FGFR redundancy limits the efficacy of FGFR4-selective inhibitors in hepatocellular carcinoma.

Aberrant fibroblast growth factor 19 (FGF19) signaling mediated by its receptor, FGF receptor 4 (FGFR4), and coreceptor, klotho ß (KLB), is a driver of hepatocellular carcinoma (HCC). Several potent FGFR4-selective inhibitors have been developed but have exhibited limited efficacy in HCC clinical trials. Here, by using HCC cell line models from the Cancer Cell Line Encyclopedia (CCLE) and the Liver Cancer Model Repository (LIMORE), we show that selective FGFR4 inactivation was not sufficient to inhibit cancer cell proliferation and tumor growth in FGF19-positive HCC. Moreover, genetic inactivation of KLB in these HCC cells resulted in a fitness defect more severe than that resulting from inactivation of FGFR4. By a combination of biochemical and genetic approaches, we found that KLB associated with FGFR3 and FGFR4 to mediate the prosurvival functions of FGF19. KLB mutants defective in interacting with FGFR3 or FGFR4 could not support the growth or survival of HCC cells. Genome-wide CRISPR loss-of-function screening revealed that FGFR3 restricted the activity of FGFR4-selective inhibitors in inducing cell death; the pan-FGFR inhibitor erdafitinib displayed superior potency than FGFR4-selective inhibitors in suppressing the growth and survival of FGF19-positive HCC cells. Among FGF19-positive HCC cases from The Cancer Genome Atlas (TCGA), FGFR3 is prevalently coexpressed with FGFR4 and KLB, suggesting that FGFR redundancy may be a common mechanism underlying the de novo resistance to FGFR4 inhibitors. Our study provides a rationale for clinical testing of pan-FGFR inhibitors as a treatment strategy for FGF19-positive HCC.

Layer-Polarized Anomalous Hall Effects from Inversion-Symmetric Single-Layer Lattices.

In the field of physics and materials science, the discovery of the layer-polarized anomalous Hall effect (LP-AHE) stands as a crucial development. The current research paradigm is rooted in topological or inversion-asymmetric valleytronic systems, making such a phenomenon rather rare. In this work, a universal design principle for achieving the LP-AHE from inversion-symmetric single-layer lattices is proposed. Through tight-binding model analysis, we demonstrate that by stacking into antiferromagnetic van der Waals bilayer lattices, the coupling physics between PT symmetry and vertical external bias can be realized. This coupling reveals the previously neutralized layer-locked Berry curvature, compelling the carriers to move in a specific direction within a given layer, thereby realizing the LP-AHE. Intriguingly, the chirality of the LP-AHE can be effectively switched by modulating the direction of vertical external bias. First-principles calculations validate this mechanism in bilayer T-FeCl2 and MnPSe3. Our results pave the way for new explorations of the LP-AHE.

Two-dimensional ferroelastic semiconductors in single-layer indium oxygen halide InOY (Y = Cl/Br).

Two-dimensional ferroelastic materials have triggered tremendous interest for applications in nonvolatile memory devices. Here using first-principles calculations, we identify a novel class of two-dimensional ferroelastic materials, single-layer InOY (Y = Cl/Br). The ferroelasticity in single-layer InOY shows a moderate switching barrier and high reversible strain, which are promising for practical applications in nonvolatile memory. Meanwhile, single-layer InOY is a semiconductor with an indirect band gap. The unique combination of being a semiconductor with ferroelastic behaviors would be beneficial for the integration of functional nonvolatile memories into nanocircuits. Moreover, both systems can readily be exfoliated from their layered bulks due to the weak interlayer interactions. These intriguing behaviors suggest the high potential of single-layer InOY for practical memory device applications.

Layer-polarized anomalous Hall effects in valleytronic van der Waals bilayers.

The layer-polarized anomalous Hall effect (LP-AHE), derived from the coupling between the Berry curvature and the layer degree of freedom, is of importance for both fundamental physics and device applications. Nonetheless, the current research paradigm is rooted in topological systems, rendering such a phenomenon rather scarce. Here, through model analysis, we propose an alternative, but general, mechanism for realizing the LP-AHE in valleytronic van der Waals bilayers by interlayer sliding. The interaction between out-of-plane ferroelectricity and A-type antiferromagnetism gives rise to the layer-locked Berry curvature and thus the long-sought LP-AHE in bilayer systems. The LP-AHE can be strongly coupled with sliding ferroelectricity, rendering it ferroelectrically controllable and reversible. The mechanism is demonstrated in a series of real valleytronic materials, including bilayer VSi2P4, VSi2N4, FeCl2, RuBr2 and VClBr. The new mechanism and phenomena provide a significant new direction to realize the LP-AHE and explore its application in electronics.

Nonvolatile electro-mechanical coupling in two-dimensional lattices.

Electro-mechanical coupling is of great interest for applications in sensors, actuators and energy harvesters. While the control of electrical charge by mechanical force has been studied extensively, reverse coupling is rarely explored, especially in two-dimensional (2D) lattices. Herein, we propose a novel mechanism for electro-mechanical coupling that realizes the electric field switching of the dimensions of a 2D lattice in a reversible and nonvolatile fashion, through the mediated strength of interlayer interactions in ferroelectric bilayer systems. Based on first-principles calculations, the validity of this mechanism is demonstrated in a series of real bilayer materials, i.e., MoS2/ReIrGe2S6, Sb/In2Se3 and bilayer In2Se3. The interface differences due to polarization play a crucial role in realizing such nonvolatile electro-mechanical coupling, and the underlying physical origin is discussed. These explored phenomena and insights offer a novel avenue for the highly desired nonvolatile electric field control of mechanical strain.

Prediction of two-dimensional antiferromagnetic ferroelasticity in an AgF2 monolayer.

Two-dimensional multiferroics, simultaneously harboring antiferromagneticity and ferroelasticity, are essential and highly sought for miniaturized device applications, such as high-density data storage, but thus far they have rarely been explored. Herein, using first principles calculations, we identified two-dimensional antiferromagnetic ferroelasticity in an AgF2 monolayer that is dynamically and thermally stable, and can be easily fabricated from its bulk. The AgF2 monolayer is an antiferromagnetic semiconductor with large spin polarization, and with great structural distortion due to its intrinsic Jahn-Teller effect when thinning the AgF2 down to a monolayer. Additionally, it features excellent ferroelasticity with high transition signal and a low switching barrier, rendering the room-temperature nonvolatile memory accessible. Such coexistence of antiferromagneticity and ferroelasticity is of great significance to the study of two-dimensional multiferroics and also renders the AgF2 monolayer a promising platform for future multifunctional device applications.

Two-Dimensional Ferroelastic Semiconductors in Nb2SiTe4 and Nb2GeTe4 with Promising Electronic Properties.

Two-dimensional crystals with coupling of ferroelasticity and attractive electronic properties offer unprecedented opportunities for achieving long-sought controllable devices. However, to date, the reported proposals are mainly based on hypothetical structures. Here, using first-principles calculations, we identify single-layer Nb2ATe4 (A = Si, Ge), which can be exfoliated from its layered bulk, as a promising candidate. Single-layer Nb2ATe4 is found to be dynamically, thermally, and chemically stable. It possesses excellent ferroelasticity with high reversible ferroelastic strain and a moderate ferroelastic transition energy barrier, which are beneficial for practical applications. Meanwhile, it harbors outstanding anisotropic electronic properties, including anisotropic carrier mobility and optical properties. More importantly, the anisotropic properties of single-layer Nb2ATe4 can be efficiently controlled through ferroelastic switching. These appealing properties combined with the experimental feasibility render single-layer Nb2ATe4 an extraordinary platform for realizing controllable devices.

Oxygen-Vacancy-Enhanced Singlet Oxygen Production for Selective Photocatalytic Oxidation.

Oxygen vacancies are usually thought to be beneficial for photogenerated charge separation. In this work, the oxygen vacancies in ov-Bi2 O3 (Bi2 O3 with oxygen vacancy) were found to be able to produce 1 O2 in the dark owing to chemical adsorption. The oxygen vacancies were further found to be responsible for ov-Bi2 O3 exhibiting higher 1 O2 generation under light irradiation with 1 O2 as the only reactive oxygen species (ROS) than Bi2 O3 with 1 O2 , H2 O2 , and others as the ROS. The photocatalytic activity was investigated for the selective photo-oxidation of phenyl methyl sulfide to phenyl methyl sulfoxide and phenyl alcohol to benzaldehyde. In either case, ov-Bi2 O3 displayed better performance than Bi2 O3 , suggesting the significant role of oxygen vacancies in modulating the photocatalytic oxidation properties. This work provides an alternative approach to obtain singlet oxygen, which may guide further design of photocatalysts with high efficiency and selectivity towards photocatalytic organic synthesis.

Nonmetal-Atom-Doping-Induced Valley Polarization in Single-Layer Tl2O.

Valleytronics that relies on the valley degree of freedom is attracting growing interest because it provides a new platform for information storage. One obstacle in this field is to realize valley polarization in an efficient route to manipulate the valley physics. Here we propose a strategy to induce valley polarization by nonmetal atom doping in single-layer Tl2O. Owing to the intrinsic inversion asymmetry and large spin-orbit coupling, there are a two-fold valley degeneracy and an excellent spin-valley independence in single-layer Tl2O. Upon introducing C/N atoms in single-layer Tl2O, the intriguing valley polarization successfully appears, and the obtained polarization strengths are considerable. In particular, for N-doped case, the top valence band locates around the Fermi level, and there are no impurity states in the band gap, which is desirable for practical applications. It is predicted that these valley polarizations can be effectively engineered under the magnetic field and external strain, suggesting that the control of valley physics in single-layer Tl2O is accessible.

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity.

Ribosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.