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Abstract The self-consistent field (SCF) generation of the three-dimensional (3D) electron density distribution (ρ) represents a fundamental aspect of density functional theory (DFT) and related first-principles calculations, and how one can shorten or bypass the SCF loop represents a critical question in electronic structure theory from both practical and fundamental standpoints. Herein, a machine learning strategy, DeepSCF, is presented in which the map between the SCF ρ and the initial guess density (ρ 0) constructed by the summation of neutral atomic densities is learned using 3D convolutional neural networks (CNNs). High accuracy and transferability of DeepSCF are achieved by first encoding ρ 0 on a 3D grid and then expanding the input features to include atomic fingerprints beyond ρ 0. The prediction of the residual density (δρ) rather than ρ itself is targeted, and given that δρ is indicative of chemical bonding information, a dataset of small-sized organic molecules featuring diverse bonding characters is adopted. The fidelity of DeepSCF is finally enhanced by subjecting the atomic geometries of the dataset to random rotations and strains. The effectiveness of DeepSCF is demonstrated using a complex carbon nanotube-based DNA sequencer model. This work evidences that the nearsightedness in electronic structure can be optimally represented via the spatial locality in CNNs, offering insight into the success of various machine learning-based atomistic materials simulations.

Abstract Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Abstract The emergence of high-form-factor electronics has led to a demand for high-density integration of inorganic thin-film devices and circuits with full stretchability. However, the intrinsic stiffness and brittleness of inorganic materials have impeded their utilization in free-form electronics. Here, we demonstrate highly integrated strain-insensitive stretchable metal-oxide transistors and circuitry (442 transistors/cm2) via a photolithography-based bottom-up approach, where transistors with fluidic liquid metal interconnection are embedded in large-area molecular-tailored heterogeneous elastic substrates (5 × 5 cm2). Amorphous indium-gallium-zinc-oxide transistor arrays (7 × 7), various logic gates, and ring-oscillator circuits exhibited strain-resilient properties with performance variation less than 20% when stretched up to 50% and 30% strain (10,000 cycles) for unit transistor and circuits, respectively. The transistors operate with an average mobility of 12.7 ( ± 1.7) cm2 V−1s−1, on/off current ratio of > 107, and the inverter, NAND, NOR circuits operate quite logically. Moreover, a ring oscillator comprising 14 cross-wired transistors validated the cascading of the multiple stages and device uniformity, indicating an oscillation frequency of ~70 kHz.

Abstract While first-principles calculations of electrode-molecule adsorption play an indispensable role in obtaining atomic-level understanding in surface science and electrochemistry, a significant challenge remains because the adsorption energy is well-defined only in equilibrium. Herein, a theory to calculate the electric enthalpy for electrified interfaces is formulated within the multi-space constrained-search density functional theory (MS-DFT), which provides the nonequilibrium total energy of a nanoscale electrode-channel-electrode junction. An additional MS-DFT calculation for the electrode-only counterpart that maintains the same bias voltage allows one to identify the internal energy of the channel as well as the electric field and the channel polarization, which together determine the electric enthalpy and the nonequilibrium adsorption energy. Application of the developed scheme to the water-Au and water-graphene interface models shows that the Au and graphene electrodes induce very different behaviors in terms of the electrode potential-dependent stabilization of water configurations. The theory developed here will be a valuable tool in the ongoing effort to obtain atomic-scale understanding of bias-dependent molecular reorganizations in electrified interfaces.

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD.

Tactile sensory systems play a vital role in various emerging fields including robotics, prosthetics, and human–machine interfaces. However, traditional tactile sensors are typically designed to detect a single stimulus through a lock‐and‐key mechanism, which poses substantial challenges in the realization of multimodal tactile sensors. To address this issue, the convergence of tactile sensory systems with artificial neural network and machine learning (ML) platforms has been utilized to enhance the capabilities of multimodal sensors and enable signal decoupling/interpretation of mixed tactile stimuli. Herein, recent progress in multimodal sensors that can simultaneously identify various stimuli such as strain, pressure, and temperature is reviewed, providing in‐depth understanding of materials, structures, and methodologies. In addition, accurate interpretation of signals from mixed tactile stimuli under complex conditions remains challenging. This review presents a comprehensive exploration of ML algorithms that mimic human neural networks, discussing their significance in advancing smart sensory systems and improving signal interpretation in complex and dynamic environments.

Abstract To overcome the intrinsic inefficiency of the von Neumann architecture, neuromorphic devices that perform analog vector–matrix multiplication have been highlighted for achieving power‐ and time‐efficient data processing. In particular, artificial synapses, of which conductance should be programmed to represent the synaptic weights of the artificial neural network, have been intensively researched to realize neuromorphic devices. Here, inspired by excitatory and inhibitory synapses, we develop an artificial optoelectronic synapse that shows both potentiation and depression characteristics triggered only by optical inputs. The design of the artificial optoelectronic synapse, in which excitatory and inhibitory synaptic phototransistors are serially connected, enables these characteristics by spatiotemporally irradiating the phototransistor channels with optical pulses. Furthermore, a negative synaptic weight can be realized without the need for electronic components such as comparators. With such attributes, the artificial optoelectronic synapse is demonstrated to classify three digits with a high recognition rate (98.3%) and perform image preprocessing via analog vector–matrix multiplication.

Abstract The latest developments in bio-inspired neuromorphic vision sensors can be summarized in 3 keywords: smaller, faster, and smarter. (1) Smaller: Devices are becoming more compact by integrating previously separated components such as sensors, memory, and processing units. As a prime example, the transition from traditional sensory vision computing to in-sensor vision computing has shown clear benefits, such as simpler circuitry, lower power consumption, and less data redundancy. (2) Swifter: Owing to the nature of physics, smaller and more integrated devices can detect, process, and react to input more quickly. In addition, the methods for sensing and processing optical information using various materials (such as oxide semiconductors) are evolving. (3) Smarter: Owing to these two main research directions, we can expect advanced applications such as adaptive vision sensors, collision sensors, and nociceptive sensors. This review mainly focuses on the recent progress, working mechanisms, image pre-processing techniques, and advanced features of two types of neuromorphic vision sensors based on near-sensor and in-sensor vision computing methodologies.

Abstract Inkjet printing is a cost-effective and scalable way to assemble colloidal materials into desired patterns in a vacuum- and lithography-free manner. Two-dimensional (2D) nanosheets are a promising material category for printed electronics because of their compatibility with solution processing for stable ink formulations as well as a wide range of electronic types from metal, semiconductor to insulator. Furthermore, their dangling bond-free surface enables atomically thin, electronically-active thin films with van der Waals contacts which significantly reduce the junction resistance. Here, we demonstrate all inkjet-printed thin-film transistors consisting of electrochemically exfoliated graphene, MoS2, and HfO2 as metallic electrodes, a semiconducting channel, and a high-k dielectric layer, respectively. In particular, the HfO2 dielectric layer is prepared via two-step; electrochemical exfoliation of semiconducting HfS2 followed by a thermal oxidation process to overcome the incompatibility of electrochemical exfoliation with insulating crystals. Consequently, all inkjet-printed 2D nanosheets with various electronic types enable high-performance, thin-film transistors which demonstrate field-effect mobilities and current on/off ratios of ~10 cm2 V−1 s−1 and >105, respectively, at low operating voltage.

The exponential increase in greenhouse gas emissions necessitates urgent measures to mitigate climate change impacts. Carbon capture and storage (CCS) has emerged as a promising solution, capturing CO2 from industrial processes and storing it underground. However, CCS implementation poses risks that demand sophisticated modeling. This review focuses on the numerical modeling of CO2 plume dispersion from reservoir leaks during offshore CCS projects, including near- and far-field modeling and the comparison between Lagrangian and Eulerian modeling in particular. Near-field modeling examines CO2 behavior in jet plume, considering depth-related changes. Far-field modeling, employing Eulerian and Lagrangian methods, evaluates dispersion in marine environments. Case studies illustrate the complexity and uniqueness of CO2 dispersion events. The Lagrangian approach emphasizes gas bubble tracking, while the Eulerian approach employs fixed grid systems for detailed hydrodynamic modeling. Both approaches contribute valuable insights, with Eulerian models excelling in site-specific complexities and Lagrangian models offering computational efficiency. A hybrid approach may offer a comprehensive understanding of CO2 dispersion.

Valley depolarization processes in 2D transition metal dichalcogenides have been linked to acoustic phonons, but optical verification is ambiguous, due to the nearly degenerate acoustic phonon frequencies at the zone-edge. Here, the authors determine the phonon momentum of the longitudinal acoustic (LA) phonons at the K point as responsible for the ultrafast valley depolarization in monolayer MoSe2.

Abstract While low-dimensional organometal halide perovskites are expected to open up new opportunities for a diverse range of device applications, like in their bulk counterparts, the toxicity of Pb-based halide perovskite materials is a significant concern that hinders their practical use. We recently predicted that lead triiodide (PbI3) columns derived from trimethylsulfonium (TMS) lead triiodide (CH3)3SPbI3 (TMSPbI3) by stripping off TMS ligands should be semimetallic, and additionally ultrahigh negative differential resistance (NDR) can arise from the heterojunction composed of a TMSPbI3 channel sandwiched by PbI3 electrodes. Herein, we computationally explore whether similar material and device characteristics can be obtained from other one-dimensional halide perovskites based on non-Pb metal elements, and in doing so deepen the understanding of their mechanistic origins. First, scanning through several candidate metal halide inorganic frameworks as well as their parental form halide perovskites, we find that the germanium triiodide (GeI3) column also assumes a semimetallic character by avoiding the Peierls distortion. Next, adopting the bundled nanowire GeI3-TMSGeI3-GeI3 junction configuration, we obtain a drastically high peak current density and ultrahigh NDR at room temperature. Furthermore, the robustness and controllability of NDR signals from GeI3-TMSGeI3-GeI3 devices under strain are revealed, establishing its potential for flexible electronics applications. It will be emphasized that, despite the performance metrics notably enhanced over those from the TMSPbI3 case, these device characteristics still arise from the identical quantum hybridization NDR mechanism.

Measurement(s) Microbiome Technology Type(s) Metagenome • Bacterial 16 S RNA Factor Type(s) Ageing • Co-housing • Parabiosis • Serum-injection • Akkermansia (AK) treatment Sample Characteristic - Organism Mus musculus Sample Characteristic - Environment animal cage Sample Characteristic - Location South Korea

Abstract To enable the computer-aided design of vertically stacked two-dimensional (2D) van der Waals (vdW) heterostructure devices, we here introduce a non-equilibrium first-principles simulation method based on the multi-space constrained-search density functional formalism. Applying it to graphene/few-layer hBN/graphene field-effect transistors, we show that the negative differential resistance (NDR) characteristics can be produced not only from the gating-induced mismatch between two graphene Dirac cones in energy-momentum space but from the bias-dependent energetic shift of defect levels. Specifically, for a carbon atom substituted for a nitrogen atom (CN) within inner hBN layers, the increase of bias voltage is found to induce a self-consistent electron filling of in-gap CN states, which in turn changes voltage drop profiles and produces symmetric NDR characteristics. With the CN placed on outer hBN layers, however, the pinning of CN states to nearby graphene significantly modifies device characteristics, demonstrating the critical impact of atomic details for 2D vdW devices.

Abstract Background The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging. Results Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy. Conclusions In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing. Video abstract

Abstract The achievement of ultraclean Ohmic van der Waals (vdW) contacts at metal/transition-metal dichalcogenide (TMDC) interfaces would represent a critical step for the development of high-performance electronic and optoelectronic devices based on two-dimensional (2D) semiconductors. Herein, we report the fabrication of ultraclean vdW contacts between indium (In) and molybdenum disulfide (MoS2) and the clarification of the atomistic origins of its Ohmic-like transport properties. Atomically clean In/MoS2 vdW contacts are achieved by evaporating In with a relatively low thermal energy and subsequently cooling the substrate holder down to ~100 K by liquid nitrogen. We reveal that the high-quality In/MoS2 vdW contacts are characterized by a small interfacial charge transfer and the Ohmic-like transport based on the field-emission mechanism over a wide temperature range from 2.4 to 300 K. Accordingly, the contact resistance reaches ~600 Ω μm and ~1000 Ω μm at cryogenic temperatures for the few-layer and monolayer MoS2 cases, respectively. Density functional calculations show that the formation of large in-gap states due to the hybridization between In and MoS2 conduction band edge states is the microscopic origins of the Ohmic charge injection. We suggest that seeking a mechanism to generate strong density of in-gap states while maintaining the pristine contact geometry with marginal interfacial charge transfer could be a general strategy to simultaneously avoid Fermi-level pinning and minimize contact resistance for 2D vdW materials.

Abstract To provide a unique opportunity for on‐chip scaled bioelectronics, a symmetrically gated metal‐oxide electric double layer transistor (EDLT) with ion‐gel (IG) gate dielectric and simple in‐plane Corbino electrode architecture is proposed. Using amorphous indium‐gallium‐zinc oxide (a‐IGZO) semiconductor and IG dielectric layers, low‐voltage driven EDLTs with high ionotronic effects can be realized. More importantly, in contrast to the conventional asymmetric rectangular EDLTs which can cause non‐uniform potential variation in the active channel layer and eventually degrade the sensing performance, the new symmetrical in‐plane type EDLTs achieve high and spatially uniform ion responsive behaviors. The symmetrically gated a‐IGZO EDLTs exhibited a responsivity of 129.4% to 5 ppm mercury (Hg2+) ions which are approximately three times higher than that with conventional electrode structure (responsivity of 38.5%). To confirm the viability of the new device architectures and the findings, the detailed mechanism of the symmetric gating effects in the in‐plane EDLTs with a variety of electrical characterization and 3D fine element analysis simulations is also discussed.

Summary: Recently, multifunctional textile-based sensory systems have attracted a lot of attention because of the growing demand for wearable electronics performing real-time monitoring of various body signals and movements. In particular, textile-based physical sensors often require multimodal sensing capabilities to accurately detect and identify multiple mixed stimuli simultaneously. Here, we demonstrate a textile-based strain/pressure multimodal sensor using high-k poly(vinylidene fluoride)-co-hexafluoropropylene ion-gel film and silver nanowire/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate-coated conducting fibers. The multimodal sensors exhibited reliable strain and pressure-sensing characteristics for strain ranges up to 25% and pressures up to 50 kPa, respectively, with a relatively high strain gauge factor (up to 2.74) and pressure sensitivity (0.32 kPa−1). More importantly, the textile-based multimodal sensor was able to detect the strain and pressure independently, allowing facile discrimination of strain and pressure. Using this approach, we demonstrated a textile-based multimodal sensor that incorporates one strain sensor and two pressure sensors detecting multiple weights simultaneously.

Kallikrein-related peptidase (KLK)6 is associated with inflammatory diseases and neoplastic progression. KLK6 is aberrantly expressed in several solid tumors and regulates cancer development, metastatic progression, and drug resistance. However, the function of KLK6 in the tumor microenvironment remains unclear. This study aimed to determine the role of KLK6 in the tumor microenvironment. Here, we uncovered the mechanism underlying KLK6-mediated cross-talk between cancer cells and macrophages. Compared with wild-type mice, KLK6−/− mice showed less tumor growth and metastasis in the B16F10 melanoma and Lewis lung carcinoma (LLC) xenograft model. Mechanistically, KLK6 promoted the secretion of tumor necrosis factor-alpha (TNF-α) from macrophages via the activation of protease-activated receptor-1 (PAR1) in an autocrine manner. TNF-α secreted from macrophages induced the release of the C-X-C motif chemokine ligand 1 (CXCL1) from melanoma and lung carcinoma cells in a paracrine manner. The introduction of recombinant KLK6 protein in KLK6−/− mice rescued the production of TNF-α and CXCL1, tumor growth, and metastasis. Inhibition of PAR1 activity suppressed these malignant phenotypes rescued by rKLK6 in vitro and in vivo. Our findings suggest that KLK6 functions as an important molecular link between macrophages and cancer cells during malignant progression, thereby providing opportunities for therapeutic intervention.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.

Neuromorphic electronics draw attention as innovative approaches that facilitate hardware implementation of next‐generation artificial intelligent system including neuromorphic in‐memory computing, artificial sensory perception, and humanoid robotics. Among the various neuromorphic devices, optoelectronic synapses are promising neuromorphic devices that use optical means to mimic synaptic plasticity and related functions. Compared with classical neuromorphic chip based on electronic synapses using electrical means, photonic neuromorphic chip using light as input spike signal can be attractive alternative approach for next‐generation artificial intelligent system capable of high density, low power consumption, and low crosstalk. Thus, various optoelectronic synaptic electronics have been developed to overcome the drawback of conventional artificial intelligent system based on electrical synapses. Herein, the recent progresses in transistor‐based optoelectronic synapses for artificial intelligent system and review their device architecture, neuromorphic operational mechanisms, manufacturing methodologies, and advanced applications for artificial intelligent computing and visual perception systems are focused. Finally, the future challenges and research direction in the optoelectronic synaptic research are discussed.

Indoor air filtration received significant attention owing to the growing threat to the environment and human health caused by air pollutants such as volatile organic compound (VOC) gases. However, owing to the limited adsorption capacity of VOC adsorbents, such as activated carbon, a rapid breakthrough can occur, reducing the service life of the filter. Therefore, TiO2-coated zeolite (TiO2/zeolite) was utilized as a photo-regenerative VOC adsorbent to increase the service life of VOC filters. In particular, with photoactive TiO2 forms on zeolite, efficient and repetitive photo-regeneration is attainable through the dissociation of VOC molecules by the photocatalytic reaction. We optimized the TiO2 coating amount to obtain TiO2/zeolite particles with a high surface area (BET surface area > 500 m2/g) and high adsorption capacity. A VOC filter with an adsorption efficiency of 72.1% for formaldehyde was realized using TiO2/zeolite as the adsorbent. Furthermore, the TiO2/zeolite filter exhibits a photo-regeneration efficiency of >90% for the initial two regeneration cycles using ultraviolet illumination, and >60% up to five cycles. Based on these observations, we consider that TiO2/zeolite is a potential adsorbent candidate for photo-regenerative VOC filters.

The data presented in this article are related to “Odd-even phonon transport effects in strained carbon atomic chains bridging graphene nanoribbon electrodes” (Kim et al., 2019). To provide the information that can be utilized in reproducing our results, we provide the fully optimized graphene nanoribbon (GNR)–carbon chain (CC)–GNR junction atomic configurations at different strain values, the computational setting for quantum phonon transport calculations, and several computational data that were not included in the main manuscript. Data on graphene–CC–graphene junctions are additionally presented.

Conventional von Neumann–based computing systems have inherent limitations such as high hardware complexity, relatively inferior energy efficiency, and low bandwidth. As an alternative, neuromorphic computation is emerging as a platform for next‐generation artificial intelligence computing systems due to their potential advantages such as highly energy‐efficient computing, robust learning, fault tolerance, and parallel processing. Moreover, to further enhance the energy efficiency and processing speed, photonic‐based neuromorphic systems have gathered significant interest in the past few years. Herein, the recent progress and development of optoelectronic and all‐optical neuromorphic devices is summarized, focusing on their structures, materials, and potential applications. Particularly, for optoelectronic neuromorphic devices, devices with planar and vertical structures are described along with their key strategies in materials and device structures. Next, all‐optical memory and neuromorphic devices for neuromorphic computing are reviewed. Finally, the applications of optoelectronic neuromorphic devices are discussed for their potential utilization in neuromorphic computing systems.

N-Myc downstream regulated gene 3 (NDRG3) is a unique pro-tumorigenic member among NDRG family genes, mediating growth signals. Here, we investigated the pathophysiological roles of NDRG3 in relation to cell metabolism by disrupting its functions in liver. Mice with liver-specific KO of NDRG3 (Ndrg3 LKO) exhibited glycogen storage disease (GSD) phenotypes including excessive hepatic glycogen accumulation, hypoglycemia, elevated liver triglyceride content, and several signs of liver injury. They suffered from impaired hepatic glucose homeostasis, due to the suppression of fasting-associated glycogenolysis and gluconeogenesis. Consistently, the expression of glycogen phosphorylase (PYGL) and glucose-6-phosphate transporter (G6PT) was significantly down-regulated in an Ndrg3 LKO-dependent manner. Transcriptomic and metabolomic analyses revealed that NDRG3 depletion significantly perturbed the methionine cycle, redirecting its flux towards branch pathways to upregulate several metabolites known to have hepatoprotective functions. Mechanistically, Ndrg3 LKO-dependent downregulation of glycine N-methyltransferase in the methionine cycle and the resultant elevation of the S-adenosylmethionine level appears to play a critical role in the restructuring of the methionine metabolism, eventually leading to the manifestation of GSD phenotypes in Ndrg3 LKO mice. Our results indicate that NDRG3 is required for the homeostasis of liver cell metabolism upstream of the glucose–glycogen flux and methionine cycle and suggest therapeutic values for regulating NDRG3 in disorders with malfunctions in these pathways.

The pineal hormone, melatonin, plays important roles in circadian rhythms and energy metabolism. The hepatic peptide hormone, hepcidin, regulates iron homeostasis by triggering the degradation of ferroportin (FPN), the protein that transfers cellular iron to the blood. However, the role of melatonin in the transcriptional regulation of hepcidin is largely unknown. Here, we showed that melatonin upregulates hepcidin gene expression by enhancing the melatonin receptor 1 (MT1)-mediated c-Jun N-terminal kinase (JNK) activation in hepatocytes. Interestingly, hepcidin gene expression was increased during the dark cycle in the liver of mice, whereas serum iron levels decreased following hepcidin expression. In addition, melatonin significantly induced hepcidin gene expression and secretion, as well as the subsequent FPN degradation in hepatocytes, which resulted in cellular iron accumulation. Melatonin-induced hepcidin expression was significantly decreased by the melatonin receptor antagonist, luzindole, and by the knockdown of MT1. Moreover, melatonin activated JNK signaling and upregulated hepcidin expression, both of which were significantly decreased by SP600125, a specific JNK inhibitor. Chromatin immunoprecipitation analysis showed that luzindole significantly blocked melatonin-induced c-Jun binding to the hepcidin promoter. Finally, melatonin induced hepcidin expression and secretion by activating the JNK-c-Jun pathway in mice, which were reversed by the luzindole treatment. These findings reveal a previously unrecognized role of melatonin in the circadian regulation of hepcidin expression and iron homeostasis.

Abstract While the Landauer viewpoint constitutes a modern basis to understand nanoscale electronic transport and to realize first‐principles implementations of the nonequilibrium Green's function (NEGF) formalism, seeking an alternative picture can be beneficial for the fundamental understanding and practical calculations of quantum transport processes. Herein, introducing a micro‐canonical picture that maps the finite‐bias quantum transport process to a drain‐to‐source or multi‐electrode optical excitation, the multi‐space constrained‐search density functional theory (MS‐DFT) formalism for first‐principles electronic structure and quantum transport calculations is developed. Performing MS‐DFT calculations for the benzenedithiolate single‐molecule junction, it is shown that MS‐DFT and standard DFT‐NEGF calculations produce practically equivalent electronic and transmission data. Importantly, the variational convergence of “nonequilibrium total energy” within MS‐DFT is demonstrated, which should have significant implications for in operando studies of nanoscale devices. Establishing a viable alternative to the Landauer viewpoint, the developed formalism should provide valuable atomistic information in the development of next‐generation nanodevices.

Sirtuin1 (Sirt1) is an unusual target for aging and aging-associated diseases. During the screening for Sirt1 activators from natural compounds, piperlongumine (PL), one of the major constituents of Piper longum, potently activated the deacetylase ability of Sirt1 in vitro. Treatment with PL, which regulated the gene transcription of antioxidant response element in hippocampal neurons, attenuated the cytotoxicity induced by intraneuronal Aβ1-42 expression. The oral administration of PL, at a dose of 50 mg/kg/day for 2.5 months, significantly reduced the occupied area of beta-amyloid in parietal cortex of APP/PS1 mice. Novel object recognition and working memory impairment also markedly improved. Moreover, activated microglia and astrocytes in the cortex notably decreased, indicating the anti-inflammatory activity of PL. Finally, vesicular glutamate transporter 1 significantly increased in the hippocampus of APP/PS1 mice following PL treatment. These results suggested the beneficial effects PL and its therapeutic potential to ameliorate AD-like pathology.

Objective: We aimed to investigate the effect of Sicyos angulatus (SA) ethanolic extracts as antioxidants and potential treatments for liver disease. Methods: To establish a mouse model of liver injury, C57BL/6 male mice were injected via the caudal vein with a single dose of concanavalin A (Con A, 15 mg kg−1). SA extracts were administered once by oral gavage 30 min before Con A injection. Results: In vitro studies showed that SA decreased tert-butyl hydroperoxide (t-BHP)-induced reactive oxygen species (ROS) production. SA administration reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as hepatic ROS levels, in a dose-dependent manner. Moreover, SA increased the activities of the hepatic antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. Furthermore, SA treatment reduced pro-apoptotic protein levels. Con A-mediated cytosolic release of Smac/DIABLO and apoptosis-inducing factor (AIF), which are markers of necrosis, were dramatically decreased in HepG2 cells treated with SA. Conclusion: SA ameliorated liver injury and might be a good strategy for the treatment of liver injury.

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is an important transcription factor modulating gene transcription involved in endocrine control of liver metabolism. Transferrin receptor 2 (TFR2), a carrier protein for transferrin, is involved in hepatic iron overload in alcoholic liver disease (ALD). However, TFR2 gene transcriptional regulation in hepatocytes remains largely unknown. In this study, we described a detailed molecular mechanism of hepatic TFR2 gene expression involving ERRγ in response to an endocannabinoid 2-arachidonoylglycerol (2-AG). Treatment with 2-AG and arachidonyl-2′-chloroethylamide, a selective cannabinoid receptor type 1 (CB1) receptor agonist, increased ERRγ and TFR2 expression in hepatocytes. Overexpression of ERRγ was sufficient to induce TFR2 expression in both human and mouse hepatocytes. In addition, ERRγ knockdown significantly decreased 2-AG or alcohol-mediated TFR2 gene expression in cultured hepatocytes and mouse livers. Finally, deletion and mutation analysis of the TFR2 gene promoter demonstrated that ERRγ directly modulated TFR2 gene transcription via binding to an ERR-response element. This was further confirmed by chromatin immunoprecipitation assay. Taken together, these results reveal a previously unrecognized role of ERRγ in the transcriptional regulation of TFR2 gene expression in response to alcohol.

Summary: Small heterodimer partner (SHP) is an orphan nuclear receptor that acts as a transcriptional co-repressor by interacting with nuclear receptors and transcription factors. Although SHP plays a negative regulatory function in various signaling pathways, its role in virus infection has not been studied. Here, we report that SHP is a potent negative regulator of the virus-mediated type I IFN signaling that maintains homeostasis within the antiviral innate immune system. Upon virus infection, SHP interacts specifically with CREB-binding protein (CBP) in the nucleus, thereby obstructing CBP/β-catenin interaction competitively. Consequently, SHP-deficient cells enhance antiviral responses, including transcription of the type I IFN gene, upon virus infection. Furthermore, SHP-deficient mice show higher levels of IFN production and are more resistant to influenza A virus infection. Our results suggest that SHP is a nuclear regulator that blocks transcription of the type I IFN gene to inhibit excessive innate immune responses. : Interferon (IFN), which has an antiviral effect, must be tightly modulated to prevent excessive induction that adversely affects the host. Kim et al. demonstrate that SHP acts as negative regulator of type I IFN signaling, which inhibits IFN gene transcription by blocking the interaction of CBP and β-catenin. Keywords: SHP, type I interferon, CBP, β-catenin

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions.

Akkermansia muciniphila is widely considered a next-generation beneficial microbe. This bacterium resides in the mucus layer of its host and regulates intestinal homeostasis and intestinal barrier integrity by affecting host signaling pathways. However, it remains unknown how the expression of genes encoding extracellular proteins is regulated in response to dynamic mucosal environments. In this study, we elucidated the effect of mucin on the gene expression and probiotic traits of A. muciniphila. Transcriptome analysis showed that the genes encoding most mucin-degrading enzymes were significantly upregulated in the presence of mucin. By contrast, most genes involved in glycolysis and energy metabolic pathways were upregulated under mucin-depleted conditions. Interestingly, the absence of mucin resulted in the upregulation of 79 genes encoding secreted protein candidates, including Amuc-1100 as well as members of major protein secretion systems. These transcript level changes were consistent with the fact that administration of A. muciniphila grown under mucin-depleted conditions to high-fat diet-induced diabetic mice reduced obesity and improved intestinal barrier integrity more efficiently than administration of A. muciniphila grown under mucin-containing conditions. In conclusion, mucin content in the growth medium plays a critical role in the improvement by A. muciniphila of high-fat diet-induced obesity, intestinal inflammation, and compromised intestinal barrier integrity related to a decrease in goblet cell density. Our findings suggest the depletion of animal-derived mucin in growth medium as a novel principle for the development of A. muciniphila for human therapeutics.

In response to the increasing demand for flexible devices, there is increasing effort to manufacture flexible electrodes. However, the difficulty of handling a thin film is an obstacle to the production of flexible electrodes. In this study, a heat-induced peelable pressure-sensitive adhesive (h-PSA) was fabricated and used to manufacture a flexible electrode with sub-tenth micron thickness. Unlike the control PSA, the incorporation of amide groups made the h-PSA fail through adhesive failure at temperatures ranging from 20 to 80 °C. Compared to the peeling adhesion (1719 gf/in) of h-PSA measured at 20 °C, the value (171 gf/in) measured at 80 °C was decreased by one order of magnitude. Next, the 8 μm thick polyethylene terephthalate (PET) film was attached on a thick substrate (50 μm) via h-PSA, and Mo/Al/Mol patterns were fabricated on the PET film through sputtering, photolithography, and wet-etching processes. The thick substrate alleviated the difficulty of handling the thin PET film during the electrode fabrication process. Thanks to the low peel force and clean separation of the h-PSA at 80 °C, the flexible electrode of metal patterns on the PET (8 μm) film was isolated from the substrate with little change (

In this study, we demonstrate solution-processed memristor devices using a CdSe/ZnS colloidal quantum dot (CQD)/poly(methyl methacrylate) (PMMA) composite and their electrical characteristics were investigated. Particularly, to obtain stable memristive characteristics with a large current switching ratio, the concentration of CdSe/ZnS QDs in the PMMA matrix was optimized. It was found that with the CdSe/ZnS QD concentration of 1 wt%, the memristor device exhibited a high current switching ratio of ~104 and a retention time over 104 s, owing to the efficient charge trapping and de-trapping during the set and reset processes, respectively. In addition, we investigated the operational stability of the device by carrying out the cyclic endurance test and it was found that the memristor device showed stable switching behavior up to 400 cycles. Furthermore, by analyzing the conduction behavior of the memristor device, we have deduced the possible mechanisms for the degradation of the switching characteristics over long switching cycles. Specifically, it was observed that the dominant conduction mechanism changed from trap-free space charge-limited current conduction to trap charge-limited current conduction, indicating the creation of additional trap states during the repeated operation, disturbing the memristive operation.

Textile-based pressure sensors have garnered considerable interest in electronic textiles due to their diverse applications, including human–machine interface and healthcare monitoring systems. We studied a textile-based capacitive pressure sensor array using a poly(vinylidene fluoride)-co-hexafluoropropylene (PVDF-HFP)/ionic liquid (IL) composite film. By constructing a capacitor structure with Ag-plated conductive fiber electrodes that are embedded in fabrics, a capacitive pressure sensor showing high sensitivity, good operation stability, and a wide sensing range could be created. By optimizing the PVDF-HFP:IL ratio (6.5:3.5), the fabricated textile pressure sensors showed sensitivity of 9.51 kPa−1 and 0.69 kPa−1 in the pressure ranges of 0–20 kPa and 20–100 kPa, respectively. The pressure-dependent capacitance variation in our device was explained based on the change in the contact-area formed between the multi-filament fiber electrodes and the PVDF-HFP/IL film. To demonstrate the applicability and scalability of the sensor device, a 3 × 3 pressure sensor array was fabricated. Due to its matrix-type array structure and capacitive sensing mechanism, multi-point detection was possible, and the different positions and the weights of the objects could be identified.

The development of novel dielectric materials with reliable dielectric properties and low-temperature processibility is crucial to manufacturing flexible and high-performance organic thin-film transistors (OTFTs) for next-generation roll-to-roll organic electronics. Here, we investigate the solution-based fabrication of high-k aluminum oxide (Al2O3) thin films for high-performance OTFTs. Nanocluster-based Al2O3 films fabricated by highly energetic photochemical activation, which allows low-temperature processing, are compared to the conventional nitrate-based Al2O3 films. A wide array of spectroscopic and surface analyses show that ultralow-temperature photochemical activation (2O3 dielectric layer from Al-13 nanocluster-based solutions. The fabricated nanocluster-based Al2O3 films exhibit a low leakage current density (−7 A/cm2) at 2 MV/cm and high dielectric breakdown strength (>6 MV/cm). Using this dielectric layer, precisely aligned microrod-shaped 2,7-dioctyl[1]benzothieno [3,2-b][1] benzothiophene (C8-BTBT) single-crystal OTFTs were fabricated via solvent vapor annealing and photochemical patterning of the sacrificial layer.

The dopamine precursor 3,4-dihydroxyphenyl-l-alanine (L-DOPA) is currently the most efficacious pharmacotherapy for Parkinson's disease (PD). However, long-term L-DOPA treatment leads to the development of abnormal involuntary movements (AIMs) in patients and animal models of PD. Recently, involvement of growth arrest and DNA damage-inducible 45β (Gadd45β) was reported in neurological and neurobehavioral dysfunctions. However, little is known about the role of Gadd45β in the dopaminergic nigrostriatal pathway or L-DOPA-induced dyskinesia (LID). To address this issue, we prepared an animal model of PD using unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra of Gadd45β+/+ and Gadd45β−/− mice. Dyskinetic symptoms were triggered by repetitive administration of L-DOPA in these 6-OHDA-lesioned mice. Whereas dopamine denervation in the dorsal striatum decreased Gadd45β mRNA, chronic L-DOPA treatment significantly increased Gadd45β mRNA expression in the 6-OHDA-lesioned striatum of wild-type mice. Using unilaterally 6-OHDA-lesioned Gadd45β+/+ and Gadd45β−/− mice, we found that mice lacking Gadd45β exhibited long-lasting increases in AIMs following repeated administration of L-DOPA. By contrast, adeno-associated virus-mediated expression of Gadd45β in the striatum reduced AIMs in Gadd45β knockout mice. The deficiency of Gadd45β in LID increased expression of ΔFosB and c-Fos in the lesioned striatum 90 min after the last administration of L-DOPA following 11 days of daily L-DOPA treatments. These data suggest that the increased expression of Gadd45β induced by repeated administration of L-DOPA may be beneficial in patients with PD.

For high-speed and large-area active-matrix displays, metal-oxide thin-film transistors (TFTs) with high field-effect mobility, stability, and good uniformity are essential. Moreover, reducing the RC delay is also important to achieve high-speed operation, which is induced by the parasitic capacitance formed between the source/drain (S/D) and the gate electrodes. From this perspective, self-aligned top-gate oxide TFTs can provide advantages such as a low parasitic capacitance for high-speed displays due to minimized overlap between the S/D and the gate electrodes. Here, we demonstrate self-aligned top-gate oxide TFTs using a solution-processed indium-gallium-zinc-oxide (IGZO) channel and crosslinked poly(4-vinylphenol) (PVP) gate dielectric layers. By applying a selective Ar plasma treatment on the IGZO channel, low-resistance IGZO regions could be formed, having a sheet resistance value of ~20.6 kΩ/sq., which can act as the homojunction S/D contacts in the top-gate IGZO TFTs. The fabricated self-aligned top-gate IGZO TFTs exhibited a field-effect mobility of 3.93 cm2/Vs and on/off ratio of ~106, which are comparable to those fabricated using a bottom-gate structure. Furthermore, we also demonstrated self-aligned top-gate TFTs using electrospun indium-gallium-oxide (IGO) nanowires (NWs) as a channel layer. The IGO NW TFTs exhibited a field-effect mobility of 0.03 cm2/Vs and an on/off ratio of >105. The results demonstrate that the Ar plasma treatment for S/D contact formation and the solution-processed PVP gate dielectric can be implemented in realizing self-aligned top-gate oxide TFTs.

For wearable health monitoring systems and soft robotics, stretchable/flexible pressure sensors have continuously drawn attention owing to a wide range of potential applications such as the detection of human physiological and activity signals, and electronic skin (e-skin). Here, we demonstrated a highly stretchable pressure sensor using silver nanowires (AgNWs) and photo-patternable polyurethane acrylate (PUA). In particular, the characteristics of the pressure sensors could be moderately controlled through a micro-patterned hole structure in the PUA spacer and size-designs of the patterned hole area. With the structural-tuning strategies, adequate control of the site-specific sensitivity in the range of 47~83 kPa−1 and in the sensing range from 0.1 to 20 kPa was achieved. Moreover, stacked AgNW/PUA/AgNW (APA) structural designed pressure sensors with mixed hole sizes of 10/200 µm and spacer thickness of 800 µm exhibited high sensitivity (~171.5 kPa−1) in the pressure sensing range of 0~20 kPa, fast response (100~110 ms), and high stretchability (40%). From the results, we envision that the effective structural-tuning strategy capable of controlling the sensing properties of the APA pressure sensor would be employed in a large-area stretchable pressure sensor system, which needs site-specific sensing properties, providing monolithic implementation by simply arranging appropriate micro-patterned hole architectures.

Bone morphogenetic protein 6 (BMP6) is a multifunctional growth factor involved in organ development and homeostasis. BMP6 controls expression of the liver hormone, hepcidin, and thereby plays a crucial role in regulating iron homeostasis. BMP6 gene transcriptional regulation in liver is largely unknown, but would be of great help to externally modulate iron load in pathologic conditions. Here, we describe a detailed molecular mechanism of hepatic BMP6 gene expression by an orphan nuclear receptor, estrogen-related receptor γ (ERRγ), in response to the pro-inflammatory cytokine interleukin 6 (IL-6). Recombinant IL-6 treatment increases hepatic ERRγ and BMP6 expression. Overexpression of ERRγ is sufficient to increase BMP6 gene expression in hepatocytes, suggesting that IL-6 is upstream of ERRγ. In line, knock-down of ERRγ in cell lines or a hepatocyte specific knock-out of ERRγ in mice significantly decreases IL-6 mediated BMP6 expression. Promoter studies show that ERRγ directly binds to the ERR response element (ERRE) in the mouse BMP6 gene promoter and positively regulates BMP6 gene transcription in IL-6 treatment conditions, which is further confirmed by ERRE mutated mBMP6-luciferase reporter assays. Finally, an inverse agonist of ERRγ, GSK5182, markedly inhibits IL-6 induced hepatic BMP6 expression in vitro and in vivo. Taken together, these results reveal a novel molecular mechanism on ERRγ mediated transcriptional regulation of hepatic BMP6 gene expression in response to IL-6.

Epistasis, which indicates the difficulty of a problem, can be used to evaluate the basis of the space in which the problem lies. However, calculating epistasis may be challenging as it requires all solutions to be searched. In this study, a method for constructing a surrogate model, based on deep neural networks, that estimates epistasis is proposed for basis evaluation. The proposed method is applied to the Variant-OneMax problem and the NK-landscape problem. The method is able to make successful estimations on a similar level to basis evaluation based on actual epistasis, while significantly reducing the computation time. In addition, when compared to the epistasis-based basis evaluation, the proposed method is found to be more efficient.

The oxygen vacancies in the TiOx active layer play the key role in determining the electrical characteristics of TiOx−based memristors such as resistive-switching behaviour. In this paper, we investigated the effect of a multi-layer stacking sequence of TiOx active layers on the resistive-switching characteristics of memristor devices. In particular, the stacking sequence of the multi-layer TiOx sub-layers, which have different oxygen contents, was varied. The optimal stacking sequence condition was confirmed by measuring the current−voltage characteristics, and also the retention test confirmed that the characteristics were maintained for more than 10,000 s. Finally, the simulation using the Modified National Institute of Standards and Technology handwriting recognition data set revealed that the multi-layer TiOx memristors showed a learning accuracy of 89.18%, demonstrating the practical utilization of the multi-layer TiOx memristors in artificial intelligence systems.

In this paper, we demonstrate high-mobility inkjet-printed indium-gallium-zinc-oxide (IGZO) thin-film transistors (TFTs) using a solution-processed Sr-doped Al2O3 (SAO) gate dielectric. Particularly, to enhance to the electrical properties of inkjet-printed IGZO TFTs, a linear-type printing pattern was adopted for printing the IGZO channel layer. Compared to dot array printing patterns (4 × 4 and 5 × 5 dot arrays), the linear-type pattern resulted in the formation of a relatively thin and uniform IGZO channel layer. Also, to improve the subthreshold characteristics and low-voltage operation of the device, a high-k and thin (~10 nm) SAO film was used as the gate dielectric layer. Compared to the devices with SiO2 gate dielectric, the inkjet-printed IGZO TFTs with SAO gate dielectric exhibited substantially high field-effect mobility (30.7 cm2/Vs). Moreover, the subthreshold slope and total trap density of states were also significantly reduced to 0.14 V/decade and 8.4 × 1011/cm2·eV, respectively.

For the elimination of radio-frequency interference (RFI) in a passive microwave radiometer, the threshold level is generally calculated from the mean value and standard deviation. However, a serious problem that can arise is an error in the retrieved brightness temperature from a higher threshold level owing to the presence of RFI. In this paper, we propose a method to detect and mitigate RFI contamination using the threshold level from statistical criteria based on a spectrogram technique. Mean and skewness spectrograms are created from a brightness temperature spectrogram by shifting the 2-D window to discriminate the form of the symmetric distribution as a natural thermal emission signal. From the remaining bins of the mean spectrogram eliminated by RFI-flagged bins in the skewness spectrogram for data captured at 0.1-s intervals, two distribution sides are identically created from the left side of the distribution by changing the standard position of the distribution. Simultaneously, kurtosis calculations from these bins for each symmetric distribution are repeatedly performed to determine the retrieved brightness temperature corresponding to the closest kurtosis value of three. The performance is evaluated using experimental data, and the maximum error and root-mean-square error (RMSE) in the retrieved brightness temperature are served to be less than approximately 3 K and 1.7 K, respectively, from a window with a size of 100 × 100 time–frequency bins according to the RFI levels and cases.

Fibroblast growth factor 21 (FGF21), a stress inducible hepatokine, is synthesized in the liver and plays important roles in glucose and lipid metabolism. However, the mechanism of hepatic cannabinoid type 1 (CB1) receptor-mediated induction of FGF21 gene expression is largely unknown.Activation of the hepatic CB1 receptor by arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor selective agonist, significantly increased FGF21 gene expression. Overexpression of estrogen-related receptor (ERR) γ increased FGF21 gene expression and secretion both in hepatocytes and mice, whereas knockdown of ERRγ decreased ACEA-mediated FGF21 gene expression and secretion. Moreover, ERRγ, but not ERRα and ERRβ, induced FGF21 gene promoter activity. In addition, deletion and mutation analysis of the FGF21 promoter identified a putative ERRγ-binding motif (AGGTGC, a near-consensus response element). A chromatin immunoprecipitation assay revealed direct binding of ERRγ to the FGF21 gene promoter. Finally, GSK5182, an ERRγ inverse agonist, significantly inhibited hepatic CB1 receptor-mediated FGF21 gene expression and secretion.Based on our data, we conclude that ERRγ plays a key role in hepatic CB1 receptor-mediated induction of FGF21 gene expression and secretion.

In this paper, we demonstrate high mobility solution-processed metal-oxide thin-film transistors (TFTs) by using a high-frequency-stable ionic-type hybrid gate dielectric (HGD). The HGD gate dielectric, a blend of sol-gel aluminum oxide (AlOx) and poly(4-vinylphenol) (PVP), exhibited high dielectric constant (ε~8.15) and high-frequency-stable characteristics (1 MHz). Using the ionic-type HGD as a gate dielectric layer, an minimal electron-double-layer (EDL) can be formed at the gate dielectric/InOx interface, enhancing the field-effect mobility of the TFTs. Particularly, using the ionic-type HGD gate dielectrics annealed at 350 °C, InOx TFTs having an average field-effect mobility of 16.1 cm2/Vs were achieved (maximum mobility of 24 cm2/Vs). Furthermore, the ionic-type HGD gate dielectrics can be processed at a low temperature of 150 °C, which may enable their applications in low-thermal-budget plastic and elastomeric substrates. In addition, we systematically studied the operational stability of the InOx TFTs using the HGD gate dielectric, and it was observed that the HGD gate dielectric effectively suppressed the negative threshold voltage shift during the negative-illumination-bias stress possibly owing to the recombination of hole carriers injected in the gate dielectric with the negatively charged ionic species in the HGD gate dielectric.

Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process. We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo alongwith significant increase in Crebh gene expression and activation. Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis. Overexpression of Crebh increased the expression of key bile acid synthesis enzyme genes via direct binding of Crebh to their promoters, whereas Cb1r knockout and Crebh-knockdown mice were protected against alcohol-induced perturbation of bile acid homeostasis. Interestingly, insulin treatment protected against Cb1r-mediated Crebh-induced disruption of bile acid homeostasis. Furthermore, Crebh expression and activation was found to be markedly increased in insulin resistance conditions and Crebh knockdown in diabetic mice model (db/db) significantly reversed alcohol-induced disruption of bile acid homeostasis. Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.