Unveiling contact-mediated cellular crosstalk.

Cell-cell interactions orchestrate complex functions in multicellular organisms, forming a regulatory network for diverse biological processes. Their disruption leads to disease states. Recent advancements - including single-cell sequencing and spatial transcriptomics, coupled with powerful bioengineering and molecular tools - have revolutionized our understanding of how cells respond to each other. Notably, spatial transcriptomics allows us to analyze gene expression changes based on cell proximity, offering a unique window into the impact of cell-cell contact. Additionally, computational approaches are being developed to decipher how cell contact governs the symphony of cellular responses. This review explores these cutting-edge approaches, providing valuable insights into deciphering the intricate cellular changes influenced by cell-cell communication.

Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis.

Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment of mitochondrial proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, is enriched in the mitochondrial matrix of muscle tissues and is an NADPH oxidoreductase. Interactome analysis and in vitro enzymatic assays revealed an essential role for RTN4IP1 in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3. Rtn4ip1-knockout myoblasts had markedly decreased CoQ9 levels and impaired cellular respiration. Furthermore, muscle-specific knockdown of dRtn4ip1 in flies resulted in impaired muscle function, which was reversed by dietary supplementation with soluble CoQ. Collectively, these results demonstrate that RTN4IP1 is a mitochondrial NAD(P)H oxidoreductase essential for supporting mitochondrial respiration activity in the muscle tissue.

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease.

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.

Genome surgery using Cas9 ribonucleoproteins for the treatment of age-related macular degeneration.

RNA-guided genome surgery using CRISPR-Cas9 nucleases has shown promise for the treatment of diverse genetic diseases. Yet, the potential of such nucleases for therapeutic applications in nongenetic diseases is largely unexplored. Here, we focus on age-related macular degeneration (AMD), a leading cause of blindness in adults, which is associated with retinal overexpression of, rather than mutations in, the VEGFA gene. Subretinal injection of preassembled, Vegfa gene-specific Cas9 ribonucleoproteins (RNPs) into the adult mouse eye gave rise to mutagenesis at the target site in the retinal pigment epithelium. Furthermore, Cas9 RNPs effectively reduced the area of laser-induced choroidal neovascularization (CNV) in a mouse model of AMD. Genome-wide profiling of Cas9 off-target effects via Digenome-seq showed that off-target mutations were rarely induced in the human genome. Because Cas9 RNPs can function immediately after in vivo delivery and are rapidly degraded by endogenous proteases, their activities are unlikely to be hampered by antibody- and cell-mediated adaptive immune systems. Our results demonstrate that in vivo genome editing with Cas9 RNPs has the potential for the local treatment for nongenetic degenerative diseases, expanding the scope of RNA-guided genome surgery to a new dimension.

UV/Ozone-Treated and Sol-Gel-Processed Y2O3 Insulators Prepared Using Gelation-Delaying Precursors.

In this study, a Y2O3 insulator was fabricated via the sol-gel process and the effect of precursors and annealing processes on its electrical performance was studied. Yttrium(III) acetate hydrate, yttrium(III) nitrate tetrahydrate, yttrium isopropoxide oxide, and yttrium(III) tris (isopropoxide) were used as precursors, and UV/ozone treatment and high-temperature annealing were performed to obtain Y2O3 films from the precursors. The structure and surface morphologies of the films were characterized via grazing-incidence X-ray diffraction and scanning probe microscopy. Chemical component analysis was performed via X-ray spectroscopy. Electrical insulator characteristics were analyzed based on current density versus electrical field data and frequency-dependent dielectric constants. The Y2O3 films fabricated using the acetate precursor and subjected to the UV/ozone treatment showed a uniform and flat surface morphology with the lowest number of oxygen vacancy defects and unwanted byproducts. The corresponding fabricated capacitors showed the lowest current density (Jg) value of 10-8 A/cm2 at 1 MV/cm and a stable dielectric constant in a frequency range of 20 Hz-100 KHz. At 20 Hz, the dielectric constant was 12.28, which decreased to 10.5 at 105 Hz. The results indicate that high-quality, high-k insulators can be fabricated for flexible electronics using suitable precursors and the suggested low-temperature fabrication methods.

Effect of Electrochemically Active Top Electrode Materials on Nanoionic Conductive Bridge Y2O3 Random-Access Memory.

Herein, sol-gel-processed Y2O3 resistive random-access memory (RRAM) devices were fabricated. The top electrodes (TEs), such as Ag or Cu, affect the electrical characteristics of the Y2O3 RRAM devices. The oxidation process, mobile ion migration speed, and reduction process all impact the conductive filament formation of the indium-tin-oxide (ITO)/Y2O3/Ag and ITO/Y2O3/Cu RRAM devices. Between Ag and Cu, Cu can easily be oxidized due to its standard redox potential values. However, the conductive filament is easily formed using Ag TEs. After triggering the oxidation process, the formed Ag mobile metal ions can migrate faster inside Y2O3 active channel materials when compared to the formed Cu mobile metal ions. The fast migration inside the Y2O3 active channel materials successfully reduces the SET voltage and improves the number of programming-erasing cycles, i.e., endurance, which is one of the nonvolatile memory parameters. These results elucidate the importance of the electrochemical properties of TEs, providing a deeper understanding of how these factors influence the resistive switching characteristics of metal oxide-based atomic switches and conductive-metal-bridge-filament-based cells.

A tunnel coaxial 3D hyperspectral scanning system for underground mine investigation.

A hyperspectral scanning system was developed for three-dimensional (3D) surface mapping in underground spaces, such as mine shafts and tunnels. A hyperspectral line-scanning camera was mounted on the rotating driver unit coaxial with the tunnel to image both the mine wall and the ceiling. Uniform light was illuminated on the target surface to be imaged using a halogen lamp rotating together with the hyperspectral imaging sensor. Inertial Measuring Unit (IMU) was also attached to the sensor unit together with the hyperspectral camera so that sensor's geometric information could be acquired simultaneously during imaging. All sensor and controller units were mounted on a cart-type platform for easy movement in the tunnel, and a battery mounted on the platform supplied power for system operation and the halogen light source. The developed scanning system was tested in an actual mine, and 3D hyperspectral images of the internal surface of the mine shaft were successfully obtained.

Sol-Gel-Processed Y2O3-Al2O3 Mixed Oxide-Based Resistive Random-Access-Memory Devices.

Herein, sol-gel-processed Y2O3-Al2O3 mixed oxide-based resistive random-access-memory (RRAM) devices with different proportions of the involved Y2O3 and Al2O3 precursors were fabricated on indium tin oxide/glass substrates. The corresponding structural, chemical, and electrical properties were investigated. The fabricated devices exhibited conventional bipolar RRAM characteristics without requiring a high-voltage forming process. With an increase in the percentage of Al2O3 precursor above 50 mol%, the crystallinity reduced, with the amorphous phase increasing owing to internal stress. Moreover, with increasing Al2O3 percentage, the lattice oxygen percentage increased and the oxygen vacancy percentage decreased. A 50% Y2O3-50% Al2O3 mixed oxide-based RRAM device exhibited the maximum high-resistance-state/low-resistance-state (HRS/LRS) ratio, as required for a large readout margin and array size. Additionally, this device demonstrated good endurance characteristics, maintaining stability for approximately 100 cycles with a high HRS/LRS ratio (>104). The HRS and LRS resistances were also retained up to 104 s without considerable degradation.

Sol-Gel-Processed Y2O3 Multilevel Resistive Random-Access Memory Cells for Neural Networks.

Yttrium oxide (Y2O3) resistive random-access memory (RRAM) devices were fabricated using the sol-gel process on indium tin oxide/glass substrates. These devices exhibited conventional bipolar RRAM characteristics without requiring a high-voltage forming process. The effect of current compliance on the Y2O3 RRAM devices was investigated, and the results revealed that the resistance values gradually decreased with increasing set current compliance values. By regulating these values, the formation of pure Ag conductive filament could be restricted. The dominant oxygen ion diffusion and migration within Y2O3 leads to the formation of oxygen vacancies and Ag metal-mixed conductive filaments between the two electrodes. The filament composition changes from pure Ag metal to Ag metal mixed with oxygen vacancies, which is crucial for realizing multilevel cell (MLC) switching. Consequently, intermediate resistance values were obtained, which were suitable for MLC switching. The fabricated Y2O3 RRAM devices could function as a MLC with a capacity of two bits in one cell, utilizing three low-resistance states and one common high-resistance state. The potential of the Y2O3 RRAM devices for neural networks was further explored through numerical simulations. Hardware neural networks based on the Y2O3 RRAM devices demonstrated effective digit image classification with a high accuracy rate of approximately 88%, comparable to the ideal software-based classification (~92%). This indicates that the proposed RRAM can be utilized as a memory component in practical neuromorphic systems.

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice.

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis.

Room-Temperature High-Detectivity Flexible Near-Infrared Photodetectors with Chalcogenide Silver Telluride Nanoparticles.

Herein, flexible near-infrared (NIR) photodetectors were prepared using silver telluride (Ag5Te3) nanoparticles (NPs) for optoelectronic applications. For the main channel materials of the photodetectors, Ag5Te3 NPs were used, which were synthesized in an aqueous solution. Moreover, Ag5Te3 thin films were successfully fabricated on plastic substrates at 150 °C using redistributed Ag5Te3 NPs in aqueous inks. The crystal structure, chemistry, and optoelectronic properties of the synthesized photodetectors were studied. The fabricated flexible Ag5Te3-based photodetectors achieved a detectivity of 6.27 × 109 cm Hz1/2 W-1 (>109) at room temperature under ∼0.35% compressive and tensile strains. The obtained detectivity value exceeds those of two-dimensional inorganic layered material phototransistors-such as MoS2-or commercial thermistor bolometers at room temperature (∼109). Furthermore, the proposed novel method for the synthesis of Ag5Te3 thin films on plastic substrates can be applied to other Ag5Te3-based applications in the future.

Improved Environment Stability of Y2O3 RRAM Devices with Au Passivated Ag Top Electrodes.

In this study, we fabricated sol-gel-processed Y2O3-based resistive random-access memory (RRAM) devices. The fabricated Y2O3 RRAM devices exhibited conventional bipolar RRAM device characteristics and did not require the forming process. The long-term stability of the RRAM devices was investigated. The Y2O3 RRAM devices with a 20 nm thick Ag top electrode showed an increase in the low resistance state (LRS) and high resistance state (HRS) and a decrease in the HRS/LRS ratio after 30 days owing to oxidation and corrosion of the Ag electrodes. However, Y2O3 RRAM devices with inert Au-passivated Ag electrodes showed a constant RRAM device performance after 30 days. The 150 nm-thick Au passivation layer successfully suppressed the oxidation and corrosion of the Ag electrode by minimizing the chance of contact between water or oxygen molecules and Ag electrodes. The Au/Ag/Y2O3/ITO RRAM devices exhibited more than 300 switching cycles with a decent resistive window (>103). They maintained constant LRS and HRS resistances for up to 104 s, without significant degradation of nonvolatile memory properties for 30 days while stored in air.

Environmentally and Electrically Stable Sol-Gel-Deposited SnO2 Thin-Film Transistors with Controlled Passivation Layer Diffusion Penetration Depth That Minimizes Mobility Degradation.

This study examines the effect of the annealing time of the Y2O3 passivation layer on the electrical performances and bias stabilities of sol-gel-deposited SnO2 thin-film transistors (TFTs). The environmental stabilities of SnO2 TFTs were examined. After optimizing the Y2O3 passivation layers in SnO2 TFTs, the field-effect mobility was 7.59 cm2/V•s, the VTH was 9.16 V, the subthreshold swing (SS) was 0.88 V/decade, and the on/off-current ratio was approximately 1 × 108. VTH shifts were only -0.18 and +0.06 V under negative and positive bias stresses, respectively. The SnO2 channel layer thickness and oxygen-vacancy concentration in SnO2, which determine the carrier concentration, were successfully tuned by controlling the annealing time of the Y2O3 passivation layers. An extremely thin Y2O3 passivation layer effectively blocked external molecules, thus affecting the device performance. The electrical performance was maximized in SnO2 TFTs using a 15 min-annealed Y2O3 passivation layer. In this TFT, the field-effect mobility was maximally retained and the bias and environmental stabilities were sustained over 90 days of air exposure.

Flexible Sol-Gel-Processed Y2O3 RRAM Devices Obtained via UV/Ozone-Assisted Photochemical Annealing Process.

Flexible indium tin oxide (ITO)/Y2O3/Ag resistive random access memory (RRAM) devices were successfully fabricated using a thermal-energy-free ultraviolet (UV)/ozone-assisted photochemical annealing process. Using the UV/ozone-assisted photochemical process, the organic residue can be eliminated, and thinner and smother Y2O3 films than those formed using other methods can be fabricated. The flexible UV/ozone-assisted photochemical annealing process-based ITO/Y2O3/Ag RRAM devices exhibited the properties of conventional bipolar RRAM without any forming process. Furthermore, the pure and amorphous-phase Y2O3 films formed via this process showed a decreased leakage current and an increased high-resistance status (HRS) compared with the films formed using other methods. Therefore, RRAM devices can be realized on plastic substrates using a thermal-energy-free UV/ozone-assisted photochemical annealing process. The fabricated devices exhibited a resistive window (ratio of HRS/low-resistance status (LRS)) of >104, with the HRS and LRS values remaining almost the same (i.e., limited deterioration occurred) for 104 s and up to 102 programming/erasing operation cycles.

Enhanced Switching Reliability of Sol-Gel-Processed Y2O3 RRAM Devices Based on Y2O3 Surface Roughness-Induced Local Electric Field.

Sol-gel-processed Y2O3 films were used as active channel layers for resistive random access memory (RRAM) devices. The fabricated ITO/Y2O3/Ag RRAM devices exhibited the properties of conventional bipolar memory devices. A triethylamine stabilizer with a high vapor pressure and low surface tension was added to realize the local electric field area. During drying and high-temperature post-annealing processes, the large convective flow enhanced the surface elevation, and the increased -OH groups accelerated the hydrolysis reaction and aggregation. These phenomena afforded Y2O3 films with an uneven surface morphology and an increased surface roughness. The increased roughness of the Y2O3 films attributable to the triethylamine stabilizer enhanced the local electrical field, improved device reliability, and achieved successful repetition of the switching properties over an extended period.

Electrically driven lasing in light-emitting devices composed of n-ZnO and p-Si nanowires.

Electrically driven lasing was demonstrated in light-emitting devices composed of n-ZnO and p-Si nanowires (NWs). The ZnO NWs were synthesized by thermal chemical vapor deposition and the Si NWs were formed by crystallographic wet etching of a Si wafer. The p-n heterojunction devices were constructed using the NWs by the direct transfer and dielectrophoresis methods. At an excitation current of 2 µA, the electroluminescence spectrum showed lasing behavior, and this phenomenon was explained by the ZnO-nanostructure-related cavity property.

Investigation on light emission in light-emitting diodes constructed with n-ZnO and p-Si nanowires.

The light emission was investigated in light-emitting diodes (LEDs) constructed with n-ZnO and p-Si nanowires (NWs). ZnO NWs were synthesized by thermal chemical vapor deposition and Si NWs were formed by crystallographic wet etching of a Si wafer. The LEDs were fabricated using the NWs via dielectrophoresis (DEP) and direct transfer methods. The DEP method enabled to align the ZnO NW at the position that led to p-n heterojunction diodes by crossing with the transferred Si NW. The I-V curve of the p-n heterojunction diode showed the well-defined current-rectifying characteristic, with a turn-on voltage of 3 V. The electroluminescence spectrum in the dark showed the strong emission at approximately 385 nm and the broad emission centered at approximately 510 nm, at a forward bias of 30 V. Under the illumination of 325-nm-wavelength light, the luminescence intensity at 385 nm was dramatically enhanced, compared to that in the dark, probably due to the electric-field-induced enhancement of luminescence.

Performance Optimization of Nitrogen Dioxide Gas Sensor Based on Pd-AlGaN/GaN HEMTs by Gate Bias Modulation.

We investigated the sensing characteristics of NO2 gas sensors based on Pd-AlGaN/GaN high electron mobility transistors (HEMTs) at high temperatures. In this paper, we demonstrated the optimization of the sensing performance by the gate bias, which exhibited the advantage of the FET-type sensors compared to the diode-type ones. When the sensor was biased near the threshold voltage, the electron density in the channel showed a relatively larger change with a response to the gas exposure and demonstrated a significant improvement in the sensitivity. At 300 °C under 100 ppm concentration, the sensor's sensitivities were 26.7% and 91.6%, while the response times were 32 and 9 s at VG = 0 V and VG = -1 V, respectively. The sensor demonstrated the stable repeatability regardless of the gate voltage at a high temperature.

Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice.

Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe iSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate iSLET in a whole-body system, we express iSLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver iSLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together, iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.

Photolithography-Based Nanopatterning Using Re-entrant Photoresist Profile.

Photolithography based on optical mask is widely used in academic research laboratories due to its low cost, simple mechanism, and ability to pattern in micron-sized features on a wafer-scale area. Because the resolution is bound by diffraction limits of the light source, nanoscale patterning using photolithography requires short-wavelength light source combined with sophisticated optical elements, adding complexity and cost. In this paper, a novel method of subwavelength patterning process using conventional i-line mercury lamp is introduced, without the use of such advanced optical tools. The method utilizes the re-entrant geometry of image reversal photoresist produced from the developing process, where a secondary mask is generated by isotropically depositing a metal layer to cover the re-entrant profile of the photoresist. Removing the photoresist by applying ultrasonic vibrations in acetone bath uniformly cracks the metal layer at the sidewalls of the re-entrant profile, exposing the substrate with a reduced feature size. The width of the initial mask pattern can be reduced by 400 nm in a controlled manner, regardless of the original width choice. As a result, the method is shown to achieve sub-100 nm scale linear patterns compatible for both subsequent deposition process and dry-etching process. Our approach is applicable to various shapes of the patterns and can be used in electronic device fabrication requiring nanoscale lithography patterning, such as the gate fabrication of AlGaN/GaN high-electron-mobility transistor.