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Chiral magnetic domains are topological spin textures in which the Dzyaloshinskii–Moriya interaction assigns a given chirality to the domain walls. Notably, despite rapid progress in chiral magnetic research, one fundamental issue that remains unclear is how the chirality of chiral magnetic domains change as a magnetic field deforms the spin texture. Using spin-polarized low energy electron microscopy, the evolution of Fe/Ni chiral magnetic stripe domains are investigated in single-crystalline Fe/Ni/Cu/Co/Cu(001) multilayers in which the interlayer magnetic coupling between the Co and Fe/Ni films serves as an in-plane magnetic field. Contrary to theoretical works, it is found that the chirality of the Néel walls results in a parallel alignment of the magnetic stripes with the in-plane magnetic field direction. The transformation of chiral Néel walls into achiral Bloch walls can be precisely controlled by tuning the Cu spacer layer thickness. In addition, the domain wall exhibits a spontaneous asymmetry within the in-plane magnetic field, leading to an unbalanced chirality between the left-handed and right-handed Bloch walls. These new results foster a better understanding of the chiral domain properties within a magnetic field.

van der Waals (vdW) magnetic materials provide an ideal platform to study low-dimensional magnetism. However, observations of magnetic characteristics of these layered materials truly distinguishing them from conventional magnetic thin film systems have been mostly lacking. In an effort to investigate magnetic properties unique to vdW magnetic materials, we examine the exchange bias effect, a magnetic phenomenon emerging at the ferromagnetic-antiferromagnetic interface. Exchange bias is observed in the naturally oxidized vdW ferromagnet Fe3GeTe2, owing to an antiferromagnetic ordering in the surface oxide layer. Interestingly, the magnitude and thickness dependence of the effect is unlike those expected in typical thin-film systems. We propose a possible mechanism for this behavior, based on the weak interlayer magnetic coupling inherent to vdW magnets, demonstrating the distinct properties of these materials. Furthermore, the robust and sizable exchange bias for vdW magnets persisting up to relatively high temperatures presents a significant advance for realizing practical two-dimensional spintronics.

Searching for the ground state of a given system is one of the most fundamental and classical questions in scientific research fields. However, when the system is complex and large, it often becomes an intractable problem; there is essentially no possibility of finding a global energy minimum state with reasonable computational resources. Recently, a novel method based on deep learning techniques was devised as an innovative optimization method to estimate the ground state. We apply this method to one of the most complicated spin-ice systems, aperiodic Penrose P3 patterns. From the results, we discover new configurations of topologically induced emergent frustrated spins, different from those previously known. Additionally, a candidate of the ground state for a still unexplored type of Penrose P3 spin-ice system is first proposed through this study. We anticipate that the capabilities of the deep learning techniques will not only improve our understanding on the physical properties of artificial spin-ice systems, but also bring about significant advances in a wide range of scientific research fields requiring computational approaches for optimization.

We studied the motion of a skyrmion pair under the action of independently controllable spin transfer torques. A skyrmion pair made of two coupled skyrmions with opposite skyrmion numbers moves along the direction of the current flow when the currents flowing in the two skyrmions, are identical while it moves perpendicular to the direction of current flow where the currents flow in opposite directions. Manipulating all the degrees of freedom for the strengths of both currents enables the directional motion of the skyrmion pair. We used the Thiele equation to investigate how the strengths of the currents are related with the motion of the skyrmion, and we obtained a tensor that provided the relation between the currents and the force that binds the two skyrmions, and we were able to realize a designed motion. We performed a dynamic simulation of the motion of the skyrmion pair and compared the results with those calculated using the Thiele equation.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion: CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P

Magnetic skyrmions are topologically nontrivial spin textures with envisioned applications in energy-efficient magnetic information storage. Toggling the presence of magnetic skyrmions via writing/deleting processes is essential for spintronics applications, which usually require the application of a magnetic or electric field or an electric current. Here we demonstrate the reversible field-free writing/deleting of skyrmions at room temperature, via hydrogen chemisorption/desorption on the surface of Ni and Co films. Supported by Monte-Carlo simulations, the skyrmion creation/annihilation is attributed to the hydrogen-induced magnetic anisotropy change on ferromagnetic surfaces. We also demonstrate the role of hydrogen and oxygen on magnetic anisotropy and skyrmion deletion on other magnetic surfaces. Our results open up new possibilities for designing skyrmionic and magneto-ionic devices.

The properties of complicated magnetic domain structures induced by various spin–spin interactions in magnetic systems have been extensively investigated in recent years. To understand the statistical and dynamic properties of complex magnetic structures, it is crucial to obtain information on the effective field distribution over the structure, which is not directly provided by magnetization. In this study, we use a deep learning technique to estimate the effective fields of spin configurations. We construct a deep neural network and train it with spin configuration datasets generated by Monte Carlo simulation. We show that the trained network can successfully estimate the magnetic effective field even though we do not offer explicit Hamiltonian parameter values. The estimated effective field information is highly applicable; it is utilized to reduce noise, correct defects in the magnetization data, generate spin configurations, estimate external field responses, and interpret experimental images.

Plant-derived polyphenols have emerged as molecular building blocks for biomedical architectures. However, the isolation of polyphenols from other components requires labor-intensive procedures, which increases costs and often raises environmental concerns. Here, we suggest that decaffeination can be a convenient and cost-effective method for enhancing the antibacterial performance of polyphenol-rich tea extracts. As a demonstration, we compared the properties of a nano-thin coating made of decaffeinated (dGT coating) and raw green tea extract (GT coating). The dGT coating exhibited enhanced antibacterial performance with regard to bacterial killing and prevention of bacterial attachment compared with the GT coating. Moreover, the chemical reactivity of the dGT coating was further utilized for secondary modifications, which enhanced the overall antibacterial performance of the modified surface. Given its intrinsic low toxicity, we envision that the developed antibacterial coating is ready for the next steps toward application in real clinical settings.

Numerical generation of physical states is essential to all scientific research fields. The role of a numerical generator is not limited to understanding experimental results; it can also be employed to predict or investigate characteristics of uncharted systems. A variational autoencoder model is devised and applied to a magnetic system to generate energetically stable magnetic states with low local deformation. The spin structure stabilization is made possible by taking the explicit magnetic Hamiltonian into account to minimize energy in the training process. A significant advantage of the model is that the generator can create a long‐range ordered ground state of spin configuration by increasing the role of stabilization even if the ground states are not necessarily included in the training process. It is expected that the proposed Hamiltonian‐guided generative model can bring about great advances in numerical approaches used in various scientific research fields., An energy‐minimization variational autoencoder model is devised to generate energetically stable physical states by taking the explicit Hamiltonian into the training process. A significant advantage of the model is that the generator can produce the ground states of various systems even if the ground states are not necessarily included in the training process.

van der Waals (vdW) magnetic materials provide an ideal platform to study low-dimensional magnetism. However, observations of magnetic characteristics of these layered materials truly distinguishing them from conventional magnetic thin film systems have been mostly lacking. In an effort to investigate magnetic properties unique to vdW magnetic materials, we examine the exchange bias effect, a magnetic phenomenon emerging at the ferromagnetic-antiferromagnetic interface. Exchange bias is observed in the naturally oxidized vdW ferromagnet Fe

Investigating the effects of the complex magnetic interactions on the formation of nontrivial magnetic phases enables a better understanding of magnetic materials. Moreover, an effective method to systematically control those interactions and phases could be extensively utilized in spintronic devices. SrRuO3 heterostructures function as a suitable material system to investigate the complex magnetic interactions and the resultant formation of topological magnetic phases, as the heterostructuring approach provides an accessible controllability to modulate the magnetic interactions. In this study, we have observed that the Hall effect of SrRuO3/SrTiO3 superlattices varies nonmonotonically with the repetition number (z). Using Monte Carlo simulations, we identify a possible origin of this experimental observation: the interplay between the Dzyaloshinskii-Moriya interaction and dipole-dipole interaction, which have differing z-dependence, might result in a z-dependent modulation of topological magnetic phases. This approach provides not only a collective understanding of the magnetic interactions in artificial heterostructures but also a facile control over the skyrmion phases., Comment: 3 figures

The domain structure in in-plane magnetized Fe/Ni/W(110) films is investigated using spin-polarized low-energy electron microscopy. A novel transition of the domain wall shape from a zigzag-like pattern to straight is observed as a function of the film thickness, which is triggered by the transition of the domain wall type from out-of-plane chiral wall to in-plane N\'eel wall. The contribution of the Dzyaloshinskii-Moriya interaction to the wall energy is proposed to explain the transition of the domain wall shape, which is supported by Monte-Carlo simulations., Comment: 12 pages, 3 figures

Understanding spin textures in magnetic systems is extremely important to the spintronics and it is vital to extrapolate the magnetic Hamiltonian parameters through the experimentally determined spin. It can provide a better complementary link between theories and experimental results. We demonstrate deep learning can quantify the magnetic Hamiltonian from magnetic domain images. To train the deep neural network, we generated domain configurations with Monte Carlo method. The errors from the estimations was analyzed with statistical methods and confirmed the network was successfully trained to relate the Hamiltonian parameters with magnetic structure characteristics. The network was applied to estimate experimentally observed domain images. The results are consistent with the reported results, which verifies the effectiveness of our methods. On the basis of our study, we anticipate that the deep learning techniques make a bridge to connect the experimental and theoretical approaches not only in magnetism but also throughout any scientific research.

Obstructive sleep apnea (OSA) is a common disease associated with significant morbidity and mortality. Sleep quality is an important issue; some patients with acute lung injury (ALI) have underlying OSA. However, the potential influences of OSA on ALI have not been reported until now. In this study, we evaluated the impact of preceding intermittent hypoxia (IH), a typical characteristic of OSA, on lipopolysaccharide (LPS)-induced ALI in a mouse model.C57BL/6J mice were randomly divided into four groups: room air-control (RA-CTL), intermittent hypoxia-control (IH-CTL), room air-lipopolysaccharide (RA-LPS), and intermittent hypoxia-lipopolysaccharide (IH-LPS) groups. The mice were exposed to RA or IH (20 cycles/h, FiOThe IH-LPS group tended to exhibit more severe inflammation, fibrosis, and oxidative stress compared to the other groups, including the RA-LPS group. Total cell, neutrophil, and eosinophil counts in bronchoalveolar lavage fluid increased significantly in the IH-LPS group compared to the RA-LPS group. Compared to the RA-LPS group, the hydroxyproline level increased significantly in the IH-LPS group. In addition, the IH-LPS group exhibited significantly more terminal deoxynucleotidyl transferase dUTP nick end labeled-positive cells compared to the RA-LPS group.We found that prior IH may negatively impact LPS-induced ALI in a mouse model. This result suggests that ALI in patients with OSA may be more of a concern. Further research into the mechanisms underlying the effects of IH on ALI is needed.

Autoencoder , an artificial neural network , was adopted to generate spin structures that interpolate and extrapolate between two distinct magnetic chiral states, the labyrinth structure and the skyrmion structure. We trained the autoencoder using two distinct magnetic chiral structures. Each input data is encoded through a deep learning process into a latent code, a new representation of the information in a reduced dimensional space. We investigated the latent space to acquire information on the structure of the latent code distribution. With the acquired information, we successfully produced various magnetic structures that exhibit plausible properties under various external fields not provided in the training data. The latent codes were modified by two algorithms. The first algorithm utilizes inversion and translation operation in the latent space and the second algorithm uses recursive flow with a modification bias. The first produced structures preserving the chiral structure of original data and the second produced statistically plausible states.

Using Monte-Carlo simulations and micromagnetic simulations, we reveal how the spin structural correlation and the skyrmion dynamics are affected by the interlayer coupling in a chiral magnetic bilayer system, in which the two layers have opposite chirality. The interaction through interlayer coupling between chiral magnetic structures influences the static and dynamics properties profoundly. The competition between the Dzyaloshinskii-Moriya interaction and the interlayer interaction allows multiple magnetic structures to be energetically stable, which includes sole skyrmion states (skyrmion appears in only one of the layers) and skyrmion pair states (coupled skyrmions in top and bottom layers). When current driven spin transfer torques are applied to each state, the sole skyrmion state is mainly propelled by a spin transfer torque causing the skyrmion hall effect, but the skyrmion pair state is propelled by a torque from skyrmion-skyrmion interaction and not influenced by the skyrmion hall effect. Also upon application of an external magnetic field, we found the skyrmions in a skyrmion pair state extinguish in an exclusive way, as the annihilation of a skyrmion in one of the layers stabilizes the once paired skyrmion in the other layer, i.e. the skyrmion lattice sites have only one skyrmion in either layer.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with high mortality worldwide. Here the underlying antitumor mechanism of gallotannin was elucidated in HCC cells. Gallotannin suppressed viability and colony formation, increased subG1 portion and also induced senescence via upregulation of p21, G0/G1 arrest and higher SA-β-gal activity in HepG2 and SK-Hep1 cells. However, pan-caspase inhibitor Z-VAD-FMK reversed the ability of gallotannin to activate caspase 3 at 48 h after treatment in two HCC cells. Of note, gallotannin also induced autophagic features by increasing LC3 punctae, LC3B-II conversion, autophagic vacuoles and decreasing the expression of Beclin1 in two HCC cells. Furthermore, autophagy flux assay using GFP–mRFP–LC3 plasmid revealed increased yellowish color and late autophagy inhibitor CQ or NH4Cl enhanced cytotoxicity, LC3B-II conversion, and LC3 punctae in gallotannin-treated HepG2 and SK-Hep1 cells compared to early autophagy inhibitor 3-MA or wortmannin. Interestingly, gallotannin attenuated the expression of SIRT1 and mTOR and activated phosphorylation of AMPK in two HCC cells. Furthermore, AMPK activator AICAR significantly enhanced SA-β-gal activity and antiproliferation induced by gallotannin, while AMPK inhibitor compound C did not in two HCC cells. Consistently, LC3B-II conversion by gallotannin was not shown in AMPKα1 −/− MEF cells compared to WT AMPK +/+ MEF cells. Consistently, gallotannin reduced in vivo growth of HepG2 cells implanted in NCr nude mice along with decreased expression of PCNA and SIRT1 and increased AMPKα1 and TUNEL. Overall, these findings highlight evidence that regulation of SIRT1/AMPK is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in HCC cells.

// Kwon Jeong 1, * , Hee Young Kwon 1, * , Myoung Seok Jeong 1 , Eun Jung Sohn 1 and Sung-Hoon Kim 1 1 Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea * These authors have contributed equally to this work Correspondence to: Sung-Hoon Kim, email: sungkim7@khu.ac.kr Keywords: CNOT2, p62/SQSTM1, ATG5, PB1 domain, autophagy Received: October 19, 2016 Accepted: April 20, 2017 Published: May 08, 2017 ABSTRACT Though CNOT2 is involved in regulation of adipogenic differentiation, apoptotic cell death and metastasis, the underlying autophagic mechanism of CNOT2 was unknown until now. Thus, in the present study, the critical role of CNOT2 in autophagy was elucidated in association with p62/SQSTM1 signaling. CNOT2 depletion induced p62/SQSTM1 accumulation and LC3B-II conversion, and also increased the number of puncta with impaired autophagic flux. In contrast, CNOT2 overexpression induced downregulation and ubiquitination of p62/SQSTM1 in HEK293 QBI. Furthermore, ubiquitination of p62/SQSTM1 was blocked by autophagy inhibition. Interestingly, CNOT2 was correlated with p62/SQSTM1 in HEK293 QBI cells and also was colocalized with p62/SQSTM1 in H1299 cells. Additionally, ATG5 was upregulated in CNOT2-depleted H1299 cells, while degradation of p62/SQSTM1 by CNOT2 was detected in ATG5 +/+ MEF cells but not in ATG5 -/- MEF cells. Of note, CNOT2 induced degradation of p62/SQSTM1 in HEK293 QBI cells co-transfected with Myc-ΔLIR/KIR or Myc-ΔUBA, but not with Myc-ΔPB1. Sub G 1 population was increased in CNOT2-depleted H1299 cells by late autophagy inhibitors, ammonium chloride and chloroquine compared to 3-methyladenine. Overall, these findings provide novel insight into the critical role of CNOT2 as a negative regulator in ATG5 dependent autophagy.

We propose a new efficient algorithm to simulate magnetic structures numerically. It contains a generative model using a complex-valued neural network to generate k-space information. The output information is hermitized and transformed into real-space spin configurations through an inverse fast Fourier transform. The Adam version of stochastic gradient descent is used to minimize the magnetic energy, which is the cost of our algorithm. The algorithm provides the proper ground spin configurations with outstanding performance. In model cases, the algorithm was successfully applied to solve the spin configurations of magnetic chiral structures. The results also showed that a magnetic long-range order could be obtained regardless of the total simulation system size.

We use a Monte Carlo simulation to investigate the magnetic structures in a bilayer magnetic system containing a locally inverted interlayer coupling region. The stabilization of multiple magnetic structures, including the magnetic skyrmion, is possible in the locally inverted interlayer coupling region. Various factors such as the region area, anisotropy, interlayer coupling strength, and exchange coupling strength affect the properties of the structures, including their size and chirality. We obtain conditions for the stabilization and transitions of these magnetic structures. The Dzyaloshinskii-Moriya interaction (DMI) and dipolar interaction play prominent roles as they significantly enhance the formation and stability of the structures. An asymmetric feature can arise from the broken inversion symmetry in the structure formation, yielding an interfacial DMI, which stabilizes the skyrmion. It is demonstrated that the dipole interaction also acts as an effective interfacial DMI in the system.

Magnetism is a canonical example of a spontaneous symmetry breaking. The symmetry of a magnetic state below the Curie temperature is spontaneously broken even though the Hamiltonian is invariant under symmetry. Recently, machine learning algorithms have been successfully utilized to study topics in physics. We applied unsupervised machine learning algorithms to find the magnetic ground states of the Heisenberg model. A fully connected neural network was used to generate the spin configuration from randomly coded features, and the magnetic energy was selected as the cost to be minimized during the machine learning process. We found that ground states solved by the unsupervised learning process are consistent with the theoretical solution. Also, we compared the results with those from traditional computational methods and found that the machine learning algorithm provides an efficient method to solve the magnetic state numerically.

Two-dimensional (2D) magnetic van der Waals crystals have received great attentions recently owing to their novel electronic and magnetic properties and rich potentials for low-dimensional and high-density spintronic devices. We investigated the magnetization dynamics of CrI3 and CrBr3 bulk single crystals by utilizing broadband ferromagnetic resonance (FMR) in a frequency range of 1 – 40 GHz and over a wide temperature range of 10 – 300 K. Complex features observed in the FMR spectra are quantitatively described by the multi-domain FMR theory. The minimum resonance frequency fmin in FMR spectra was recognized and analyzed as characteristics of the transition of the domain structure. Micromagnetic simulation on the domain structure and spin dynamics explains that the multi-domain structure exists under strong in-plane magnetic field for CrI3 and CrBr3 and significantly influences the magnetic dynamics properties. Our results also suggest that the linewidths of FMR spectra in CrI3 and CrBr3 are dominated by the magnetic inhomogeneous broadening.

Although gallotannin contained in several medicinal plants was known to have multi-biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC-3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl-1) signaling. Gallotannin exerted dose-dependent cytotoxicity in DU145, PC-3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub-G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl-1, B-cell lymphoma 2, and B-cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl-1 reversed the ability of gallotannin to cleave PARP and increase sub-G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl-1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl-1 and activation of caspases are critically involved in gallotannin-induced apoptosis in prostate cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.

Chiral spin textures in ultrathin films, such as skyrmions or chiral domain walls, are believed to offer large performance advantages in the development of novel spintronics technologies. While in-plane magnetized films have been studied extensively as media for current- and field-driven domain wall dynamics with applications in memory or logic devices, the stabilization of chiral spin textures in in-plane magnetized films has remained rare. Here we report a phase of spin structures in an in-plane magnetized ultrathin film system where out-of-plane spin orientations within domain walls are stable. Moreover, while domain walls in in-plane films are generally expected to be non-chiral, we show that right-handed spin rotations are strongly favoured in this system, due to the presence of the interfacial Dzyaloshinskii–Moriya interaction. These results constitute a platform to explore unconventional spin dynamics and topological phenomena that may enable high-performance in-plane spin-orbitronics devices., Chiral domain walls in magnetic films can be electrically controlled, which makes them attractive for applications, but domain walls in ultrathin films are normally non-chiral. Here, the authors observe chiral domain walls in ultrathin Fe/Ni bilayers that are stabilized by the magnetic anisotropy.

Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells. Also, apoptotic bodies and terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) positive cells were observed in BK10007S treated HepG2 and SK-Hep1 cells by 4',6-diamidino-2-phenylinodole (DAPI) staining and TUNEL assay, respectively. Consistently, BK10007S increased sub G1 population in HepG2 and SK-Hep1 cells by cell cycle analysis. Furthermore, Western blotting revealed that BK10007S activated the caspase cascades (caspase 8, 9 and 3), cleaved poly (ADP-ribose) polymerase (PARP), and downregulated the expression of cyclin D1, survivin and for CUG-binding protein 1 (CUGBP1 or CELF1) in HepG2 and SK-Hep1 cells. Conversely, overexpression of CUGBP1 reduced cleavages of PARP and caspase 3, cytotoxicity and subG1 population in BK10007S treated HepG2 cells. Overall, these findings provide scientific evidences that BK10007S induces apoptosis via inhibition of CUGBP1 and activation of caspases in hepatocellular carcinomas as a potent anticancer candidate.

Recently, the domain walls of stripe domain in Fe/Ni bilayer system are found to have Neel-type domain wall with a definite chirality. We investigated how Dzyaloshinskii–Moriya (DM) interaction modifies the properties of magnetic stripe domains generated by long-range dipole interaction at spin reorientation transitions using a theoretical model calculation and a computational simulation. The chirality of the domain wall magnetism and the size of stripe domains are affected by DM interaction, and the modification depends on the direction of the DM vector. We analyzed the amount of modification and obtained a formulation with the ratio between the strengths of the DMI and dipolar interaction. It is studied how DMI affects the temperature induced spin reorientation transition.

Though gallotannin was known to have anti-oxidant and antitumor activity, the underlying antitumor mechanism of gallotannin still remains unclear. Thus, in the present study, antitumor mechanism of gallotannin was elucidated in hepatocellular carcinoma cells. Gallotannin significantly exerted cytotoxicity against Hep G2 and Chang hepatocellular carcinoma cells with the accumulation of the sub-G1 population and increase of terminal deoxynucleotidyltransferasedUTP nick end labeling (TUNEL) positive cells as an apoptotic feature. Also, gallotannin attenuated the expression of pro-caspase9, pro-caspase3, Bcl2 and integrin β1 and cleaved poly(ADP)-ribose polymerase (PARP) in Hep G2 and Chang cancer cells. Furthermore, gallotannin suppressed cell repair motility by wound healing assay and also inhibited cell adhesion in Hep G2 cells. Of note, gallotannin attenuated the expression of epithelial cadherin (E-cadherin) to form cell-cell adhesion from the early stage, and also beta-catenin at late phase in Hep G2 cells. Consistently, Immunofluorescence assay showed that E-cadherin or β-catenin expression was suppressed in a time dependent manner by gallotannin. Furthermore, silencing of E-cadherin by siRNA transfection method enhanced PAPR cleavage, caspase 3 activation and sub G1 population and attenuated the cell adhesion induced by gallotannin in Hep G2 cells. Overall, our findings demonstrate that the disruption of cell adhesion junction by suppression of E-cadherin mediates gallotannin enhanced apoptosis in Hep G2 liver cancer cells.

Though CNOT2 is involved in regulation of adipogenic differentiation, apoptotic cell death and metastasis, the underlying autophagic mechanism of CNOT2 was unknown until now. Thus, in the present study, the critical role of CNOT2 in autophagy was elucidated in association with p62/SQSTM1 signaling. CNOT2 depletion induced p62/SQSTM1 accumulation and LC3B-II conversion, and also increased the number of puncta with impaired autophagic flux. In contrast, CNOT2 overexpression induced downregulation and ubiquitination of p62/SQSTM1 in HEK293 QBI. Furthermore, ubiquitination of p62/SQSTM1 was blocked by autophagy inhibition. Interestingly, CNOT2 was correlated with p62/SQSTM1 in HEK293 QBI cells and also was colocalized with p62/SQSTM1 in H1299 cells. Additionally, ATG5 was upregulated in CNOT2-depleted H1299 cells, while degradation of p62/SQSTM1 by CNOT2 was detected in ATG5+/+ MEF cells but not in ATG5-/- MEF cells. Of note, CNOT2 induced degradation of p62/SQSTM1 in HEK293 QBI cells co-transfected with Myc-ΔLIR/KIR or Myc-ΔUBA, but not with Myc-ΔPB1. Sub G1 population was increased in CNOT2-depleted H1299 cells by late autophagy inhibitors, ammonium chloride and chloroquine compared to 3-methyladenine. Overall, these findings provide novel insight into the critical role of CNOT2 as a negative regulator in ATG5 dependent autophagy.

We numerically investigated the spread of the magnetic helical structure under the Dzyaloshinskii–Moriya interaction (DMI). During the relaxation process from initial perpendicular magnetism, half-vortex structures are first formed by thermal fluctuation at the boundary of the system. Subsequently, the helical structures extend inward to form well-aligned structures that are perpendicular to the boundary line. We obtained a formula that describes the propagation speed of the helical structure, which is proportional to the DMI strength but is not influenced by the strength of the exchange interaction. The final magnetic structure is determined by the shape of the system or the locations of defects. Therefore, magnetic domain patterns could be engineered by controlling the domain seeds through intentional inclusion of sample defects at specific locations.

The influences of uniaxial in-plane anisotropy on the properties of ordered magnetic structures generated by the DM interaction were investigated by performing Monte-Carlo simulated annealing. The uniaxial anisotropy aligns the magnetic structure along a specific direction and helps to organize magnetic skyrmions to form either a horizontal or a vertical hexagonal structure, depending on the anisotropy strength. The uniaxial in-plane anisotropy not only enhances the ordering of the structure but also enriches the phases of the system, which include a rectangular lattice structure of skyrmions and 1D skyrmion arrays separated by stripe domains. We investigate the formation conditions of the anisotropy strength and the external field for various magnetic phases.

Despite the antitumour effect of ursolic acid observed in several cancers, the underlying mechanism remains unclear. Thus, in the present study, the roles of AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK3β) were examined in ursolic acid induced apoptosis in HepG2 hepatocellular carcinoma cells. Ursolic acid significantly exerted cytotoxicity, increased the sub-G1 population and the number of ethidium homodimer and terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling positive cells in HepG2 cells. Also, ursolic acid enhanced the cleavages of poly-ADP-ribose polymerase (PARP) and caspase3, attenuated the expression of astrocyte elevated gene (AEG1) and survivin in HepG2 cells. Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells. Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells. Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells. Overall, our findings suggest that ursolic acid induced apoptosis in HepG2 cells via AMPK activation and GSK3β phosphorylation as a potent chemopreventive agent.

Self-organized long-range order structures, such as stripe domains and magnetic skyrmion lattices, are formed by the competition between ferromagnetic exchange interaction and Dzyaloshinskii–Moriya (DM) interaction. We investigated the properties of the magnetic structures generated by a DM interaction under the influence of anisotropy or magnetic dipole interaction, by performing Monte-Carlo simulated annealing. We constructed phase maps in external-field and anisotropy space to study the effect of anisotropy or dipole interaction on the phase boundaries between the magnetic structures. The simulation results show that the phase boundaries are sensitive to perpendicular anisotropy and that the skyrmion lattice region in phase space is extended under easy-plane anisotropy. The effect of the long-range dipole interaction was studied and was found to stabilize the skyrmion lattice phase and reduce the size of the magnetic structures.

Exchange bias phenomena appear not only in ferromagnetic/antiferromagnetic systems but also in ferromagnetic/ferromagnetic systems in which two layers are nearly perpendicularly coupled. We investigated the origin of the symmetry-breaking mechanism and the relationship between the exchange bias and the system's energy parameters. We compared the results of computational Monte Carlo simulations with those of theoretical model calculation. We found that the exchange bias exhibited nonlinear behaviors, including sign reversal and singularities. These complicated behaviors were caused by two distinct magnetization processes depending on the interlayer coupling strength. The exchange bias reached a maximum at the transition between the two magnetization processes.

Cisplatin shows limited therapeutic efficacy due to serious side effects such as nephrotoxicity and hepatotoxicity. In the present study, we demonstrate that 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) has protective effects against cisplatin-induced cytotoxicity and apoptosis in normal human primary renal epithelial cells (HRCs) while showing synergistic effect against cisplatin-induced cell death in human Caki-2 renal cancer cells. PGG significantly blocked cisplatin-mediated cytotoxicity and reduced cisplatin-induced sub-G1 accumulation in HRCs. Consistently, PGG reduced the number of apoptotic cell populations by TdT-mediated dUTP nick end labeling (TUNEL) and Live/Dead assays in cisplatin-treated HRCs. Furthermore, PGG suppressed PARP cleavage and caspase-3 activation, cytochrome c release, up-regulation of bax and p53 in cisplatin-treated HRCs. Moreover, PGG attenuated reactive oxygen species (ROS) production mediated by cisplatin treatment, suggesting that PGG prevented cisplatin-induced apoptosis by inhibiting ROS generation in HRCs. Notably, PGG significantly enhanced cytotoxicity and PARP cleavage in cisplatin-treated Caki-2 renal cancer cells. Combination Index (CI) revealed synergism between PGG and cisplatin in Caki-2 cells. Taken together, our findings suggest the dual effects of PGG as a protective supplement against cisplatin-induced toxicity in normal renal cells and a combination chemotherapeutic drug with cisplatin in renal cancer cells.

The spin configurations of two dimensional ferromagnetic/antiferromagnetic system were investigated using model calculations and Monte-Carlo simulation methods. The lowest energy state was obtained under various coupling conditions to investigate the role of interfacial interaction on anisotropy. We found that the total ferromagnetic layer anisotropy is contributed not only from its own crystalline anisotropy but also from the antiferromagnetic layer spin flop effect. The overall ferromagnetic layer effective anisotropy is calculated as a function of the exchange energy of antiferromagnetic layer and the interfacial interaction energy. If the effective anisotropy from the spin flop effect is comparable with the crystalline anisotropy, the asymmetric spin configuration is generated. In this configuration, the magnetization direction of the ferromagnetic layer is neither perpendicular nor parallel to the antiferromagnetic spin direction. Temperature effect on the perpendicular-to-collinear coupling transition was also investigated using Monte-Carlo simulation, and the relationship between the effective anisotropy and the temperature was obtained.