secreted plasma proteins were found in Ymac-1 cultured supernatant by proteomics analysis. The positive staining of CK7, CK8, Vimentin and the suppressed expression of AFP indicated that Ymac-1 is a SHC cell line. Compared to its original tumor, an elevated level of EMT markers, N-cadherin and Vimentin, was found in Ymac-1. Ymac-1 displayed a higher migration rate and side population percentage than a mouse ordinary HCC cell line-Hepa1-6. Microarray analysis was performed to identify potential biomarkers/therapeutic targets for SHC. G6pd, a vital enzyme in pentose phosphate pathway, is highly expressed in Ymac-1. Depletion of G6pd in Ymac-1 reduced CD133 expression and sphere formation. Positive correlations between G6PD and CD133 were observed in human specimen. Higher expression of both G6PD and CD133 in tumor were associated with poor survival. In summary Ymac-1 can be a useful SHC cell model for novel biomarker and therapy development.

Plasma-Assisted Synthesis of High-Mobility Atomically Layered Violet Phosphorus.

Two-dimensional layered materials such as graphene, transition metal dichalcogenides, and black phosphorus have demonstrated outstanding properties due to electron confinement as the thickness is reduced to atomic scale. Among the phosphorus allotropes, black phosphorus, and violet phosphorus possess layer structure with the potential to be scaled down to atomically thin film. For the first time, the plasma-assisted synthesis of atomically layered violet phosphorus has been achieved. Material characterization supports the formation of violet phosphorus/InN over InP substrate where the layer structure of violet phosphorus is clearly observed. The identification of the crystal structure and lattice constant ratifies the formation of violet phosphorus indeed. The critical concept of this synthesis method is the selective reaction induced by different variations of Gibbs free energy (ΔG) of reactions. Besides, the Hall mobility of the violet phosphorus on the InP substrate greatly increases over the theoretical values of InP bulk material without much reduction in the carrier concentration, suggesting that the mobility enhancement results from the violet phosphorus layers. Furthermore, this study demonstrates a low-cost technique with high compatibility to synthesize the high-mobility atomically layered violet phosphorus and open the space for the study of the fundamental properties of this intriguing material as a new member of the fast growing family of 2D crystals.

Highly effective field-effect mobility amorphous InGaZnO TFT mediated by directional silver nanowire arrays.

In this work, we demonstrate sputtered amorphous indium-gallium-zinc oxide thin-film transistors (a-IGZO TFTs) with a record high effective field-effect mobility of 174 cm(2)/V s by incorporating silver nanowire (AgNW) arrays to channel electron transport. Compared to the reference counterpart without nanowires, the over 5-fold enhancement in the effective field-effect mobility exhibits clear dependence on the orientation as well as the surface coverage ratio of silver nanowires. Detailed material and device analyses reveal that during the room-temperature IGZO sputtering indium and oxygen diffuse into the nanowire matrix while the nanowire morphology and good contact between IGZO and nanowires are maintained. The unchanged morphology and good interfacial contact lead to high mobility and air-ambient-stable characteristics up to 3 months. Neither hysteresis nor degraded bias stress reliability is observed. The proposed AgNW-mediated a-IGZO TFTs are promising for development of large-scale, flexible, transparent electronics.

Phase-pure iron pyrite nanocrystals for low-cost photodetectors.

Earth-abundant iron pyrite (FeS2) shows great potential as a light absorber for solar cells and photodetectors due to their high absorption coefficient (>10(5) cm(-1)). In this paper, high-quality phase-pure and single crystalline pyrite nanocrystals were synthesized via facile, low-cost, and environment friendly hydrothermal method. The molar ratio of sulphur to iron and the reaction time play a crucial role in determining the quality and morphology of FeS2 nanocrystals. X-ray diffraction and high-resolution transmission electron microscopy confirm that phase-pure and single crystalline pyrite nanocrystals can be synthesized with high sulphur to iron molar ratio and sufficient reaction time. For the first time, a crystalline nanogap pyrite photodetector with promising photocurrent and UV-visible photoresponse has been fabricated. This work further demonstrates a facile route to synthesize high-quality FeS2 nanomaterials and their potential in optoelectronic applications.

Scalable graphene synthesised by plasma-assisted selective reaction on silicon carbide for device applications.

Graphene, a two-dimensional material with honeycomb arrays of carbon atoms, has shown outstanding physical properties that make it a promising candidate material for a variety of electronic applications. To date, several issues related to the material synthesis and device fabrication need to be overcome. Despite the fact that large-area graphene films synthesised by chemical vapour deposition (CVD) can be grown with relatively few defects, the required transfer process creates wrinkles and polymer residues that greatly reduce its performance in device applications. Graphene synthesised on silicon carbide (SiC) has shown outstanding mobility and has been successfully used to develop ultra-high frequency transistors; however, this fabrication method is limited due to the use of costly ultra-high vacuum (UHV) equipment that can reach temperatures over 1500 °C. Here, we show a simple and novel approach to synthesise graphene on SiC substrates that greatly reduces the temperature and vacuum requirements and allows the use of equipment commonly used in the semiconductor processing industry. In this work, we used plasma treatment followed by annealing in order to obtain large-scale graphene films from bulk SiC. After exposure to N2 plasma, the annealing process promotes the reaction of nitrogen ions with Si and the simultaneous condensation of C on the surface of SiC. Eventually, a uniform, large-scale, n-type graphene film with remarkable transport behaviour on the SiC wafer is achieved. Furthermore, graphene field effect transistors (FETs) with high carrier mobilities on SiC were also demonstrated in this study.

A solar-thermal energy harvesting scheme: enhanced heat capacity of molten HITEC salt mixed with Sn/SiO(x) core-shell nanoparticles.

We demonstrated enhanced solar-thermal storage by releasing the latent heat of Sn/SiO(x) core-shell nanoparticles (NPs) embedded in a eutectic salt. The microstructures and chemical compositions of Sn/SiO(x) core-shell NPs were characterized. In situ heating XRD provides dynamic crystalline information about the Sn/SiO(x) core-shell NPs during cyclic heating processes. The latent heat of ∼29 J g(-1) for Sn/SiO(x) core-shell NPs was measured, and 30% enhanced heat capacity was achieved from 1.57 to 2.03 J g(-1) K(-1) for the HITEC solar salt without and with, respectively, a mixture of 5% Sn/SiO(x) core-shell NPs. In addition, an endurance cycle test was performed to prove a stable operation in practical applications. The approach provides a method to enhance energy storage in solar-thermal power plants.

Single CuO(x) nanowire memristor: forming-free resistive switching behavior.

CuOx nanowires were synthesized by a low-cost and large-scale electrochemical process with AAO membranes at room temperature and its resistive switching has been demonstrated. The switching characteristic exhibits forming-free and low electric-field switching operation due to coexistence of significant amount of defects and Cu nanocrystals in the partially oxidized nanowires. The detailed resistive switching characteristics of CuOx nanowire systems have been investigated and possible switching mechanisms are systematically proposed based on the microstructural and chemical analysis via transmission electron microscopy.

Improved efficiency of a large-area Cu(In,Ga)Se2 solar cell by a nontoxic hydrogen-assisted solid Se vapor selenization process.

A nontoxic hydrogen-assisted solid Se vapor selenization process (HASVS) technique to achieve a large-area (40 × 30 cm(2)) Cu(In,Ga)Se2 (CIGS) solar panel with enhanced efficiencies from 7.1 to 10.8% (12.0% for active area) was demonstrated. The remarkable improvement of efficiency and fill factor comes from improved open circuit voltage (Voc) and reduced dark current due to (1) decreased interface recombination raised from the formation of a widened buried homojunction with n-type Cd(Cu) participation and (2) enhanced separation of electron and hole carriers resulting from the accumulation of Na atoms on the surface of the CIGS film. The effects of microstructural, compositional, and electrical characteristics with hydrogen-assisted Se vapor selenization, including interdiffusion of atoms and formation of buried homojunction, were examined in detail. This methodology can be also applied to CIS (CuInSe2) thin film solar cells with enhanced efficiencies from 5.3% to 8.5% (9.4% for active area) and provides a facile approach to improve quality of CIGS and stimulate the nontoxic progress in the large scale CIGS PV industry.

Large scale and orientation-controllable nanotip structures on CuInS2, Cu(In,Ga)S2, CuInSe2, and Cu(In,Ga)Se2 by low energy ion beam bombardment process: growth and characterization.

One-step facile methodology to create nanotip arrays on chalcopyrite materials (such as CuInS2, Cu(In,Ga)S2, CuInSe2, and Cu(In,Ga)Se2) via a low energy ion beam bombardment process has been demonstrated. The mechanism of formation for nanotip arrays has been proposed by sputtering yields of metals and reduction of metals induced by the ion beam bombardment process. The optical reflectance of these chalcopyrite nanotip arrays has been characterized by UV-vis spectrophotometer and the efficient light-trapping effect has been observed. Large scale (∼4'') and high density (10(10) tips/cm(2)) of chalcopyrite nanotip arrays have been obtained by using low ion energy (< 1 kV), short processing duration (< 30 min), and template-free. Besides, orientation and length of these chalcopyrite nanotip arrays are controllable. Our results can be the guide for other nanostructured materials fabrication by ion sputtering and are available for industrial production as well.

Manipulated transformation of filamentary and homogeneous resistive switching on ZnO thin film memristor with controllable multistate.

A bias polarity-manipulated transformation from filamentary to homogeneous resistive switching was demonstrated on a Pt/ZnO thin film/Pt device. Two types of switching behaviors, exhibiting different resistive switching characteristics and memory performances were investigated in detail. The detailed transformation mechanisms are systematically proposed. By controlling different compliance currents and RESET-stop voltages, controllable multistate resistances in low resistance states and a high resistance states in the ZnO thin film metal-insulator-metal structure under the homogeneous resistive switching were demonstrated. We believe that findings would open up opportunities to explore the resistive switching mechanisms and performance memristor with multistate storage.

Non-antireflective scheme for efficiency enhancement of Cu(In,Ga)Se2 nanotip array solar cells.

We present systematic works in characterization of CIGS nanotip arrays (CIGS NTRs). CIGS NTRs are obtained by a one-step ion-milling process by a direct-sputtering process of CIGS thin films (CIGS TF) without a postselenization process. At the surface of CIGS NTRs, a region extending to 100 nm in depth with a lower copper concentration compared to that of CIGS TF has been discovered. After KCN washing, removal of secondary phases can be achieved and a layer with abundant copper vacancy (V(Cu)) was left. Such compositional changes can be a benefit for a CIGS solar cell by promoting formation of Cd-occupied Cu sites (Cd(Cu)) at the CdS/CIGS interface and creates a type-inversion layer to enhance interface passivation and carrier extraction. The raised V(Cu) concentration and enhanced Cd diffusion in CIGS NTRs have been verified by energy dispersive spectrometry. Strengthened adhesion of Al:ZnO (AZO) thin film on CIGS NTRs capped with CdS has also been observed in SEM images and can explain the suppressed series resistance of the device with CIGS NTRs. Those improvements in electrical characteristics are the main factors for efficiency enhancement rather than antireflection.

13% efficiency hybrid organic/silicon-nanowire heterojunction solar cell via interface engineering.

Interface carrier recombination currently hinders the performance of hybrid organic-silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open-circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics.

Formation mechanism of SiGe nanorod arrays by combining nanosphere lithography and Au-assisted chemical etching.

The formation mechanism of SiGe nanorod (NR) arrays fabricated by combining nanosphere lithography and Au-assisted chemical etching has been investigated. By precisely controlling the etching rate and time, the lengths of SiGe NRs can be tuned from 300 nm to 1 µm. The morphologies of SiGe NRs were found to change dramatically by varying the etching temperatures. We propose a mechanism involving a locally temperature-sensitive redox reaction to explain this strong temperature dependence of the morphologies of SiGe NRs. At a lower etching temperature, both corrosion reaction and Au-assisted etching process were kinetically impeded, whereas at a higher temperature, Au-assisted anisotropic etching dominated the formation of SiGe NRs. With transmission electron microscopy and scanning electron microscopy analyses, this study provides a beneficial scheme to design and fabricate low-dimensional SiGe-based nanostructures for possible applications.