These results suggested that CRISPR/Cas9 system could efficiently destroy HBV expressing templates (genotypes A-D) without apparent cytotoxicity. It may be a potential approach for eradication of persistent HBV cccDNA in chronic HBV infection patients.

In 2D magnets, interlayer exchange coupling is generally weak due to the van der Waals layered structure but it still plays a vital role in stabilizing the long‐range magnetic ordering and determining the magnetic properties. Using complementary neutron diffraction, magnetic, and torque measurements, the complete magnetic phase diagram of CrPS4 crystals is determined. CrPS4 shows an antiferromagnetic ground state (A‐type) formed by out‐of‐plane ferromagnetic monolayers with interlayer antiferromagnetic coupling along the c axis below TN = 38 K. Due to small magnetic anisotropy energy and weak interlayer coupling, the low‐field metamagnetic transitions in CrPS4, that is, a spin‐flop transition at ≈0.7 T and a spin‐flip transition from antiferromagnetic to ferromagnetic under a relatively low field of 8 T, can be realized for H∥c. Intriguingly, with an inherent in‐plane lattice anisotropy, spin‐flop‐induced moment realignment in CrPS4 for H∥c is parallel to the quasi‐1D chains of CrS6 octahedra. The peculiar metamagnetic transitions and in‐plane anisotropy make few‐layer CrPS4 flakes a fascinating platform for studying 2D magnetism and for exploring prototype device applications in spintronics and optoelectronics.

Current induced spin-orbit torques (SOT) allow for the efficient electrical manipulation of magnetism in spintronic devices. Engineering the SOT efficiency is a key goal that is pursued by maximizing the active interfacial spin accumulation or modulating the non-equilibrium spin-density that builds up through the spin Hall and inverse spin galvanic effects. Regardless of the origin, the fundamental requirement for the generation of the current-induced torques is a net spin accumulation. Here, we report the large enhancement of the SOT efficiency in TmIG / Pt by capping with a CuOx layer. Considering the weak spin-orbit coupling (SOC) of CuOx, these surprising findings are explained as a result of orbital current generated from CuOx in contact with Pt. This interface-generated orbital current is injected into Pt and converted into a spin current due to the large SOC of Pt. The converted spin current decays across the Pt and exerts a "non-local" torque on TmIG. This additional torque leads to a maximum enhancement of the SOT efficiency of a factor 16 for 1.5 nm of Pt at room temperature, thus opening a path to

Science and Technology, NO-7491 Trondheim, Norway ‡ These two authors contribute equally to this work Keywords: Magnetic insulator, SOT switching, Dzyaloshinskii-Moriya interaction, Chiral domain wall, Skyrmion. The interfacial Dzyaloshinskii-Moriya interaction (DMI) in multilayers of heavy metal and ferromagnetic metals enables the stabilization of novel chiral spin structures such as skyrmions. Magnetic insulators, on the other hand can exhibit enhanced dynamics and properties such as lower magnetic damping and therefore it is of interest to combine the properties enabled by interfacial DMI with insulating systems. Here, we demonstrate the presence of interfacial DMI in heterostructures that include insulating magnetic layers. We use a bilayer of perpendicularly magnetized insulating thulium iron garnet (TmIG) and the heavy metal platinum, and find a surprisingly strong interfacial DMI that, combined with spin-orbit torque results, in efficient switching. The interfacial origin is confirmed through thickness dependence measurements of the DMI, revealing the characteristic 1/thickness dependence with one order of magnitude longer decay length compared to metallic layers. We combine chiral spin structures and spinorbit torques for efficient switching and identify skyrmions that allow us to establish the GGG/TmIG interface as the origin of the DMI.The Dzyaloshinskii-Moriya interaction (DMI), an asymmetric exchange interaction, has been intensely studied due to the formation of chiral spin textures such as magnetic

Sex-determining region Y box 6 (SOX6) has been described as a tumor-suppressor gene in several cancers. Our previous work has suggested that SOX6 upregulated p21Waf1/Cip1(p21) expression in a p53-dependent manner; however, the underlying mechanism has remained elusive. In this study, we confirmed that SOX6 can suppress cell proliferation in vitro and in vivo by stabilizing p53 protein and subsequently upregulating p21. Co-immunoprecipitation and immunocytofluorescence assays demonstrated that SOX6 can promote formation of the p14ARF-HDM2-p53 ternary complex by promoting translocation of p14ARF (p14 alternate reading frame tumor suppressor) to the nucleoplasm, thereby inhibiting HDM2-mediated p53 nuclear export and degradation. Chromatin immunoprecipitation combined with PCR assay proved that SOX6 can bind to a potential binding site in the regulatory region of the c-Myc gene. Furthermore, we confirmed that SOX6 can downregulate the expression of c-Myc, as well as its direct target gene nucleophosmin 1 (NPM1), and that the SOX6-induced downregulation of NPM1 is linked to translocation of p14ARF to the nucleoplasm. Finally, we showed that the highly conserved high-mobility group (HMG) domain of SOX6 is required for SOX6-mediated p53 stabilization and tumor inhibitory activity. Collectively, these results reveal a new mechanism of SOX6-mediated tumor suppression involving p21 upregulation via the p14ARF-HDM2-p53 axis in an HMG domain-dependent manner.

Here, we report the realization of epitaxial Y3Fe5O12 (YIG) thin films with perpendicular magnetic anisotropy (PMA). The films are grown on the substituted gadolinium gallium garnet substrate (SGGG) by pulsed laser deposition. It was found that a thin buffer layer of Sm3Ga5O12 (SmGG) grown on top of SGGG can suppress the strain relaxation, which helps induce a large enough PMA to overcome the shape anisotropy in YIG thin films. The reciprocal space mappings analysis reveals that the in-plane strain relaxation is suppressed, while the out-of-plane strain relaxation exhibits a strong dependence on the film thickness. We found that the PMA can be achieved for both bilayer (YIG/SmGG) and tri-layer (SmGG/YIG/SmGG) structural films with YIG layer thicknesses up to 20 nm and 40 nm, respectively.

We report the observation of magnetoresistance (MR) originating from the orbital angular momentum transport (OAM) in a Permalloy (Py) / oxidized Cu (Cu*) heterostructure: the orbital Rashba-Edelstein magnetoresistance. The angular dependence of the MR depends on the relative angle between the induced OAM and the magnetization in a similar fashion as the spin Hall magnetoresistance (SMR). Despite the absence of elements with large spin-orbit coupling, we find a sizable MR ratio, which is in contrast to the conventional SMR which requires heavy elements. By varying the thickness of the Cu* layer, we confirm that the interface is responsible for the MR, suggesting that the orbital Rashba-Edelstein effect is responsible for the generation of the OAM. Through Py thickness-dependence studies, we find that the effective values for the spin diffusion and spin dephasing lengths of Py are significantly larger than the values measured in Py / Pt bilayers, approximately by the factor of 2 and 4, respectively. This implies that another mechanism beyond the conventional spin-based scenario is responsible for the MR observed in Py / Cu* structures -originated in a sizeable transport of OAM. Our findings not only unambiguously demonstrate current-induced torques without using any heavy elements via the OAM channel but also provide an important clue towards the microscopic understanding of the role that OAM transport can play for magnetization dynamics.

The CRISPR/Cas9 system is a novel genome editing technology which has been successfully used to inhibit HBV replication. Here, we described a novel gRNA-microRNA (miRNA)-gRNA ternary cassette driven by a single U6 promoter. With an anti-HBV pri-miR31 mimic integrated between two HBV-specific gRNAs, both gRNAs could be separated from the long transcript of gRNA-miR-HBV-gRNA ternary cassette through Drosha/DGCR8 processing. The results showed that the gRNA-miR-HBV-gRNA ternary cassette could efficiently express two gRNAs and miR-HBV. The optimal length of pri-miRNA flanking sequence in our ternary cassette was determined to be 38 base pairs (bp). Besides, HBV-specific gRNAs and miR-HBV in gRNA-miR-HBV-gRNA ternary cassette could exert a synergistic effect in inhibiting HBV replication and destroying HBV genome in vitro and in vivo. Most importantly, together with RNA interference (RNAi) approach, the HBV-specific gRNAs showed the potent activity on the destruction of HBV covalently closed circular DNA (cccDNA). Since HBV cccDNA is an obstacle for the elimination of chronic HBV infection, the gRNA-miR-HBV-gRNA ternary cassette may be a potential tool for the clearance of HBV cccDNA.