Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in ...a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).
The Berry phase picture provides important insights into the electronic properties of condensed matter systems. The intrinsic anomalous Hall (AH) effect can be understood as the consequence of ...non-zero Berry curvature in momentum space. Here, we fabricate TI/magnetic TI heterostructures and find that the sign of the AH effect in the magnetic TI layer can be changed from being positive to negative with increasing the thickness of the top TI layer. Our first-principles calculations show that the built-in electric fields at the TI/magnetic TI interface influence the band structure of the magnetic TI layer, and thus lead to a reconstruction of the Berry curvature in the heterostructure samples. Based on the interface-induced AH effect with a negative sign in TI/V-doped TI bilayer structures, we create an artificial "topological Hall effect"-like feature in the Hall trace of the V-doped TI/TI/Cr-doped TI sandwich heterostructures. Our study provides a new route to create the Berry curvature change in magnetic topological materials that may lead to potential technological applications.
Magnetic topological states refer to a class of exotic phases in magnetic materials with the non‐trivial topological property determined by magnetic spin configurations. An example of such states is ...the quantum anomalous Hall (QAH) state, which is a zero magnetic field manifestation of the quantum Hall effect. Current research in this direction focuses on QAH insulators with a thickness of less than 10 nm. Here, molecular beam epitaxy (MBE) is employed to synthesize magnetic TI trilayers with a thickness of up to ≈106 nm. It is found that these samples exhibit well‐quantized Hall resistance and vanishing longitudinal resistance at zero magnetic field. By varying the magnetic dopants, gate voltages, temperature, and external magnetic fields, the properties of these thick QAH insulators are examined and the robustness of the 3D QAH effect is demonstrated. The realization of the well‐quantized 3D QAH effect indicates that the nonchiral side surface states of the thick magnetic TI trilayers are gapped and thus do not affect the QAH quantization. The 3D QAH insulators of hundred‐nanometer thickness provide a promising platform for the exploration of fundamental physics, including axion physics and image magnetic monopole, and the advancement of electronic and spintronic devices to circumvent Moore's law.
The first work in synthesizing 3D quantum anomalous Hall (QAH) insulators with a thickness of one hundred nanometers, exceeding ten times the thickest QAH sample record, is reported. The hundred‐nanometer‐thick QAH insulators provide a promising platform for the exploration of the topological magnetoelectric effect, image magnetic monopole, as well as high‐order topological insulator (TI) phase.
A quantum anomalous Hall (QAH) state is a two-dimensional topological insulating state that has a quantized Hall resistance of h/(Ce
) and vanishing longitudinal resistance under zero magnetic field ...(where h is the Planck constant, e is the elementary charge, and the Chern number C is an integer)
. The QAH effect has been realized in magnetic topological insulators
and magic-angle twisted bilayer graphene
. However, the QAH effect at zero magnetic field has so far been realized only for C = 1. Here we realize a well quantized QAH effect with tunable Chern number (up to C = 5) in multilayer structures consisting of alternating magnetic and undoped topological insulator layers, fabricated using molecular beam epitaxy. The Chern number of these QAH insulators is determined by the number of undoped topological insulator layers in the multilayer structure. Moreover, we demonstrate that the Chern number of a given multilayer structure can be tuned by varying either the magnetic doping concentration in the magnetic topological insulator layers or the thickness of the interior magnetic topological insulator layer. We develop a theoretical model to explain our experimental observations and establish phase diagrams for QAH insulators with high, tunable Chern number. The realization of such insulators facilitates the application of dissipationless chiral edge currents in energy-efficient electronic devices, and opens up opportunities for developing multi-channel quantum computing and higher-capacity chiral circuit interconnects.
One-dimensional chiral interface channels can be created at the boundary of two quantum anomalous Hall (QAH) insulators with different Chern numbers. Such a QAH junction may function as a chiral edge ...current distributer at zero magnetic field, but its realization remains challenging. Here, by employing an in-situ mechanical mask, we use molecular beam epitaxy to synthesize QAH insulator junctions, in which two QAH insulators with different Chern numbers are connected along a one-dimensional junction. For the junction between Chern numbers of 1 and -1, we observe quantized transport and demonstrate the appearance of the two parallel propagating chiral interface channels along the magnetic domain wall at zero magnetic field. For the junction between Chern numbers of 1 and 2, our quantized transport shows that a single chiral interface channel appears at the interface. Our work lays the foundation for the development of QAH insulator-based electronic and spintronic devices and topological chiral networks.
A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of ...N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC
50
values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (k
off
=1.60 × 10
−3
s
−1
) from the catalytic domain.
Hepatic stellate cells (HSCs) play an important role in the initiation and development of liver fibrogenesis, and abnormal glucose metabolism is increasingly being considered a crucial factor ...controlling phenotypic transformation in HSCs. However, the role of the factors affecting glycolysis in HSCs in the experimental models of liver fibrosis has not been completely elucidated. In this study, we showed that glycolysis was significantly enhanced, while the expression of brain and muscle arnt-like protein-1 (Bmal1) was downregulated in fibrotic liver tissues of mice, primary HSCs, and transforming growth factor-β1 (TGF-β1)-induced LX2 cells. Overexpression of Bmal1 in TGF-β1-induced LX2 cells blocked glycolysis and inhibited the proliferation and phenotypic transformation of activated HSCs. We further confirmed the protective effect of Bmal1 in liver fibrosis by overexpressing Bmal1 from hepatic adeno-associated virus 8 in mice. In addition, we also showed that the regulation of glycolysis by Bmal1 is mediated by the isocitrate dehydrogenase 1/α-ketoglutarate (IDH1/α-KG) pathway. Collectively, our results indicated that a novel Bmal1-IDH1/α-KG axis may be involved in regulating glycolysis of activated HSCs and might hence be used as a therapeutic target for alleviating liver fibrosis.
Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator and the quantum anomalous Hall (QAH) effect was observed in exfoliated MnBi2Te4 flakes. Here, we used ...molecular beam epitaxy (MBE) to grow MnBi2Te4 films with thickness down to 1 septuple layer (SL) and performed thickness-dependent transport measurements. We observed a nonsquare hysteresis loop in the antiferromagnetic state for films with thickness greater than 2 SL. The hysteresis loop can be separated into two AH components. We demonstrated that one AH component with the larger coercive field is from the dominant MnBi2Te4 phase, whereas the other AH component with the smaller coercive field is from the minor Mn-doped Bi2Te3 phase. The extracted AH component of the MnBi2Te4 phase shows a clear even–odd layer-dependent behavior. Our studies reveal insights on how to optimize the MBE growth conditions to improve the quality of MnBi2Te4 films.
Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior. However, these hydrogels suffer from ...low mechanical properties, uncontrolled degradation, and insufficient osteogenic activity, which limits their applications in bone regeneration. In this study, we developed hybrid gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogels that incorporated mesoporous bioactive glass nanoparticles (MBGNs) as bioactive fillers for bone regeneration. Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax. The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation. The gelation time decreased with increasing the concentration of MBGNs added. Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength. The injectability of the hydrogels was not significantly affected by the MBGN incorporation. Also, the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs. The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities.
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•In situ self-crosslinking of hybrid Gel-OCS/MBGN hydrogels.•Hybrid hydrogels are porous, injectable and bioadhesive.•Incorporation of MBGNs enhances mechanical and mineralization properties of hydrogels.•Osteogenic differentiation of BMSCs enhanced after incorporating MBGNs into hydrogels.•The presence of MBGNs enhances in vivo rat cranial defect restoration.
Abstract
An axion insulator is a three-dimensional (3D) topological insulator (TI), in which the bulk maintains the time-reversal symmetry or inversion symmetry but the surface states are gapped by ...surface magnetization. The axion insulator state has been observed in molecular beam epitaxy (MBE)-grown magnetically doped TI sandwiches and exfoliated intrinsic magnetic TI MnBi
2
Te
4
flakes with an even number layer. All these samples have a thickness of ~ 10 nm, near the 2D-to-3D boundary. The coupling between the top and bottom surface states in thin samples may hinder the observation of quantized topological magnetoelectric response. Here, we employ MBE to synthesize magnetic TI sandwich heterostructures and find that the axion insulator state persists in a 3D sample with a thickness of ~ 106 nm. Our transport results show that the axion insulator state starts to emerge when the thickness of the middle undoped TI layer is greater than ~ 3 nm. The 3D hundred-nanometer-thick axion insulator provides a promising platform for the exploration of the topological magnetoelectric effect and other emergent magnetic topological states, such as the high-order TI phase.
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