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.

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.

Nucleic Acid Amplification Circuit-Based Hydrogel (NACH) Assay for One-Step Detection of Metastatic Gastric Cancer-Derived Exosomal miRNA.

Gastric cancer (GC) is recognized as the fifth most prevalent malignant tumor worldwide. It is characterized by diverse clinical symptoms, treatment responses, and prognoses. In GC prognosis, the promotion of epithelial-mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, thereby triggering the dissemination of tumor cells. This study proposes a nucleic acid amplification circuit-based hydrogel (NACH) assay for identifying exosomal miRNA derived from metastatic GC. The NACH assay employs the rolling circle amplification method and targets miRNA-21, a tumor-related oncogene, and miRNA-99a, which promotes EMT. Specific amplification probes for each target are immobilized within the hydrogel, enabling a streamlined, one-step amplification reaction. The NACH assay exhibits a detection limit of 1 fm for miRNA-21 and miRNA-99a, thereby enabling rapid and highly sensitive on-site detection. Performance evaluation using exosomal miRNA extracted from cell culture media, mouse plasma, and human plasma revealed fluorescence intensity patterns similar to those obtained in qRT-PCR. Furthermore, deploying a custom-developed portable fluorometer for the NACH assay allows for diagnostic performance assessment and point-of-care testing using clinical samples from GC patients. These findings emphasize the potential of the NACH assay to be used as a robust tool for the genetic diagnosis of GC based on exosome detection.

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.

Measurement depth enhancement in terahertz imaging of biological tissues.

We demonstrate the use of a THz penetration-enhancing agent (THz-PEA) to enhance the terahertz (THz) wave penetration depth in tissues. The THz-PEA is a biocompatible material having absorption lower than that of water, and it is easily absorbed into tissues. When using glycerol as a THz-PEA, the peak value of the THz signal which was transmitted through the fresh tissue and reflected by a metal target, was almost doubled compared to that of tissue without glycerol. THz time-of-flight imaging (B-scan) was used to display the sequential glycerol delivery images. Enhancement of the penetration depth was confirmed after an artificial tumor was located below fresh skin. We thus concluded that the THz-PEA technique can potentially be employed to enhance the image contrast of the abnormal lesions below the skin.

Enhanced broadband and omni-directional performance of polycrystalline Si solar cells by using discrete multilayer antireflection coatings.

The performance enhancement of polycrystalline Si solar cells by using an optimized discrete multilayer anti-reflection (AR) coating with broadband and omni-directional characteristics is presented. Discrete multilayer AR coatings are optimized by a genetic algorithm, and experimentally demonstrated by refractive-index tunable SiO2 nano-helix arrays and co-sputtered (SiO2)x(TiO2)1₋x thin film layers. The optimized multilayer AR coating shows a reduced total reflection, leading to the high incident-photon-to-electron conversion efficiency over a correspondingly wide range of wavelengths and incident angles, offering a very promising way to harvest more solar energy by virtually any type of solar cells for a longer time of a day.

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.

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.

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.

Molecular imaging with terahertz waves.

We demonstrate a highly sensitive THz molecular imaging (TMI) technique involving differential modulation of surface plasmons induced on nanoparticles and obtain target specific in vivo images of cancers. This technique can detect quantities of gold nanoparticles as small as 15 µM in vivo. A comparison of TMI images with near infrared absorption images shows the superior sensitivity of TMI. Furthermore, the quantification property of TMI is excellent, being linearly proportional to the concentration of nanoparticles. The target specificity issue is also addressed at the ex vivo and cell levels. The high thermal sensitivity of TMI can help extend photonic-based photothermal molecular imaging researches from the in vitro level to the in vivo level. The TMI technique can be used for monitoring drug delivery processes and for early cancer diagnosis.

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.

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.

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.

Smart drug-loaded polymer gold nanoshells for systemic and localized therapy of human epithelial cancer.

Near-infrared-light-sensitive multifunctional smart drug-loaded polymer gold nanoshells are fabricated as advanced prototypes, composed of chemotherapeutic agents (therapeutic antibody and anticancer drug-loaded polymeric nanoparticles) for systemic chemotherapy of human epithelial cancer and a polymer-based gold nanoshell for localized photothermal treatment by NIR light.

Nanoparticle-enabled terahertz imaging for cancer diagnosis.

This paper demonstrates the principle of the nanoparticle-contrast-agent-enabled terahertz imaging (CATHI) technique, which yields a dramatic sensitivity of the differential signal from cancer cells with nanoparticles. The terahertz (THz) reflection signal increased beam by 20% in the cancer cells with nanoparticles of gold nano-rods (GNRs) upon their irradiation with a infrared (IR) laser, due to the temperature rise of water in cancer cells by surface plasma ploritons. In the differential mode, the THz signal from the cancer cells with GNRs was 30 times higher than that from the cancer cells without GNRs. As the high sensitivity is achieved by the surface plasmon resonance through IR laser irradiation, the resolution of the CATHI technique can be as good as a few microns and THz endoscopy becomes more feasible.

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.

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.

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.