Preparation and Characterization of Bilayer Polymer-Dispersed Liquid Crystals Doped with Gd2O3 Nanoparticles and Rhodamine B Base Fluorescent Dye.

Using the polymerization-induced phase separation (PIPS) method, bilayer polymer-dispersed liquid crystal (PDLC) films with a PDLC-PVA-PDLC structure were prepared in this work. It was found that all PDLC performance indexes were affected by polymer mesh size after comparing the microscopic morphology and electro-optical properties of samples with different monomer ratios. Gd2O3 nanoparticles and rhodamine B base fluorescent dyes introduced into the bilayer PDLC optimized the samples' electro-optical properties and developed new functionalities. In addition, the bilayer PDLC doped with Gd2O3 and rhodamine B base held excellent progressive driving functions as well as stable durability properties. Samples doped with Gd2O3 nanoparticles and rhodamine B base also produced excellent anti-counterfeiting effects under UV irradiation at different angles, further exploiting the application potential of PDLC.

Preparation of Progressive Driving Bilayer Polymer-Dispersed Liquid Crystals Possessing a PDLC-PVA-PDLC Structure.

In this paper, the bilayer polymer-dispersed liquid crystals possessing a PDLC-PVA-PDLC structure were prepared by integrating two monolayer PDLCs. The effect of the polymer mesh size on the electro-optical properties of a bilayer PDLC was investigated by comparing the micro-morphology and electro-optical curves under different polymerization conditions. In addition, the impact of doping MoO2 nanoparticles with surface modification on the comprehensive performance of the bilayer PDLC was further researched. The contrast ratio of the bilayer PDLC prepared under the optimal conditions was improved by more than 90% and still maintained excellent progressive driving performance. Therefore, the development of a bilayer PDLC with optimal electro-optical properties will significantly enhance the technological prospects for the application of PDLC-based devices in smart windows, displays, and flexible devices.

Blocked metabotropic glutamate receptor 5 enhances chemosensitivity in hepatocellular carcinoma and attenuates chemotoxicity in the normal liver by regulating DNA damage.

DNA damaging agents are used as chemotherapeutics in many cancers, including hepatocellular carcinoma (HCC). However, they are associated with problems such as low sensitivity to chemotherapy and the induction of liver injury, underscoring the need to identify new therapies. Here, we investigated the differential regulatory effect of metabotropic glutamate receptor 5 (mGlu5) on chemosensitivity in HCC and chemotoxicity to the normal liver. The expression of mGlu5 was higher in HCC than in the normal liver, and correlated with poor prognosis according to The Cancer Genome Atlas database and Integrative Molecular Database of Hepatocellular Carcinoma. Cisplatin, oxaliplatin or methyl methanesulfonate (MMS) caused cell death by decreasing mGlu5 expression in HCC cells and increased mGlu5 expression in hepatic cells. In HCC cells, inhibition of mGlu5 aggravated MMS-induced DNA damage by increasing intracellular Ca2+ overload and mitogen-activated protein kinase (MAPK) activation, thereby promoting cell death, and activation of mGlu5 rescued the effect of MMS. However, in hepatic cells, mGlu5 inhibition alleviated MMS-induced DNA damage by downregulating Ca2+-derived MAPK pathways to advance hepatic cell survival. The opposite effects of mGlu5 overexpression or knockdown on MMS-induced DNA damage supported that cell death is a result of the differential regulation of mGlu5 expression. Inhibition of mGlu5 increased chemosensitivity and decreased chemotoxicity in a rat tumor model. This study suggests that mGlu5 inhibition could act synergistically with HCC chemotherapeutics with minimal side effects, which may improve the treatment of patients with HCC in the future.

Hepatic stellate cell mediates transcription of TNFSF14 in hepatocellular carcinoma cells via H2S/CSE-JNK/JunB signaling pathway.

Hepatic stellate cells (HSC) and hydrogen sulfide (H2S) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing H2S remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of H2S on biological functions and JNK/JunB-TNFSF14 signaling pathway. Specimens from HCC patients were analyzed by RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14 and CSE. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Based on the FCM and CCK-8 results, we found the LX-2 cells were able to induce HCC cells apoptosis through releasing H2S. RNA-sequencing, RT-qPCR, and Western blotting results showed that TNFSF14 gene was upregulated in both LX-2 and NaHS group. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of p-JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, TNFSF14 expression in HCC tissues was lower than the adjacent tissue. HCC patients with low expression of TNFSF14 had higher malignant degree and poor prognosis. In summary, demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.

A Bioinformatics Study of Differentially Expressed Genes in Microarrays of Dorsal Root Ganglia from Rat Models of Neuropathic Pain.

BACKGROUND Neuropathic pain is a significant complication of nerve injury. This study aimed to conduct bioinformatics analysis of differentially expressed genes (DEGs) in microarrays of dorsal root ganglia (DRG) from rat models of neuropathic pain, based on 4 GEO datasets: GSE15041, GSE38038, GSE2884, and GSE24982. MATERIAL AND METHODS We retrieved the 4 microarray datasets, which were generated using DRG samples collected in the early and late stages after spinal nerve ligation in rats. The common DEGs (co-DEGs) were identified and then subjected to Gene Ontology, pathway enrichment, and Protein-protein interaction network analyses. Drugs targeting the identified hub genes were analyzed using the Drug Gene Interaction Database. RESULTS We identified 75 early-stage co-DEGs, which were enriched in chromosome segregation and protein catabolic processes, cytosol and extracellular exosome components, and ATP binding function and metabolic pathways. We identified 29 late-stage co-DEGs, which were enriched in protein tetramerization and drug responses, extracellular and membrane raft components, and protein homodimerization and binding functions and calcium signaling pathways. We also identified several hub genes, including Snap25 (synaptosome-associated protein of 25 kDa), Vamp2 (vesicle associated membrane protein 2), and Sf3b1 (splicing factor 3b subunit 1), the first 2 of which can be targeted by botulinum toxin derivatives. SNAP25 plays a role in synaptogenesis and the exocytotic release of neurotransmitters, and VAMP2 participates in neurotransmitter release at a step between docking and fusion. CONCLUSIONS The present study reveals new mechanisms of neuropathic pain and provides key genes, including SNAP25 and VAMP2, for future studies.

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing.

Background and Aims: The multiple renal cysts (MRC) occur in some patients with noncirrhotic portal hypertension (NCPH) could be a subset of ciliopathy. However, the potential genetic influencers and/or determinants in NCPH with MRC are largely unknown. The aim of this study was to explore the potential candidate variants/genes associated with those patients. Methods: 8,295 cirrhotic patients with portal hypertension were enrolled in cohort 1 and 267 patients affected with NCPH were included in cohort 2. MRC was defined as at least two cysts in both kidneys within a patient detected by ultrasonography or computed tomography. Whole-genome sequencing (WGS) was performed in nine patients (four from cohort 1 and five from cohort 2). Then we integrated WGS and publicly available single-cell RNA sequencing (scRNA-seq) to prioritize potential candidate genes. Genes co-expressed with known pathogenic genes within same cell types were likely associated NCPH with MRC. Results: The prevalence of MRC in NCPH patients (19.5%, 52/267) was significantly higher than cirrhotic patients (6.2%, 513/8,295). Further, the clinical characteristics of NCPH patients with MRC were distinguishable from cirrhotic patients, including late-onset, more prominent portal hypertension however having preserved liver functions. In the nine whole genome sequenced patients, we identified three patients with early onset harboring compound rare putative pathogenic variants in the known disease gene PKHD1. For the remaining patients, by assessing cilia genes profile in kidney and liver scRNA-seq data, we identified CRB3 was the most co-expressed gene with PKHD1 that highly expressed in ureteric bud cell, kidney stromal cell and hepatoblasts. Moreover, we found a homozygous variant, CRB3 p.P114L, that caused conformational changes in the evolutional conserved domain, which may associate with NCPH with MRC. Conclusion: ScRNA-seq enables unravelling cell heterogeneity with cell specific gene expression across multiple tissues. With the boosting public accessible scRNA-seq data, we believe our proposed analytical strategy would effectively help disease risk gene identification.

CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis.

Hepatic inflammation is the driving force for the development and progression of NASH. Treatment targeting inflammation is believed to be beneficial. In this study, adoptive transfer of CD4+ T cells converted double negative T cells (cDNT) protects mice from diet-induced liver fat accumulation, lobular inflammation and focal necrosis. cDNT selectively suppress liver-infiltrating Th17 cells and proinflammatory M1 macrophages. IL-10 secreted by M2 macrophages decreases the survival and function of cDNT to protect M2 macrophages from cDNT-mediated lysis. NKG2A, a cell inhibitory molecule, contributes to IL-10 induced apoptosis and dampened suppressive function of cDNT. In conclusion, ex vivo-generated cDNT exert potent protection in diet induced obesity, type 2 diabetes and NASH. The improvement of outcome is due to the inhibition on liver inflammatory cells. This study supports the concept and the feasibility of potentially utilizing this autologous immune cell-based therapy for the treatment of NASH.

Tunable wideband slot antennas based on printable graphene inks.

Nano-materials could endow electronics with some new functionalities. A slot antenna with a tunable bandwidth, consisting of a planar slot antenna with graphene at the end and a gap located between the ground and a small patch, is proposed in this study. The printed graphene inks deposited onto the antenna are made of graphene powder and graphene oxide aqueous dispersion. Graphene oxide sheets function as effective surfactants providing assistance to form uniform inks; meanwhile, the tailored blending proportions endow the graphene inks with optimized original resistances. Dried graphene inks display alterable electrical resistance under DC voltages and the variation in the resistance affects the radiation of the antenna. The slot antenna realizes an operating bandwidth (reflection coefficient |S11| < -10 dB) from 2.83 GHz to 6 GHz and a maximum frequency shift of 0.54 GHz after applying a DC voltage of less than 15 V. The graphene inks reported in this work integrate the dual advantages of graphene and graphene oxide. They not only provide stable and tunable graphene solution to antennas, but also could expand their applications in many other fields of electronic devices.

Interactive floating full-parallax digital three-dimensional light-field display based on wavefront recomposing.

Advanced three-dimensional (3D) imaging techniques can acquire high-resolution 3D biomedical and biological data, but available digital display methods show this data in restricted two dimensions. 3D light-field displays optically reconstruct realistic 3D image by carefully tailoring light fields, and a natural and comfortable 3D sense of real objects or scenes is expected. An interactive floating full-parallax 3D light-field display with all depth cues is demonstrated with 3D biomedical and biological data, which are capable of achieving high efficiency and high image quality. A compound lens-array with two pieces of lens in each lens unit is designed and fabricated to suppress the aberrations and increase the viewing angle. The optimally designed holographic functional screen is used to recompose the light distribution from the lens-array. The imaging distortion can be decreased to less than 1.9% from more than 20%. The real time interactive floating full-parallax 3D light-field image with the clear displayed depth of 30 cm can be perceived with the right geometric occlusion and smooth parallax in the viewing angle of 45°, where 9216 viewpoints are used.

Anti-dispersion phase-tunable microwave mixer based on a dual-drive dual-parallel Mach-Zehnder modulator.

An optically-controlled phase-tunable microwave mixer based on a dual-drive dual-parallel Mach-Zehnder modulator (DDDP-MZM) is proposed, which supports wideband phase shift and immunity to power fading caused by chromatic dispersion. By using carrier-suppressed single side-band (CS-SSB) modulation for the local oscillator (LO) signal and carrier-suppressed double side-band (CS-DSB) modulation for the input signal, no vector superposition for the same output microwave frequency occurs, making the system immune from power fading caused by chromatic dispersion. Phase tuning is achieved by shifting the phase of the LO signal, and direct electrical tuning of the wideband microwave input signal is avoided, thus supporting large working bandwidth. A phase-shifted down-conversion experiment is carried out, where a phase shift with 0 ~390° and down-conversion are achieved with a phase variation of less than 5° and power variation less than 3.5 dBm when the input signal sweeps between 12 ~16 GHz. The mixer is simple and power-efficient since it uses a single compact modulator, and does not require any optical filters. No power notches are observed in the output microwave spectrum, proving that the dispersion-related frequency-selective fading is mitigated.

Manipulating of Different-Polarized Reflected Waves with Graphene-based Plasmonic Metasurfaces in Terahertz Regime.

A graphene-based plasmonic metasurface which can independently control different polarized electromagnetic waves with reasonably small losses in terahertz regime is proposed and demonstrated in this paper. This metasurface is composed of graphene based elements. Owing to anisotropic plasmonic resonance of the graphene-based elements, the reflected phases and magnitudes of orthogonally polarized waves can be independently controlled by varying dimensions of the element. Four types of graphene-based plasmonic metasurfaces with different reflected phases distributions are synthesized and simulated, exhibiting diverse functions such as polarized beam splitting, beam deflection, and linear-to-circular polarization conversion. The simulation results demonstrate excellent performances as theoretical expectation. The proposed graphene-based plasmonic metasurface can be applied to realize extremely light-weight, ultra-compact, and high-performances electromagnetic structures for diverse terahertz applications.

Can a fibrotic liver afford epithelial-mesenchymal transition?

The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor ß (TGF-ß) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients. Based on the available data and our clinical observations we hypothesize that EMT-like alterations in liver cirrhosis are a side effect of high levels of TGF-ß and other pro-fibrotic mediators rather than a biological process converting functional parenchyma, i.e., hepatocytes, into myofibroblasts at a time when essential liver functions are deteriorating.

A novel tri-band T-junction impedance-transforming power divider with independent power division ratios.

In this paper, a novel L network (LN) is presented, which is composed of a frequency-selected section (FSS) and a middle stub (MS). Based on the proposed LN, a tri-band T-junction power divider (TTPD) with impedance transformation and independent power division ratios is designed. Moreover, the closed-form design theory of the TTPD is derived based on the transmission line theory and circuit theory. Finally, a microstrip prototype of the TTPD is simulated, fabricated, and measured. The design is for three arbitrarily chosen frequencies, 1 GHz, 1.6 GHz, and 2.35 GHz with the independent power division ratios of 0.5, 0.7, and 0.9. The measured results show that the fabricated prototype is consistent with the simulation, which demonstrates the effectiveness of this proposed design.

An independently reconfigurable dual-mode dual-band substrate integrated waveguide filter.

In this paper, a novel perturbation approach for implementing the independently reconfigurable dual-mode dual-band substrate integrated waveguide (SIW) filter is proposed. Dual-frequency manipulation is achieved by adding perturbation via-holes (the first variable) and changing the lengths of the interference slot (the second variable) in each cavity. The independent control of the upper passband only depends on the second variable while the lower passband is independently tuned by combining the two variables. Using such a design method, a two-cavity dual-band SIW filter is designed and experimentally assessed with four via-holes and an interference slot in each cavity. The dual-band filter not only has a frequency ratio (fR) ranging from 1.14 to 1.58 but also can be considered as a single passband one with a tunable range of 40.5% from 1.26 GHz to 2.12 GHz. The scattering parameters |S11| and |S21| are in the range of -10.72 dB to -37.17 dB and -3.67 dB to -7.22 dB in the operating dual bands, respectively. All the simulated and measured results show an acceptable agreement with the predicted data.

GPC-3 in hepatocellular carcinoma: current perspectives.

Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, attaches to the cell membrane and is frequently observed to be elevated in hepatocellular carcinoma (HCC). However, GPC3 is not detected in normal liver tissues and benign liver lesions. Consequently, GPC3 is currently being used as a diagnostic biomarker and HCC-specific positron emission computed tomography probe to identify HCCs in normal liver tissues and benign liver lesions. The overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for HCC patients. In addition, GPC3 promotes HCC growth and metastasis by activating the canonical Wnt and other signaling pathways. Targeting of GPC3, including GC33, HN3 and YP7, might offer new immunotherapeutic tools for HCC treatment.

Dual-Band Dual-Mode Substrate Integrated Waveguide Filters with Independently Reconfigurable TE101 Resonant Mode.

A novel perturbation approach using additional metalized via-holes for implementation of the dual-band or wide-band dual-mode substrate integrated waveguide (SIW) filters is proposed in this paper. The independent perturbation on the first resonant mode TE101 can be constructed by applying the proposed perturbation approach, whereas the second resonant mode TE102 is not affected. Thus, new kinds of dual-band or wide-band dual-mode SIW filters with a fixed or an independently reconfigurable low-frequency band have been directly achieved. In order to experimentally verify the proposed design method, four two-cavity dual-band SIW filters, which have different numbers of perturbation via-holes in each cavity, and a two-cavity dual-band SIW filter, which includes four via-holes and eight reconfigurable states in each cavity, are designed and experimentally assessed. The measured results indicate that the available frequency-ratio range from 1 to 1.3 can be realized by using four two-cavity dual-band SIW filters. The center frequency of the first band can be tuned from 4.61 GHz to 5.24 GHz, whereas the center frequency of the second one is fixed at around 6.18 GHz for the two-cavity dual-band SIW filter with four reconfigurable states via-holes. All the simulated and measured results show an acceptable agreement with the predicted data.

A Generalized Lossy Transmission-Line Model for Tunable Graphene-Based Transmission Lines with Attenuation Phenomenon.

To investigate the frequency shift phenomenon by inserting graphene, a generalized lossy transmission-line model and the related electrical parameter-extraction theory are proposed in this paper. Three kinds of graphene-based transmission lines with attenuation phenomenon including microstrip line, double-side parallel strip line, and uniplanar coplanar waveguide are analyzed under the common conditions where different chemical potentials are loaded on graphene. The values of attenuation constant and phase constant, and the real and imaginary parts of the characteristic impedance of transmission lines are extracted to analyze in details. When the attenuation constant and the reactance part of the characteristic impedance are approximately equal to zero, this kind of transmission line has low or zero insertion loss. On the contrary, the transmission line is under the radiation mode with obvious insertion loss. The phase constant changes linearly under the transmission mode and can be varied with changing of chemical potentials which attributes to the property of frequency tunability. Furthermore, a bandwidth reconfigurable uniplanar coplanar waveguide power divider is simulated to demonstrate that this theory can be applied to the design of three-port devices. In summary, this work provides a strong potential approach and design theory to help design other kinds of terahertz and mid-infrared reconfigurable devices.

Three-dimensional multiway power dividers based on transformation optics.

The two-dimensional (2D) or three-dimensional (3D) multiway power dividers based on transformation optical theory are proposed in this paper. It comprises of several nonisotropic mediums and one isotropic medium without any lumped and distributed elements. By using finite embedded coordinate transformations, the incident beam can be split and bent arbitrarily in order to achieve effective power division and transmission. In addition, the location of the split point can be employed to obtain unequal power dividers. Finally, several typical examples of the generalized power divider without limitation in 3D space are performed, which shows that the proposed power divider can implement required functions with arbitrary power division and arbitrary transmission paths. The excellent simulated results verify the novel design method for power dividers.

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3 contributes to the progress of HCC is largely unclear. The present study investigated the association between GPC3 expression and HCC clinicopathological characteristics, and particularly focused on the role and underlying mechanisms of GPC3 in HCC epithelial-mesenchymal transition (EMT). Remarkably elevated expression of GPC3 was demonstrated in HCC tumor tissues compared with paired non-tumor tissues in 45 patients with HCC by quantitative real-time PCR, immunohistochemistry, and western blotting, respectively. Furthermore, the tissue expression of GPC3 was increased during HCC progression from Barcelona Clinic Liver Cancer stage A or B to stage C. The enhanced levels of GPC3 in HCC tumor tissues were tightly correlated to the expression of the EMT-associated proteins and tumor vascular invasion. Patients with GPC3-high expression in tumor tissues displayed significantly shorter survival time than those with GPC3-low expression (P=0.001). Consistent with the findings in patients, HepG2 cells, which expressed high levels of GPC3, showed stronger capacity of migration and significant EMT-like changes when compared to those HCC cells with low levels of GPC3, e.g., Hep3B and Huh7 in scratch, Transwell assays and western blotting. Furthermore, administration with exogenous GPC3 in HCC cells activated extracellular signal-regulated kinase (ERK) and significantly enhanced cell migration and invasion. The behavior was significantly inhibited by the ERK inhibitor PD98059. Together, our studies show that GPC3 contributes to HCC progression and metastasis through impacting EMT of cancer cells, and the effects of GPC3 are associated with ERK activation.