The transgene toggling device is recognized as a powerful tool for gene- and cell-based biological research and precision medicine. However, many of these devices often operate in binary mode, exhibit unacceptable leakiness, suffer from transgene silencing, show cytotoxicity, and have low potency. Here, we present a novel transgene switch, SIQ, wherein all the elements for gene toggling are packed into a single vector. SIQ has superior potency in inducing transgene expression in response to tebufenozide compared with the Gal4/UAS system, while completely avoiding transgene leakiness. Additionally, the ease and versatility of SIQ make it possible with a single construct to perform transient transfection, establish stable cell lines by targeting a predetermined genomic locus, and simultaneously produce adenovirus for transduction into cells and mammalian tissues. Furthermore, we integrated a cumate switch into SIQ, called SIQmate, to operate a Boolean AND logic gate, enabling swift toggling-off of the transgene after the removal of chemical inducers, tebufenozide and cumate. Both SIQ and SIQmate offer precise transgene toggling, making them adjustable for various researches, including synthetic biology, genome engineering, and therapeutics.

A novel dummy cell program (DMP) scheme has been introduced to enhance the retention characteristics of 3-D nand memory. This scheme programs dummy cells prior to the programming of target cells, aiming to induce a floating channel and reduce the channel potential. By programming dummy cells before target cells, the electric field in the tunneling oxide and charge trap layer (CTL) is alleviated, effectively mitigating both vertical and lateral charge loss mechanisms. Experimental characterization of threshold voltage (V-T) variations has been conducted based on program-verify (PV) levels and cell patterns. In the case of the erase-program-erase (EPE) pattern with PV7 dummy and PV3 target cells, a significant reduction of 31% in measured Delta V(T )has been achieved. Notably, similar improvements are observed in the program-program-program (PPP) pattern. These findings strongly support the potential of the proposed DMP scheme in enhancing the reliability of flash memory.

The sensing responses of SARS-CoV-2 spike protein using top-down-fabricated Si-based electrolyte-gated transistors (EGTs) have been investigated. An aptamer was employed as a receptor for the SARS-CoV-2 spike protein. The EGT demonstrated excellent intrinsic characteristics and higher sensitivity in the subthreshold regime compared to the linear regime. The limit of detection (LOD) was achieved as low as 0.94 pg/mL and 20 pg/mL for the current and voltage sensitivity, respectively. To analyze the sensing responses of EGT in detecting the aptamer–SARS-CoV-2 spike protein conjugate, a lumped-capacitive model with the presence of an effective dipole potential and an effective capacitance of the functionalized layer component was employed. The aptamer-functionalized EGT showed high sensitivity even in 10 mM phosphate-buffered saline (PBS) solution. These results suggest that Si-based EGTs are a highly promising method for detecting SARS-CoV-2 spike proteins.

2D memristors have demonstrated attractive resistive switching characteristics recently but also suffer from the reliability issue, which limits practical applications. Previous efforts on 2D memristors have primarily focused on exploring new material systems, while damage from the metallization step remains a practical concern for the reliability of 2D memristors. Here, the impact of metallization conditions and the thickness of MoS 2 films on the reliability and other device metrics of MoS 2 ‐based memristors is carefully studied. The statistical electrical measurements show that the reliability can be improved to 92% for yield and improved by ≈16× for average DC cycling endurance in the devices by reducing the top electrode (TE) deposition rate and increasing the thickness of MoS 2 films. Intriguing convergence of switching voltages and resistance ratio is revealed by the statistical analysis of experimental switching cycles. An “effective switching layer” model compatible with both monolayer and few‐layer MoS 2 , is proposed to understand the reliability improvement related to the optimization of fabrication configuration and the convergence of switching metrics. The Monte Carlo simulations help illustrate the underlying physics of endurance failure associated with cluster formation and provide additional insight into endurance improvement with device fabrication optimization.

Tauopathy, including frontotemporal lobar dementia and Alzheimer’s disease, describes a class of neurodegenerative diseases characterized by the aberrant accumulation of Tau protein due to defects in proteostasis. Upon generating and characterizing a stable transgenic zebrafish that expresses the human TAUP301L mutant in a neuron-specific manner, we found that accumulating Tau protein was efficiently cleared via an enhanced autophagy activity despite constant Tau mRNA expression; apparent tauopathy-like phenotypes were revealed only when the autophagy was genetically or chemically inhibited. We performed RNA-seq analysis, genetic knockdown, and rescue experiments with clinically relevant point mutations of valosin-containing protein (VCP), and showed that induced expression of VCP, an essential cytosolic chaperone for the protein quality system, was a key factor for Tau degradation via its facilitation of the autophagy flux. This novel function of VCP in Tau clearance was further confirmed in a tauopathy mouse model where VCP overexpression significantly decreased the level of phosphorylated and oligomeric/aggregate Tau and rescued Tau-induced cognitive behavioral phenotypes, which were reversed when the autophagy was blocked. Importantly, VCP expression in the brains of human Alzheimer’s disease patients was severely downregulated, consistent with its proposed role in Tau clearance. Taken together, these results suggest that enhancing the expression and activity of VCP in a spatiotemporal manner to facilitate the autophagy pathway is a potential therapeutic approach for treating tauopathy.

In this study, we investigated the influence of quasi-one-dimensional (Quasi-1D) characteristics on the source and drain contact resistances within vertical nanowire (NW) field-effect transistors (FETs) of diminutive diameter. The top contact of the NW is segregated into two distinct regions: the first encompassing the upper surface, designated as the axial contact, and the second encircling the side surface, known as the radial contact, which is formed during the top-contact metal deposition process. Quantum confinement effects, prominent within Quasi-1D NWs, exert significant constraints on radial transport, consequently inducing a noticeable impact on contact resistance. Notably, in the radial direction, electron tunneling occurs only through quantized, discrete energy levels. Conversely, along the axial direction, electron tunneling freely traverses continuous energy levels. In a meticulous numerical analysis, these disparities in transport mechanisms unveiled that NWs with diameters below 30 nm exhibit a markedly higher radial contact resistance compared to their axial counterparts. Furthermore, an increase in the overlap length (less than 5 nm) contributes to a modest reduction in radial resistance; however, it remains consistently higher than the axial contact resistance.

Retinal neurons can be regenerated from Müller glia (MG) in cold-blooded vertebrates but not in mammals, indicating the incompetence of mammalian MG for retinal regeneration. Here, we demonstrate that prospero-related homeobox 1 (Prox1) in MG is a factor that renders the mammalian retina incompetent for regeneration. Prox1 accumulates in MG in the degenerating human and mouse retinas but not in those in the regenerating zebrafish retina. Strikingly, we discovered that Prox1 in mouse MG originated from retinal neurons through intercellular protein transfer. Consequently, we induced the transition of MG to proliferative MG-derived retinal progenitor cells (MGPCs) in the injured mouse retinas by reducing the transfer of Prox1 to MG. Furthermore, we succeeded in regenerating retinal neurons and delaying vision loss in a retinitis pigmentosa disease model in mice by introducing an anti-Prox1 antibody that sequesters extracellular Prox1 in the mouse retina. Collectively, our results suggest that the regenerative potential of the mammalian retina can be restored by blocking the transfer of Prox1.### Competing Interest StatementE.J.L, S.P., J.H.S., J.A.P., and J.W.K. are co-founders and/or employees of Celliaz Inc., which develops anti-PROX1 therapeutics for retinal diseases.

Trap profiles in the bandgap-engineered tunneling oxide (BE-TOX) layer of a 3D NAND flash memory were investigated using a transient current trap spectroscopy technique. A new pulse scheme was introduced to generate channel holes and subsequently analyze the hole traps in the BE-TOX layer. In the fresh cell, the hole traps were primarily located at a trap energy level ( ET ) of 1.1 eV, whereas the electron traps exhibited two distinct peaks at ET = 0.75 and 1.25 eV. With increasing program/erase (P/E) cycling operations, the peak ET associated with hole traps shifted toward shallower levels. Conversely, the electron traps remained unchanged, although their intensities increased. The extracted trap generation exhibited the power-law characteristics.

While two-dimensional (2D) MoS2 has recently shown promise as a material for resistive random-access memory (RRAM) devices due to its demonstrated resistive switching (RS) characteristics, its practical application faces a significant challenge in industry regarding its limited yield and endurance. Our earlier work introduced an effective switching layer model to understand RS behavior in both mono- and multi-layered MoS2. However, functioning as a phenomenological percolation modeling tool, it lacks the capability to accurately simulate the intricate current-voltage (I-V) characteristics of the device, thereby hindering its practical applicability in 2D RRAM research. In contrast to the established conductive filament model for oxide-based RRAM, the RS mechanism in 2D RRAM remains elusive. This paper presents a novel simulator aimed at providing an intuitive, visual representation of the stochastic behaviors involved in the RS process of multi-layer 2D MoS2 RRAM devices. Building upon the previously proposed phenomenological simulator for 2D RRAM, users can now simulate both the I-V characteristics and the resistive switching behaviors of the RRAM devices. Through comparison with experimental data, it was observed that yield and endurance characteristics are linked to defect distributions in MoS2.

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is a crucial factor in longitudinal bone growth, which is regulated by a complex network of paracrine and endocrine signaling pathways. Here, we show that a phytochemical sulfuretin can stimulate hypertrophic chondrocyte differentiation in vitro and in vivo. We found that sulfuretin stabilized nuclear factor (erythroid-derived 2)-like 2 (Nrf2), stimulated its transcriptional activity, and induced expression of its target genes. Sulfuretin treatment resulted in an increase in body length of zebrafish larvae and induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were significantly abrogated by Nrf2 depletion, suggesting that such stimulatory effects of sulfuretin were dependent on Nrf2, at least in part. Taken together, these data show that sulfuretin has a potential use as supporting ingredients for enhancing bone growth.

We experimentally demonstrate Si-based electrolyte-gated transistors (EGTs) for detecting urea. The top-down-fabricated device exhibited excellent intrinsic characteristics, including a low subthreshold swing (SS) (~80 mV/dec) and a high on/off current ratio (~107). The sensitivity, which varied depending on the operation regime, was analyzed with the urea concentrations ranging from 0.1 to 316 mM. The current-related response could be enhanced by reducing the SS of the devices, whereas the voltage-related response remained relatively constant. The urea sensitivity in the subthreshold regime was as high as 1.9 dec/pUrea, four times higher than the reported value. The extracted power consumption of 0.3 nW was extremely low compared to other FET-type sensors.

The SARS-CoV-2 pandemic has increased the demand for low-cost, portable, and rapid biosensors, driving huge research efforts toward new nanomaterial-based approaches with high sensitivity. Many of them employ antibodies as bioreceptors, which have a costly development process that requires animal facilities. Recently, sybodies emerged as a new alternative class of synthetic binders and receptors with high antigen binding efficiency, improved chemical stability, and lower production costs via animal-free methods. Their smaller size is an important asset to consider in combination with ultrasensitive field-effect transistors (FETs) as transducers, which respond more intensely when biorecognition occurs near their surface. This work demonstrates the immobilization of sybodies against the spike protein of the virus on silicon surfaces, which are often integral parts of the semiconducting channel of FETs. Immobilized sybodies maintain the capability to capture antigens, even at low concentrations in the femtomolar range, as observed by fluorescence microscopy. Finally, the first proof of concept of sybody-modified FET sensing is provided using a nanoscopic silicon net as the sensitive area where the sybodies are immobilized. The future development of further sybodies against other biomarkers and their generalization in biosensors could be critical to decrease the cost of biodetection platforms in future pandemics.

Wide band gap (WBG) alkaline-earth stannate transparent oxide semiconductors (TOSs) have attracted increasing attention in recent years for their high carrier mobility and outstanding optoelectronic properties, and have been applied widely in various devices, such as flat-panel displays. Most alkaline-earth stannates are grown by molecular beam epitaxy (MBE); there are some intractable issues with the tin source including the volatility with SnO and Sn sources and the decomposition of the SnO2 source. In contrast, atomic layer deposition (ALD) serves as an ideal technique for the growth of complex stannate perovskites with precise stoichiometry control and tunable thickness at the atomic scale. Herein, we report the La-SrSnO3/BaTiO3 perovskite heterostructure heterogeneously integrated on Si (001), which uses ALD-grown La-doped SrSnO3 (LSSO) as a channel material and MBE-grown BaTiO3 (BTO) as a dielectric material. The reflective high-energy electron diffraction and X-ray diffraction results indicate the crystallinity of each epitaxial layer with a full width at half maximum (FWHM) of 0.62°. In situ X-ray photoelectron spectroscopy results confirm that there was no Sn0 state in ALD-deposited LSSO. Besides, we report a strategy for the post-treatment of LSSO/BTO perovskite heterostructures by controlling the oxygen annealing temperature and time, with a maximum oxide capacitance Cox of 0.31 μF cm-2 and a minimum low-frequency dispersion for the devices with 7 h oxygen annealing at 400 °C. The enhancement of capacitance properties is primarily attributed to a decrease of oxygen vacancies in the films and interface defects in the heterostructure interfaces during an additional ex situ excess oxygen annealing. This work expands current optimization methods for reducing defects in epitaxial LSSO/BTO perovskite heterostructures and shows that excess oxygen annealing is a powerful tool for enhancing the capacitance properties of LSSO/BTO heterostructures.

The 2-D materials have become promising candidates for resistive random access memory (RRAM) devices as more unique resistive switching (RS) characteristics have recently been revealed. However, endurance is a major challenge for industrialization. Unlike the well-developed and recognized conductive filament (CF) model for oxide-based RRAM, the RS mechanism for 2-D RRAM is not well understood. In this article, we first review the dissociation–diffusion–adsorption (DDA) model and the cluster model proposed in previous works on monolayer 2-D RRAM devices. The use of a Monte Carlo (MC) simulator for multilayer 2-D RRAM devices to expand the application of DDA and cluster models is then discussed. A simulator was designed to provide an intuitive physical view by visualizing the stochastic behaviors of the RS process in multilayer 2-D RRAM devices. By comparing the simulated results with experimental data, the endurance characteristic was found to be mainly determined by the formation and collapse of an effective switching layer. We also found that the thickness of the effective switching layer is independent of the total thickness of the multilayer 2-D material and the initial status of the device, which is consistent with the experimental observations. The model and results discussed in this work provide additional insights and guidance for improving the reliability of 2-D RRAM devices.

Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 μg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance and richness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 μg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, Bifidobacterium adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host-microbiome interactions.

Abstract The recent Coronavirus Disease 2019 (COVID‐19) outbreak strongly propels advancements in biosensor technology, leading to the emergence of novel methods for virus detection. Among them, those using nanostructured field‐effect transistors (FETs) provide an ultrasensitive approach toward point‐of‐care diagnostics. However, the application of these biosensors in analyzing biofluids has been limited by their reduced screening length in high ionic strength liquids. To address this challenge, a solution is presented involving the surface modification of FETs with a hydrogel based on star‐shaped polyethylene glycol. This hydrogel is loaded with specific antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein. By incorporating the hydrogel, the effective Debye length is effectively increased, thereby preserving the sensitivity in biofluids. The efficacy of this approach is demonstrated by employing silicon nanonet‐based FETs for the detection of viral antigens in both buffer and saliva, as well as cultured viral particle dispersions. Moreover, positive and negative patient samples are successfully differentiated, showcasing the practical application of this method. Finally, a theoretical frame is proposed to elucidate the underlying mechanism behind the preservation of sensitivity.

A dual-function memory with CMOS compatibility has been presented with the feasibility of future embedded applications. The self-selective memory composed of bilayer oxide stacks is presented with the immunity of sneak-path current (SPC) and improved thermal stability for the high storage class memory array application. Meanwhile, the one-time programmable (OTP) memory is realized by the identical bilayer structure which has improved the yield of dielectric-fuse phenomena by increasing the operating temperature up to 423 K. The physical mechanisms and modeling are investigated with experimental and simulated results. Our results provide pathfinding of high density, CMOS back-end-of-line (BEOL) integration capability, land ow power multi-functionality in the future embedded applications.

Electrical characteristics with various program temperatures (TPGM) in three-dimensional (3-D) NAND flash memory are investigated. The cross-temperature conditions of the TPGM up to 120 °C and the read temperature (TREAD) at 30 °C are used to analyze the influence of grain boundaries (GB) on the bit line current (IBL) and threshold voltage (VT). The VT shift in the E-P-E pattern is successfully decomposed into the charge loss (ΔVT,CL) component and the poly-Si GB (ΔVT,GB) component. The extracted ΔVT,GB increases at higher TPGM due to the reduced GB potential barrier. Additionally, the ΔVT,GB is evaluated using the Technology Computer Aided Design (TCAD) simulation, depending on the GB position (XGB) and the bit line voltage (VBL).

The SARS-CoV-2 pandemic has triggered many studies worldwide in the area of biosensors, leading to innovative approaches for the quantitative assessment of COVID-19. A nanostructured field-effect transistor (FET) is one type of device shown to be ultrasensitive for virus determination. FETs can be used as transducers to analyze changes in electrical current caused by the bonding of viral molecules to the surface of the semiconducting nanomaterial layer of the FETs. Although nano-transistors require simple setups amenable to be miniaturized for point-of-care diagnostic of COVID-19, this type of sensor usually has limited sensitivity in biological fluids. The reason behind this is the shortened screening length in the presence of high ionic strength solutions. In the frame of this study, we propose a methodology consisting of the FET surface modification with a hydrogel based on the star-shaped polyethylene glycol (starPEG), which hosts specific antibodies against SARS-CoV-2 spike protein in its porous structure. The deposition of the hydrogel increases the effective Debye length, preserving the biosensor’s sensitivity. We demonstrate the capability of silicon nanonet-based FETs to detect viral antigens and cultured viral particles in phosphate-buffered saline (PBS) as well as in human-purified saliva. Finally, we discriminated between positive and negative patients’ nasopharyngeal swab samples.

The instability in threshold voltage (VTH) and charge distributions in noncircular cells of three-dimensional (3D) NAND flash memory are investigated. Using TCAD simulation, we aim to identify the main factors influencing the VTH of noncircular cells. The key focus is on the nonuniform trapped electron density in the charge trapping layer (CTL) caused by the change in electric field between the circular region and the spike region. There are less-trapped electron (LT) regions within the CTL of programmed noncircular cells, which significantly enhances current flow. Remarkably, more than 50% of the total current flows through these LT regions when the spike size reaches 15 nm. We also performed a comprehensive analysis of the relationship between charge distribution and VTH in two-spike cells with different heights (HSpike) and angles between spikes (θ). The results of this study demonstrate the potential to improve the reliability of next-generation 3D NAND flash memory.