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Hepatic zonation determines tumorigenic potential of mutant β-catenin
Abstract Oncogenic mutations in phenotypically normal tissue are common across adult organs 1,2 . This suggests that multiple events need to converge to drive tumorigenesis and that many processes such as tissue differentiation may protect against carcinogenesis. WNT–β-catenin signalling maintains zonal differentiation during liver homeostasis 3,4 . However, the CTNNB1 oncogene—encoding β-catenin—is also frequently mutated in hepatocellular carcinoma, resulting in aberrant WNT signalling that promotes cell growth 5,6 . Here we investigated the antagonistic interplay between WNT-driven growth and differentiation in zonal hepatocyte populations during liver tumorigenesis. We found that β-catenin mutations co-operate with exogenous MYC expression to drive a proliferative translatome. Differentiation of hepatocytes to an extreme zone 3 fate suppressed this proliferative translatome. Furthermore, a GLUL and Lgr5 -positive perivenous subpopulation of zone 3 hepatocytes were refractory to WNT-induced and MYC-induced tumorigenesis. However, when mutant CTNNB1 and MYC alleles were activated sporadically across the liver lobule, a subset of mutant hepatocytes became proliferative and tumorigenic. These early lesions were characterized by reduced WNT pathway activation and elevated MAPK signalling, which suppresses zone 3 differentiation. The proliferative lesions were also dependent on IGFBP2–mTOR–cyclin D1 pathway signalling, in which inhibition of either IGFBP2 or mTOR suppressed proliferation and tumorigenesis. Therefore, we propose that zonal identity dictates hepatocyte susceptibility to WNT-driven tumorigenesis and that escaping WNT-induced differentiation is essential for liver cancer.
Active guidance in ultrasound bladder scanning using reinforcement learning
Inhibiting autophagy enhances anti-cancer properties of sulforaphane
Abstract Bladder cancer (BC) has an extremely low survival rate due to its tendency to metastasize. The antimalarial drug chloroquine (CQ) can inhibit BC progression and invasiveness by targeting basal autophagy. However, the mechanism by which CQ affects BC is not defined. Here, we revealed that although CQ showed an anticancer effect by reducing the migration and proliferation of the analyzed bladder cancer cells, it increased the expression of ICAM-1, a protein whose expression is associated with higher tumorigenic potential. Sulforaphane (SFN), a well-known ICAM-1 inhibitor, significantly contributed to the enhancement of anticancer effect of CQ, through regulation of both AKT/GSK-3β and mTOR/ULK pathways, which led to effective inhibition of autophagy, reduced proliferation level or inhibition of migration of the analyzed bladder cells. Moreover, regulation of pathways related to autophagy contributed to the reduction of mitochondrial membrane potential and regulation of ROS level. Nevertheless, the level of influence of CQ and SFN on the anticancer effects strongly depended on the molecular basis of the analyzed bladder cell lines. Our data indicate that although CQ exerts antitumor effects on bladder cancer cells, it should be noted that activation of some pro-tumor pathways may be associated with subsequent disease relapse or treatment resistance.
Interpreting artificial neural network-based modeling of 4 H-SiC mosfets using explainable AI
Correction: Comparative performance of bagging and boosting ensemble models for predicting lumpy skin disease with multiclass-imbalanced data
Suppressing proximity effects during rapid serial two-photon lithography through tuning of reaction–diffusion kinetics
The ability of two-photon lithography (TPL) to print deterministic nanoporous 3D structures is highly valuable for many applications. However, it is challenging to print such structures rapidly due to the proximity effects that cause closely spaced features to enlarge and merge. A key challenge is the limited understanding of the origins and spatiotemporal dynamics of the long-range proximity effects that extend beyond the optical focal spot. Here, we empirically investigate these proximity effects in serial TPL using custom-made acrylate-based photoresists. We demonstrate that the complex spatiotemporal dynamics of the proximity effects can be explained through the kinetics of the reaction–diffusion photopolymerization mechanisms that underlie the curing process. Specifically, we show that the proximity effects arise due to comparable timescales of reaction and diffusion of oxygen. Furthermore, we demonstrate that long-range proximity effects can be suppressed by introducing phenolic inhibitors, which reduce oxygen consumption through non-inhibiting side reactions and promote faster termination of curing reactions. These insights enabled improving the linewidths from >400 to 260 nm during printing of nanoporous 3D woodpiles at scanning speeds of 50 mm s−1. Thus, the knowledge generated here can be applied to deterministically tune the proximity effects and enable rapid printing of high-resolution nanoporous 3D structures.
Tracking Interphase Growth at Alloy Anode Interfaces in Sulfide Solid-State Batteries
Inverse design of two-dimensional tunable acoustic valley-Hall insulators via deep learning
Acoustic valley-Hall insulators leverage topological protection properties to enable unidirectional waveguiding, defect immunity, and low-loss transmission, exhibiting significant potential in applications such as energy harvesting, sensing, and signal processing. In the present work, a novel deep learning model is developed for designing topological configurations of acoustic valley-Hall insulators to simultaneously satisfy dual requirements of target Dirac point frequencies and temperature parameters. The deep learning model consists of a generation module and an evaluation module. The generation module uses a variational autoencoder to generate candidate topological configurations. The evaluation module employs a four-level physical constraint processing system, which implements four-stage progressive screening through the frequency domain screening layer, physical field verification layer, feature compression layer, and regression prediction layer. The two modules form a closed-loop optimization through dynamic feedback. The results show that the model can inversely generate corresponding topological configurations of acoustic valley-Hall insulators for given Dirac point frequencies and temperature parameters with high accuracy. Compared to conventional trial-and-error approaches constrained by the combinatorial complexity of parameters, this method enhances design efficiency while enabling exploration across high-dimensional design spaces. Finally, based on the unit cell of acoustic valley-Hall insulators obtained from the inverse design model, a topological valley-locked waveguide of sound waves was realized.
Nonclassical Crystallization of Covalent Organic Frameworks Guided by Exogenous Noncovalent Interactions
Research on periodic discharge characteristics of atmospheric-pressure dual-pulse-modulated microwave Ar/N2 plasma jet
Atmospheric-pressure microwave plasma jet has significant advantages, including high reactivity, high density, and direct treatment of complex-shaped surfaces. Pulse-modulated microwave technology, which periodically turns the microwave energy input on or off, provides a vital means to precisely control the spatiotemporal characteristics of the plasma jet and thereby optimize its processing efficacy. To further investigate the periodic characteristics of an atmospheric-pressure pulse-modulated microwave plasma jet, a coaxial resonator with a dual-gas channel structure was first employed by applying a dual-pulse-modulated microwave. This generated a stratified Ar/N2 plasma jet in which periodically evolving appearances were observed. Using a high-speed camera to capture dynamic images, it is found that the size of plasma jet is larger during the first three pulse cycles of each pulse train; starting from the fourth pulse cycle, both the length and radius of its luminous contour gradually decrease and eventually stabilize. Subsequently, time-resolved electron density was measured using a microwave Rayleigh scattering system. This revealed that variations in electron density are the root cause changing the optical radiation characteristics and the appearance of plasma jet, thereby leading to the differences in discharge characteristics between pulse cycles. Finally, transient spectra were measured using a monochromator, which show that the plasma jet appearance is related to changes in the relative spectral intensity of N2. Comprehensive analysis indicates that the skin effect and the development of vibrational excited states of N2 are the main physical mechanisms responsible for the transition of periodic characteristics in the atmospheric-pressure Ar/N2 plasma jet under dual-pulse-modulated microwave.
Biosensors characterize the routes taken by receptors to different active states
Study on stress response and collapse mechanism induced by shallow-buried defective pipelines in river alluvial plains
Intrinsic and tunable lattice thermal conductivity of single- and multi-layer goldene: A machine-learning molecular dynamics study
The recent successful fabrication of single- and multi-layer gold, referred to as goldene, represents a significant breakthrough in low-dimensional materials research. A fundamental understanding of its phonon transport properties, both intrinsic and extrinsic, is crucial for assessing its potential in applications such as thermal management, sensing, solar cells, and photothermal therapy. Here, we perform extensive machine-learning molecular dynamics simulations using an accurate and efficient unified neuroevolution potential to investigate the intrinsic lattice thermal conductivity of goldene and its tunability through external strain, defects, and layer thickness, drawing close comparisons with bulk gold. We find that single-layer goldene exhibits a high intrinsic lattice thermal conductivity of 34.4±0.4Wm−1K−1, which is approximately 17 times as large as that of bulk gold. While both systems exhibit a κ∼T−p dependence (p=1.69 for goldene, p=1.30 for bulk), they respond oppositely to tensile strain: κ decreases in bulk gold but increases in goldene. We attribute this contrasting behavior to the fundamentally different effects of strain on their phonon modes, hardening the dominant flexural phonons in goldene while softening all the phonon modes in bulk gold. Furthermore, both vacancy and adatom defects significantly reduce κ, with adatoms having a more pronounced effect. Finally, κ decreases monotonically with increasing layer number, rapidly converging toward the bulk value. Our results elucidate the intrinsic lattice thermal transport in goldene and demonstrate versatile strategies for tuning it, thereby enriching the understanding of heat transport in two-dimensional metallic systems.
A General Approach to Stereoregular Pseudo-Polysaccharides: Cationic Ring-Opening Polymerization of Monosaccharide Cyclic Thionocarbonates
Federated lung nodule segmentation using a hybrid transformer–U-Net architecture
Influence of electrical properties on thermal boundary conductance at metal/semiconductor interface
Recent experimental investigations have demonstrated that doping a semiconductor is a route to increase the thermal boundary conductance at metal/semiconductor interfaces. In this work, the influence of the electrical properties on heat transfer across metal/doped semiconductor junctions is investigated. Specifically, thermal boundary conductance at the interfaces between p- and n-doped silicon and titanium is measured by employing frequency-domain photothermal radiometry under varying external conditions. The influence of the doping level of the semiconductor, the barrier height, and the space charge area is analyzed. In particular, a 40% increase in the interface thermal conductance with the application of a current at n-doped silicon/titanium interfaces is reported. The enhancement of the thermal boundary conductance is explained by the shrinking of the surface charga area induced by the electric current. This study opens the way to modulating interfacial heat transfer at metal/semiconductor interfaces through fine tuning of electrical effects.
Synthesizing Polymer Woven Metal–Organic Framework Glass Membranes for Exceptional Pressure-Tolerant Carbon Capture
Image encryption with 6D hyperchaotic system and vision transformer autoencoder
Abstract This study proposes a fast image encryption method for color images, integrating an autoencoder to compress the image and a 6D hyperchaotic system to ensure enhanced security. Initially, a hash value is obtained from the original color image. The hash value, which serves as the secret key of the proposed encryption method, is used to initialize the state variables of the hyperchaotic system, which produces six distinct pseudo-random sequences. The input image is then compressed into a latent image (lossy) using a Vision Transformer Autoencoder model. This latent image is scrambled using chaotic sequences and a Random Shuffle technique. Diffusion is achieved through the Trifid Cipher transformation, which utilizes the remaining chaotic sequences to manipulate pixel values, thereby yielding a cipher version of the latent image. The suggested technique is faster and significantly enhances security compared to the state-of-the-art methods. This method achieves an average entropy of 7.9986, a correlation coefficient close to zero $$\approx$$ 0.00004, and key sensitivity analysis gives NPCR = 99.6110% and UACI = 33.4637%. Moreover, the key space of $$2^{512}$$ confirms that the proposed scheme offers strong resistance against brute-force attacks.
Density functional theory study on the formation mechanism and electronic properties of two-dimensional electron gas in LaInO3/BaSnO3 heterostructures with ferroelectric engineering
Compared to the well-studied LaAlO3/SrTiO3 heterostructure (HS), the regulation mechanism of ferroelectric on the interfacial properties of LaInO3/BaSnO3 HS remains relatively unexplored. Here, we investigate the interfacial properties of the LaInO3/BaSnO3 HS models with the BaTiO3 ferroelectric film on different positions and with different ferroelectric polarization directions and intensities using first-principles density functional theory calculations. Our results reveal that the BaTiO3 film deposited on the top of LaInO3/BaSnO3 HS can significantly improve the interfacial electron density of the HS. Moreover, the ferroelectric polarization (electric field) direction and intensity of the upper BaTiO3 film play an important role in optimizing the interfacial electronic property of LaInO3/BaSnO3 HS. When the direction of the electric field in the BaTiO3 film is the same as that in the LaInO3 film, it provides an extra force to drive the electron transfer from the surface to the (LaO)+/(SnO2)0 interface. The largest interfacial charge density is 1.56 × 1014 cm−2 in BaTiO3(−0.005)/LaInO3/BaSnO3 HS. When the direction of the electric field in the BaTiO3 film is opposite to that in the LaInO3 film, the force from the LaInO3 film is counteracted by the BaTiO3 film, resulting in less electron transfer to the (LaO)+/(SnO2)0 interface. The interfacial charge density in BaTiO3(+0.005)/LaInO3/BaSnO3 HS is approximately one-tenth of that in BaTiO3(−0.005)/LaInO3/BaSnO3 HS. These findings provide new insights into ferroelectric-dependent interfacial phenomena and offer valuable guidance for designing functional perovskite oxide interfaces.