J-Net: Improved U-Net for Terahertz Image Super-Resolution.

Terahertz (THz) waves are electromagnetic waves in the 0.1 to 10 THz frequency range, and THz imaging is utilized in a range of applications, including security inspections, biomedical fields, and the non-destructive examination of materials. However, THz images have a low resolution due to the long wavelength of THz waves. Therefore, improving the resolution of THz images is a current hot research topic. We propose a novel network architecture called J-Net, which is an improved version of U-Net, to achieve THz image super-resolution. It employs simple baseline blocks which can extract low-resolution (LR) image features and learn the mapping of LR images to high-resolution (HR) images efficiently. All training was conducted using the DIV2K+Flickr2K dataset, and we employed the peak signal-to-noise ratio (PSNR) for quantitative comparison. In our comparisons with other THz image super-resolution methods, J-Net achieved a PSNR of 32.52 dB, surpassing other techniques by more than 1 dB. J-Net also demonstrates superior performance on real THz images compared to other methods. Experiments show that the proposed J-Net achieves a better PSNR and visual improvement compared with other THz image super-resolution methods.

Exploring the impedance-matching effect in terahertz reflection imaging of skin tissue.

Terahertz (THz) electromagnetic waves, known for their unique response to water, offer promising opportunities for next-generation biomedical diagnostics and novel cancer therapy technologies. This study investigated the impedance-matching effect, which enhances the efficiency of THz wave delivery into tissues and compensates for the signal distortion induced by the refractive index mismatch between the target and the sample substrate. Three candidate biocompatible materials, water, glycerol, and petroleum jelly were applied to a skin phantom and compared using THz two-dimensional imaging and time-of-flight imaging methods. Finally, we successfully demonstrated impedance-matching effect on mouse skin tissues.

Ptychographic lens-less birefringence microscopy using a mask-modulated polarization image sensor.

Birefringence, an inherent characteristic of optically anisotropic materials, is widely utilized in various imaging applications ranging from material characterizations to clinical diagnosis. Polarized light microscopy enables high-resolution, high-contrast imaging of optically anisotropic specimens, but it is associated with mechanical rotations of polarizer/analyzer and relatively complex optical designs. Here, we present a form of lens-less polarization-sensitive microscopy capable of complex and birefringence imaging of transparent objects without an optical lens and any moving parts. Our method exploits an optical mask-modulated polarization image sensor and single-input-state LED illumination design to obtain complex and birefringence images of the object via ptychographic phase retrieval. Using a camera with a pixel size of 3.45 µm, the method achieves birefringence imaging with a half-pitch resolution of 2.46 µm over a 59.74 mm2 field-of-view, which corresponds to a space-bandwidth product of 9.9 megapixels. We demonstrate the high-resolution, large-area, phase and birefringence imaging capability of our method by presenting the phase and birefringence images of various anisotropic objects, including a monosodium urate crystal, and excised mouse eye and heart tissues.

C5α secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres.

PURPOSE: Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model. METHODS: PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5α, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays. RESULTS: Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5α, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5α, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5α. CONCLUSIONS: Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5α as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.

Terahertz Spectral Properties of PEO-Based Anti-Adhesion Films Cross-Linked by Electron Beam Irradiation.

We investigated the spectral property changes in anti-adhesion films, which were cross-linked and surface-modified through electron beam irradiation, using terahertz time-domain spectroscopy (THz-TDS). Polyethylene oxide (PEO), which is a biocompatible and biodegradable polymer, was the main component of these anti-adhesion films being manufactured for testing. The terahertz characteristics of the films were affected by the porosity generated during the freeze-drying and compression processes of sample preparation, and this was confirmed using optical coherence tomography (OCT) imaging. An anti-adhesion polymer film made without porosity was measured by using the THz-TDS method, and it was confirmed that the refractive index and absorption coefficient were dependent on the crosslinking state. To our knowledge, this is the first experiment on the feasibility of monitoring cross-linking states using terahertz waves. The THz-TDS method has potential as a useful nondestructive technique for polymer inspection and analysis.

miRNA sensing hydrogels capable of self-signal amplification for early diagnosis of Alzheimer's disease.

Alzheimer's disease (AD), one of the leading senile disorders in the world, causes severe memory loss and cognitive impairment. To date, there is no clear cure for AD. However, early diagnosis and monitoring can help mitigate the effects of this disease. In this study, we reported a platform for diagnosing early-stage AD using microRNAs (miRNAs) in the blood as biomarkers. First, we selected an appropriate target miRNA (miR-574-5p) using AD model mice (4-month-old 5XFAD mice) and developed a hydrogel-based sensor that enabled high-sensitivity detection of the target miRNA. This hydrogel contained catalytic hairpin assembly (CHA) reaction-based probes, leading to fluorescence signal amplification without enzymes and temperature changes, at room temperature. This sensor exhibited high sensitivity and selectivity, as evidenced by its picomolar-level detection limit (limit of detection: 1.29 pM). Additionally, this sensor was evaluated using the plasma of AD patients and non-AD control to validate its clinical applicability. Finally, to use this sensor as a point-of-care-testing (POCT) diagnostic system, a portable fluorometer was developed and verified for feasibility of application.

MAX-Phase Films Overcome Scaling Limitations to the Resistivity of Metal Thin Films.

Metal thin films have been widely used as conductors in semiconductor devices for several decades. However, the resistivity of metal thin films such as Cu and TiN increases substantially (>1000%) as they become thinner (<10 nm) when using high-density integration to improve device performance. In this study, the resistivities of MAX-phase V2AlC films grown on sapphire substrates exhibited a significantly weaker dependence on the film thickness than conventional metal films that resulted in a resistivity increase of only 30%, as the V2AlC film thickness decreased from approximately 45 to 5 nm. The resistivity was almost identical for film thicknesses of 10-50 nm. The small change in the resistivity of V2AlC films with decreasing film thickness originated from the highly ordered crystalline quality and a small electron mean free path (11-13.6 nm). Thus, MAX-phase thin films have great potential for advanced metal technology applications to overcome the current scaling limitations of semiconductor devices.

Label-free brain tissue imaging using large-area terahertz metamaterials.

Terahertz (THz) imaging technology has shown significant potential for use in biomedical imaging owing to its non-ionizing characteristics by its low photon energy and its ultrabroadband spectral comparability with many molecular vibrational resonances. However, despite the significant advantage of being able to identify bio-materials in label-free configurations, most meaningful signals are buried by huge water absorption, thus it is very difficult to distinguish them using the small differences in optical constants at THz regime, limiting the practical application of this technology. Here, we demonstrate advanced THz imaging with enhanced color contrast by the use of THz field that is localized and enhanced by a nanometer-scale slot array. THz images of a biological specimen, such as mouse brain tissue and fingerprint, on a nano-slot array-based metamaterial sensing chip, which is elaborately fabricated in large-area, show a higher contrast and clearer boundary information in reflectance without any labeling. A reliable numerical solution to find accurate optical constants using THz nano-slot resonance for the quantitative analysis of target bio-specimens is also introduced. Finally, the precise optical properties of real bio-samples and atlas information are provided for specific areas where amyloid beta proteins, known to cause dementia, have accumulated in a mouse brain.

Anodically Induced Chemical Etching of GaAs Wafers for a GaAs Nanowire-Based Flexible Terahertz Wave Emitter.

A generic top-down approach for the preparation of extended arrays of high-aspect ratio GaAs nanowires (NWs) with different crystallographic orientations (i.e., [100] or [111]) and morphologies (i.e., porous, nonporous, tapered, or awl-like NWs) is reported. The method is based on the anodically induced chemical etching (AICE) of GaAs wafers in an oxidant-free aqueous HF solution at room temperature by using a patterned metal mesh and allows us to overcome the drawbacks of conventional metal-assisted chemical etching (MACE) processes. Local oxidative dissolution of GaAs in contact with a metal is achieved by externally injecting holes (h+) into the valence band (VB) of GaAs through the metal mesh. It is found that injection of holes (h+) through direct GaAs contact, rather than the metal mesh, does not yield uniform nanowires but porosify GaAs wafers due to the high cell potential. On the basis of experiments and numerical simulation for the spatial distribution of an electric field, a phenomenological model that explains the formation of GaAs NWs and their porosification behaviors is proposed. GaAs NWs exhibit excellent terahertz (THz) wave emission properties, which vary with either the length or the shape of the nanowires. By taking advantage of controlled porosification and easy transfer of GaAs NWs to foreign substrates, a flexible THz wave emitter is realized.

Spheroid-Induced Epithelial-Mesenchymal Transition Provokes Global Alterations of Breast Cancer Lipidome: A Multi-Layered Omics Analysis.

Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of SCD, ACOX3, and FADS1 and the down-regulation of PTPLB, PECR, and ELOVL2 were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of ELOVL2. Following mechanistic study confirmed the up-regulation of SCD and down-regulation of PTPLB, PECR, ELOVL2, and ELOVL3 in the spheroid cells. Furthermore, the depletion of ELOVL2 induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of ELOVL2 in basal-like phenotypes. Breast cancer patients with low ELOVL2 expression exhibited poor prognoses (HR = 0.76, CI = 0.67-0.86). Collectively, ELOVL2 expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of ELOVL2 induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes.

Epitaxial van der Waals Contacts between Transition-Metal Dichalcogenide Monolayer Polymorphs.

We have achieved heteroepitaxial stacking of a van der Waals ( vdW) monolayer metal, 1T'-WTe2, and a semiconductor, 2H-WSe2, in which a distinctively low contact barrier was established across a clean epitaxial vdW gap. Our epitaxial 1T'-WTe2 films were identified as a semimetal by low temperature transport and showed the robust breakdown current density of 5.0 × 107 A/cm2. In comparison with a series of planar metal contacts, our epitaxial vdW contact was identified to possess intrinsic Schottky barrier heights below 100 meV for both electron and hole injections, contributing to superior ambipolar field-effect transistor (FET) characteristics, i.e., higher FET mobilities and higher on-off current ratios at smaller threshold gate voltages. We discuss our observations around the critical roles of the epitaxial vdW heterointerfaces, such as incommensurate stacking sequences and absence of extrinsic interfacial defects that are inaccessible by other contact methods.

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death.

BACKGROUND: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. METHODS: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. RESULTS: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. CONCLUSION: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

Measuring water contents in animal organ tissues using terahertz spectroscopic imaging.

We investigated the water contents in several organ tissues such as the liver, spleen, kidney, and brain tissue of rats using the terahertz spectroscopic imaging technique. The water contents of the tissues were determined by using a simple equation containing the absorption coefficients of fresh and lyophilized tissues and water. We compared the measured water contents with the difference in mass of tissues before and after lyophilization. All results showed a good match except for the kidney, which has several Bowman's capsules.

Small bowel obstruction from distant metastasis of primary breast cancer: a case report.

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

Photodynamic therapy inhibits melanogenesis through paracrine effects by keratinocytes and fibroblasts.

Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In this study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in vivo. Exposure of MCs to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing MCs to conditioned media of PDT-treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due to a decreased release of melanocyte-stimulating cytokines such as Kit ligand and hepatocyte growth factor from these cells. Furthermore, we observed that PDT reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting the clinical importance of skin whitening by PDT.

Terahertz reflectometry imaging for low and high grade gliomas.

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

Improvement of Terahertz Wave Radiation for InAs Nanowires by Simple Dipping into Tap Water.

We report improvement of terahertz (THz) wave radiation for Si-based catalyst-free InAs nanowires (NWs) by simple dipping into tap water (DTW). In addition, the possibility of using InAs NWs as a cost-effective method for biomedical applications is discussed by comparison to bulk InAs. The peak-to-peak current signals (PPCSs) of InAs NWs measured from THz time-domain spectroscopy increased with increasing NW height. For example, the PPCS of 10 µm-long InAs NWs was 2.86 times stronger than that of 2.1 µm-long NWs. The THz spectra of the InAs NWs obtained by applying a fast Fourier transformation to the current signals showed a main frequency of 0.5 THz, which can be applied to a variety of medical imaging systems. After the DTW process, structural variation was not observed for 2.1 µm-long InAs NWs. However, the top region of several InAs NWs with heights of 4.6 and 5.8 µm merged into a conical structure. InAs NWs with a height of 10 µm resulted in a bundle feature forming above the conical shape, where the length of bundle region was 4 µm. After the DTW process, the PPCS for 10 µm-long InAs NWs increased by 15 percent compared to that of the as-grown case.

Terahertz otoscope and potential for diagnosing otitis media.

We designed and fabricated a novel terahertz (THz) otoscope to help physicians to diagnose otitis media (OM) with both THz diagnostics and conventional optical diagnostics. We verified the potential of this tool for diagnosing OM using mouse skin tissue and a human tympanic membrane samples prior to clinical application.

Unassisted photoelectrochemical water splitting exceeding 7% solar-to-hydrogen conversion efficiency using photon recycling.

Various tandem cell configurations have been reported for highly efficient and spontaneous hydrogen production from photoelectrochemical solar water splitting. However, there is a contradiction between two main requirements of a front photoelectrode in a tandem cell configuration, namely, high transparency and high photocurrent density. Here we demonstrate a simple yet highly effective method to overcome this contradiction by incorporating a hybrid conductive distributed Bragg reflector on the back side of the transparent conducting substrate for the front photoelectrochemical electrode, which functions as both an optical filter and a conductive counter-electrode of the rear dye-sensitized solar cell. The hybrid conductive distributed Bragg reflectors were designed to be transparent to the long-wavelength part of the incident solar spectrum (λ>500 nm) for the rear solar cell, while reflecting the short-wavelength photons (λ<500 nm) which can then be absorbed by the front photoelectrochemical electrode for enhanced photocurrent generation.

Feasibility of terahertz reflectometry for discrimination of human early gastric cancers.

We have investigated the feasibility of THz time-domain reflectometry for the discrimination of human early gastric cancer (EGC) from the normal gastric region. Eight fresh EGC tissues, which were resected by endoscopic submucosal dissection, were studied. Of them, six lesions were well discriminated on THz images and the regions well correlated with tumor regions on pathologically mapped images. Four THz parameters could be suggested for quantitative discrimination of EGCs.